Libre Pathology - User contributions [en]

Brain metastasis

2024-04-26T11:04:29Z

Jensflorian: /* General */ Treatment

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Metastatic_adenocarcinoma_-_cerebellum_-_high_mag.jpg
| Width =
| Caption = Metastatic adenocarcinoma, compatible with colorectal primary. [[HPS stain]].
| Synonyms =
| Micro = usu. well-demarcated border between brain and lesion, no cytoplasmic processes (seen in glial tumours), usu. have [[nuclear atypia]] of malignancy, +/-glandular architecture, +/-nucleoli seen
| Subtypes =
| LMDDx = primary brain tumour - see ''[[Neuropathology_tumours#Primary_versus_secondary|primary brain tumour versus secondary brain tumour]]''
| Stains =
| IHC = GFAP -ve, dependent on primary - typical +ve for keratins (as carcinoma)
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site = [[brain]]
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence = most common brain tumour (adults)
| Bloodwork =
| Rads = intra-axial, typically grey-white junction, cerebellum (esp. in adults)
| Endoscopy =
| Prognosis = poor
| Other =
| ClinDDx = primary brain tumour, cerebral abscess or infection
| Tx = surgery, chemotherapy, radiation therapy
}}
'''Brain metastasis''', also '''metastatic brain tumour''',<ref>URL: [http://www.nlm.nih.gov/medlineplus/ency/article/000769.htm http://www.nlm.nih.gov/medlineplus/ency/article/000769.htm]. Accessed on: November 8, 2014.</ref> is a [[brain tumour]] that arose elsewhere and spread to the brain.

==General==
*Most common brain tumour in adults.<ref>{{Cite journal | last1 = Pekmezci | first1 = M. | last2 = Perry | first2 = A. | title = Neuropathology of brain metastases. | journal = Surg Neurol Int | volume = 4 | issue = Suppl 4 | pages = S245-55 | month = | year = 2013 | doi = 10.4103/2152-7806.111302 | PMID = 23717796 }}</ref><ref>{{Cite journal | last1 = Suki | first1 = D. | last2 = Khoury Abdulla | first2 = R. | last3 = Ding | first3 = M. | last4 = Khatua | first4 = S. | last5 = Sawaya | first5 = R. | title = Brain metastases in patients diagnosed with a solid primary cancer during childhood: experience from a single referral cancer center. | journal = J Neurosurg Pediatr | volume = 14 | issue = 4 | pages = 372-85 | month = Oct | year = 2014 | doi = 10.3171/2014.7.PEDS13318 | PMID = 25127097 }}</ref>
** Brain metastases are found in up to 25% cancer patients at autopsy. <ref>{{Cite journal | last1 = Gavrilovic | first1 = IT. | last2 = Posner | first2 = JB. | title = Brain metastases: epidemiology and pathophysiology. | journal = J Neurooncol | volume = 75 | issue = 1 | pages = 5-14 | month = Oct | year = 2005 | doi = 10.1007/s11060-004-8093-6 | PMID = 16215811 }}</ref>
**Incidence of brain metastases increases with age.
** 80% of brain metastases are located supratentorial, usu. at the border between white and grey matter.
*In more than 50% there are multiple metastases in the brain.
*Common primary sites (in order of prevalence): [[lung cancer|lung]], [[invasive breast cancer|breast]], [[renal cell carcinoma|kidney]], [[Gastrointestinal pathology|gastrointestinal]], [[melanoma]].<ref>{{Ref TN2007|NS9}}</ref>
*Percentage of previously diagnosed cancers with brain metastases - by primary site: lung cancer 19.9%, melanoma 6.9%, breast cancer 5.1%, renal cancer 6.5%, colorectal cancer 1.8%.<ref name=pmid15254054>{{Cite journal | last1 = Barnholtz-Sloan | first1 = JS. | last2 = Sloan | first2 = AE. | last3 = Davis | first3 = FG. | last4 = Vigneau | first4 = FD. | last5 = Lai | first5 = P. | last6 = Sawaya | first6 = RE. | title = Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. | journal = J Clin Oncol | volume = 22 | issue = 14 | pages = 2865-72 | month = Jul | year = 2004 | doi = 10.1200/JCO.2004.12.149 | PMID = 15254054 }}</ref>
**''Lung'' followed by ''kidney'' is the order in a smaller series.<ref>{{Cite journal | last1 = Schouten | first1 = LJ. | last2 = Rutten | first2 = J. | last3 = Huveneers | first3 = HA. | last4 = Twijnstra | first4 = A. | title = Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. | journal = Cancer | volume = 94 | issue = 10 | pages = 2698-705 | month = May | year = 2002 | doi = | PMID = 12173339 }}</ref>
*Treatment: Surgery 1-3 metastases, Stereotactic RT in 1-4(rarely up to 10) metastases, >4-10 metastases: Whole Brain RT.

==Gross/Radiology==
*Intra-axial location.
**Typically at the grey-white junction.<ref name=pmid19727563>{{Cite journal | last1 = Della Puppa | first1 = A. | last2 = Dal Pos | first2 = S. | last3 = Zovato | first3 = S. | last4 = Orvieto | first4 = E. | last5 = Ciccarino | first5 = P. | last6 = Manara | first6 = R. | last7 = Zustovich | first7 = F. | last8 = Berti | first8 = F. | last9 = Gardiman | first9 = MP. | title = Solitary intra-ventricular brain metastasis from a breast carcinoma. | journal = J Neurooncol | volume = 97 | issue = 1 | pages = 123-6 | month = Mar | year = 2010 | doi = 10.1007/s11060-009-9988-z | PMID = 19727563 }}</ref>

Image:
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3656562/figure/F1/ Brain metastases (nih.gov)].<ref name=pmid23717796 >{{Cite journal | last1 = Pekmezci | first1 = M. | last2 = Perry | first2 = A. | title = Neuropathology of brain metastases. | journal = Surg Neurol Int | volume = 4 | issue = Suppl 4 | pages = S245-55 | month = | year = 2013 | doi = 10.4103/2152-7806.111302 | PMID = 23717796 }}</ref>

<gallery>
File:AFIP403613G-THYROID PAPILLARY CARCINOMA METASTATIC TO BRAIN.jpg | Well demarcated metastasis (WC/Dr. Kostich)
File:BrainMetastasisFromBreastCancer.jpg | 3 brain metastases in breast cancer (WC/Jmarchn)
</gallery>

==Microscopic==
Appearance varies by subtype.

Features of [[metastatic carcinoma]]:
*Tubule formation/glands.
*Usually well-circumscribed/sharply demarcated from surrounding tissue.
*Usually nuclear atypia including:
**Nuclear hyperchromasia.
**Variation of nuclear size.
**Variation of nuclear shape.
*Mitoses - common.

DDx:
*Primary brain tumour - ''see [[Neuropathology_tumours#Primary_versus_secondary|primary brain tumour versus secondary brain tumour]]''.

===Images===
<gallery>
Image:Metastatic_adenocarcinoma_-_cerebellum_-_very_low_mag.jpg | [[CRC]] metastasis to cerebellum - very low mag. (WC)
Image:Metastatic adenocarcinoma - cerebellum - intermed mag.jpg| CRC metastasis to the cerebellum - intermed. mag. (WC)
Image:Metastatic_adenocarcinoma_-_cerebellum_-_high_mag.jpg | CRC metastasis to cerebellum - high mag. (WC)
Image:Brain metastasis - high mag.jpg | Brain metastasis - high mag. (WC)
File:Adenocarcinoma infiltrating the brain.jpg | Adenocarcinoma of the lung metastasis. (WC/jensflorian)
</gallery>

==IHC==
{{Main|Immunohistochemistry}}
*Carcinoma: pankeratin +ve.
**[[Lung adenocarcinoma]] and SCLC: TTF-1 +ve, CK7 +ve, CK20 -ve.
**Breast carcinoma: CK7 +ve, ER +ve, PR +ve, BRST2 +ve/-ve.
**Colorectal carcinoma: CK7 -ve, CK20 +ve, CDX2 +ve, TTF-1 -ve.
**[[Clear cell renal cell carcinoma]]: PAX8 +ve, CK7 -ve, CK20 -ve, vimentin +ve, CD10 +ve.
*Melanoma: S-100 +ve, HMB-45 +ve, Melan A +ve.
*GFAP -ve.<ref name=pmid23717796 >{{Cite journal | last1 = Pekmezci | first1 = M. | last2 = Perry | first2 = A. | title = Neuropathology of brain metastases. | journal = Surg Neurol Int | volume = 4 | issue = Suppl 4 | pages = S245-55 | month = | year = 2013 | doi = 10.4103/2152-7806.111302 | PMID = 23717796 }}</ref>

Other glial markers (suggest primary):<ref name=pmid23717796/>
*OLIG2, SOX2.

<gallery>
File:Immunhistochemie Bronchialkarzinom.jpg | CK7+/CK20-/TTF1+ profile in pulmonary adenocarcinoma metastasis. (WC/Marvin101)
</gallery>

==Origin==
===Breast===
*8-30% BM.
*Triple-negative cases have a poor prognosis.
==See also==
*[[Neuropathology tumours]].
*[[Metastasis]].

==References==
{{Reflist|2}}

[[Category:Neuropathology]]
[[Category:Diagnosis]]

Brain metastasis

2024-04-26T11:02:56Z

Jensflorian: BM

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Metastatic_adenocarcinoma_-_cerebellum_-_high_mag.jpg
| Width =
| Caption = Metastatic adenocarcinoma, compatible with colorectal primary. [[HPS stain]].
| Synonyms =
| Micro = usu. well-demarcated border between brain and lesion, no cytoplasmic processes (seen in glial tumours), usu. have [[nuclear atypia]] of malignancy, +/-glandular architecture, +/-nucleoli seen
| Subtypes =
| LMDDx = primary brain tumour - see ''[[Neuropathology_tumours#Primary_versus_secondary|primary brain tumour versus secondary brain tumour]]''
| Stains =
| IHC = GFAP -ve, dependent on primary - typical +ve for keratins (as carcinoma)
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site = [[brain]]
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence = most common brain tumour (adults)
| Bloodwork =
| Rads = intra-axial, typically grey-white junction, cerebellum (esp. in adults)
| Endoscopy =
| Prognosis = poor
| Other =
| ClinDDx = primary brain tumour, cerebral abscess or infection
| Tx = surgery, chemotherapy, radiation therapy
}}
'''Brain metastasis''', also '''metastatic brain tumour''',<ref>URL: [http://www.nlm.nih.gov/medlineplus/ency/article/000769.htm http://www.nlm.nih.gov/medlineplus/ency/article/000769.htm]. Accessed on: November 8, 2014.</ref> is a [[brain tumour]] that arose elsewhere and spread to the brain.

==General==
*Most common brain tumour in adults.<ref>{{Cite journal | last1 = Pekmezci | first1 = M. | last2 = Perry | first2 = A. | title = Neuropathology of brain metastases. | journal = Surg Neurol Int | volume = 4 | issue = Suppl 4 | pages = S245-55 | month = | year = 2013 | doi = 10.4103/2152-7806.111302 | PMID = 23717796 }}</ref><ref>{{Cite journal | last1 = Suki | first1 = D. | last2 = Khoury Abdulla | first2 = R. | last3 = Ding | first3 = M. | last4 = Khatua | first4 = S. | last5 = Sawaya | first5 = R. | title = Brain metastases in patients diagnosed with a solid primary cancer during childhood: experience from a single referral cancer center. | journal = J Neurosurg Pediatr | volume = 14 | issue = 4 | pages = 372-85 | month = Oct | year = 2014 | doi = 10.3171/2014.7.PEDS13318 | PMID = 25127097 }}</ref>
** Brain metastases are found in up to 25% cancer patients at autopsy. <ref>{{Cite journal | last1 = Gavrilovic | first1 = IT. | last2 = Posner | first2 = JB. | title = Brain metastases: epidemiology and pathophysiology. | journal = J Neurooncol | volume = 75 | issue = 1 | pages = 5-14 | month = Oct | year = 2005 | doi = 10.1007/s11060-004-8093-6 | PMID = 16215811 }}</ref>
**Incidence of brain metastases increases with age.
** 80% of brain metastases are located supratentorial, usu. at the border between white and grey matter.
*In more than 50% there are multiple metastases in the brain.
*Common primary sites (in order of prevalence): [[lung cancer|lung]], [[invasive breast cancer|breast]], [[renal cell carcinoma|kidney]], [[Gastrointestinal pathology|gastrointestinal]], [[melanoma]].<ref>{{Ref TN2007|NS9}}</ref>
*Percentage of previously diagnosed cancers with brain metastases - by primary site: lung cancer 19.9%, melanoma 6.9%, breast cancer 5.1%, renal cancer 6.5%, colorectal cancer 1.8%.<ref name=pmid15254054>{{Cite journal | last1 = Barnholtz-Sloan | first1 = JS. | last2 = Sloan | first2 = AE. | last3 = Davis | first3 = FG. | last4 = Vigneau | first4 = FD. | last5 = Lai | first5 = P. | last6 = Sawaya | first6 = RE. | title = Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. | journal = J Clin Oncol | volume = 22 | issue = 14 | pages = 2865-72 | month = Jul | year = 2004 | doi = 10.1200/JCO.2004.12.149 | PMID = 15254054 }}</ref>
**''Lung'' followed by ''kidney'' is the order in a smaller series.<ref>{{Cite journal | last1 = Schouten | first1 = LJ. | last2 = Rutten | first2 = J. | last3 = Huveneers | first3 = HA. | last4 = Twijnstra | first4 = A. | title = Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. | journal = Cancer | volume = 94 | issue = 10 | pages = 2698-705 | month = May | year = 2002 | doi = | PMID = 12173339 }}</ref>

==Gross/Radiology==
*Intra-axial location.
**Typically at the grey-white junction.<ref name=pmid19727563>{{Cite journal | last1 = Della Puppa | first1 = A. | last2 = Dal Pos | first2 = S. | last3 = Zovato | first3 = S. | last4 = Orvieto | first4 = E. | last5 = Ciccarino | first5 = P. | last6 = Manara | first6 = R. | last7 = Zustovich | first7 = F. | last8 = Berti | first8 = F. | last9 = Gardiman | first9 = MP. | title = Solitary intra-ventricular brain metastasis from a breast carcinoma. | journal = J Neurooncol | volume = 97 | issue = 1 | pages = 123-6 | month = Mar | year = 2010 | doi = 10.1007/s11060-009-9988-z | PMID = 19727563 }}</ref>

Image:
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3656562/figure/F1/ Brain metastases (nih.gov)].<ref name=pmid23717796 >{{Cite journal | last1 = Pekmezci | first1 = M. | last2 = Perry | first2 = A. | title = Neuropathology of brain metastases. | journal = Surg Neurol Int | volume = 4 | issue = Suppl 4 | pages = S245-55 | month = | year = 2013 | doi = 10.4103/2152-7806.111302 | PMID = 23717796 }}</ref>

<gallery>
File:AFIP403613G-THYROID PAPILLARY CARCINOMA METASTATIC TO BRAIN.jpg | Well demarcated metastasis (WC/Dr. Kostich)
File:BrainMetastasisFromBreastCancer.jpg | 3 brain metastases in breast cancer (WC/Jmarchn)
</gallery>

==Microscopic==
Appearance varies by subtype.

Features of [[metastatic carcinoma]]:
*Tubule formation/glands.
*Usually well-circumscribed/sharply demarcated from surrounding tissue.
*Usually nuclear atypia including:
**Nuclear hyperchromasia.
**Variation of nuclear size.
**Variation of nuclear shape.
*Mitoses - common.

DDx:
*Primary brain tumour - ''see [[Neuropathology_tumours#Primary_versus_secondary|primary brain tumour versus secondary brain tumour]]''.

===Images===
<gallery>
Image:Metastatic_adenocarcinoma_-_cerebellum_-_very_low_mag.jpg | [[CRC]] metastasis to cerebellum - very low mag. (WC)
Image:Metastatic adenocarcinoma - cerebellum - intermed mag.jpg| CRC metastasis to the cerebellum - intermed. mag. (WC)
Image:Metastatic_adenocarcinoma_-_cerebellum_-_high_mag.jpg | CRC metastasis to cerebellum - high mag. (WC)
Image:Brain metastasis - high mag.jpg | Brain metastasis - high mag. (WC)
File:Adenocarcinoma infiltrating the brain.jpg | Adenocarcinoma of the lung metastasis. (WC/jensflorian)
</gallery>

==IHC==
{{Main|Immunohistochemistry}}
*Carcinoma: pankeratin +ve.
**[[Lung adenocarcinoma]] and SCLC: TTF-1 +ve, CK7 +ve, CK20 -ve.
**Breast carcinoma: CK7 +ve, ER +ve, PR +ve, BRST2 +ve/-ve.
**Colorectal carcinoma: CK7 -ve, CK20 +ve, CDX2 +ve, TTF-1 -ve.
**[[Clear cell renal cell carcinoma]]: PAX8 +ve, CK7 -ve, CK20 -ve, vimentin +ve, CD10 +ve.
*Melanoma: S-100 +ve, HMB-45 +ve, Melan A +ve.
*GFAP -ve.<ref name=pmid23717796 >{{Cite journal | last1 = Pekmezci | first1 = M. | last2 = Perry | first2 = A. | title = Neuropathology of brain metastases. | journal = Surg Neurol Int | volume = 4 | issue = Suppl 4 | pages = S245-55 | month = | year = 2013 | doi = 10.4103/2152-7806.111302 | PMID = 23717796 }}</ref>

Other glial markers (suggest primary):<ref name=pmid23717796/>
*OLIG2, SOX2.

<gallery>
File:Immunhistochemie Bronchialkarzinom.jpg | CK7+/CK20-/TTF1+ profile in pulmonary adenocarcinoma metastasis. (WC/Marvin101)
</gallery>

==Origin==
===Breast===
*8-30% BM.
*Triple-negative cases have a poor prognosis.
==See also==
*[[Neuropathology tumours]].
*[[Metastasis]].

==References==
{{Reflist|2}}

[[Category:Neuropathology]]
[[Category:Diagnosis]]

High-grade astrocytoma with piloid features

2022-10-17T13:54:06Z

Jensflorian: HGAP

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Pilocytic astrocytoma with anaplastic features.jpg
| Width =
| Caption = High-grade astrocytoma with piloid features. [[H&E stain]].
| Synonyms =
| Micro =
| Subtypes =
| LMDDx = [[astrocytoma]], [[PXA]], [[glioblastoma]]
| Stains = PAS-D +ve (eosinophilic granular bodies)
| IHC = GFAP +ve
| EM =
| Molecular =
| IF =
| Gross = usually cerebellar
| Grossing =
| Site = brain - usu. [[cerebellum]]
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence = very rare - esp. in children
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis = poor (analog to WHO Grade III)
| Other =
| ClinDDx =
| Tx =
}}

'''High-grade astrocytoma with piloid features''' (HGAP) is a rare [[Glioma|glial]] tumor which often requires methylation analyis to secure diagnosis. There is currently no definitive grading, but clinical behaviour suggests WHO CNS grade 3.

=Clinical=
*Rare (1-3% of all brain tumor in adults).
*Usu. posterior fossa (75%).
*Supratentorial or spinal locations possible.
*Imaging may be similiar to [[Glioblastoma]].
*5-year OS: 50%.
*De novo cases in the setting of neurofibromatosis 1 reported.
*Tumors may have history of previous radiation.

=Histology=
*Often so variable, so molecular testing is essential to secure diagnosis.
*Astrocytic nature of tumor cells.
*Frequent mitoses.
*Elongated glial tumor cell processes ("piloid").
*Rosenthal fibers or eosinophilic granular bodies.
*Perivascular lymphocytic cuffing.
*Necrosis may be present.

==Images==
<gallery>
Image:Pilocytic astrocytoma with anaplastic features.jpg | HGAP, [[FFPE]] specimen, HE (WC).
Image:Pilocytic astrocytoma with anaplastic features mimicking focally a GBM.jpg | Vacular proliferations and necrosis in HGAP mimicking [[GBM]] (WC).
</gallery>

=IHC=
*[[GFAP]]+ve.
*ATRX: nuclear loss in approx. 40%.

=Molecular=
*DNA Methylation profile of high-grade astrocytoma with piloid features is essential for diagnosis.
*MAPK genes often altered (NF1, BRAF fusion, FGFR1, KRAS).
*CDKN2A/B homozygous deletion.
*CDK4 amplification.
*TERT promotor mutations are rare.
*Absence of IDH1/2 hotspot mutation.

=Prognosis=
*Poor, but better than conventional glioblastoma.<ref>{{Cite journal | last1 = Rodriguez | first1 = FJ. | last2 = Scheithauer | first2 = BW. | last3 = Burger | first3 = PC. | last4 = Jenkins | first4 = S. | last5 = Giannini | first5 = C. | title = Anaplasia in pilocytic astrocytoma predicts aggressive behavior. | journal = Am J Surg Pathol | volume = 34 | issue = 2 | pages = 147-60 | month = Feb | year = 2010 | doi = 10.1097/PAS.0b013e3181c75238 | PMID = 20061938 }}</ref>
*Prognostic unfavourable paramters include: Necrosis, Mitoses and previous radiation.

=DDx:=
*[[Glioblastoma]]
*[[Pleomorphic xanthoastrocytoma]]

=See also=
*[[Astrocytoma]].
*[[Neuropathology_tumours#Infiltrative_astrocytomas]]

{{Reflist|2}}

[[Category:Diagnosis]]
[[Category:Neuropathology tumours]]

Anaplastic pilocytic astrocytoma

2022-10-17T13:52:30Z

Jensflorian: /* General */ tumor is outdated

'''Anaplastic pilocytic astrocytoma''', abbreviated '''APA''', is an outdated tumor terminology. Most of these tumors are now classified either as [[High-grade astrocytoma with piloid features]], [[Pleomorphic xanthoastrocytoma]] or as [[Glioblastoma]], IDH-wildtype.

==General==
*High-grade [[astrocytoma]] - behaviour corresponded in older classifications to ''WHO Grade III''.
*Some authors prefered the designation '''pilocytic astrocytoma with anaplastic features'''.
*Less than 2% of all pilocytic astrocytomas.<ref>{{Cite journal | last1 = Rodriguez | first1 = FJ. | last2 = Scheithauer | first2 = BW. | last3 = Burger | first3 = PC. | last4 = Jenkins | first4 = S. | last5 = Giannini | first5 = C. | title = Anaplasia in pilocytic astrocytoma predicts aggressive behavior. | journal = Am J Surg Pathol | volume = 34 | issue = 2 | pages = 147-60 | month = Feb | year = 2010 | doi = 10.1097/PAS.0b013e3181c75238 | PMID = 20061938 }}</ref>
*De novo cases in the setting of neurofibromatosis 1 reported.
*Many tumors have history of previous radiation.

==Old microscopic criteria==
Features:<ref>{{Cite journal | last1 = Rodriguez | first1 = FJ. | last2 = Scheithauer | first2 = BW. | last3 = Burger | first3 = PC. | last4 = Jenkins | first4 = S. | last5 = Giannini | first5 = C. | title = Anaplasia in pilocytic astrocytoma predicts aggressive behavior. | journal = Am J Surg Pathol | volume = 34 | issue = 2 | pages = 147-60 | month = Feb | year = 2010 | doi = 10.1097/PAS.0b013e3181c75238 | PMID = 20061938 }}</ref>
*At least 4 mitoses/10 high power fields - see [[HPFitis]].
*Hypercellularity.
*Necrosis +/-.
*Pilocytic like (biphasic) - most common.
*#Eosinophilic granular bodies +/-.
*Small cell (32%)
*Epithelioid cells (15%)
*Fibrillary areas resembling [[diffuse astrocytoma]].

==IHC==
Features:<ref>{{Cite journal | last1 = Rodriguez | first1 = FJ. | last2 = Scheithauer | first2 = BW. | last3 = Burger | first3 = PC. | last4 = Jenkins | first4 = S. | last5 = Giannini | first5 = C. | title = Anaplasia in pilocytic astrocytoma predicts aggressive behavior. | journal = Am J Surg Pathol | volume = 34 | issue = 2 | pages = 147-60 | month = Feb | year = 2010 | doi = 10.1097/PAS.0b013e3181c75238 | PMID = 20061938 }}</ref>
*GFAP +ve (fibres).
*p53: +ve.
*KI-67: high 25%.
*[[ATRX]] loss may be present.<ref>{{Cite journal | last1 = Ebrahimi | first1 = A. | last2 = Skardelly | first2 = M. | last3 = Bonzheim | first3 = I. | last4 = Ott | first4 = I. | last5 = Mühleisen | first5 = H. | last6 = Eckert | first6 = F. | last7 = Tabatabai | first7 = G. | last8 = Schittenhelm | first8 = J. | title = ATRX immunostaining predicts IDH and H3F3A status in gliomas. | journal = Acta Neuropathol Commun | volume = 4 | issue = 1 | pages = 60 | month = Jun | year = 2016 | doi = 10.1186/s40478-016-0331-6 | PMID = 27311324 }}</ref>
*[[IDH1]] (R132H) -ve.
*[[H3F3A]] (K27M) -ve.

==See also==
*[[Neuropathology tumours]].
*[[Pilocytic Astrocytoma]].

==References==
{{Reflist|2}}

[[Category:Diagnosis]]
[[Category:Neuropathology tumours]]

Anaplastic pilocytic astrocytoma

2022-10-17T13:51:23Z

Jensflorian: Outdated tumor

'''Anaplastic pilocytic astrocytoma''', abbreviated '''APA''', is an outdated tumor terminology. Most of these tumors are now classified either as [[High-grade astrocytoma with piloid features]], [[Pleomorphic xanthoastrocytoma]] or as [[Glioblastoma]], IDH-wildtype.

==General==
*High-grade [[astrocytoma]] - behaviour corresponds to ''WHO Grade III''.
*Some authors prefered the designation '''pilocytic astrocytoma with anaplastic features'''.
*Less than 2% of all pilocytic astrocytomas.<ref>{{Cite journal | last1 = Rodriguez | first1 = FJ. | last2 = Scheithauer | first2 = BW. | last3 = Burger | first3 = PC. | last4 = Jenkins | first4 = S. | last5 = Giannini | first5 = C. | title = Anaplasia in pilocytic astrocytoma predicts aggressive behavior. | journal = Am J Surg Pathol | volume = 34 | issue = 2 | pages = 147-60 | month = Feb | year = 2010 | doi = 10.1097/PAS.0b013e3181c75238 | PMID = 20061938 }}</ref>
*De novo cases in the setting of neurofibromatosis 1 reported.
*Many tumors have history of previous radiation.

==Old microscopic criteria==
Features:<ref>{{Cite journal | last1 = Rodriguez | first1 = FJ. | last2 = Scheithauer | first2 = BW. | last3 = Burger | first3 = PC. | last4 = Jenkins | first4 = S. | last5 = Giannini | first5 = C. | title = Anaplasia in pilocytic astrocytoma predicts aggressive behavior. | journal = Am J Surg Pathol | volume = 34 | issue = 2 | pages = 147-60 | month = Feb | year = 2010 | doi = 10.1097/PAS.0b013e3181c75238 | PMID = 20061938 }}</ref>
*At least 4 mitoses/10 high power fields - see [[HPFitis]].
*Hypercellularity.
*Necrosis +/-.
*Pilocytic like (biphasic) - most common.
*#Eosinophilic granular bodies +/-.
*Small cell (32%)
*Epithelioid cells (15%)
*Fibrillary areas resembling [[diffuse astrocytoma]].

==IHC==
Features:<ref>{{Cite journal | last1 = Rodriguez | first1 = FJ. | last2 = Scheithauer | first2 = BW. | last3 = Burger | first3 = PC. | last4 = Jenkins | first4 = S. | last5 = Giannini | first5 = C. | title = Anaplasia in pilocytic astrocytoma predicts aggressive behavior. | journal = Am J Surg Pathol | volume = 34 | issue = 2 | pages = 147-60 | month = Feb | year = 2010 | doi = 10.1097/PAS.0b013e3181c75238 | PMID = 20061938 }}</ref>
*GFAP +ve (fibres).
*p53: +ve.
*KI-67: high 25%.
*[[ATRX]] loss may be present.<ref>{{Cite journal | last1 = Ebrahimi | first1 = A. | last2 = Skardelly | first2 = M. | last3 = Bonzheim | first3 = I. | last4 = Ott | first4 = I. | last5 = Mühleisen | first5 = H. | last6 = Eckert | first6 = F. | last7 = Tabatabai | first7 = G. | last8 = Schittenhelm | first8 = J. | title = ATRX immunostaining predicts IDH and H3F3A status in gliomas. | journal = Acta Neuropathol Commun | volume = 4 | issue = 1 | pages = 60 | month = Jun | year = 2016 | doi = 10.1186/s40478-016-0331-6 | PMID = 27311324 }}</ref>
*[[IDH1]] (R132H) -ve.
*[[H3F3A]] (K27M) -ve.

==See also==
*[[Neuropathology tumours]].
*[[Pilocytic Astrocytoma]].

==References==
{{Reflist|2}}

[[Category:Diagnosis]]
[[Category:Neuropathology tumours]]

Astrocytoma

2022-10-17T13:48:17Z

Jensflorian: /* Uncommon Astrocytomas */ link

An '''astrocytoma''' is a neoplasm thought to be derived from an [[neurohistology|astrocyte]]. Astrocytomas/Glioblastomas are most common type of glial tumours and grouped together with [[Oligodendroglioma]] and glioneuronal tumours in the current WHO brain tumor classficiation. Some (often circumscribed) astrocytic tumors and pediatric tumours are biologically different from adult-onset diffuse astrocytomas. An overview of other CNS tumours is found in the ''[[CNS tumours]]'' article.

=Categorization=
Astrocytomas can be categorized in serveral ways.
* Common vs. uncommon tumours.
* Adult vs. pediatric tumours.
* Circumscribed vs. diffusely growing astrocytomas.

Until 2016 WHO classification, roman numerals I-IV were used for grading. The current 2021 WHO classification uses arabic numbering 1-4 for CNS WHO grading instead.

=Overview=
These astrocytic tumors are frequently diagnosed in neuropathology practice:
{| class="wikitable sortable"
! Name
! Type
! Age
! Variants / Patterns / Other designations
! Image
|-
| Astrocytoma, IDH mutant WHO CNS grade 2
| diffuse
| adults
| Diffuse, protoplasmatic, fibrillar or gemistocytic astrocytoma.
| [[File:Astrocytoma whoII HE.jpg|thumb|center|150px]]
|-
| Astrocytoma, IDH mutant WHO CNS grade 3
| diffuse
| adults
| Anaplastic astrocytoma, gliomatosis cerebri
| [[File:Anaplastic_astrocytoma_-_very_high_mag.jpg|thumb|center|150px]]
|-
| Astrocytoma, IDH mutant WHO CNS grade 4
| diffuse
| adults
|
| [[File:IDH1_GBM_20x.jpg|thumb|center|150px]]
|-
| Glioblastoma, WHO CNS grade 4
| diffuse
| adults
| small cell, epitheloid/rhabdoid, with PNET componet, with granular cell component, giant cell, gliosarcoma
| [[File:Glioblastoma_(1).jpg|thumb|center|150px]]
|-
| Diffuse midline glioma, H3 K27M-mutant, WHO CNS grade 4
| diffuse
| children
|
| [[File:K27M mutant diffuse glioma of the midline.jpg|thumb|center|150px]]
|-
|-
| Pilocytic astrocytoma, WHO CNS grade 1
| circumscribed
| children
| pilomyxoid astrocytoma, anaplastic pilocytic astrocytoma
| [[File:Rosenthal_HE_40x.jpg|thumb|center|150px]]
|-
| Pleomorphic xanthoastrocytoma, WHO CNS grade 2 (PXA)
| circumscribed
| young adults
|
| [[File:PXA_HE_x20.jpg|thumb|center|150px]]
|-
| Pleomorphic xanthoastrocytoma, WHO CNS grade 3 (PXA)
| circumscribed
| young adults
| Anaplastic PXA.
| [[File:Anaplastic_pxa_histology.jpg|thumb|center|150px]]
|-
| Subependymal giant cell astrocytoma, WHO CNS grade 1 (SEGA)
| circumscribed
| young adults
| SEGA in tuberous sclerosis
| [[File:SEGA_HE.jpg|thumb|center|150px]]
|}

=Adult-type astrocytomas=
*[[Astrocytoma, IDH-mutant]].
*[[Glioblastoma]], IDH wildtype.
*[[High-grade astrocytoma with piloid features]].
*[[Pleomorphic xanthroastrocytoma]].
*[[Subependymal giant cell astrocytoma]].
*Chordoid glioma.

=Pediatric-type astrocytomas=
*[[Pilocytic astrocytoma]].
*[[Pediatric-type diffuse high-grade glioma]].
*[[Pediatric-type diffuse low-grade glioma]].
*[[Astroblastoma]], MN1-altered.

=Diffuse growing astrocytomas=
*[[Astrocytoma, IDH-mutant]].
*[[Glioblastoma]], IDH wildtype.
*[[Diffuse midline glioma, H3 K27-altered]].
*[[Diffuse hemispheric glioma, H3 G34-mutant]].
*[[Diffuse astrocytoma, MYB- or MYBL-altered]].
*Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype.
*Angiocentric glioma.
*Diffuse low-grade glioma, MAPK pathway-altered.

=Circumscribed astrocytomas=
*[[Pilocytic astrocytoma]].
*[[High-grade astrocytoma with piloid features]].
*[[Pleomorphic xanthroastrocytoma]].
*[[Subependymal giant cell astrocytoma]].
*[[Chordoid glioma]].
*[[Astroblastoma]], MN1-altered.

=Common Astrocytomas=
==Pilocytic astrocytoma==
* Benign, cystic, infratentorial.
* Classic childhood tumor, surgically resectable.
* Circumscribed astrocytic glioma
* Variant: [[Pilomyxoid astrocytoma]]
{{Main|Pilocytic astrocytoma}}

==Astrocytoma, IDH mutant==
* Astrocytoma, IDH mutant are less common than glioblastoma.
* Grade 2-4 depends on histological and molecular criteria:
{{Main|Astrocytoma, IDH-mutant}}

=== Astrocytoma, IDH mutant grade 2===
* Formerly designated as Diffuse astrocytoma Grade II.
* Typically seen in adults.
* Usually shows progression to astrocytoma IDH mutant, grade 4.

===Astrocytoma, IDH mutant grade 3===
* Formerly designated Anaplastic astrocytoma Grade III.
* Typically seen in adults.
* Increased cellularity, cell atypia and mitotic activity.
* Lacks endothelial proliferations and necrosis of glioblastoma.

===Astrocytoma, IDH mutant grade 4===
* Formerly called Glioblastoma, IDH mutant.
* Endothelial proliferations and necrosis indistinguishable from glioblastoma.
* Homozygous CDKN2A deletion qualifies grade 2 and grade 3 astrocytomas as grade 4 tumor.

==Glioblastoma==
* Most common malignant brain tumor peaking around 65 years.
* Prognosis very poor.
* Variant: [[Giant cell glioblastoma]]
* Variant: [[Gliosarcoma]]
{{Main|Glioblastoma}}

=Uncommon Astrocytomas=
==Diffuse astrocytoma, MYB- or MYBL-altered==
* Pediatric-type diffuse low-grade glioma.
* Associated with epileptic seizures.
* Excellent prognosis.
{{Main|Diffuse astrocytoma, MYB- or MYBL-altered}}

==Subependymal giant cell astrocytoma==
* Intraventricular benign tumor of adolescents.
* Associated with [[Tuberous sclerosis]].
{{Main|Subependymal giant cell astrocytoma}}

==Pleomorphic xanthroastrocytoma (PXA)==
* Kids & young adults usually with good prognosis.
* Large lipidized cells mimicking a malignant tumor
{{Main|Pleomorphic xanthoastrocytoma}}

==Diffuse midline glioma, H3 K27-altered==
* High-grade astrocytic neoplasm associated with midline structures (thalamus, brain stem, spinal cord).
* Mostly in children and adolescents.
* Includes diffuse intrinsic pontine gliomas (DPIG).

{{Main|Diffuse midline glioma, H3 K27-altered}}

==Diffuse hemispheric glioma, H3 G34-mutant==
* Infiltrative hemispheric glioma of young adults.
* Glioblastoma-like appearance (CNS WHO grade 4 tumor).
* Newly defined entity in WHO 2021 classification.
* H3F3A missense mutation G34R or G34V.
{{Main|Diffuse hemispheric glioma, H3 G34-mutant}}

==High-grade astrocytoma with piloid features==
* Frequent in posterior fossa (75%).
* 1-3% of all brain tumors.
* Histology may resemble Glionblastoma or Pleomorphic xanthoastrocytoma.
* Tumor is enriched for piloid cell processes.
* ATRX nuclear loss is frequent.
* Usu. MAPK-pathway alterations + CDKN2A homozygous deletion.
* Distinct methylation profile.
{{Main|High-grade astrocytoma with piloid features}}

==Gliomatosis cerebri==
* Depreceated entity.
* Was used for extensively diffusely growing astrocytic neoplasms.
**Introduced in 1938 as a post-mortem diagnosis.<ref>SAMUEL NEVIN - GLIOMATOSIS CEREBRI, DOI: http://dx.doi.org/10.1093/brain/61.2.170 170-191 First published online: 1 June 1938</ref>
**Since 2016 it is no longer considered a distinct entity.<ref>{{Cite journal | last1 = Johnson | first1 = DR. | last2 = Guerin | first2 = JB. | last3 = Giannini | first3 = C. | last4 = Morris | first4 = JM. | last5 = Eckel | first5 = LJ. | last6 = Kaufmann | first6 = TJ. | title = 2016 Updates to the WHO Brain Tumor Classification System: What the Radiologist Needs to Know. | journal = Radiographics | volume = 37 | issue = 7 | pages = 2164-2180 | month = | year = | doi = 10.1148/rg.2017170037 | PMID = 29028423 }}</ref><ref>{{Cite journal | last1 = Herrlinger | first1 = U. | last2 = Jones | first2 = DT. | last3 = Glas | first3 = M. | last4 = Hattingen | first4 = E. | last5 = Gramatzki | first5 = D. | last6 = Stuplich | first6 = M. | last7 = Felsberg | first7 = J. | last8 = Bähr | first8 = O. | last9 = Gielen | first9 = GH. | title = Gliomatosis cerebri: no evidence for a separate brain tumor entity. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Oct | year = 2015 | doi = 10.1007/s00401-015-1495-z | PMID = 26493382 }}</ref>
* More than 3 lobes have to be involved, us. bilateral (radiology required).
* biologic behaviour corresponds to WHO III (ICD-O: 9381/3)
* Based on presence / absence of a solid component authors propose two types:<ref>{{Cite journal | last1 = Seiz | first1 = M. | last2 = Tuettenberg | first2 = J. | last3 = Meyer | first3 = J. | last4 = Essig | first4 = M. | last5 = Schmieder | first5 = K. | last6 = Mawrin | first6 = C. | last7 = von Deimling | first7 = A. | last8 = Hartmann | first8 = C. | title = Detection of IDH1 mutations in gliomatosis cerebri, but only in tumors with additional solid component: evidence for molecular subtypes. | journal = Acta Neuropathol | volume = 120 | issue = 2 | pages = 261-7 | month = Aug | year = 2010 | doi = 10.1007/s00401-010-0701-2 | PMID = 20514489 }}</ref>
** GC type 1: classic diffuse growth, without IDH1/2 mutation.
** GC type 2: with a solid portion, mostly IDH1 mutant.
* Genetic studies indicate strong overlap with diffuse astrocytic gliomas, oligodendrogliomas and glioblastoma.

==Gliosarcoma==
===General===
*Considered to be a variant of [[glioblastoma]] by WHO.<ref name=pmid19618114>{{cite journal |author=Han SJ, Yang I, Tihan T, Prados MD, Parsa AT |title=Primary gliosarcoma: key clinical and pathologic distinctions from glioblastoma with implications as a unique oncologic entity |journal=J. Neurooncol. |volume=96 |issue=3 |pages=313–20 |year=2010 |month=February |pmid=19618114 |pmc=2808523 |doi=10.1007/s11060-009-9973-6 |url=}}</ref>
*Rare ~ 200 cases reported in the literature.<ref name=pmid19618114/>
*Definition: gliosarcoma = glioblastoma + sarcomatous component.<ref name=pmid20415184>{{cite journal |author=Ayadi L, Charfi S, Khabir A, ''et al.'' |title=[Cerebral gliosarcoma: clinico-pathologic study of 8 cases] |language=French |journal=Tunis Med |volume=88 |issue=3 |pages=142–6 |year=2010 |month=March |pmid=20415184 |doi= |url=}}</ref>
*Usual location (like glioblastoma): temporal lobe.
*Prognosis is similiar to [[glioblastoma]].<ref>{{Cite journal | last1 = Frandsen | first1 = J. | last2 = Orton | first2 = A. | last3 = Jensen | first3 = R. | last4 = Colman | first4 = H. | last5 = Cohen | first5 = AL. | last6 = Tward | first6 = J. | last7 = Shrieve | first7 = DC. | last8 = Suneja | first8 = G. | title = Patterns of care and outcomes in gliosarcoma: an analysis of the National Cancer Database. | journal = J Neurosurg | volume = | issue = | pages = 1-6 | month = Jun | year = 2017 | doi = 10.3171/2016.12.JNS162291 | PMID = 28621623 }}</ref>
** Age below 65 years is prognostic.

===Microscopic===
Features:
*[[Glioblastoma]].
*Sarcomatous component (one of the following):<ref name=pmid19618114/><ref name=pmid20415184/>
**Fibroblastic.
**Cartilaginous.
**Osseous.
**Smooth muscle.
**Striated muscle.
**Adipocyte.

====Images====
<gallery>
Image:Gliosarcoma_Histopathology_200x_EVG.jpg | Gliosarcoma - elastica van Giesson. (WC)
</gallery>
www:
*[http://path.upmc.edu/cases/case169/micro.html Gliosarcoma - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case361.html Gliosarcoma - case 2 - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case367.html Gliosarcoma - case 3 - several images (upmc.edu)].

===IHC===
*GFAP +ve -- astrocytic component.<ref name=pmid9736406>{{Cite journal | last1 = Horiguchi | first1 = H. | last2 = Hirose | first2 = T. | last3 = Kannuki | first3 = S. | last4 = Nagahiro | first4 = S. | last5 = Sano | first5 = T. | title = Gliosarcoma: an immunohistochemical, ultrastructural and fluorescence in situ hybridization study. | journal = Pathol Int | volume = 48 | issue = 8 | pages = 595-602 | month = Aug | year = 1998 | doi = | PMID = 9736406 }}</ref>
**Spindle cell component -ve.<ref>URL: [http://path.upmc.edu/cases/case361.html http://path.upmc.edu/cases/case361.html]. Accessed on: 15 January 2012.</ref>

Gliosarcoma with smooth muscle component (gliomyosarcoma):<ref name=pmid21393877>{{Cite journal | last1 = Khanna | first1 = M. | last2 = Siraj | first2 = F. | last3 = Chopra | first3 = P. | last4 = Bhalla | first4 = S. | last5 = Roy | first5 = S. | title = Gliosarcoma with prominent smooth muscle component (gliomyosarcoma): a report of 10 cases. | journal = Indian J Pathol Microbiol | volume = 54 | issue = 1 | pages = 51-4 | month = | year = | doi = 10.4103/0377-4929.77324 | PMID = 21393877 }}</ref>
*SMA +ve.
*Factor VIII +ve.

==Gliofibroma==
* Very rare indolent tumor in children <ref>{{Cite journal | last1 = Deb | first1 = P. | last2 = Sarkar | first2 = C. | last3 = Garg | first3 = A. | last4 = Singh | first4 = VP. | last5 = Kale | first5 = SS. | last6 = Sharma | first6 = MC. | title = Intracranial gliofibroma mimicking a meningioma: a case report and review of literature. | journal = Clin Neurol Neurosurg | volume = 108 | issue = 2 | pages = 178-86 | month = Feb | year = 2006 | doi = 10.1016/j.clineuro.2004.11.021 | PMID = 16412839 }}</ref>
* Usually not dura-based (DD: Desmoplastic infantile astrocytoma)
* Glial tumor with non-neoplastic fibromatous component.

=See also=
*[[CNS tumours]].

=References=
{{Reflist|2}}

[[Category:Neuropathology]]

High-grade astrocytoma with piloid features

2022-10-17T13:47:41Z

Jensflorian: Update infobox

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Pilocytic astrocytoma with anaplastic features.jpg
| Width =
| Caption = High-grade astrocytoma with piloid features. [[H&E stain]].
| Synonyms =
| Micro =
| Subtypes =
| LMDDx = [[astrocytoma]], [[PXA]], [[glioblastoma]]
| Stains = PAS-D +ve (eosinophilic granular bodies)
| IHC = GFAP +ve
| EM =
| Molecular =
| IF =
| Gross = usually cerebellar
| Grossing =
| Site = brain - usu. [[cerebellum]]
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence = very rare - esp. in children
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis = poor (analog to WHO Grade III)
| Other =
| ClinDDx =
| Tx =
}}

'''High-grade astrocytoma with piloid features''' is a rare [[Glioma|glial]] tumor which often requires methylation analyis to secure diagnosis. There is currently no definitive grading, but clinical behaviour suggests WHO CNS grade 3.

=Clinical=
*Rare (1-3% of all brain tumor in adults).
*Usu. posterior fossa (75%).
*Supratentorial or spinal locations possible.
*Imaging may be similiar to [[Glioblastoma]].
*5-year OS: 50%.
*De novo cases in the setting of neurofibromatosis 1 reported.
*Tumors may have history of previous radiation.

=Histology=
*Often so variable, so molecular testing is essential to secure diagnosis.
*Astrocytic nature of tumor cells.
*Frequent mitoses.
*Elongated glial tumor cell processes ("piloid").
*Rosenthal fibers or eosinophilic granular bodies.
*Perivascular lymphocytic cuffing.
*Necrosis may be present.

==Images==
<gallery>
Image:Pilocytic astrocytoma with anaplastic features.jpg | APA, [[FFPE]] specimen, HE (WC).
Image:Pilocytic astrocytoma with anaplastic features mimicking focally a GBM.jpg | Vacular proliferations and necrosis in APA mimicking [[GBM]] (WC).
</gallery>

=IHC=
*[[GFAP]]+ve.
*ATRX: nuclear loss in approx. 40%.

=Molecular=
*DNA Methylation profile of high-grade astrocytoma with piloid features is essential for diagnosis.
*MAPK genes often altered (NF1, BRAF fusion, FGFR1, KRAS).
*CDKN2A/B homozygous deletion.
*CDK4 amplification.
*TERT promotor mutations are rare.
*Absence of IDH1/2 hotspot mutation.

=Prognosis=
*Poor, but better than conventional glioblastoma.<ref>{{Cite journal | last1 = Rodriguez | first1 = FJ. | last2 = Scheithauer | first2 = BW. | last3 = Burger | first3 = PC. | last4 = Jenkins | first4 = S. | last5 = Giannini | first5 = C. | title = Anaplasia in pilocytic astrocytoma predicts aggressive behavior. | journal = Am J Surg Pathol | volume = 34 | issue = 2 | pages = 147-60 | month = Feb | year = 2010 | doi = 10.1097/PAS.0b013e3181c75238 | PMID = 20061938 }}</ref>
*Prognostic unfavourable paramters include: Necrosis, Mitoses and previous radiation.

=DDx:=
*[[Glioblastoma]]
*[[Pleomorphic xanthoastrocytoma]]

=See also=
*[[Astrocytoma]].
*[[Neuropathology_tumours#Infiltrative_astrocytomas]]

{{Reflist|2}}

[[Category:Diagnosis]]
[[Category:Neuropathology tumours]]

Astrocytoma

2022-10-17T13:42:43Z

Jensflorian: /* Uncommon Astrocytomas */ HGAP

An '''astrocytoma''' is a neoplasm thought to be derived from an [[neurohistology|astrocyte]]. Astrocytomas/Glioblastomas are most common type of glial tumours and grouped together with [[Oligodendroglioma]] and glioneuronal tumours in the current WHO brain tumor classficiation. Some (often circumscribed) astrocytic tumors and pediatric tumours are biologically different from adult-onset diffuse astrocytomas. An overview of other CNS tumours is found in the ''[[CNS tumours]]'' article.

=Categorization=
Astrocytomas can be categorized in serveral ways.
* Common vs. uncommon tumours.
* Adult vs. pediatric tumours.
* Circumscribed vs. diffusely growing astrocytomas.

Until 2016 WHO classification, roman numerals I-IV were used for grading. The current 2021 WHO classification uses arabic numbering 1-4 for CNS WHO grading instead.

=Overview=
These astrocytic tumors are frequently diagnosed in neuropathology practice:
{| class="wikitable sortable"
! Name
! Type
! Age
! Variants / Patterns / Other designations
! Image
|-
| Astrocytoma, IDH mutant WHO CNS grade 2
| diffuse
| adults
| Diffuse, protoplasmatic, fibrillar or gemistocytic astrocytoma.
| [[File:Astrocytoma whoII HE.jpg|thumb|center|150px]]
|-
| Astrocytoma, IDH mutant WHO CNS grade 3
| diffuse
| adults
| Anaplastic astrocytoma, gliomatosis cerebri
| [[File:Anaplastic_astrocytoma_-_very_high_mag.jpg|thumb|center|150px]]
|-
| Astrocytoma, IDH mutant WHO CNS grade 4
| diffuse
| adults
|
| [[File:IDH1_GBM_20x.jpg|thumb|center|150px]]
|-
| Glioblastoma, WHO CNS grade 4
| diffuse
| adults
| small cell, epitheloid/rhabdoid, with PNET componet, with granular cell component, giant cell, gliosarcoma
| [[File:Glioblastoma_(1).jpg|thumb|center|150px]]
|-
| Diffuse midline glioma, H3 K27M-mutant, WHO CNS grade 4
| diffuse
| children
|
| [[File:K27M mutant diffuse glioma of the midline.jpg|thumb|center|150px]]
|-
|-
| Pilocytic astrocytoma, WHO CNS grade 1
| circumscribed
| children
| pilomyxoid astrocytoma, anaplastic pilocytic astrocytoma
| [[File:Rosenthal_HE_40x.jpg|thumb|center|150px]]
|-
| Pleomorphic xanthoastrocytoma, WHO CNS grade 2 (PXA)
| circumscribed
| young adults
|
| [[File:PXA_HE_x20.jpg|thumb|center|150px]]
|-
| Pleomorphic xanthoastrocytoma, WHO CNS grade 3 (PXA)
| circumscribed
| young adults
| Anaplastic PXA.
| [[File:Anaplastic_pxa_histology.jpg|thumb|center|150px]]
|-
| Subependymal giant cell astrocytoma, WHO CNS grade 1 (SEGA)
| circumscribed
| young adults
| SEGA in tuberous sclerosis
| [[File:SEGA_HE.jpg|thumb|center|150px]]
|}

=Adult-type astrocytomas=
*[[Astrocytoma, IDH-mutant]].
*[[Glioblastoma]], IDH wildtype.
*[[High-grade astrocytoma with piloid features]].
*[[Pleomorphic xanthroastrocytoma]].
*[[Subependymal giant cell astrocytoma]].
*Chordoid glioma.

=Pediatric-type astrocytomas=
*[[Pilocytic astrocytoma]].
*[[Pediatric-type diffuse high-grade glioma]].
*[[Pediatric-type diffuse low-grade glioma]].
*[[Astroblastoma]], MN1-altered.

=Diffuse growing astrocytomas=
*[[Astrocytoma, IDH-mutant]].
*[[Glioblastoma]], IDH wildtype.
*[[Diffuse midline glioma, H3 K27-altered]].
*[[Diffuse hemispheric glioma, H3 G34-mutant]].
*[[Diffuse astrocytoma, MYB- or MYBL-altered]].
*Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype.
*Angiocentric glioma.
*Diffuse low-grade glioma, MAPK pathway-altered.

=Circumscribed astrocytomas=
*[[Pilocytic astrocytoma]].
*[[High-grade astrocytoma with piloid features]].
*[[Pleomorphic xanthroastrocytoma]].
*[[Subependymal giant cell astrocytoma]].
*[[Chordoid glioma]].
*[[Astroblastoma]], MN1-altered.

=Common Astrocytomas=
==Pilocytic astrocytoma==
* Benign, cystic, infratentorial.
* Classic childhood tumor, surgically resectable.
* Circumscribed astrocytic glioma
* Variant: [[Pilomyxoid astrocytoma]]
{{Main|Pilocytic astrocytoma}}

==Astrocytoma, IDH mutant==
* Astrocytoma, IDH mutant are less common than glioblastoma.
* Grade 2-4 depends on histological and molecular criteria:
{{Main|Astrocytoma, IDH-mutant}}

=== Astrocytoma, IDH mutant grade 2===
* Formerly designated as Diffuse astrocytoma Grade II.
* Typically seen in adults.
* Usually shows progression to astrocytoma IDH mutant, grade 4.

===Astrocytoma, IDH mutant grade 3===
* Formerly designated Anaplastic astrocytoma Grade III.
* Typically seen in adults.
* Increased cellularity, cell atypia and mitotic activity.
* Lacks endothelial proliferations and necrosis of glioblastoma.

===Astrocytoma, IDH mutant grade 4===
* Formerly called Glioblastoma, IDH mutant.
* Endothelial proliferations and necrosis indistinguishable from glioblastoma.
* Homozygous CDKN2A deletion qualifies grade 2 and grade 3 astrocytomas as grade 4 tumor.

==Glioblastoma==
* Most common malignant brain tumor peaking around 65 years.
* Prognosis very poor.
* Variant: [[Giant cell glioblastoma]]
* Variant: [[Gliosarcoma]]
{{Main|Glioblastoma}}

=Uncommon Astrocytomas=
==Diffuse astrocytoma, MYB- or MYBL-altered==
* Pediatric-type diffuse low-grade glioma.
* Associated with epileptic seizures.
* Excellent prognosis.
{{Main|Diffuse astrocytoma, MYB- or MYBL-altered}}

==Subependymal giant cell astrocytoma==
* Intraventricular benign tumor of adolescents.
* Associated with [[Tuberous sclerosis]].
{{Main|Subependymal giant cell astrocytoma}}

==Pleomorphic xanthroastrocytoma (PXA)==
* Kids & young adults usually with good prognosis.
* Large lipidized cells mimicking a malignant tumor
{{Main|Pleomorphic xanthoastrocytoma}}

==Diffuse midline glioma, H3 K27-altered==
* High-grade astrocytic neoplasm associated with midline structures (thalamus, brain stem, spinal cord).
* Mostly in children and adolescents.
* Includes diffuse intrinsic pontine gliomas (DPIG).

{{Main|Diffuse midline glioma, H3 K27-altered}}

==Diffuse hemispheric glioma, H3 G34-mutant==
* Infiltrative hemispheric glioma of young adults.
* Glioblastoma-like appearance (CNS WHO grade 4 tumor).
* Newly defined entity in WHO 2021 classification.
* H3F3A missense mutation G34R or G34V.
{{Main|Diffuse hemispheric glioma, H3 G34-mutant}}

==High-grade astrocytoma with piloid features==
* Frequent in posterior fossa (75%).
* 1-3% of all brain tumors.
* Histology may resemble Glionblastoma or Pleomorphic xanthoastrocytoma.
* Tumor is enriched for piloid cell processes.
* ATRX nuclear loss is frequent.
* Usu. MAPK-pathway alterations + CDKN2A homozygous deletion.
* Distinct methylation profile.
* Depreceated terminology: Anaplastic pilocytic astrocytoma.

==Gliomatosis cerebri==
* Depreceated entity.
* Was used for extensively diffusely growing astrocytic neoplasms.
**Introduced in 1938 as a post-mortem diagnosis.<ref>SAMUEL NEVIN - GLIOMATOSIS CEREBRI, DOI: http://dx.doi.org/10.1093/brain/61.2.170 170-191 First published online: 1 June 1938</ref>
**Since 2016 it is no longer considered a distinct entity.<ref>{{Cite journal | last1 = Johnson | first1 = DR. | last2 = Guerin | first2 = JB. | last3 = Giannini | first3 = C. | last4 = Morris | first4 = JM. | last5 = Eckel | first5 = LJ. | last6 = Kaufmann | first6 = TJ. | title = 2016 Updates to the WHO Brain Tumor Classification System: What the Radiologist Needs to Know. | journal = Radiographics | volume = 37 | issue = 7 | pages = 2164-2180 | month = | year = | doi = 10.1148/rg.2017170037 | PMID = 29028423 }}</ref><ref>{{Cite journal | last1 = Herrlinger | first1 = U. | last2 = Jones | first2 = DT. | last3 = Glas | first3 = M. | last4 = Hattingen | first4 = E. | last5 = Gramatzki | first5 = D. | last6 = Stuplich | first6 = M. | last7 = Felsberg | first7 = J. | last8 = Bähr | first8 = O. | last9 = Gielen | first9 = GH. | title = Gliomatosis cerebri: no evidence for a separate brain tumor entity. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Oct | year = 2015 | doi = 10.1007/s00401-015-1495-z | PMID = 26493382 }}</ref>
* More than 3 lobes have to be involved, us. bilateral (radiology required).
* biologic behaviour corresponds to WHO III (ICD-O: 9381/3)
* Based on presence / absence of a solid component authors propose two types:<ref>{{Cite journal | last1 = Seiz | first1 = M. | last2 = Tuettenberg | first2 = J. | last3 = Meyer | first3 = J. | last4 = Essig | first4 = M. | last5 = Schmieder | first5 = K. | last6 = Mawrin | first6 = C. | last7 = von Deimling | first7 = A. | last8 = Hartmann | first8 = C. | title = Detection of IDH1 mutations in gliomatosis cerebri, but only in tumors with additional solid component: evidence for molecular subtypes. | journal = Acta Neuropathol | volume = 120 | issue = 2 | pages = 261-7 | month = Aug | year = 2010 | doi = 10.1007/s00401-010-0701-2 | PMID = 20514489 }}</ref>
** GC type 1: classic diffuse growth, without IDH1/2 mutation.
** GC type 2: with a solid portion, mostly IDH1 mutant.
* Genetic studies indicate strong overlap with diffuse astrocytic gliomas, oligodendrogliomas and glioblastoma.

==Gliosarcoma==
===General===
*Considered to be a variant of [[glioblastoma]] by WHO.<ref name=pmid19618114>{{cite journal |author=Han SJ, Yang I, Tihan T, Prados MD, Parsa AT |title=Primary gliosarcoma: key clinical and pathologic distinctions from glioblastoma with implications as a unique oncologic entity |journal=J. Neurooncol. |volume=96 |issue=3 |pages=313–20 |year=2010 |month=February |pmid=19618114 |pmc=2808523 |doi=10.1007/s11060-009-9973-6 |url=}}</ref>
*Rare ~ 200 cases reported in the literature.<ref name=pmid19618114/>
*Definition: gliosarcoma = glioblastoma + sarcomatous component.<ref name=pmid20415184>{{cite journal |author=Ayadi L, Charfi S, Khabir A, ''et al.'' |title=[Cerebral gliosarcoma: clinico-pathologic study of 8 cases] |language=French |journal=Tunis Med |volume=88 |issue=3 |pages=142–6 |year=2010 |month=March |pmid=20415184 |doi= |url=}}</ref>
*Usual location (like glioblastoma): temporal lobe.
*Prognosis is similiar to [[glioblastoma]].<ref>{{Cite journal | last1 = Frandsen | first1 = J. | last2 = Orton | first2 = A. | last3 = Jensen | first3 = R. | last4 = Colman | first4 = H. | last5 = Cohen | first5 = AL. | last6 = Tward | first6 = J. | last7 = Shrieve | first7 = DC. | last8 = Suneja | first8 = G. | title = Patterns of care and outcomes in gliosarcoma: an analysis of the National Cancer Database. | journal = J Neurosurg | volume = | issue = | pages = 1-6 | month = Jun | year = 2017 | doi = 10.3171/2016.12.JNS162291 | PMID = 28621623 }}</ref>
** Age below 65 years is prognostic.

===Microscopic===
Features:
*[[Glioblastoma]].
*Sarcomatous component (one of the following):<ref name=pmid19618114/><ref name=pmid20415184/>
**Fibroblastic.
**Cartilaginous.
**Osseous.
**Smooth muscle.
**Striated muscle.
**Adipocyte.

====Images====
<gallery>
Image:Gliosarcoma_Histopathology_200x_EVG.jpg | Gliosarcoma - elastica van Giesson. (WC)
</gallery>
www:
*[http://path.upmc.edu/cases/case169/micro.html Gliosarcoma - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case361.html Gliosarcoma - case 2 - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case367.html Gliosarcoma - case 3 - several images (upmc.edu)].

===IHC===
*GFAP +ve -- astrocytic component.<ref name=pmid9736406>{{Cite journal | last1 = Horiguchi | first1 = H. | last2 = Hirose | first2 = T. | last3 = Kannuki | first3 = S. | last4 = Nagahiro | first4 = S. | last5 = Sano | first5 = T. | title = Gliosarcoma: an immunohistochemical, ultrastructural and fluorescence in situ hybridization study. | journal = Pathol Int | volume = 48 | issue = 8 | pages = 595-602 | month = Aug | year = 1998 | doi = | PMID = 9736406 }}</ref>
**Spindle cell component -ve.<ref>URL: [http://path.upmc.edu/cases/case361.html http://path.upmc.edu/cases/case361.html]. Accessed on: 15 January 2012.</ref>

Gliosarcoma with smooth muscle component (gliomyosarcoma):<ref name=pmid21393877>{{Cite journal | last1 = Khanna | first1 = M. | last2 = Siraj | first2 = F. | last3 = Chopra | first3 = P. | last4 = Bhalla | first4 = S. | last5 = Roy | first5 = S. | title = Gliosarcoma with prominent smooth muscle component (gliomyosarcoma): a report of 10 cases. | journal = Indian J Pathol Microbiol | volume = 54 | issue = 1 | pages = 51-4 | month = | year = | doi = 10.4103/0377-4929.77324 | PMID = 21393877 }}</ref>
*SMA +ve.
*Factor VIII +ve.

==Gliofibroma==
* Very rare indolent tumor in children <ref>{{Cite journal | last1 = Deb | first1 = P. | last2 = Sarkar | first2 = C. | last3 = Garg | first3 = A. | last4 = Singh | first4 = VP. | last5 = Kale | first5 = SS. | last6 = Sharma | first6 = MC. | title = Intracranial gliofibroma mimicking a meningioma: a case report and review of literature. | journal = Clin Neurol Neurosurg | volume = 108 | issue = 2 | pages = 178-86 | month = Feb | year = 2006 | doi = 10.1016/j.clineuro.2004.11.021 | PMID = 16412839 }}</ref>
* Usually not dura-based (DD: Desmoplastic infantile astrocytoma)
* Glial tumor with non-neoplastic fibromatous component.

=See also=
*[[CNS tumours]].

=References=
{{Reflist|2}}

[[Category:Neuropathology]]

Astrocytoma

2022-10-17T13:36:11Z

Jensflorian: diffuse vs. adult category

An '''astrocytoma''' is a neoplasm thought to be derived from an [[neurohistology|astrocyte]]. Astrocytomas/Glioblastomas are most common type of glial tumours and grouped together with [[Oligodendroglioma]] and glioneuronal tumours in the current WHO brain tumor classficiation. Some (often circumscribed) astrocytic tumors and pediatric tumours are biologically different from adult-onset diffuse astrocytomas. An overview of other CNS tumours is found in the ''[[CNS tumours]]'' article.

=Categorization=
Astrocytomas can be categorized in serveral ways.
* Common vs. uncommon tumours.
* Adult vs. pediatric tumours.
* Circumscribed vs. diffusely growing astrocytomas.

Until 2016 WHO classification, roman numerals I-IV were used for grading. The current 2021 WHO classification uses arabic numbering 1-4 for CNS WHO grading instead.

=Overview=
These astrocytic tumors are frequently diagnosed in neuropathology practice:
{| class="wikitable sortable"
! Name
! Type
! Age
! Variants / Patterns / Other designations
! Image
|-
| Astrocytoma, IDH mutant WHO CNS grade 2
| diffuse
| adults
| Diffuse, protoplasmatic, fibrillar or gemistocytic astrocytoma.
| [[File:Astrocytoma whoII HE.jpg|thumb|center|150px]]
|-
| Astrocytoma, IDH mutant WHO CNS grade 3
| diffuse
| adults
| Anaplastic astrocytoma, gliomatosis cerebri
| [[File:Anaplastic_astrocytoma_-_very_high_mag.jpg|thumb|center|150px]]
|-
| Astrocytoma, IDH mutant WHO CNS grade 4
| diffuse
| adults
|
| [[File:IDH1_GBM_20x.jpg|thumb|center|150px]]
|-
| Glioblastoma, WHO CNS grade 4
| diffuse
| adults
| small cell, epitheloid/rhabdoid, with PNET componet, with granular cell component, giant cell, gliosarcoma
| [[File:Glioblastoma_(1).jpg|thumb|center|150px]]
|-
| Diffuse midline glioma, H3 K27M-mutant, WHO CNS grade 4
| diffuse
| children
|
| [[File:K27M mutant diffuse glioma of the midline.jpg|thumb|center|150px]]
|-
|-
| Pilocytic astrocytoma, WHO CNS grade 1
| circumscribed
| children
| pilomyxoid astrocytoma, anaplastic pilocytic astrocytoma
| [[File:Rosenthal_HE_40x.jpg|thumb|center|150px]]
|-
| Pleomorphic xanthoastrocytoma, WHO CNS grade 2 (PXA)
| circumscribed
| young adults
|
| [[File:PXA_HE_x20.jpg|thumb|center|150px]]
|-
| Pleomorphic xanthoastrocytoma, WHO CNS grade 3 (PXA)
| circumscribed
| young adults
| Anaplastic PXA.
| [[File:Anaplastic_pxa_histology.jpg|thumb|center|150px]]
|-
| Subependymal giant cell astrocytoma, WHO CNS grade 1 (SEGA)
| circumscribed
| young adults
| SEGA in tuberous sclerosis
| [[File:SEGA_HE.jpg|thumb|center|150px]]
|}

=Adult-type astrocytomas=
*[[Astrocytoma, IDH-mutant]].
*[[Glioblastoma]], IDH wildtype.
*[[High-grade astrocytoma with piloid features]].
*[[Pleomorphic xanthroastrocytoma]].
*[[Subependymal giant cell astrocytoma]].
*Chordoid glioma.

=Pediatric-type astrocytomas=
*[[Pilocytic astrocytoma]].
*[[Pediatric-type diffuse high-grade glioma]].
*[[Pediatric-type diffuse low-grade glioma]].
*[[Astroblastoma]], MN1-altered.

=Diffuse growing astrocytomas=
*[[Astrocytoma, IDH-mutant]].
*[[Glioblastoma]], IDH wildtype.
*[[Diffuse midline glioma, H3 K27-altered]].
*[[Diffuse hemispheric glioma, H3 G34-mutant]].
*[[Diffuse astrocytoma, MYB- or MYBL-altered]].
*Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype.
*Angiocentric glioma.
*Diffuse low-grade glioma, MAPK pathway-altered.

=Circumscribed astrocytomas=
*[[Pilocytic astrocytoma]].
*[[High-grade astrocytoma with piloid features]].
*[[Pleomorphic xanthroastrocytoma]].
*[[Subependymal giant cell astrocytoma]].
*[[Chordoid glioma]].
*[[Astroblastoma]], MN1-altered.

=Common Astrocytomas=
==Pilocytic astrocytoma==
* Benign, cystic, infratentorial.
* Classic childhood tumor, surgically resectable.
* Circumscribed astrocytic glioma
* Variant: [[Pilomyxoid astrocytoma]]
{{Main|Pilocytic astrocytoma}}

==Astrocytoma, IDH mutant==
* Astrocytoma, IDH mutant are less common than glioblastoma.
* Grade 2-4 depends on histological and molecular criteria:
{{Main|Astrocytoma, IDH-mutant}}

=== Astrocytoma, IDH mutant grade 2===
* Formerly designated as Diffuse astrocytoma Grade II.
* Typically seen in adults.
* Usually shows progression to astrocytoma IDH mutant, grade 4.

===Astrocytoma, IDH mutant grade 3===
* Formerly designated Anaplastic astrocytoma Grade III.
* Typically seen in adults.
* Increased cellularity, cell atypia and mitotic activity.
* Lacks endothelial proliferations and necrosis of glioblastoma.

===Astrocytoma, IDH mutant grade 4===
* Formerly called Glioblastoma, IDH mutant.
* Endothelial proliferations and necrosis indistinguishable from glioblastoma.
* Homozygous CDKN2A deletion qualifies grade 2 and grade 3 astrocytomas as grade 4 tumor.

==Glioblastoma==
* Most common malignant brain tumor peaking around 65 years.
* Prognosis very poor.
* Variant: [[Giant cell glioblastoma]]
* Variant: [[Gliosarcoma]]
{{Main|Glioblastoma}}

=Uncommon Astrocytomas=
==Diffuse astrocytoma, MYB- or MYBL-altered==
* Pediatric-type diffuse low-grade glioma.
* Associated with epileptic seizures.
* Excellent prognosis.
{{Main|Diffuse astrocytoma, MYB- or MYBL-altered}}

==Subependymal giant cell astrocytoma==
* Intraventricular benign tumor of adolescents.
* Associated with [[Tuberous sclerosis]].
{{Main|Subependymal giant cell astrocytoma}}

==Pleomorphic xanthroastrocytoma (PXA)==
* Kids & young adults usually with good prognosis.
* Large lipidized cells mimicking a malignant tumor
{{Main|Pleomorphic xanthoastrocytoma}}

==Diffuse midline glioma, H3 K27-altered==
* High-grade astrocytic neoplasm associated with midline structures (thalamus, brain stem, spinal cord).
* Mostly in children and adolescents.
* Includes diffuse intrinsic pontine gliomas (DPIG).

{{Main|Diffuse midline glioma, H3 K27-altered}}

==Diffuse hemispheric glioma, H3 G34-mutant==
* Infiltrative hemispheric glioma of young adults.
* Glioblastoma-like appearance (CNS WHO grade 4 tumor).
* Newly defined entity in WHO 2021 classification.
* H3F3A missense mutation G34R or G34V.
{{Main|Diffuse hemispheric glioma, H3 G34-mutant}}

==Gliomatosis cerebri==
* Depreceated entity.
* Was used for extensively diffusely growing astrocytic neoplasms.
**Introduced in 1938 as a post-mortem diagnosis.<ref>SAMUEL NEVIN - GLIOMATOSIS CEREBRI, DOI: http://dx.doi.org/10.1093/brain/61.2.170 170-191 First published online: 1 June 1938</ref>
**Since 2016 it is no longer considered a distinct entity.<ref>{{Cite journal | last1 = Johnson | first1 = DR. | last2 = Guerin | first2 = JB. | last3 = Giannini | first3 = C. | last4 = Morris | first4 = JM. | last5 = Eckel | first5 = LJ. | last6 = Kaufmann | first6 = TJ. | title = 2016 Updates to the WHO Brain Tumor Classification System: What the Radiologist Needs to Know. | journal = Radiographics | volume = 37 | issue = 7 | pages = 2164-2180 | month = | year = | doi = 10.1148/rg.2017170037 | PMID = 29028423 }}</ref><ref>{{Cite journal | last1 = Herrlinger | first1 = U. | last2 = Jones | first2 = DT. | last3 = Glas | first3 = M. | last4 = Hattingen | first4 = E. | last5 = Gramatzki | first5 = D. | last6 = Stuplich | first6 = M. | last7 = Felsberg | first7 = J. | last8 = Bähr | first8 = O. | last9 = Gielen | first9 = GH. | title = Gliomatosis cerebri: no evidence for a separate brain tumor entity. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Oct | year = 2015 | doi = 10.1007/s00401-015-1495-z | PMID = 26493382 }}</ref>
* More than 3 lobes have to be involved, us. bilateral (radiology required).
* biologic behaviour corresponds to WHO III (ICD-O: 9381/3)
* Based on presence / absence of a solid component authors propose two types:<ref>{{Cite journal | last1 = Seiz | first1 = M. | last2 = Tuettenberg | first2 = J. | last3 = Meyer | first3 = J. | last4 = Essig | first4 = M. | last5 = Schmieder | first5 = K. | last6 = Mawrin | first6 = C. | last7 = von Deimling | first7 = A. | last8 = Hartmann | first8 = C. | title = Detection of IDH1 mutations in gliomatosis cerebri, but only in tumors with additional solid component: evidence for molecular subtypes. | journal = Acta Neuropathol | volume = 120 | issue = 2 | pages = 261-7 | month = Aug | year = 2010 | doi = 10.1007/s00401-010-0701-2 | PMID = 20514489 }}</ref>
** GC type 1: classic diffuse growth, without IDH1/2 mutation.
** GC type 2: with a solid portion, mostly IDH1 mutant.
* Genetic studies indicate strong overlap with diffuse astrocytic gliomas, oligodendrogliomas and glioblastoma.

==Gliosarcoma==
===General===
*Considered to be a variant of [[glioblastoma]] by WHO.<ref name=pmid19618114>{{cite journal |author=Han SJ, Yang I, Tihan T, Prados MD, Parsa AT |title=Primary gliosarcoma: key clinical and pathologic distinctions from glioblastoma with implications as a unique oncologic entity |journal=J. Neurooncol. |volume=96 |issue=3 |pages=313–20 |year=2010 |month=February |pmid=19618114 |pmc=2808523 |doi=10.1007/s11060-009-9973-6 |url=}}</ref>
*Rare ~ 200 cases reported in the literature.<ref name=pmid19618114/>
*Definition: gliosarcoma = glioblastoma + sarcomatous component.<ref name=pmid20415184>{{cite journal |author=Ayadi L, Charfi S, Khabir A, ''et al.'' |title=[Cerebral gliosarcoma: clinico-pathologic study of 8 cases] |language=French |journal=Tunis Med |volume=88 |issue=3 |pages=142–6 |year=2010 |month=March |pmid=20415184 |doi= |url=}}</ref>
*Usual location (like glioblastoma): temporal lobe.
*Prognosis is similiar to [[glioblastoma]].<ref>{{Cite journal | last1 = Frandsen | first1 = J. | last2 = Orton | first2 = A. | last3 = Jensen | first3 = R. | last4 = Colman | first4 = H. | last5 = Cohen | first5 = AL. | last6 = Tward | first6 = J. | last7 = Shrieve | first7 = DC. | last8 = Suneja | first8 = G. | title = Patterns of care and outcomes in gliosarcoma: an analysis of the National Cancer Database. | journal = J Neurosurg | volume = | issue = | pages = 1-6 | month = Jun | year = 2017 | doi = 10.3171/2016.12.JNS162291 | PMID = 28621623 }}</ref>
** Age below 65 years is prognostic.

===Microscopic===
Features:
*[[Glioblastoma]].
*Sarcomatous component (one of the following):<ref name=pmid19618114/><ref name=pmid20415184/>
**Fibroblastic.
**Cartilaginous.
**Osseous.
**Smooth muscle.
**Striated muscle.
**Adipocyte.

====Images====
<gallery>
Image:Gliosarcoma_Histopathology_200x_EVG.jpg | Gliosarcoma - elastica van Giesson. (WC)
</gallery>
www:
*[http://path.upmc.edu/cases/case169/micro.html Gliosarcoma - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case361.html Gliosarcoma - case 2 - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case367.html Gliosarcoma - case 3 - several images (upmc.edu)].

===IHC===
*GFAP +ve -- astrocytic component.<ref name=pmid9736406>{{Cite journal | last1 = Horiguchi | first1 = H. | last2 = Hirose | first2 = T. | last3 = Kannuki | first3 = S. | last4 = Nagahiro | first4 = S. | last5 = Sano | first5 = T. | title = Gliosarcoma: an immunohistochemical, ultrastructural and fluorescence in situ hybridization study. | journal = Pathol Int | volume = 48 | issue = 8 | pages = 595-602 | month = Aug | year = 1998 | doi = | PMID = 9736406 }}</ref>
**Spindle cell component -ve.<ref>URL: [http://path.upmc.edu/cases/case361.html http://path.upmc.edu/cases/case361.html]. Accessed on: 15 January 2012.</ref>

Gliosarcoma with smooth muscle component (gliomyosarcoma):<ref name=pmid21393877>{{Cite journal | last1 = Khanna | first1 = M. | last2 = Siraj | first2 = F. | last3 = Chopra | first3 = P. | last4 = Bhalla | first4 = S. | last5 = Roy | first5 = S. | title = Gliosarcoma with prominent smooth muscle component (gliomyosarcoma): a report of 10 cases. | journal = Indian J Pathol Microbiol | volume = 54 | issue = 1 | pages = 51-4 | month = | year = | doi = 10.4103/0377-4929.77324 | PMID = 21393877 }}</ref>
*SMA +ve.
*Factor VIII +ve.

==Gliofibroma==
* Very rare indolent tumor in children <ref>{{Cite journal | last1 = Deb | first1 = P. | last2 = Sarkar | first2 = C. | last3 = Garg | first3 = A. | last4 = Singh | first4 = VP. | last5 = Kale | first5 = SS. | last6 = Sharma | first6 = MC. | title = Intracranial gliofibroma mimicking a meningioma: a case report and review of literature. | journal = Clin Neurol Neurosurg | volume = 108 | issue = 2 | pages = 178-86 | month = Feb | year = 2006 | doi = 10.1016/j.clineuro.2004.11.021 | PMID = 16412839 }}</ref>
* Usually not dura-based (DD: Desmoplastic infantile astrocytoma)
* Glial tumor with non-neoplastic fibromatous component.

=See also=
*[[CNS tumours]].

=References=
{{Reflist|2}}

[[Category:Neuropathology]]

Chronic traumatic encephalopathy

2022-10-17T12:43:20Z

Jensflorian: CTE staging

[[Image:Chronic Traumatic Encephalopathy.png|thumb|right|Gross images showing a brain with chronic traumatic encephalopathy (CTE) and a normal brain. (WC/BU)]]
'''Chronic traumatic encephalopathy''', abbreviated '''CTE''', is a [[Neurodegenerative diseases|neurodegenerative disease]] due to repeated trauma.

The in the context of boxing it is known as '''dementia pugilistica'''; ''pugil'' is ''boxer'' in Latin.<ref>URL: [http://dictionary.reference.com/browse/pugilism http://dictionary.reference.com/browse/pugilism]. Accessed on: 21 November 2011.</ref>

==General==
*Due to head trauma - usually repetitive.
**Seen in ''American football'' and ''boxing''.
*May be associated with motor neuron disease.<ref name=pmid22050943>{{Cite journal | last1 = Daneshvar | first1 = DH. | last2 = Riley | first2 = DO. | last3 = Nowinski | first3 = CJ. | last4 = McKee | first4 = AC. | last5 = Stern | first5 = RA. | last6 = Cantu | first6 = RC. | title = Long-term consequences: effects on normal development profile after concussion. | journal = Phys Med Rehabil Clin N Am | volume = 22 | issue = 4 | pages = 683-700 | month = Nov | year = 2011 | doi = 10.1016/j.pmr.2011.08.009 | PMID = 22050943 }}</ref>

==Microscopic==
Features:<ref name=pmid22035690>{{Cite journal | last1 = Stern | first1 = RA. | last2 = Riley | first2 = DO. | last3 = Daneshvar | first3 = DH. | last4 = Nowinski | first4 = CJ. | last5 = Cantu | first5 = RC. | last6 = McKee | first6 = AC. | title = Long-term Consequences of Repetitive Brain Trauma: Chronic Traumatic Encephalopathy. | journal = PM R | volume = 3 | issue = 10 Suppl 2 | pages = S460-7 | month = Oct | year = 2011 | doi = 10.1016/j.pmrj.2011.08.008 | PMID = 22035690 }}</ref>
*Wall-to-wall neurofibrillary tangles.
**Common in olfactory bulb, mammillary bodies, hippocampus.
**Usually perivascular around small blood vessels.
**Often superficial (unlike [[Alzheimer disease]]) and at the deep aspect of sulci.
*** But not restricted to superficial regions of sulci (also deep in parenchyma).
**Staging according to Bienik et al.: NFT in <5 regions: low CTE, in 5 or more: high CTE.<ref>{{cite journal |vauthors=Snijders RJ, De Courcy-Wheeler RH, Nicolaides KH |title=Intrauterine growth retardation and fetal transverse cerebellar diameter |journal=Prenat Diagn |volume=14 |issue=12 |pages=1101–5 |date=December 1994 |pmid=7899277 |doi=10.1002/pd.1970141202 |url=}}</ref>

==IHC==
*Increased TDP-43 staining.
*p-Tau neuronal aggregates.
**+/. thron shaped-astrocytes.
*Usu. absence of beta-amyloid.

Note:
*[[ALS]] associated with traumatic brain injuries.<ref name=pmid21696410>{{Cite journal | last1 = Costanza | first1 = A. | last2 = Weber | first2 = K. | last3 = Gandy | first3 = S. | last4 = Bouras | first4 = C. | last5 = Hof | first5 = PR. | last6 = Giannakopoulos | first6 = P. | last7 = Canuto | first7 = A. | title = Review: Contact sport-related chronic traumatic encephalopathy in the elderly: clinical expression and structural substrates. | journal = Neuropathol Appl Neurobiol | volume = 37 | issue = 6 | pages = 570-84 | month = Oct | year = 2011 | doi = 10.1111/j.1365-2990.2011.01186.x | PMID = 21696410 }}</ref>

==See also==
*[[Neurodegenerative diseases]].
*[[Neuropathology]].

==References==
{{Reflist|1}}

[[Category:Diagnosis]]
[[Category:Neuropathology]]

Neurohistology

2022-10-17T12:34:45Z

Jensflorian: /* Glial cells */ microglia

This article covers basic (normal) '''neurohistology'''. It is essential to have a good grasp on neurohistology and [[neuroanatomy]]... before doing [[neuropathology]].

''This article'' has some overlap with the ''[[neuroanatomy]]'' article, as there isn't a clear divider between microscopic and macroscopic.

=Normal cells=
This section deals with normal cellular constituents of the CNS.

==Overview==
===Central nervous system===
====Neuron====
*Abundant cytoplasm - '''key feature'''.
*Often very large cells, with angled edges.
*Prominent nucleolus.
*Nissl substance (granular perinuclear material = rough endoplasmic reticulum).

====Glial cells====
*Oligodendrocyte.
**Small round nuclei (lymphocyte-like nucleus) - '''key feature'''.
**May resemble a ''fried egg'' on H&E (clear cytoplasm, central nucleus).
**Image: [http://www.urmc.rochester.edu/libraries/courses/neuroslides/lab1a/images/1-11.png oligodendrocyte urmc.rochester.edu]
*Astrocyte.
**Irregular non-ovoid nucleus - '''key feature'''.
**Nuclei less dense than in oligodendrocyte.
**Close to blood vessels.
**Form blood-brain barrier.
**Cytoplasm normally ''not'' visible.
**Image: [http://embryology.med.unsw.edu.au/histology/endocrine/pin42he.jpg astrocyte (med.unsw.edu.au)] (in [http://embryology.med.unsw.edu.au/notes/endocrine12.htm endocrine development]).
*Microglia - macrophage of the brain (derived from monocyte).
**Typically large cells with abundant cytoplasm.
***Often have vesicles.
**Rarely seen in normal tissue.
**Three morphologic types:
***Ramified microglia.
***Hypertrophic microglia.
***Dystrophic microglia - often seen in neurodegnerative disease.
*Ependyma.
**Simple ciliated cuboidal epithelium.
**Image: [http://www.stonybrookmedicalcenter.org/sbumcfiles/images/221-001.jpg Ependyma (stonybrookmedicalcenter.org)].
*Choroid plexus.
**Specialized ependymal cells
**Cuboidal epithelial cells surrounding a core of capillaries and loose connective tissue.
**Ventricular location.
=====Images=====
[[File:Blausen 0870 TypesofNeuroglia.png |500px| Types of neuroglia (WC/Blausen)]]
<gallery>
File:Astrocytes.jpg | Astrocytes highlighted by GFAP (WC/Jeffery J. Iliff)
Image:Oligodendrocyte_HE_stain_high_mag.jpg | Oligodendrocytes with fried-egg appearance (WC/jensflorian)
Image:Ependyma.png|Ependymal cells. (WC/marvin101)
File:Psammoma bodies in the choroid plexus, HE.JPG | Choroid plexus (WC/Patho)
File:Mikroglej 1.jpg | Microglial cells, Lectin stain (WC/Grzegorz Wicher)
</gallery>

===Peripheral nervous system===
====Ganglion cell====
*Nerve cell body.
*Found in ganglions - encapsulated body ~ 100-300 μm.
*Large round nucleus with prominent nucleolus - '''key feature'''.
*Abundant eosinophilic granular cytoplasm.
====Schwann cell====
*Principal glia of the PNS.
*Myelinated or unmyelinated.
*Ovoid, wavy nuclei.
*Cells have a basal membrane.
*Found in peripheral nerves.
*Aka ''neurolemmocytes''.
=====Images=====
<gallery>
Image:Ganglion_very_high_mag.jpg | Ganglion - very high mag. (WC/Nephron)
Image:Peripheral nerve, cross section.jpg | Peripheral nerve - cross section. (WC/Reytan)
File:Nerve root - very high mag.jpg | Nerve root HPS stain (WC/Nephron)
</gallery>

WC:
*[http://commons.wikimedia.org/wiki/File:Ganglion_intermed_mag.jpg Ganglion - intermed. mag. (WC/Nephron)].

==Normal cellular constituents in a table==
{| class="wikitable sortable"
! Cell
! Key feature
! Other features
! Image
|-
|Neuron
| cytoplasm
| Nissl substance (prominent RER), "sharp" corners in cell membrane, nucleolus - usu. prominent<ref name=Ref_PSNP16>{{Ref PSNP|16}}</ref>
| [http://commons.wikimedia.org/wiki/File:Alzheimer_type_II_astrocyte_high_mag_cropped.jpg red neurons (WC)]
|-
|Astrocyte
| non-ovoid nucleus
| no cytoplasm
| [http://embryology.med.unsw.edu.au/histology/endocrine/pin42he.jpg (unsw.edu)]
|-
|Oligodendrocyte
| round small nucleus
| peri-nuclear clearing
| [http://education.vetmed.vt.edu/Curriculum/VM8054/Labs/Lab9/IMAGES/OLIGODENDROCYTE%20400X%20B.jpg (vetmed.vt.edu)]
|-
|Microglia
| rod-like shape, may have "bent" nucleus
| typically have a sharply demarcated bubbly cytoplasm; rarely seen in normal tissue
| [http://www.neuropathologyweb.org/chapter1/chapter1dMicroglia.html (neuropathologyweb.org)], [http://missinglink.ucsf.edu/lm/ids_104_cns_injury/Response%20_to_Injury/Microglia.htm (ucsf.edu)],[http://www.pathology.vcu.edu/WirSelfInst/neuro_medStudents/glialpath.html (vcu.edu)]
|-
|}

==Neurons==
There are many types of 'em. Broadly, they can be classified as:
#Pyramidal - have a pyramidal shape.
##Dentrites go to molecular layer.
##Axons go to outside of cortex.
#Non-pyramidal.

Motor neurons:
*Coarse Nissl substance - '''key feature'''.
**Nissl described as having a ''tigroid appearance''.<ref>URL: [http://www.stonybrookmedicalcenter.org/pathology/neuropathology/chapter1 http://www.stonybrookmedicalcenter.org/pathology/neuropathology/chapter1]. Accessed on: 5 July 2010.</ref>
*Polygonal shape.
*Send dendrites in all directions.

===Images===
www:
*[http://www.stonybrookmedicalcenter.org/sbumcfiles/images/238-002.jpg Motor neuron (stonybrookmedicalcenter.org)].
<gallery>
Image:Medulla_oblongata_-_posterior_-_cn_xii_-_very_high_mag.jpg | Motor neurons - nucleus of CN XII - very high mag. (WC)
</gallery>

=Structures=
This section deals with structures seen at several places in the CNS.

==Grey matter and white matter==
{| class="wikitable"
|
| '''Grey matter'''
| '''White matter'''
|-
| Definition
| neurons present
| neurons absent
|-
| Extracellular space (neuropil)
| dense - darker pink (on [[H&E stain|H&E]]/[[HPS stain|HPS]])
| fine mesh - lighter pink (on H&E/HPS)
|-
| Image
| [[Image:Grey_matter_and_white_matter_-_very_high_mag.jpg|thumb|Right 2/3 of image. (WC/Nephron)]]
| [[Image:Grey_matter_and_white_matter_-_very_high_mag.jpg|thumb|Left 1/3 of image. (WC/Nephron)]]
|}

Additional images (white matter vs. grey matter):
<gallery>
Image:Grey_matter_and_white_matter_-_high_mag.jpg | Grey-white matter interface - high mag. (WC)
Image:Grey_matter_and_white_matter_-_intermed_mag.jpg | Grey and white matter - intermed. mag. (WC)
File:LFB_CNS_cortex_supratentorial.jpg | Normal cortex - LFB. (WC/jensflorian)
File:LFB_CNS_cortex_grey-white_matter_junction.jpg | White-grey matter junction - LFB. (WC/jensflorian)
</gallery>

==Vessels==
The small blood vessels in the CNS are separated from the surrounding tissue in histologic sections. This is normal. The spaces are called ''Virchow-Robin spaces''.<ref>URL: [http://www.whonamedit.com/synd.cfm/43.html http://www.whonamedit.com/synd.cfm/43.html]. Accessed on: 2 August 2011.</ref>

=Histology by anatomical structure=
This section deals with specific anatomical structures.

==Subependyma==
Features:<ref>Croul SE. 28 June 2010.</ref>
*Ependyma (simple ciliated cuboidal epithelium).
*Subependymal plate - connective tissue with blood vessels.

==Caudate==
Features:
*Neurons with adjacent ependymal lining.<ref>URL: [http://www.stonybrookmedicalcenter.org/pathology/neuropathology/chapter1 http://www.stonybrookmedicalcenter.org/pathology/neuropathology/chapter1]. Accessed on: 2 July 2010.</ref>
**The caudate forms lateral wall of lateral ventricle.

Notes:
*Caudate, putamen and nucleus accumbens are collectively called ''neostriatum''.<ref name=Ref_PSNP23-24>{{Ref PSNP|23-34}}</ref>
==Putamen==
Features:
*Striatopallidal fibers [[AKA]] ''pencils of Wilson'' (also ''pencil fibers of Wilson''<ref name=Ref_PSNP23-24>{{Ref PSNP|23-34}}</ref> and ''Wilson's pencils''<ref name=pmid8985875>{{cite journal |author=Kimura M, Kato M, Shimazaki H, Watanabe K, Matsumoto N |title=Neural information transferred from the putamen to the globus pallidus during learned movement in the monkey |journal=J. Neurophysiol. |volume=76 |issue=6 |pages=3771–86 |year=1996 |month=December |pmid=8985875 |doi= |url=http://jn.physiology.org/cgi/pmidlookup?view=long&pmid=8985875}}</ref>) - bundles of blue fibres (on H&E LFB).
*Neurons:
*#Small - GABA.
*#Large (very rare: ~1 in 100-200) - cholingeric.

Notes:
*Histologically identical to the ''caudate'' - but not adjacent to a ventricle.
**The caudate is adjacent to an ependymal lined space, putamen is not.<ref>URL: [http://www.stonybrookmedicalcenter.org/pathology/neuropathology/chapter1 http://www.stonybrookmedicalcenter.org/pathology/neuropathology/chapter1]. Accessed on: 22 December 2010.</ref>
*[[Necrotic]] putamen in methanol poisoning.<ref name=pmid19015300>{{Cite journal | last1 = Bhatia | first1 = R. | last2 = Kumar | first2 = M. | last3 = Garg | first3 = A. | last4 = Nanda | first4 = A. | title = Putaminal necrosis due to methanol toxicity. | journal = Pract Neurol | volume = 8 | issue = 6 | pages = 386-7 | month = Dec | year = 2008 | doi = 10.1136/jnnp.2008.161976 | PMID = 19015300 }}</ref>

===Images===
<gallery>
Image:Globus_pallidus_and_putamen_-_very_low_mag.jpg | Globus pallidus & putamen - showing Wilson's pencils - very low mag. (WC)
Image:Putamen_-_intermed_mag.jpg | Putamen - intermed. mag. (WC)
</gallery>
www:
*[http://frontalcortex.com/?page=oll&topic=24&qid=760 Pencils of Wilson (frontalcortex.com)].

==Globus pallidus==
*[[AKA]] ''paleostriatum''.<ref name=Ref_PSNP23>{{Ref PSNP|23}}</ref>
*Location:
**Superior of the ''substantia innominata''.
**Medial to the ''putamen''.

Features:
*Histologically distinct from caudate and putamen.

===Image===
<gallery>
Image:Nucleus_basalis_of_Meynert_-l-_very_low_mag.jpg | Globus pallidus, putamen and the nucleus basalis in the substantia innominata - very low mag. (WC)
</gallery>

==Hippocampus==
===Structures===
Hippocampal formation:<ref>URL: [http://www.stonybrookmedicalcenter.org/pathology/neuropathology/chapter1 http://www.stonybrookmedicalcenter.org/pathology/neuropathology/chapter1]. Accessed on: 2 July 2010.</ref>
#Dentate gyrus.
#*"Dense" thin layer of nuclei.
#*Quasi "U-shaped"; "open" (top) portion of "U" is superolateral.
#*Image: [http://www.stonybrookmedicalcenter.org/sbumcfiles/images/225-001.jpg Dentate gyrus (stonybrookmedicalcenter.org)].
#Hippocampus proper ([[AKA]] ''Ammon's horn'') - this is subdivided:
#*Cornu ammonis 3 (CA3) - location: superior.
#**Large pyramidal neurons.
#*CA1 (AKA Sommer's sector) - location: inferior (next to subiculum).
#**Small dispersed pyramidal neurons.
#*CA2 - location: in between CA3 and CA1, lateral.
#**Narrow band of neurons between CA3 and CA1.
#*CA4 - location: medial (closest to dentate gyrus; CA4 sits in "open" part of "U").
#Subiculum ([[AKA]] subicular complex).
#*Transitions to the six layers in the ''entorhinal cortex''.
#**No vacuolated looking stuff next to it.

Important notes:
*CA1 - weak link, dies in ischemia, affected by hypoglycemia, degenerative diseases and toxins.
*CA2 - resistant to ischemia.
*CA4 - involved in [[epilepsy]],<ref name=pmid3518570>{{Cite journal | last1 = Ingvar | first1 = M. | title = Cerebral blood flow and metabolic rate during seizures. Relationship to epileptic brain damage. | journal = Ann N Y Acad Sci | volume = 462 | issue = | pages = 194-206 | month = | year = 1986 | doi = | PMID = 3518570 }}</ref> usu. normal in degenerative diseases.<ref>D. Munoz. 27 July 2011.</ref>
====Images====
<gallery>
Image:Brainmaps-macaque-hippocampus.jpg | Hippocampus - frontal section. (WC)
Image:Hippocampus_%28brain%29.jpg | Hippocampus - schematic. (WC)
</gallery>
www:
*[http://www.ajnr.org/cgi/content-nw/full/28/5/958/F1 Hippocampus (ajnr.org)].
*[http://edoc.hu-berlin.de/dissertationen/schubert-stephan-nicolas-2003-09-26/HTML/schubert_html_21d219b1.png Hippocampus and subiculum (hu-berlin.de)].
*[http://spinwarp.ucsd.edu/NeuroWeb/Text/br-800epi/br-800epi1.gif Hippocampus - crappy schematic (ucsd.edu)].

===Layers of CA<ref name=Ref_PSNP25>{{Ref PSNP|25}}</ref>===
#Molecular layer - opposed to the dentate gyrus (of Hippocampal formation).
#Neurons (described above).
#Alveus - opposed to the lateral ventricle.
#*Connects to the ''mammillary bodies'' via the ''fornix'' (circuit of Papez).

==Cerebellum==
Main components:
*Cortex (superficial) - branches (Christmas tree-like).
*Dentate nucleus (deep) - looks like the bite impression of a molar.
**Image: [http://www.stonybrookmedicalcenter.org/sbumcfiles/images/227-scout.jpg Cerebellum, cortex & dendate nucleus - low power (stonybrookmedicalcenter.org)].

===Dentate nucleus===
Features:<ref name=Ref_PSNP27>{{Ref PSNP|27}}</ref>
*Ribbon of grey matter.
**Large neurons.
**Small neurons.

====Images====
<gallery>
Image:Dentate_nucleus_-_cerebellum_-_intermed_mag.jpg | Dentate nucleus of the cerebellum - intermed. mag. (WC)
Image:Dentate_nucleus_-_cerebellum_-_high_mag.jpg | Dentate nucleus of the cerebellum - high mag. (WC)
</gallery>

===Cerebellar cortex===
*Layers (superficial to deep) - mnemonic ''MPG'':<ref>URL: [http://www.stonybrookmedicalcenter.org/pathology/neuropathology/chapter1 http://www.stonybrookmedicalcenter.org/pathology/neuropathology/chapter1]. Accessed on: 2 July 2010.</ref>
*#Molecular layer -- "very pink" on H&E.
*#*Inhibitory interneurons: stellate cells, basket cells.
*#Purkinje cell layer.
*#*One cell layer thick - hueuege cells (~50-80 micrometers<ref name=Ref_PSNP16>{{Ref PSNP|16}}</ref>).
*#**Very large nucleus (~4x RBC diameter =~ 4x the size of granule cell).
*#***Large nucleolus (~1x RBC diameter =~ size of granule cell).
*#Granule cell layer -- "very blue" on H&E.
*#*Granule cells (neurons) - majority of cells, small (~10 micrometres), round.
*#**May look like small cell carcinoma to the uninitiated.
*#*Golgi cells (interneurons) - few in number, elongated/columnar, 3-5x size of granule cell.

Notes:
*''Bergmann glia'' are found between the molecular layer & granular layer. They are normally not seen. They are increased & prominent in pathologic states (e.g. ischemia); "[[Bergmann gliosis]]".<ref name=Ref_PSNP18>{{Ref PSNP|18}}</ref>

====Images====
www:
*[http://www.stonybrookmedicalcenter.org/sbumcfiles/images/227_001.jpg Cerebellar cortex - micrograph with labels (stonybrookmedicalcenter.org)].
<gallery>
Image:Gray706.png | Cerebellar cortex - schematic. (Gray's Anatomy/WC)
Image:Cerebellar_cortex_-_intermed_mag.jpg | Cerebellar cortex - intermed. mag. (WC)
Image:Cerebellum_-_biel_-_high_mag.jpg | Cerebellar cortex - high mag. [[Bielschowsky stain]]. (WC)
</gallery>

==Cerebral cortex==
Layers (superficial to deep):
#Molecular layer.
#*Empty appearing.
#Outer granular layer.
#*Higher cell density & smaller cells than pyramidal layer.
#Outer pyramidal layer.
#Inner granular layer.
#*Not prominent in frontal cortex.
#*Where the thalamic axons end.
#*Divided in three (''a'', ''b'', ''c'') in the calcarine cortex due to two white matter bands (external band of Baillarger, internal band of Baillarger) that are grossly identified as the ''line of Gennari''.<ref name=Ref_PSNP24>{{Ref PSNP|24}}</ref><ref>URL: [http://www.ncbi.nlm.nih.gov/books/NBK11524/ http://www.ncbi.nlm.nih.gov/books/NBK11524/]. Accessed on: 7 January 2011.</ref>
#**Image: [http://moon.ouhsc.edu/kfung/iacp-olp/APAQ-Images/N1-MS-01-01.gif Calcarine cortex (ouhsc.edu)].<ref>URL: [http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/N1-MS-01-01-Ans.htm http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/N1-MS-01-01-Ans.htm] and [http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/n1-ms-01.htm http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/n1-ms-01.htm]. Accessed on: 31 October 2010.</ref>
#Inner pyramidal layer.
#*Location of ''Betz neurons'' - large motor neurons of cerebral cortex.
#Multiforme layer (Polymorphic layer).

Images:
*[http://commons.wikimedia.org/wiki/File:Cajal_cortex_drawings.png Cajal drawings - different areas (WC)].
*[http://commons.wikimedia.org/wiki/File:Visual_cortex_-_intermed_mag.jpg Visual cortex - intermed. mag. (WC)].
*[http://www.ncbi.nlm.nih.gov/books/NBK11524/figure/ch31visualcortex.F13/?report=objectonly Visual cortex - nissl stain (nlm.nih.gov)].<ref>URL: [http://www.ncbi.nlm.nih.gov/books/NBK11524/ http://www.ncbi.nlm.nih.gov/books/NBK11524/]. Accessed on: 7 January 2011.</ref>
*[http://www.ruf.rice.edu/~lngbrain/cglidden/Lab8_fig1.gif Different stains (rice.edu)].
*[http://williamcalvin.com/bk7/img/bk7p31.jpg Cerebral cortex (williamcalvin.com)].
*[http://www.benbest.com/science/anatmind/anatmd5.html Cerebral cortex (benbest.com)].

===Cingulate cortex===
*Spindle neurons, [[AKA]] ''von Economo neurons''.
**Thought to be important in cognition and problem solving.<ref name=pmid11411161>{{Cite journal | last1 = Allman | first1 = JM. | last2 = Hakeem | first2 = A. | last3 = Erwin | first3 = JM. | last4 = Nimchinsky | first4 = E. | last5 = Hof | first5 = P. | title = The anterior cingulate cortex. The evolution of an interface between emotion and cognition. | journal = Ann N Y Acad Sci | volume = 935 | issue = | pages = 107-17 | month = May | year = 2001 | doi = | PMID = 11411161 }}</ref>

====Images====
<gallery>
Image:Spindle_neurons_-_high_mag.jpg | Spindle neurons - high mag. (WC)
Image:Spindle_neurons_-_very_high_mag_-_cropped.jpg | Spindle neurons - cropped - very high mag. (WC)
</gallery>

==Pineal gland==
{{Main|Pineal gland}}
Features:<ref name=Ref_PSNP25-26>{{Ref_PSNP|25-26}}</ref><ref name=Blue_Histology_-_Endocrines>URL: [http://www.lab.anhb.uwa.edu.au/mb140/corepages/endocrines/endocrin.htm http://www.lab.anhb.uwa.edu.au/mb140/corepages/endocrines/endocrin.htm]. Accessed on: 31 October 2010.</ref>
*Cells in lobulated clusters or linear arrays (low power).
*Pinealocyte:
**Light staining and round nuclei with neuroendocrine look (i.e. salt-and-pepper chromatin).
**Broad rim of light cytoplasm.
*Astrocytes:
**Cylindrical hyperchromatic nucleus ~ 1/2 the size of pinealocyte.

Notes:
*Highly cellular structure - may be confused with (metastatic) [[small cell carcinoma]].
*Often calcified.
===Images===
<gallery>
Image:Pineal_gland_-_very_high_mag.jpg | Pineal gland - very high mag. (WC/Nephron)
Image:Pineal_gland_-_intermed_mag.jpg | Pineal gland - intermed. mag. (WC/Nephron)
Image:Pineal.jpg | Pineal gland. (WC)
</gallery>
www:
*[http://www.lab.anhb.uwa.edu.au/mb140/corepages/endocrines/Images/pin42he.jpg Pineal gland (anhb.uwa.edu.au)].<ref name=Blue_Histology_-_Endocrines>URL: [http://www.lab.anhb.uwa.edu.au/mb140/corepages/endocrines/endocrin.htm http://www.lab.anhb.uwa.edu.au/mb140/corepages/endocrines/endocrin.htm]. Accessed on: 31 October 2010.</ref>
===IHC===
*Synaptophysin +ve.<ref name=Ref_PSNP25-26>{{Ref_PSNP|25-26}}</ref>

==Midbrain==
Structures:
*Substantia nigra ([[Parkinson's disease]]).
*Nuclei of CN IV (posterior).
*Nuclei of CN III (anterior).
*Cerebral penduncles (anterior).
*Red nuclei.

===Schematics===
<gallery>
Image:Cn3nucleus.png | Midbrain (WC)
Image:Gray696.png | Nuclei of the CNs (WC)
Image:Brain_stem_sagittal_section.svg | Nuclei of the CNs - sagittal section of brain stem (WC)
</gallery>

==Pons==
Features:
*Looks like bacon (at very low power).<ref>Croul SE. 28 June 2010.</ref>
*Images:
**[http://www.stonybrookmedicalcenter.org/sbumcfiles/images/243-scout.jpg Pons (stonybrookmedicalcenter.org)].
**[http://commons.wikimedia.org/wiki/File:Pons_-_intermed_mag.jpg Pons - intermed. mag. (WC)].

===Locus ceruleus===
*Literally means ''blue spot''.
*Location: adjacent to midline + anterior to 4th ventricle.

Microscopic features:
*Pigmented neurons.
**Produce norepinephrine.

Notes:
*Pale in [[Parkinson disease]] due to neuronal loss.<ref name=Ref_PCPBoD8_677>{{Ref PCPBoD8|677}}</ref>

====Images====
<gallery>
Image:Locus_ceruleus_-_very_low_mag.jpg | Locus ceruleus (LC) - very low mag. (WC)
Image:Locus_ceruleus_-_low_mag.jpg | Locus ceruleus (LC) - low mag. (WC)
Image:Locus_ceruleus_-_intermed_mag.jpg | Locus ceruleus (LC) - intermed. mag. (WC)
Image:Locus_ceruleus_-_high_mag.jpg | Locus ceruleus (LC) - high mag. (WC)
</gallery>
www:
*[http://www.scholarpedia.org/article/File:Bouret_LC_anat2.jpg LC - labeled on MRI - (scholarpedia.org)].

==Medulla oblongata==
*[[AKA]] ''medulla''.
===Anatomy===
Schematic: [http://commons.wikimedia.org/wiki/File:Gray694.png Medulla oblongata - Gray's anatomy (WC)].

====Anterior====
*Pyramids: adjacent to midline, anterior.
*Olives: lateral and posterior to pyramids.

====Posterior - important nuclei (location)====
*CN XII: 4th ventricle + adjacent to midline; medial to nucleus of CN X.<ref name=Ref_Neuroanat13>{{Ref Neuroanat|13}}</ref>
*CN X: 4th ventricle + lateral to nucleus of CN XII.
**This is were [[Lewy body]] formation starts.<ref name=pmid19501577>{{cite journal |author=Miller VM, Kenny RA, Oakley AE, Hall R, Kalaria RN, Allan LM |title=Dorsal motor nucleus of vagus protein aggregates in Lewy body disease with autonomic dysfunction |journal=Brain Res. |volume=1286 |issue= |pages=165–73 |year=2009 |month=August |pmid=19501577 |doi=10.1016/j.brainres.2009.05.083 |url=}}</ref>

=====Image=====
<gallery>
Image:Medulla_oblongata_-_posterior_-_very_low_mag.jpg | Medulla oblongata - very low mag. (WC)
</gallery>

==Pituitary gland==
===Anatomy===
*Located in sella turcica below optic chiasm.
*Anterior lobe is epithelial.
*Posterior lobe is neuroepithelial.
*The infundibulum connects the pituitary to the brain
Schematic: [[File:Gray1181.png Pituitary gland - Gray's anatomy (WC)]].

====Images====
<gallery>
File:Anterior and posterior pituitary.jpg | Anterior & posterior pituitary. (WC)
File:Adenohypofýza HE.jpg | Adenohypophysis. (WC/Držiak)
</gallery>

=See also=
*[[Neuropathology]].
*[[Muscle biopsy]].
*[[CNS tumours]].

=References=
{{reflist|2}}

=External links=
*[http://www.stonybrookmedicalcenter.org/pathology/neuropathology/chapter1 Neuropathology micrographs - identifying the site (stonybrookmedicalcenter.org)].
*[http://education.vetmed.vt.edu/Curriculum/VM8054/Labs/Lab9/lab9.htm Neural tissues - veterinary histology (vetmed.vt.edu)].
*[http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/n1-ms-01.htm Basic neurohistology - quiz (ouhsc.edu)].

[[Category:Neuropathology]]

Pituitary gland

2022-09-30T11:30:26Z

Jensflorian: /* Pituitary carcinoma */ Update

The '''pituitary gland''' is known as the ''master gland''.

Divisions:<ref>[http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo.html http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo.html]</ref>
*Anterior pituitary ([[AKA]] adenohypophysis, pars distalis).
*Posterior pituitary (AKA neurohypophysis, neural pituitary, pars nervosa).

=Function=
===Anterior===
Hormones:<ref name=rcn_com>[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Pituitary.html http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Pituitary.html]</ref>
*Growth hormone (GH).
*Luteinizing hormone (LH)
*Follicle-stimulating hormone (FSH)
*Thyroid stimulating hormone (TSH)
*Adrenocorticotropic hormone (ACTH)
*Prolactin (PRL)

Mnemonic: "Go Look For The Adenoma Please" = GH, LH, FSH, TSH, ACTH, PRL.

===Intermedia===
* Originates from the posterior wall of the Rathke’s pouch.
* Hormones: MSH, ACTH precursor.
* Contains colloid cysts.

===Posterior===
Hormones:<ref name=rcn_com/>
*Oxytocin.
*Antidiuretic hormone (ADH).

=Anatomy and histology=
===Anatomy===
Basic anatomy (simplified):<ref name=bowen>URL: [http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo_pit.html http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo_pit.html]. Accessed on: 31 October 2010.</ref>
*Anterior:
**Pars distalis.
**Pars intermedia.
*Posterior:
**Pars nervosa.

Embryological origin:<ref name=bowen/>
*Anterior - Rathke's pouch (roof of mouth).
*Posterior - diencephalon (ventral aspect).

Images:
*[http://www.ouhsc.edu/histology/Glass%20slides/38_01.jpg Pituitary gland (ouhsc.edu)].
*[http://www.lab.anhb.uwa.edu.au/mb140/corepages/endocrines/Images/HypDevAni.gif Development of the pituitary - animation (anhb.uwa.edu)].

===Histology===
====Anterior====
*Acidophils (40% of cells) = red or orange.
**GH, PRL.
*Basophils (10% of cells) = basophilic (light blue).
**TSH, LH, FSH, ACTH.
*Chromophobes (50% of cells) = amphophilic (purplish/grey).

Notes:
*The cellular product (i.e. hormone produced) is not strictly correlated with the cell type.<ref name=Ref_PSNP26>{{Ref PSNP|26}}</ref>
*The cells can be typed using [[IHC]]; somatotrophs (GH), lactotrophs (PRL), corticotrophs (ACTH), thyrotrophs (TSH), gonadotrophs (FSH, LH).<ref>{{Ref PBoD8|1098-9}}</ref>

====Posterior====
Features:<ref name=Ref_PSNP26>{{Ref PSNP|26}}</ref>
*Herring bodies - '''key feature'''.
**Eosinophilic axonal dilations filled with lysosomes and neurosecretory granules.
*Less cellular.
**Usually more cellular in perivascular location.
Image: [http://www.ouhsc.edu/histology/Glass%20slides/38_09.jpg Herring bodies (ouhsc.edu)].

<gallery>
File:Pituitary gland histology 2014.jpg | Pituitary gland, low magnification (WC/Athikhun.suw)
</gallery>

=DDx for sella turcica lesions=
*[[Pituitary adenoma|PitNET]].
*[[Rathke cleft cyst]].
*[[Craniopharyngioma]].
*[[Germ cell tumour]].
*[[Meningioma]].

=Pituitary necrosis=
*Rare.

===Causes of pituitary necrosis===
*Sheehan syndrome - secondary to blood loss in childbirth.<ref>URL: [http://www.mayoclinic.com/health/sheehans-syndrome/DS00889 http://www.mayoclinic.com/health/sheehans-syndrome/DS00889]. Accessed on: 16 November 2010.</ref>
*[[Syphilis]] (fetal-maternal transmission).<ref>URL: [http://pediatrics.aappublications.org/cgi/content/full/104/1/e4 http://pediatrics.aappublications.org/cgi/content/full/104/1/e4]. Accessed on: 16 November 2010.</ref>
*Mollaret's meningitis - very rare.<ref name=pmid18715308>{{cite journal |author=Dancer CM, Woods ML, Henderson RD, Robertson T, Mungomery M, Allworth A |title=Mollaret's meningitis and pituitary failure associated with a Rathke's cleft cyst |journal=Intern Med J |volume=38 |issue=7 |pages=609–11 |year=2008 |month=July |pmid=18715308 |doi=10.1111/j.1445-5994.2008.01709.x |url=}}</ref> (???)
*Spontaneous necrosis of pituitary tumours - case reports.<ref>{{cite journal |author=Sachdev Y, Evered DC, Hall R |title=Spontaneous pituitary necrosis |journal=Br Med J |volume=1 |issue=6015 |pages=942 |year=1976 |month=April |pmid=1268492 |pmc=1639254 |doi= |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1639254/pdf/brmedj00512-0028a.pdf}}</ref>

Images:
*[http://path.upmc.edu/cases/case288.html Pituitary necrosis - several images (upmc.edu)].

=Specific entities=
==Pituitary neuroendocrine tumor (PitNET)==
Old terminology '''Pituitary adenoma''' is depreceated.
The WHO 2022 Classification of tumours of endocrine organs recoginizes following tumours:<ref>{{cite journal |vauthors=Asa SL, Mete O, Perry A, Osamura RY |title=Overview of the 2022 WHO Classification of Pituitary Tumors |journal=Endocr Pathol |volume=33 |issue=1 |pages=6–26 |date=March 2022 |pmid=35291028 |doi=10.1007/s12022-022-09703-7 |url=}}</ref>

{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! PitNET lineage
! PitNET type
! subtypes
! Hormone IHC
! Transcription factor IHC
|-
| PIT1
| Somatotroph tumor
| Densely and sparsely granulated tumor
| GH, a-subunit+/-, CK+
| PIT1
|-
| PIT1
| Lactotroph tumor
| Densely and sparsely granulated tumor
| PRL, CK-ve or weak
| PIT1, [[Estrogen receptor|ER]]
|-
| PIT1
| Mammosomatotroph tumor
|
| GH, PRL (usu. less), CK perinuclear +ve
| PIT1, [[Estrogen receptor|ER]]
|-
| PIT1
| Thyrotroph tumor
|
| TSH, CK-ve or weak
| PIT1, GATA3
|-
| PIT1
| Mature plurihormonal PIT1 lineage tumor
|
| GH, PRL, TSH, a-subunit +/-ve, CK perinuclear
| PIT1, [[Estrogen receptor|ER]], GATA3
|-
| PIT1
| Immature PIT1 lineage tumor
|
| Only focal GH, PRL, TSH, a-subunit +/-ve, CK variable
| PIT1, [[Estrogen receptor|ER]] +/-ve, GATA3 +/-ve
|-
| PIT1
| Acidophilic stem cell tumor
|
| PRL, GH (focal/variable), CK fibrous bodies
| PIT1, [[Estrogen receptor|ER]]
|-
| PIT1
| Mixed somatotroph and lactotroph tumor
|
| PRL, GH (in separate cells)
| PIT1, [[Estrogen receptor|ER]] (only in lactotroph component)
|-
| TPIT
| Corticotroph tumor
| Densely and sparsely granulated tumors, Crooke cell adenoma
| ACTH,CK+ve
| TPIT
|-
| SF1
| Gonadotroph tumor
|
| FSH, LH, a-Subunit or none
| SF1, ER, GATA3, CK+/-ve
|-
| None
| Plurihormonal tumor
|
| All combinations possible
| All combinations possible, CK+/-ve
|-
| None
| Null cell adenoma
|
| None (adenohypophyseal?)
| None
|}

Other tumours may be classified as plurhormonal or double adenomas or as adenomas with unusual IHC combination.

===General===
*Clinical:<ref>{{Ref PBoD8|1100}}</ref>
**Classically: visual field defects (bitemporal hemianopsia).
**Others (increased intracranial pressure): headache, nausea, vomiting.
**Tumor of adults.

Morphologic Classification:
#Microtumor <= 1 cm.
#Macrotumor 1-4 cm.
#Giant tumor > 4cm.

May be classified by what they secrete.
#Functional (endocrine hyperfunction).
#*Acromegaly/giantism.
#*Hyperprolactinemia.
#*Cushing disease.
#*Hyperthyroidism.
#*Significant elevation of FSH/LH.
#Clinically nonfunctioning.

Notes:
''Cushing disease'' is due to pituitary gland hypersecretion of ACTH (due to a pituitary adenoma ''or'' CRH hypersecretion from the hypothalamus).<ref name=Ref_PBoD8_1148>{{Ref PBoD8|1148}}</ref> [[Cushing syndrome]] is hypercortisolism ''not'' due to pituitary gland pathology.

Imaging:
*Sellar enlargement.
*Bone erosion, invasive growth esp. cavernous sinus (35-45%).
*Inhomogenous signal in T1w MRI.

====Familial pituitary adenomas====
A pituitary adenoma may be part of a familial syndrome:<ref name=pmid19564887>{{Cite journal | last1 = Elston | first1 = MS. | last2 = McDonald | first2 = KL. | last3 = Clifton-Bligh | first3 = RJ. | last4 = Robinson | first4 = BG. | title = Familial pituitary tumor syndromes. | journal = Nat Rev Endocrinol | volume = 5 | issue = 8 | pages = 453-61 | month = Aug | year = 2009 | doi = 10.1038/nrendo.2009.126 | PMID = 19564887 }}</ref><ref name=Ref_PCPBoD8|554>{{Ref PCPBoD8|554}}</ref>
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Syndrome
! Gene
! Notes
|-
| [[Multiple endocrine neoplasia]] I
| MEN1
| characterized by the 3 Ps: '''p'''ituitary adenoma, [[parathyroid adenoma|'''p'''arathyroid adenoma]], [[pancreatic neuroendocrine tumour|'''p'''ancreatic neuroendocrine tumour]]
|-
| MEN-1-like syndrome
| CDKN1B<ref name=omim600778>{{OMIM|600778}}</ref>
| also known as ''Multiple endocrine neoplasia IV'' <ref name=omim600778>{{OMIM|600778}}</ref>
|-
| [[Carney syndrome]]
| PRKAR1A
| other findings (mnemonic ''NAME''): nevi, [[atrial myxoma]], myxoid neurofibroma, ephelides (freckles)
|-
| Isolated pituitary adenoma<ref name=pmid22612670>{{Cite journal | last1 = Korbonits | first1 = M. | last2 = Storr | first2 = H. | last3 = Kumar | first3 = AV. | title = Familial pituitary adenomas - Who should be tested for AIP mutations? | journal = Clin Endocrinol (Oxf) | volume = | issue = | pages = | month = May | year = 2012 | doi = 10.1111/j.1365-2265.2012.04445.x | PMID = 22612670 }}</ref>
| AIP
| classically GH-producing adenoma - leads to acromegaly
|}

===Microscopic===
Features:<ref name=Ref_PSNP36>{{Ref PSNP|36}}</ref>
*Loss of fibrous stroma.
**The cells of a normal (anterior) pituitary are nested.
*Basophilic cells (corticotrophs).
*Eosinophilic cells(somatotrophs).
*Extensive fibrosis often seen in TSH-producing tumors.

Notes:
*Smears very well.<ref>MUN. 24 November 2010.</ref>

====Images====
<gallery>
Image:Nonfunctioning_pituitary_adenoma_%281%29.jpg | Pituitary adenoma - non-functioning. (WC/KGH)
File:HE fibrosis pituitary adenoma.jpg | Extensive interstitial and perivascular fibrosis in a pituitary adenoma (WC/jensflorian)
File:PRL HE histology.jpg | Pituitary adenoma - PRL producing, HE. Note the basophilic appearance of the cells (WC/jensflorian)
File:PRL adenoma treatment HE.jpg | Pituitary adenoma - PRL producing, HE. Extensive regressive changes after after dopamine agonist treatment (WC/jensflorian)
File:PRL IHC pituitary adenoma.jpg | Pituitary adenoma - PRL producing, Prolactin IHC (WC/jensflorian)
File:Densely granulated HGH producing adenoma.jpg | Pituitary adenoma - HGH producing, HE. The cells have a slightly eosinophilic appearance (WC/jensflorian)
File:Sparsely granulated HGH adenoma.jpg | Sparsely granulated adenoma - HGH producing. Note the numerous fibrous bodies in HE stain (WC/jensflorian)
File:HGH adenoma CK8.jpg | Sparsely granulated adenoma - HGH producing. CK8 IHC highlighting fibrous bodies (WC/jensflorian)
File:TSHoma HE.jpg | Pituitary adenoma - TSH producing. HE stain showing pleomorphism (WC/jensflorian)
File:TSHoma IHC-TSH.jpg | Pituitary adenoma - TSH producing. TSH IHC can be heterogeneous (WC/jensflorian)
Image:Pituitary_adenoma_%281%29_GH_production.jpg | Pituitary adenoma - GH producing. (WC/KGH)
File:HE-GHoma.jpg | Pituitary adenoma , HE. This gonadotropin producing adenoma has a papillary architecture (WC/jensflorian)
File:FSH-GHoma.jpg | Pituitary adenoma, IHC for FSH (WC/jensflorian)
File:LH-GHoma.jpg | Pituitary adenoma, IHC for LH (WC/jensflorian)
File:ACTHoma-PAS-O-G.jpg | Pituitary adenoma , ACTH producing. PAS-O-G stain showing basophilic adenoma cells (WC/jensflorian)
File:ACTHoma-IHC.jpg | Pituitary adenoma , ACTH producing. Strong ACTH IHC in this basophilic adenoma (WC/jensflorian)
File:Pituitary_adenoma-nonfunctioning.jpg |Pituitary adenoma with vascular pseudorosettes, nonfunctioning (WC/jensflorian)
Crooke_HE_40x.jpg | Crooke cell adenoma, HE (WC/Marvin101)
File:Crooke Cytokeratins.jpg | Crooke cell adenoma, panCK (WC/Marvin101)
HE_fibrosis_pituitary_adenoma.jpg | Fibrosis in pituitary adenoma.
</gallery>

===Stains===
*Reticulin - loss of reticulin between tumour cells.

===IHC===
*LH.
*FSH.
*TSH - [[Hyperthyroidism]]
*GH - [[Acromegaly]].
*Prolactin -Galactorrhea, Amenorrhea, Gynecomastia. Golgi staining pattern in sparsely granulated cases.
*ACTH - [[Cushing syndrome]].
*PIT-1: stains somatotrophs, lactotrophs and thyrothrops.
*TPIT: stains corticotrophs.
*SF1: stains gonadotrophs.
*Chromogranin A +ve
*Synaptophysin strongly +ve (except lactotrophs)
*CAM5.2: fibrous bodies in sparsely granulated somatotroph adenoma, Ring-like staining in Crooke cell adenoma.
*MIB-1: Usu less than 3%.

Note:
Null-cell adenoma must be hormone immunonegative and negative for transcription factors.

===Variants===
*Corticotroph adenomas exhibiting Crooke's hyaline change: agressive course.<ref>{{Cite journal | last1 = George | first1 = DH. | last2 = Scheithauer | first2 = BW. | last3 = Kovacs | first3 = K. | last4 = Horvath | first4 = E. | last5 = Young | first5 = WF. | last6 = Lloyd | first6 = RV. | last7 = Meyer | first7 = FB. | title = Crooke's cell adenoma of the pituitary: an aggressive variant of corticotroph adenoma. | journal = Am J Surg Pathol | volume = 27 | issue = 10 | pages = 1330-6 | month = Oct | year = 2003 | doi = | PMID = 14508394 }}</ref>
*Acidophilic stem cell adenomas: large, locally invasive adenoma with low GH activity. <ref>{{Cite journal | last1 = Horvath | first1 = E. | last2 = Kovacs | first2 = K. | last3 = Singer | first3 = W. | last4 = Smyth | first4 = HS. | last5 = Killinger | first5 = DW. | last6 = Erzin | first6 = C. | last7 = Weiss | first7 = MH. | title = Acidophil stem cell adenoma of the human pituitary: clinicopathologic analysis of 15 cases. | journal = Cancer | volume = 47 | issue = 4 | pages = 761-71 | month = Feb | year = 1981 | doi = | PMID = 6261917 }}</ref>
*Sparsely granulated somatotroph adenomas are more invasive than other variants and respond less to medical treatment. <ref>{{Cite journal | last1 = Kato | first1 = M. | last2 = Inoshita | first2 = N. | last3 = Sugiyama | first3 = T. | last4 = Tani | first4 = Y. | last5 = Shichiri | first5 = M. | last6 = Sano | first6 = T. | last7 = Yamada | first7 = S. | last8 = Hirata | first8 = Y. | title = Differential expression of genes related to drug responsiveness between sparsely and densely granulated somatotroph adenomas. | journal = Endocr J | volume = 59 | issue = 3 | pages = 221-8 | month = | year = 2012 | doi = | PMID = 22200580 }}</ref>
* Lactotroph adenomas in men may show aggressive clinical behavior. <ref>{{Cite journal | last1 = Delgrange | first1 = E. | last2 = Vasiljevic | first2 = A. | last3 = Wierinckx | first3 = A. | last4 = François | first4 = P. | last5 = Jouanneau | first5 = E. | last6 = Raverot | first6 = G. | last7 = Trouillas | first7 = J. | title = Expression of estrogen receptor alpha is associated with prolactin pituitary tumor prognosis and supports the sex-related difference in tumor growth. | journal = Eur J Endocrinol | volume = 172 | issue = 6 | pages = 791-801 | month = Jun | year = 2015 | doi = 10.1530/EJE-14-0990 | PMID = 25792376 }}</ref>
*Immature PIT-1 lineage tumors may show aggresive growth. <ref> {{Cite journal | last1 = Mete | first1 = O. | last2 = Gomez-Hernandez | first2 = K. | last3 = Kucharczyk | first3 = W. | last4 = Ridout | first4 = R. | last5 = Zadeh | first5 = G. | last6 = Gentili | first6 = F. | last7 = Ezzat | first7 = S. | last8 = Asa | first8 = SL. | title = Silent subtype 3 pituitary adenomas are not always silent and represent poorly differentiated monomorphous plurihormonal Pit-1 lineage adenomas. | journal = Mod Pathol | volume = 29 | issue = 2 | pages = 131-42 | month = Feb | year = 2016 | doi = 10.1038/modpathol.2015.151 | PMID = 26743473 }}</ref>

===Molecular===
*GNAS mutations frequently in densely granulated somatotroph tumors.

==Pituitary blastoma==
* New entity introduced in 2017<ref>{{Cite journal | last1 = Lopes | first1 = MBS. | title = The 2017 World Health Organization classification of tumors of the pituitary gland: a summary. | journal = Acta Neuropathol | volume = 134 | issue = 4 | pages = 521-535 | month = Oct | year = 2017 | doi = 10.1007/s00401-017-1769-8 | PMID = 28821944 }}</ref>
* Epithelial glands with rosette-like formations resembling immature Rathke epithelium.
* Synaptophysin +ve, usu. ACTH+ve
* DICER1 mutations<ref>{{Cite journal | last1 = de Kock | first1 = L. | last2 = Sabbaghian | first2 = N. | last3 = Plourde | first3 = F. | last4 = Srivastava | first4 = A. | last5 = Weber | first5 = E. | last6 = Bouron-Dal Soglio | first6 = D. | last7 = Hamel | first7 = N. | last8 = Choi | first8 = JH. | last9 = Park | first9 = SH. | title = Pituitary blastoma: a pathognomonic feature of germ-line DICER1 mutations. | journal = Acta Neuropathol | volume = 128 | issue = 1 | pages = 111-22 | month = Jul | year = 2014 | doi = 10.1007/s00401-014-1285-z | PMID = 24839956 }}</ref>

==Pituitary carcinoma==
* Depreceated in the WHO2022 classification.
* It is acknowledged that PitNETs can be invasive or spread to other sites.

==Rathke cleft cyst==
===General===
*Benign counterpart of [[craniopharyngioma]].
*Arises from intermediate lobe of pituitary gland (''pars intermedia of pituitary gland'').

Radiology:
*Typically no calcifications.<ref name=emed_rcc>URL: [http://emedicine.medscape.com/article/343629-overview http://emedicine.medscape.com/article/343629-overview]. Accessed on: 14 November 2010.</ref>

Radiologic DDx:<ref name=emed_rcc>URL: [http://emedicine.medscape.com/article/343629-overview http://emedicine.medscape.com/article/343629-overview]. Accessed on: 14 November 2010.</ref>
*Arachnoid cyst.
*[[Craniopharyngioma]].
*[[Cysticercosis]].
*[[Pituitary adenoma]].
*Epidermoid of brain.

===Microscopic===
Features:
*Lined by a layer of cuboidal ''or'' columnar epithelial with cilia.
*+/-Goblet cells.<ref>URL: [http://www.endotext.org/neuroendo/neuroendo3/neuroendo3.html http://www.endotext.org/neuroendo/neuroendo3/neuroendo3.html]. Accessed on: 27 May 2010.</ref>
*+/-Squamous metaplasia ~ may be several layers thick.
**May be confused with ''[[papillary craniopharyngioma]]''.<ref name=Ref_PSNP408>{{Ref PSNP|408}}</ref>
*Cholesterol clefts may be seen in association with rupture.<ref>URL: [http://path.upmc.edu/cases/case177/dx.html http://path.upmc.edu/cases/case177/dx.html]. Accessed on: 8 January 2012.</ref>

DDx:
*[[Papillary craniopharyngioma]].

Images:
*[http://www.endotext.org/neuroendo/neuroendo3/figures/figure11.jpg Rathke cleft cyst (endotext.org)].
*[http://path.upmc.edu/cases/case177/micro.html Rathke cleft cyst (upmc.edu)].

==Craniopharyngioma==
{{Main|Craniopharyngioma}}

==Gangliocytoma==
* Neuronal cells in abundant neuropil.
* S-100, Synaptophysin +ve.
* Isolated sellar cases are very rare.

Image: [[https://twitter.com/sty_md/status/664676241111252992]]

==Mixed Gangliocytoma-adenoma==
AKA: ganglioneuroma, pituitary adenoma with neuronal choristoma (PANCH)
*Neuronal cells mixed with pituitary adenoma cells.
* Approx. 0.25% of all pituitary adenomas.
* Association with somatotroph adenomas (acromegaly).

==Pituicytoma==
{{Main|Pituicytoma}}

==Spindle cell oncocytoma==
*Origin: Neurohypophysis or infundibulum.
*Benign clinical course - WHO grade I.
*Elongated bipolar, spindle cells.
*Fascicular or storiform growth patterns.
*EMA: patchy, S-100+/-ve, GFAP+/-ve, TTF1+ve.

*It is thought that Spindle cell oncocytomas and Granular cell tumors of the neurohypophysis are variants of Pituicyoma.<ref>{{Cite journal | last1 = Mete | first1 = O. | last2 = Lopes | first2 = MB. | last3 = Asa | first3 = SL. | title = Spindle cell oncocytomas and granular cell tumors of the pituitary are variants of pituicytoma. | journal = Am J Surg Pathol | volume = 37 | issue = 11 | pages = 1694-9 | month = Nov | year = 2013 | doi = 10.1097/PAS.0b013e31829723e7 | PMID = 23887161 }}</ref>

==Granular cell tumor of the sellar region==
{{Main|Granular_cell_tumour}}

*Origin: Neurohypophysis or infundibulum.
*Benign clinical course - WHO grade I.
*Well circumscribed.
*Polygonal cells with abundant granular cytoplasm.
*CD68+ve, S-100+/-ve, GFAP+/-ve, TTF1+ve.

<gallery>
File:Granular_cell_tumor_pituitary.jpg | Granular cell tumor of the sellar region (HE).
</gallery>

==Autoimmune hypophysitis==
===General===
Features:<ref name=pmid18388197/>
*Rare.
*Autoantigens are unknown.
*May occur in pregnancy.
*May be misdiagnosed as a nonsecreting adenoma.

===Microscopic===
Features:<ref name=pmid18388197>{{cite journal |author=Tzou SC, Lupi I, Landek M, ''et al.'' |title=Autoimmune hypophysitis of SJL mice: clinical insights from a new animal model |journal=Endocrinology |volume=149 |issue=7 |pages=3461–9 |year=2008 |month=July |pmid=18388197 |pmc=2453094 |doi=10.1210/en.2007-1692 |url=}}</ref>
*Lymphocytic infiltration.

<gallery>
File:Lymphocytic_hypophysitis_CD3.jpg | Lymphocytic hypophysitis, CD3 IHC. (WC/jensflorian)
</gallery>

=See also=
*[[CNS cytopathology]].
*[[Neuropathology]].
*[[Brain tumours]].

=References=
{{reflist|2}}

=External links=
*[http://www.neuropathologyweb.org/ Neuropathology] - neuropathologyweb.org.
*[http://www.lab.anhb.uwa.edu.au/mb140/corepages/endocrines/endocrin.htm Endocrine histology (anhb.uwa.edu.au)].

[[Category:Neuropathology]]

Pituitary gland

2022-09-30T11:28:44Z

Jensflorian: /* Pituitary neuroendocrine tumor (PitNET) */ Update

The '''pituitary gland''' is known as the ''master gland''.

Divisions:<ref>[http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo.html http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo.html]</ref>
*Anterior pituitary ([[AKA]] adenohypophysis, pars distalis).
*Posterior pituitary (AKA neurohypophysis, neural pituitary, pars nervosa).

=Function=
===Anterior===
Hormones:<ref name=rcn_com>[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Pituitary.html http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Pituitary.html]</ref>
*Growth hormone (GH).
*Luteinizing hormone (LH)
*Follicle-stimulating hormone (FSH)
*Thyroid stimulating hormone (TSH)
*Adrenocorticotropic hormone (ACTH)
*Prolactin (PRL)

Mnemonic: "Go Look For The Adenoma Please" = GH, LH, FSH, TSH, ACTH, PRL.

===Intermedia===
* Originates from the posterior wall of the Rathke’s pouch.
* Hormones: MSH, ACTH precursor.
* Contains colloid cysts.

===Posterior===
Hormones:<ref name=rcn_com/>
*Oxytocin.
*Antidiuretic hormone (ADH).

=Anatomy and histology=
===Anatomy===
Basic anatomy (simplified):<ref name=bowen>URL: [http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo_pit.html http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo_pit.html]. Accessed on: 31 October 2010.</ref>
*Anterior:
**Pars distalis.
**Pars intermedia.
*Posterior:
**Pars nervosa.

Embryological origin:<ref name=bowen/>
*Anterior - Rathke's pouch (roof of mouth).
*Posterior - diencephalon (ventral aspect).

Images:
*[http://www.ouhsc.edu/histology/Glass%20slides/38_01.jpg Pituitary gland (ouhsc.edu)].
*[http://www.lab.anhb.uwa.edu.au/mb140/corepages/endocrines/Images/HypDevAni.gif Development of the pituitary - animation (anhb.uwa.edu)].

===Histology===
====Anterior====
*Acidophils (40% of cells) = red or orange.
**GH, PRL.
*Basophils (10% of cells) = basophilic (light blue).
**TSH, LH, FSH, ACTH.
*Chromophobes (50% of cells) = amphophilic (purplish/grey).

Notes:
*The cellular product (i.e. hormone produced) is not strictly correlated with the cell type.<ref name=Ref_PSNP26>{{Ref PSNP|26}}</ref>
*The cells can be typed using [[IHC]]; somatotrophs (GH), lactotrophs (PRL), corticotrophs (ACTH), thyrotrophs (TSH), gonadotrophs (FSH, LH).<ref>{{Ref PBoD8|1098-9}}</ref>

====Posterior====
Features:<ref name=Ref_PSNP26>{{Ref PSNP|26}}</ref>
*Herring bodies - '''key feature'''.
**Eosinophilic axonal dilations filled with lysosomes and neurosecretory granules.
*Less cellular.
**Usually more cellular in perivascular location.
Image: [http://www.ouhsc.edu/histology/Glass%20slides/38_09.jpg Herring bodies (ouhsc.edu)].

<gallery>
File:Pituitary gland histology 2014.jpg | Pituitary gland, low magnification (WC/Athikhun.suw)
</gallery>

=DDx for sella turcica lesions=
*[[Pituitary adenoma|PitNET]].
*[[Rathke cleft cyst]].
*[[Craniopharyngioma]].
*[[Germ cell tumour]].
*[[Meningioma]].

=Pituitary necrosis=
*Rare.

===Causes of pituitary necrosis===
*Sheehan syndrome - secondary to blood loss in childbirth.<ref>URL: [http://www.mayoclinic.com/health/sheehans-syndrome/DS00889 http://www.mayoclinic.com/health/sheehans-syndrome/DS00889]. Accessed on: 16 November 2010.</ref>
*[[Syphilis]] (fetal-maternal transmission).<ref>URL: [http://pediatrics.aappublications.org/cgi/content/full/104/1/e4 http://pediatrics.aappublications.org/cgi/content/full/104/1/e4]. Accessed on: 16 November 2010.</ref>
*Mollaret's meningitis - very rare.<ref name=pmid18715308>{{cite journal |author=Dancer CM, Woods ML, Henderson RD, Robertson T, Mungomery M, Allworth A |title=Mollaret's meningitis and pituitary failure associated with a Rathke's cleft cyst |journal=Intern Med J |volume=38 |issue=7 |pages=609–11 |year=2008 |month=July |pmid=18715308 |doi=10.1111/j.1445-5994.2008.01709.x |url=}}</ref> (???)
*Spontaneous necrosis of pituitary tumours - case reports.<ref>{{cite journal |author=Sachdev Y, Evered DC, Hall R |title=Spontaneous pituitary necrosis |journal=Br Med J |volume=1 |issue=6015 |pages=942 |year=1976 |month=April |pmid=1268492 |pmc=1639254 |doi= |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1639254/pdf/brmedj00512-0028a.pdf}}</ref>

Images:
*[http://path.upmc.edu/cases/case288.html Pituitary necrosis - several images (upmc.edu)].

=Specific entities=
==Pituitary neuroendocrine tumor (PitNET)==
Old terminology '''Pituitary adenoma''' is depreceated.
The WHO 2022 Classification of tumours of endocrine organs recoginizes following tumours:<ref>{{cite journal |vauthors=Asa SL, Mete O, Perry A, Osamura RY |title=Overview of the 2022 WHO Classification of Pituitary Tumors |journal=Endocr Pathol |volume=33 |issue=1 |pages=6–26 |date=March 2022 |pmid=35291028 |doi=10.1007/s12022-022-09703-7 |url=}}</ref>

{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! PitNET lineage
! PitNET type
! subtypes
! Hormone IHC
! Transcription factor IHC
|-
| PIT1
| Somatotroph tumor
| Densely and sparsely granulated tumor
| GH, a-subunit+/-, CK+
| PIT1
|-
| PIT1
| Lactotroph tumor
| Densely and sparsely granulated tumor
| PRL, CK-ve or weak
| PIT1, [[Estrogen receptor|ER]]
|-
| PIT1
| Mammosomatotroph tumor
|
| GH, PRL (usu. less), CK perinuclear +ve
| PIT1, [[Estrogen receptor|ER]]
|-
| PIT1
| Thyrotroph tumor
|
| TSH, CK-ve or weak
| PIT1, GATA3
|-
| PIT1
| Mature plurihormonal PIT1 lineage tumor
|
| GH, PRL, TSH, a-subunit +/-ve, CK perinuclear
| PIT1, [[Estrogen receptor|ER]], GATA3
|-
| PIT1
| Immature PIT1 lineage tumor
|
| Only focal GH, PRL, TSH, a-subunit +/-ve, CK variable
| PIT1, [[Estrogen receptor|ER]] +/-ve, GATA3 +/-ve
|-
| PIT1
| Acidophilic stem cell tumor
|
| PRL, GH (focal/variable), CK fibrous bodies
| PIT1, [[Estrogen receptor|ER]]
|-
| PIT1
| Mixed somatotroph and lactotroph tumor
|
| PRL, GH (in separate cells)
| PIT1, [[Estrogen receptor|ER]] (only in lactotroph component)
|-
| TPIT
| Corticotroph tumor
| Densely and sparsely granulated tumors, Crooke cell adenoma
| ACTH,CK+ve
| TPIT
|-
| SF1
| Gonadotroph tumor
|
| FSH, LH, a-Subunit or none
| SF1, ER, GATA3, CK+/-ve
|-
| None
| Plurihormonal tumor
|
| All combinations possible
| All combinations possible, CK+/-ve
|-
| None
| Null cell adenoma
|
| None (adenohypophyseal?)
| None
|}

Other tumours may be classified as plurhormonal or double adenomas or as adenomas with unusual IHC combination.

===General===
*Clinical:<ref>{{Ref PBoD8|1100}}</ref>
**Classically: visual field defects (bitemporal hemianopsia).
**Others (increased intracranial pressure): headache, nausea, vomiting.
**Tumor of adults.

Morphologic Classification:
#Microtumor <= 1 cm.
#Macrotumor 1-4 cm.
#Giant tumor > 4cm.

May be classified by what they secrete.
#Functional (endocrine hyperfunction).
#*Acromegaly/giantism.
#*Hyperprolactinemia.
#*Cushing disease.
#*Hyperthyroidism.
#*Significant elevation of FSH/LH.
#Clinically nonfunctioning.

Notes:
''Cushing disease'' is due to pituitary gland hypersecretion of ACTH (due to a pituitary adenoma ''or'' CRH hypersecretion from the hypothalamus).<ref name=Ref_PBoD8_1148>{{Ref PBoD8|1148}}</ref> [[Cushing syndrome]] is hypercortisolism ''not'' due to pituitary gland pathology.

Imaging:
*Sellar enlargement.
*Bone erosion, invasive growth esp. cavernous sinus (35-45%).
*Inhomogenous signal in T1w MRI.

====Familial pituitary adenomas====
A pituitary adenoma may be part of a familial syndrome:<ref name=pmid19564887>{{Cite journal | last1 = Elston | first1 = MS. | last2 = McDonald | first2 = KL. | last3 = Clifton-Bligh | first3 = RJ. | last4 = Robinson | first4 = BG. | title = Familial pituitary tumor syndromes. | journal = Nat Rev Endocrinol | volume = 5 | issue = 8 | pages = 453-61 | month = Aug | year = 2009 | doi = 10.1038/nrendo.2009.126 | PMID = 19564887 }}</ref><ref name=Ref_PCPBoD8|554>{{Ref PCPBoD8|554}}</ref>
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Syndrome
! Gene
! Notes
|-
| [[Multiple endocrine neoplasia]] I
| MEN1
| characterized by the 3 Ps: '''p'''ituitary adenoma, [[parathyroid adenoma|'''p'''arathyroid adenoma]], [[pancreatic neuroendocrine tumour|'''p'''ancreatic neuroendocrine tumour]]
|-
| MEN-1-like syndrome
| CDKN1B<ref name=omim600778>{{OMIM|600778}}</ref>
| also known as ''Multiple endocrine neoplasia IV'' <ref name=omim600778>{{OMIM|600778}}</ref>
|-
| [[Carney syndrome]]
| PRKAR1A
| other findings (mnemonic ''NAME''): nevi, [[atrial myxoma]], myxoid neurofibroma, ephelides (freckles)
|-
| Isolated pituitary adenoma<ref name=pmid22612670>{{Cite journal | last1 = Korbonits | first1 = M. | last2 = Storr | first2 = H. | last3 = Kumar | first3 = AV. | title = Familial pituitary adenomas - Who should be tested for AIP mutations? | journal = Clin Endocrinol (Oxf) | volume = | issue = | pages = | month = May | year = 2012 | doi = 10.1111/j.1365-2265.2012.04445.x | PMID = 22612670 }}</ref>
| AIP
| classically GH-producing adenoma - leads to acromegaly
|}

===Microscopic===
Features:<ref name=Ref_PSNP36>{{Ref PSNP|36}}</ref>
*Loss of fibrous stroma.
**The cells of a normal (anterior) pituitary are nested.
*Basophilic cells (corticotrophs).
*Eosinophilic cells(somatotrophs).
*Extensive fibrosis often seen in TSH-producing tumors.

Notes:
*Smears very well.<ref>MUN. 24 November 2010.</ref>

====Images====
<gallery>
Image:Nonfunctioning_pituitary_adenoma_%281%29.jpg | Pituitary adenoma - non-functioning. (WC/KGH)
File:HE fibrosis pituitary adenoma.jpg | Extensive interstitial and perivascular fibrosis in a pituitary adenoma (WC/jensflorian)
File:PRL HE histology.jpg | Pituitary adenoma - PRL producing, HE. Note the basophilic appearance of the cells (WC/jensflorian)
File:PRL adenoma treatment HE.jpg | Pituitary adenoma - PRL producing, HE. Extensive regressive changes after after dopamine agonist treatment (WC/jensflorian)
File:PRL IHC pituitary adenoma.jpg | Pituitary adenoma - PRL producing, Prolactin IHC (WC/jensflorian)
File:Densely granulated HGH producing adenoma.jpg | Pituitary adenoma - HGH producing, HE. The cells have a slightly eosinophilic appearance (WC/jensflorian)
File:Sparsely granulated HGH adenoma.jpg | Sparsely granulated adenoma - HGH producing. Note the numerous fibrous bodies in HE stain (WC/jensflorian)
File:HGH adenoma CK8.jpg | Sparsely granulated adenoma - HGH producing. CK8 IHC highlighting fibrous bodies (WC/jensflorian)
File:TSHoma HE.jpg | Pituitary adenoma - TSH producing. HE stain showing pleomorphism (WC/jensflorian)
File:TSHoma IHC-TSH.jpg | Pituitary adenoma - TSH producing. TSH IHC can be heterogeneous (WC/jensflorian)
Image:Pituitary_adenoma_%281%29_GH_production.jpg | Pituitary adenoma - GH producing. (WC/KGH)
File:HE-GHoma.jpg | Pituitary adenoma , HE. This gonadotropin producing adenoma has a papillary architecture (WC/jensflorian)
File:FSH-GHoma.jpg | Pituitary adenoma, IHC for FSH (WC/jensflorian)
File:LH-GHoma.jpg | Pituitary adenoma, IHC for LH (WC/jensflorian)
File:ACTHoma-PAS-O-G.jpg | Pituitary adenoma , ACTH producing. PAS-O-G stain showing basophilic adenoma cells (WC/jensflorian)
File:ACTHoma-IHC.jpg | Pituitary adenoma , ACTH producing. Strong ACTH IHC in this basophilic adenoma (WC/jensflorian)
File:Pituitary_adenoma-nonfunctioning.jpg |Pituitary adenoma with vascular pseudorosettes, nonfunctioning (WC/jensflorian)
Crooke_HE_40x.jpg | Crooke cell adenoma, HE (WC/Marvin101)
File:Crooke Cytokeratins.jpg | Crooke cell adenoma, panCK (WC/Marvin101)
HE_fibrosis_pituitary_adenoma.jpg | Fibrosis in pituitary adenoma.
</gallery>

===Stains===
*Reticulin - loss of reticulin between tumour cells.

===IHC===
*LH.
*FSH.
*TSH - [[Hyperthyroidism]]
*GH - [[Acromegaly]].
*Prolactin -Galactorrhea, Amenorrhea, Gynecomastia. Golgi staining pattern in sparsely granulated cases.
*ACTH - [[Cushing syndrome]].
*PIT-1: stains somatotrophs, lactotrophs and thyrothrops.
*TPIT: stains corticotrophs.
*SF1: stains gonadotrophs.
*Chromogranin A +ve
*Synaptophysin strongly +ve (except lactotrophs)
*CAM5.2: fibrous bodies in sparsely granulated somatotroph adenoma, Ring-like staining in Crooke cell adenoma.
*MIB-1: Usu less than 3%.

Note:
Null-cell adenoma must be hormone immunonegative and negative for transcription factors.

===Variants===
*Corticotroph adenomas exhibiting Crooke's hyaline change: agressive course.<ref>{{Cite journal | last1 = George | first1 = DH. | last2 = Scheithauer | first2 = BW. | last3 = Kovacs | first3 = K. | last4 = Horvath | first4 = E. | last5 = Young | first5 = WF. | last6 = Lloyd | first6 = RV. | last7 = Meyer | first7 = FB. | title = Crooke's cell adenoma of the pituitary: an aggressive variant of corticotroph adenoma. | journal = Am J Surg Pathol | volume = 27 | issue = 10 | pages = 1330-6 | month = Oct | year = 2003 | doi = | PMID = 14508394 }}</ref>
*Acidophilic stem cell adenomas: large, locally invasive adenoma with low GH activity. <ref>{{Cite journal | last1 = Horvath | first1 = E. | last2 = Kovacs | first2 = K. | last3 = Singer | first3 = W. | last4 = Smyth | first4 = HS. | last5 = Killinger | first5 = DW. | last6 = Erzin | first6 = C. | last7 = Weiss | first7 = MH. | title = Acidophil stem cell adenoma of the human pituitary: clinicopathologic analysis of 15 cases. | journal = Cancer | volume = 47 | issue = 4 | pages = 761-71 | month = Feb | year = 1981 | doi = | PMID = 6261917 }}</ref>
*Sparsely granulated somatotroph adenomas are more invasive than other variants and respond less to medical treatment. <ref>{{Cite journal | last1 = Kato | first1 = M. | last2 = Inoshita | first2 = N. | last3 = Sugiyama | first3 = T. | last4 = Tani | first4 = Y. | last5 = Shichiri | first5 = M. | last6 = Sano | first6 = T. | last7 = Yamada | first7 = S. | last8 = Hirata | first8 = Y. | title = Differential expression of genes related to drug responsiveness between sparsely and densely granulated somatotroph adenomas. | journal = Endocr J | volume = 59 | issue = 3 | pages = 221-8 | month = | year = 2012 | doi = | PMID = 22200580 }}</ref>
* Lactotroph adenomas in men may show aggressive clinical behavior. <ref>{{Cite journal | last1 = Delgrange | first1 = E. | last2 = Vasiljevic | first2 = A. | last3 = Wierinckx | first3 = A. | last4 = François | first4 = P. | last5 = Jouanneau | first5 = E. | last6 = Raverot | first6 = G. | last7 = Trouillas | first7 = J. | title = Expression of estrogen receptor alpha is associated with prolactin pituitary tumor prognosis and supports the sex-related difference in tumor growth. | journal = Eur J Endocrinol | volume = 172 | issue = 6 | pages = 791-801 | month = Jun | year = 2015 | doi = 10.1530/EJE-14-0990 | PMID = 25792376 }}</ref>
*Immature PIT-1 lineage tumors may show aggresive growth. <ref> {{Cite journal | last1 = Mete | first1 = O. | last2 = Gomez-Hernandez | first2 = K. | last3 = Kucharczyk | first3 = W. | last4 = Ridout | first4 = R. | last5 = Zadeh | first5 = G. | last6 = Gentili | first6 = F. | last7 = Ezzat | first7 = S. | last8 = Asa | first8 = SL. | title = Silent subtype 3 pituitary adenomas are not always silent and represent poorly differentiated monomorphous plurihormonal Pit-1 lineage adenomas. | journal = Mod Pathol | volume = 29 | issue = 2 | pages = 131-42 | month = Feb | year = 2016 | doi = 10.1038/modpathol.2015.151 | PMID = 26743473 }}</ref>

===Molecular===
*GNAS mutations frequently in densely granulated somatotroph tumors.

==Pituitary blastoma==
* New entity introduced in 2017<ref>{{Cite journal | last1 = Lopes | first1 = MBS. | title = The 2017 World Health Organization classification of tumors of the pituitary gland: a summary. | journal = Acta Neuropathol | volume = 134 | issue = 4 | pages = 521-535 | month = Oct | year = 2017 | doi = 10.1007/s00401-017-1769-8 | PMID = 28821944 }}</ref>
* Epithelial glands with rosette-like formations resembling immature Rathke epithelium.
* Synaptophysin +ve, usu. ACTH+ve
* DICER1 mutations<ref>{{Cite journal | last1 = de Kock | first1 = L. | last2 = Sabbaghian | first2 = N. | last3 = Plourde | first3 = F. | last4 = Srivastava | first4 = A. | last5 = Weber | first5 = E. | last6 = Bouron-Dal Soglio | first6 = D. | last7 = Hamel | first7 = N. | last8 = Choi | first8 = JH. | last9 = Park | first9 = SH. | title = Pituitary blastoma: a pathognomonic feature of germ-line DICER1 mutations. | journal = Acta Neuropathol | volume = 128 | issue = 1 | pages = 111-22 | month = Jul | year = 2014 | doi = 10.1007/s00401-014-1285-z | PMID = 24839956 }}</ref>

==Pituitary carcinoma==
* ICD-O: 8272/3
* Requires presence of cerebrospinal or systemic metastasis.
* Very rare.
* 75% are hormonally active (mostly PRL or ACTH).
* IHC: Synaptophysin, Chromogranin +ve

==Rathke cleft cyst==
===General===
*Benign counterpart of [[craniopharyngioma]].
*Arises from intermediate lobe of pituitary gland (''pars intermedia of pituitary gland'').

Radiology:
*Typically no calcifications.<ref name=emed_rcc>URL: [http://emedicine.medscape.com/article/343629-overview http://emedicine.medscape.com/article/343629-overview]. Accessed on: 14 November 2010.</ref>

Radiologic DDx:<ref name=emed_rcc>URL: [http://emedicine.medscape.com/article/343629-overview http://emedicine.medscape.com/article/343629-overview]. Accessed on: 14 November 2010.</ref>
*Arachnoid cyst.
*[[Craniopharyngioma]].
*[[Cysticercosis]].
*[[Pituitary adenoma]].
*Epidermoid of brain.

===Microscopic===
Features:
*Lined by a layer of cuboidal ''or'' columnar epithelial with cilia.
*+/-Goblet cells.<ref>URL: [http://www.endotext.org/neuroendo/neuroendo3/neuroendo3.html http://www.endotext.org/neuroendo/neuroendo3/neuroendo3.html]. Accessed on: 27 May 2010.</ref>
*+/-Squamous metaplasia ~ may be several layers thick.
**May be confused with ''[[papillary craniopharyngioma]]''.<ref name=Ref_PSNP408>{{Ref PSNP|408}}</ref>
*Cholesterol clefts may be seen in association with rupture.<ref>URL: [http://path.upmc.edu/cases/case177/dx.html http://path.upmc.edu/cases/case177/dx.html]. Accessed on: 8 January 2012.</ref>

DDx:
*[[Papillary craniopharyngioma]].

Images:
*[http://www.endotext.org/neuroendo/neuroendo3/figures/figure11.jpg Rathke cleft cyst (endotext.org)].
*[http://path.upmc.edu/cases/case177/micro.html Rathke cleft cyst (upmc.edu)].

==Craniopharyngioma==
{{Main|Craniopharyngioma}}

==Gangliocytoma==
* Neuronal cells in abundant neuropil.
* S-100, Synaptophysin +ve.
* Isolated sellar cases are very rare.

Image: [[https://twitter.com/sty_md/status/664676241111252992]]

==Mixed Gangliocytoma-adenoma==
AKA: ganglioneuroma, pituitary adenoma with neuronal choristoma (PANCH)
*Neuronal cells mixed with pituitary adenoma cells.
* Approx. 0.25% of all pituitary adenomas.
* Association with somatotroph adenomas (acromegaly).

==Pituicytoma==
{{Main|Pituicytoma}}

==Spindle cell oncocytoma==
*Origin: Neurohypophysis or infundibulum.
*Benign clinical course - WHO grade I.
*Elongated bipolar, spindle cells.
*Fascicular or storiform growth patterns.
*EMA: patchy, S-100+/-ve, GFAP+/-ve, TTF1+ve.

*It is thought that Spindle cell oncocytomas and Granular cell tumors of the neurohypophysis are variants of Pituicyoma.<ref>{{Cite journal | last1 = Mete | first1 = O. | last2 = Lopes | first2 = MB. | last3 = Asa | first3 = SL. | title = Spindle cell oncocytomas and granular cell tumors of the pituitary are variants of pituicytoma. | journal = Am J Surg Pathol | volume = 37 | issue = 11 | pages = 1694-9 | month = Nov | year = 2013 | doi = 10.1097/PAS.0b013e31829723e7 | PMID = 23887161 }}</ref>

==Granular cell tumor of the sellar region==
{{Main|Granular_cell_tumour}}

*Origin: Neurohypophysis or infundibulum.
*Benign clinical course - WHO grade I.
*Well circumscribed.
*Polygonal cells with abundant granular cytoplasm.
*CD68+ve, S-100+/-ve, GFAP+/-ve, TTF1+ve.

<gallery>
File:Granular_cell_tumor_pituitary.jpg | Granular cell tumor of the sellar region (HE).
</gallery>

==Autoimmune hypophysitis==
===General===
Features:<ref name=pmid18388197/>
*Rare.
*Autoantigens are unknown.
*May occur in pregnancy.
*May be misdiagnosed as a nonsecreting adenoma.

===Microscopic===
Features:<ref name=pmid18388197>{{cite journal |author=Tzou SC, Lupi I, Landek M, ''et al.'' |title=Autoimmune hypophysitis of SJL mice: clinical insights from a new animal model |journal=Endocrinology |volume=149 |issue=7 |pages=3461–9 |year=2008 |month=July |pmid=18388197 |pmc=2453094 |doi=10.1210/en.2007-1692 |url=}}</ref>
*Lymphocytic infiltration.

<gallery>
File:Lymphocytic_hypophysitis_CD3.jpg | Lymphocytic hypophysitis, CD3 IHC. (WC/jensflorian)
</gallery>

=See also=
*[[CNS cytopathology]].
*[[Neuropathology]].
*[[Brain tumours]].

=References=
{{reflist|2}}

=External links=
*[http://www.neuropathologyweb.org/ Neuropathology] - neuropathologyweb.org.
*[http://www.lab.anhb.uwa.edu.au/mb140/corepages/endocrines/endocrin.htm Endocrine histology (anhb.uwa.edu.au)].

[[Category:Neuropathology]]

Pituitary gland

2022-09-30T11:25:38Z

Jensflorian: /* Microscopic */ TSH

The '''pituitary gland''' is known as the ''master gland''.

Divisions:<ref>[http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo.html http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo.html]</ref>
*Anterior pituitary ([[AKA]] adenohypophysis, pars distalis).
*Posterior pituitary (AKA neurohypophysis, neural pituitary, pars nervosa).

=Function=
===Anterior===
Hormones:<ref name=rcn_com>[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Pituitary.html http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Pituitary.html]</ref>
*Growth hormone (GH).
*Luteinizing hormone (LH)
*Follicle-stimulating hormone (FSH)
*Thyroid stimulating hormone (TSH)
*Adrenocorticotropic hormone (ACTH)
*Prolactin (PRL)

Mnemonic: "Go Look For The Adenoma Please" = GH, LH, FSH, TSH, ACTH, PRL.

===Intermedia===
* Originates from the posterior wall of the Rathke’s pouch.
* Hormones: MSH, ACTH precursor.
* Contains colloid cysts.

===Posterior===
Hormones:<ref name=rcn_com/>
*Oxytocin.
*Antidiuretic hormone (ADH).

=Anatomy and histology=
===Anatomy===
Basic anatomy (simplified):<ref name=bowen>URL: [http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo_pit.html http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo_pit.html]. Accessed on: 31 October 2010.</ref>
*Anterior:
**Pars distalis.
**Pars intermedia.
*Posterior:
**Pars nervosa.

Embryological origin:<ref name=bowen/>
*Anterior - Rathke's pouch (roof of mouth).
*Posterior - diencephalon (ventral aspect).

Images:
*[http://www.ouhsc.edu/histology/Glass%20slides/38_01.jpg Pituitary gland (ouhsc.edu)].
*[http://www.lab.anhb.uwa.edu.au/mb140/corepages/endocrines/Images/HypDevAni.gif Development of the pituitary - animation (anhb.uwa.edu)].

===Histology===
====Anterior====
*Acidophils (40% of cells) = red or orange.
**GH, PRL.
*Basophils (10% of cells) = basophilic (light blue).
**TSH, LH, FSH, ACTH.
*Chromophobes (50% of cells) = amphophilic (purplish/grey).

Notes:
*The cellular product (i.e. hormone produced) is not strictly correlated with the cell type.<ref name=Ref_PSNP26>{{Ref PSNP|26}}</ref>
*The cells can be typed using [[IHC]]; somatotrophs (GH), lactotrophs (PRL), corticotrophs (ACTH), thyrotrophs (TSH), gonadotrophs (FSH, LH).<ref>{{Ref PBoD8|1098-9}}</ref>

====Posterior====
Features:<ref name=Ref_PSNP26>{{Ref PSNP|26}}</ref>
*Herring bodies - '''key feature'''.
**Eosinophilic axonal dilations filled with lysosomes and neurosecretory granules.
*Less cellular.
**Usually more cellular in perivascular location.
Image: [http://www.ouhsc.edu/histology/Glass%20slides/38_09.jpg Herring bodies (ouhsc.edu)].

<gallery>
File:Pituitary gland histology 2014.jpg | Pituitary gland, low magnification (WC/Athikhun.suw)
</gallery>

=DDx for sella turcica lesions=
*[[Pituitary adenoma|PitNET]].
*[[Rathke cleft cyst]].
*[[Craniopharyngioma]].
*[[Germ cell tumour]].
*[[Meningioma]].

=Pituitary necrosis=
*Rare.

===Causes of pituitary necrosis===
*Sheehan syndrome - secondary to blood loss in childbirth.<ref>URL: [http://www.mayoclinic.com/health/sheehans-syndrome/DS00889 http://www.mayoclinic.com/health/sheehans-syndrome/DS00889]. Accessed on: 16 November 2010.</ref>
*[[Syphilis]] (fetal-maternal transmission).<ref>URL: [http://pediatrics.aappublications.org/cgi/content/full/104/1/e4 http://pediatrics.aappublications.org/cgi/content/full/104/1/e4]. Accessed on: 16 November 2010.</ref>
*Mollaret's meningitis - very rare.<ref name=pmid18715308>{{cite journal |author=Dancer CM, Woods ML, Henderson RD, Robertson T, Mungomery M, Allworth A |title=Mollaret's meningitis and pituitary failure associated with a Rathke's cleft cyst |journal=Intern Med J |volume=38 |issue=7 |pages=609–11 |year=2008 |month=July |pmid=18715308 |doi=10.1111/j.1445-5994.2008.01709.x |url=}}</ref> (???)
*Spontaneous necrosis of pituitary tumours - case reports.<ref>{{cite journal |author=Sachdev Y, Evered DC, Hall R |title=Spontaneous pituitary necrosis |journal=Br Med J |volume=1 |issue=6015 |pages=942 |year=1976 |month=April |pmid=1268492 |pmc=1639254 |doi= |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1639254/pdf/brmedj00512-0028a.pdf}}</ref>

Images:
*[http://path.upmc.edu/cases/case288.html Pituitary necrosis - several images (upmc.edu)].

=Specific entities=
==Pituitary neuroendocrine tumor (PitNET)==
Old terminology '''Pituitary adenoma''' is depreceated.
The WHO 2022 Classification of tumours of endocrine organs recoginizes following tumours:<ref>{{cite journal |vauthors=Asa SL, Mete O, Perry A, Osamura RY |title=Overview of the 2022 WHO Classification of Pituitary Tumors |journal=Endocr Pathol |volume=33 |issue=1 |pages=6–26 |date=March 2022 |pmid=35291028 |doi=10.1007/s12022-022-09703-7 |url=}}</ref>

{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! PitNET lineage
! PitNET type
! subtypes
! Hormone IHC
! Transcription factor IHC
|-
| PIT1
| Somatotroph tumor
| Densely and sparsely granulated tumor
| GH, a-subunit+/-, CK+
| PIT1
|-
| PIT1
| Lactotroph tumor
| Densely and sparsely granulated tumor
| PRL, CK-ve or weak
| PIT1, [[Estrogen receptor|ER]]
|-
| PIT1
| Mammosomatotroph tumor
|
| GH, PRL (usu. less), CK perinuclear +ve
| PIT1, [[Estrogen receptor|ER]]
|-
| PIT1
| Thyrotroph tumor
|
| TSH, CK-ve or weak
| PIT1, GATA3
|-
| PIT1
| Mature plurihormonal PIT1 lineage tumor
|
| GH, PRL, TSH, a-subunit +/-ve, CK perinuclear
| PIT1, [[Estrogen receptor|ER]], GATA3
|-
| PIT1
| Immature PIT1 lineage tumor
|
| Only focal GH, PRL, TSH, a-subunit +/-ve, CK variable
| PIT1, [[Estrogen receptor|ER]] +/-ve, GATA3 +/-ve
|-
| PIT1
| Acidophilic stem cell tumor
|
| PRL, GH (focal/variable), CK fibrous bodies
| PIT1, [[Estrogen receptor|ER]]
|-
| PIT1
| Mixed somatotroph and lactotroph tumor
|
| PRL, GH (in separate cells)
| PIT1, [[Estrogen receptor|ER]] (only in lactotroph component)
|-
| TPIT
| Corticotroph tumor
| Densely and sparsely granulated tumors, Crooke cell adenoma
| ACTH,CK+ve
| TPIT
|-
| SF1
| Gonadotroph tumor
|
| FSH, LH, a-Subunit or none
| SF1, ER, GATA3, CK+/-ve
|-
| None
| Plurihormonal tumor
|
| All combinations possible
| All combinations possible, CK+/-ve
|-
| None
| Null cell adenoma
|
| None (adenohypophyseal?)
| None
|}

Other tumours may be classified as plurhormonal or double adenomas or as adenomas with unusual IHC combination.

===General===
*Clinical:<ref>{{Ref PBoD8|1100}}</ref>
**Classically: visual field defects (bitemporal hemianopsia).
**Others (increased intracranial pressure): headache, nausea, vomiting.
**Tumor of adults.

Morphologic Classification:
#Microtumor <= 1 cm.
#Macrotumor 1-4 cm.
#Giant tumor > 4cm.

May be classified by what they secrete.
#Functional (endocrine hyperfunction).
#*Acromegaly/giantism.
#*Hyperprolactinemia.
#*Cushing disease.
#*Hyperthyroidism.
#*Significant elevation of FSH/LH.
#Clinically nonfunctioning.

Notes:
''Cushing disease'' is due to pituitary gland hypersecretion of ACTH (due to a pituitary adenoma ''or'' CRH hypersecretion from the hypothalamus).<ref name=Ref_PBoD8_1148>{{Ref PBoD8|1148}}</ref> [[Cushing syndrome]] is hypercortisolism ''not'' due to pituitary gland pathology.

Imaging:
*Sellar enlargement.
*Bone erosion, invasive growth esp. cavernous sinus (35-45%).
*Inhomogenous signal in T1w MRI.

====Familial pituitary adenomas====
A pituitary adenoma may be part of a familial syndrome:<ref name=pmid19564887>{{Cite journal | last1 = Elston | first1 = MS. | last2 = McDonald | first2 = KL. | last3 = Clifton-Bligh | first3 = RJ. | last4 = Robinson | first4 = BG. | title = Familial pituitary tumor syndromes. | journal = Nat Rev Endocrinol | volume = 5 | issue = 8 | pages = 453-61 | month = Aug | year = 2009 | doi = 10.1038/nrendo.2009.126 | PMID = 19564887 }}</ref><ref name=Ref_PCPBoD8|554>{{Ref PCPBoD8|554}}</ref>
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Syndrome
! Gene
! Notes
|-
| [[Multiple endocrine neoplasia]] I
| MEN1
| characterized by the 3 Ps: '''p'''ituitary adenoma, [[parathyroid adenoma|'''p'''arathyroid adenoma]], [[pancreatic neuroendocrine tumour|'''p'''ancreatic neuroendocrine tumour]]
|-
| MEN-1-like syndrome
| CDKN1B<ref name=omim600778>{{OMIM|600778}}</ref>
| also known as ''Multiple endocrine neoplasia IV'' <ref name=omim600778>{{OMIM|600778}}</ref>
|-
| [[Carney syndrome]]
| PRKAR1A
| other findings (mnemonic ''NAME''): nevi, [[atrial myxoma]], myxoid neurofibroma, ephelides (freckles)
|-
| Isolated pituitary adenoma<ref name=pmid22612670>{{Cite journal | last1 = Korbonits | first1 = M. | last2 = Storr | first2 = H. | last3 = Kumar | first3 = AV. | title = Familial pituitary adenomas - Who should be tested for AIP mutations? | journal = Clin Endocrinol (Oxf) | volume = | issue = | pages = | month = May | year = 2012 | doi = 10.1111/j.1365-2265.2012.04445.x | PMID = 22612670 }}</ref>
| AIP
| classically GH-producing adenoma - leads to acromegaly
|}

===Microscopic===
Features:<ref name=Ref_PSNP36>{{Ref PSNP|36}}</ref>
*Loss of fibrous stroma.
**The cells of a normal (anterior) pituitary are nested.
*Basophilic cells (corticotrophs).
*Eosinophilic cells(somatotrophs).
*Extensive fibrosis often seen in TSH-producing tumors.

Notes:
*Smears very well.<ref>MUN. 24 November 2010.</ref>

====Images====
<gallery>
Image:Nonfunctioning_pituitary_adenoma_%281%29.jpg | Pituitary adenoma - non-functioning. (WC/KGH)
File:HE fibrosis pituitary adenoma.jpg | Extensive interstitial and perivascular fibrosis in a pituitary adenoma (WC/jensflorian)
File:PRL HE histology.jpg | Pituitary adenoma - PRL producing, HE. Note the basophilic appearance of the cells (WC/jensflorian)
File:PRL adenoma treatment HE.jpg | Pituitary adenoma - PRL producing, HE. Extensive regressive changes after after dopamine agonist treatment (WC/jensflorian)
File:PRL IHC pituitary adenoma.jpg | Pituitary adenoma - PRL producing, Prolactin IHC (WC/jensflorian)
File:Densely granulated HGH producing adenoma.jpg | Pituitary adenoma - HGH producing, HE. The cells have a slightly eosinophilic appearance (WC/jensflorian)
File:Sparsely granulated HGH adenoma.jpg | Sparsely granulated adenoma - HGH producing. Note the numerous fibrous bodies in HE stain (WC/jensflorian)
File:HGH adenoma CK8.jpg | Sparsely granulated adenoma - HGH producing. CK8 IHC highlighting fibrous bodies (WC/jensflorian)
File:TSHoma HE.jpg | Pituitary adenoma - TSH producing. HE stain showing pleomorphism (WC/jensflorian)
File:TSHoma IHC-TSH.jpg | Pituitary adenoma - TSH producing. TSH IHC can be heterogeneous (WC/jensflorian)
Image:Pituitary_adenoma_%281%29_GH_production.jpg | Pituitary adenoma - GH producing. (WC/KGH)
File:HE-GHoma.jpg | Pituitary adenoma , HE. This gonadotropin producing adenoma has a papillary architecture (WC/jensflorian)
File:FSH-GHoma.jpg | Pituitary adenoma, IHC for FSH (WC/jensflorian)
File:LH-GHoma.jpg | Pituitary adenoma, IHC for LH (WC/jensflorian)
File:ACTHoma-PAS-O-G.jpg | Pituitary adenoma , ACTH producing. PAS-O-G stain showing basophilic adenoma cells (WC/jensflorian)
File:ACTHoma-IHC.jpg | Pituitary adenoma , ACTH producing. Strong ACTH IHC in this basophilic adenoma (WC/jensflorian)
File:Pituitary_adenoma-nonfunctioning.jpg |Pituitary adenoma with vascular pseudorosettes, nonfunctioning (WC/jensflorian)
Crooke_HE_40x.jpg | Crooke cell adenoma, HE (WC/Marvin101)
File:Crooke Cytokeratins.jpg | Crooke cell adenoma, panCK (WC/Marvin101)
HE_fibrosis_pituitary_adenoma.jpg | Fibrosis in pituitary adenoma.
</gallery>

===Stains===
*Reticulin - loss of reticulin between tumour cells.

===IHC===
*LH.
*FSH.
*TSH - [[Hyperthyroidism]]
*GH - [[Acromegaly]].
*Prolactin -Galactorrhea, Amenorrhea, Gynecomastia. Golgi staining pattern in sparsely granulated cases.
*ACTH - [[Cushing syndrome]].
*PIT-1: stains somatotrophs, lactotrophs and thyrothrops.
*TPIT: stains corticotrophs.
*SF1: stains gonadotrophs.
*Chromogranin A +ve
*Synaptophysin strongly +ve (except lactotrophs)
*CAM5.2: fibrous bodies in sparsely granulated somatotroph adenoma, Ring-like staining in Crooke cell adenoma.
*MIB-1: Usu less than 3%.

Note:
Null-cell adenoma must be hormone immunonegative and negative for transcription factors.

===Variants===
*Corticotroph adenomas exhibiting Crooke's hyaline change: agressive course.<ref>{{Cite journal | last1 = George | first1 = DH. | last2 = Scheithauer | first2 = BW. | last3 = Kovacs | first3 = K. | last4 = Horvath | first4 = E. | last5 = Young | first5 = WF. | last6 = Lloyd | first6 = RV. | last7 = Meyer | first7 = FB. | title = Crooke's cell adenoma of the pituitary: an aggressive variant of corticotroph adenoma. | journal = Am J Surg Pathol | volume = 27 | issue = 10 | pages = 1330-6 | month = Oct | year = 2003 | doi = | PMID = 14508394 }}</ref>
*Acidophilic stem cell adenomas: large, locally invasive adenoma with low GH activity. <ref>{{Cite journal | last1 = Horvath | first1 = E. | last2 = Kovacs | first2 = K. | last3 = Singer | first3 = W. | last4 = Smyth | first4 = HS. | last5 = Killinger | first5 = DW. | last6 = Erzin | first6 = C. | last7 = Weiss | first7 = MH. | title = Acidophil stem cell adenoma of the human pituitary: clinicopathologic analysis of 15 cases. | journal = Cancer | volume = 47 | issue = 4 | pages = 761-71 | month = Feb | year = 1981 | doi = | PMID = 6261917 }}</ref>
*Sparsely granulated somatotroph adenomas are more invasive than other variants and respond less to medical treatment. <ref>{{Cite journal | last1 = Kato | first1 = M. | last2 = Inoshita | first2 = N. | last3 = Sugiyama | first3 = T. | last4 = Tani | first4 = Y. | last5 = Shichiri | first5 = M. | last6 = Sano | first6 = T. | last7 = Yamada | first7 = S. | last8 = Hirata | first8 = Y. | title = Differential expression of genes related to drug responsiveness between sparsely and densely granulated somatotroph adenomas. | journal = Endocr J | volume = 59 | issue = 3 | pages = 221-8 | month = | year = 2012 | doi = | PMID = 22200580 }}</ref>
* Lactotroph adenomas in men may show aggressive clinical behavior. <ref>{{Cite journal | last1 = Delgrange | first1 = E. | last2 = Vasiljevic | first2 = A. | last3 = Wierinckx | first3 = A. | last4 = François | first4 = P. | last5 = Jouanneau | first5 = E. | last6 = Raverot | first6 = G. | last7 = Trouillas | first7 = J. | title = Expression of estrogen receptor alpha is associated with prolactin pituitary tumor prognosis and supports the sex-related difference in tumor growth. | journal = Eur J Endocrinol | volume = 172 | issue = 6 | pages = 791-801 | month = Jun | year = 2015 | doi = 10.1530/EJE-14-0990 | PMID = 25792376 }}</ref>
*Poorly differentiated PIT-1 positive adenomas may show aggresive growth. <ref> {{Cite journal | last1 = Mete | first1 = O. | last2 = Gomez-Hernandez | first2 = K. | last3 = Kucharczyk | first3 = W. | last4 = Ridout | first4 = R. | last5 = Zadeh | first5 = G. | last6 = Gentili | first6 = F. | last7 = Ezzat | first7 = S. | last8 = Asa | first8 = SL. | title = Silent subtype 3 pituitary adenomas are not always silent and represent poorly differentiated monomorphous plurihormonal Pit-1 lineage adenomas. | journal = Mod Pathol | volume = 29 | issue = 2 | pages = 131-42 | month = Feb | year = 2016 | doi = 10.1038/modpathol.2015.151 | PMID = 26743473 }}</ref>

==Pituitary blastoma==
* New entity introduced in 2017<ref>{{Cite journal | last1 = Lopes | first1 = MBS. | title = The 2017 World Health Organization classification of tumors of the pituitary gland: a summary. | journal = Acta Neuropathol | volume = 134 | issue = 4 | pages = 521-535 | month = Oct | year = 2017 | doi = 10.1007/s00401-017-1769-8 | PMID = 28821944 }}</ref>
* Epithelial glands with rosette-like formations resembling immature Rathke epithelium.
* Synaptophysin +ve, usu. ACTH+ve
* DICER1 mutations<ref>{{Cite journal | last1 = de Kock | first1 = L. | last2 = Sabbaghian | first2 = N. | last3 = Plourde | first3 = F. | last4 = Srivastava | first4 = A. | last5 = Weber | first5 = E. | last6 = Bouron-Dal Soglio | first6 = D. | last7 = Hamel | first7 = N. | last8 = Choi | first8 = JH. | last9 = Park | first9 = SH. | title = Pituitary blastoma: a pathognomonic feature of germ-line DICER1 mutations. | journal = Acta Neuropathol | volume = 128 | issue = 1 | pages = 111-22 | month = Jul | year = 2014 | doi = 10.1007/s00401-014-1285-z | PMID = 24839956 }}</ref>

==Pituitary carcinoma==
* ICD-O: 8272/3
* Requires presence of cerebrospinal or systemic metastasis.
* Very rare.
* 75% are hormonally active (mostly PRL or ACTH).
* IHC: Synaptophysin, Chromogranin +ve

==Rathke cleft cyst==
===General===
*Benign counterpart of [[craniopharyngioma]].
*Arises from intermediate lobe of pituitary gland (''pars intermedia of pituitary gland'').

Radiology:
*Typically no calcifications.<ref name=emed_rcc>URL: [http://emedicine.medscape.com/article/343629-overview http://emedicine.medscape.com/article/343629-overview]. Accessed on: 14 November 2010.</ref>

Radiologic DDx:<ref name=emed_rcc>URL: [http://emedicine.medscape.com/article/343629-overview http://emedicine.medscape.com/article/343629-overview]. Accessed on: 14 November 2010.</ref>
*Arachnoid cyst.
*[[Craniopharyngioma]].
*[[Cysticercosis]].
*[[Pituitary adenoma]].
*Epidermoid of brain.

===Microscopic===
Features:
*Lined by a layer of cuboidal ''or'' columnar epithelial with cilia.
*+/-Goblet cells.<ref>URL: [http://www.endotext.org/neuroendo/neuroendo3/neuroendo3.html http://www.endotext.org/neuroendo/neuroendo3/neuroendo3.html]. Accessed on: 27 May 2010.</ref>
*+/-Squamous metaplasia ~ may be several layers thick.
**May be confused with ''[[papillary craniopharyngioma]]''.<ref name=Ref_PSNP408>{{Ref PSNP|408}}</ref>
*Cholesterol clefts may be seen in association with rupture.<ref>URL: [http://path.upmc.edu/cases/case177/dx.html http://path.upmc.edu/cases/case177/dx.html]. Accessed on: 8 January 2012.</ref>

DDx:
*[[Papillary craniopharyngioma]].

Images:
*[http://www.endotext.org/neuroendo/neuroendo3/figures/figure11.jpg Rathke cleft cyst (endotext.org)].
*[http://path.upmc.edu/cases/case177/micro.html Rathke cleft cyst (upmc.edu)].

==Craniopharyngioma==
{{Main|Craniopharyngioma}}

==Gangliocytoma==
* Neuronal cells in abundant neuropil.
* S-100, Synaptophysin +ve.
* Isolated sellar cases are very rare.

Image: [[https://twitter.com/sty_md/status/664676241111252992]]

==Mixed Gangliocytoma-adenoma==
AKA: ganglioneuroma, pituitary adenoma with neuronal choristoma (PANCH)
*Neuronal cells mixed with pituitary adenoma cells.
* Approx. 0.25% of all pituitary adenomas.
* Association with somatotroph adenomas (acromegaly).

==Pituicytoma==
{{Main|Pituicytoma}}

==Spindle cell oncocytoma==
*Origin: Neurohypophysis or infundibulum.
*Benign clinical course - WHO grade I.
*Elongated bipolar, spindle cells.
*Fascicular or storiform growth patterns.
*EMA: patchy, S-100+/-ve, GFAP+/-ve, TTF1+ve.

*It is thought that Spindle cell oncocytomas and Granular cell tumors of the neurohypophysis are variants of Pituicyoma.<ref>{{Cite journal | last1 = Mete | first1 = O. | last2 = Lopes | first2 = MB. | last3 = Asa | first3 = SL. | title = Spindle cell oncocytomas and granular cell tumors of the pituitary are variants of pituicytoma. | journal = Am J Surg Pathol | volume = 37 | issue = 11 | pages = 1694-9 | month = Nov | year = 2013 | doi = 10.1097/PAS.0b013e31829723e7 | PMID = 23887161 }}</ref>

==Granular cell tumor of the sellar region==
{{Main|Granular_cell_tumour}}

*Origin: Neurohypophysis or infundibulum.
*Benign clinical course - WHO grade I.
*Well circumscribed.
*Polygonal cells with abundant granular cytoplasm.
*CD68+ve, S-100+/-ve, GFAP+/-ve, TTF1+ve.

<gallery>
File:Granular_cell_tumor_pituitary.jpg | Granular cell tumor of the sellar region (HE).
</gallery>

==Autoimmune hypophysitis==
===General===
Features:<ref name=pmid18388197/>
*Rare.
*Autoantigens are unknown.
*May occur in pregnancy.
*May be misdiagnosed as a nonsecreting adenoma.

===Microscopic===
Features:<ref name=pmid18388197>{{cite journal |author=Tzou SC, Lupi I, Landek M, ''et al.'' |title=Autoimmune hypophysitis of SJL mice: clinical insights from a new animal model |journal=Endocrinology |volume=149 |issue=7 |pages=3461–9 |year=2008 |month=July |pmid=18388197 |pmc=2453094 |doi=10.1210/en.2007-1692 |url=}}</ref>
*Lymphocytic infiltration.

<gallery>
File:Lymphocytic_hypophysitis_CD3.jpg | Lymphocytic hypophysitis, CD3 IHC. (WC/jensflorian)
</gallery>

=See also=
*[[CNS cytopathology]].
*[[Neuropathology]].
*[[Brain tumours]].

=References=
{{reflist|2}}

=External links=
*[http://www.neuropathologyweb.org/ Neuropathology] - neuropathologyweb.org.
*[http://www.lab.anhb.uwa.edu.au/mb140/corepages/endocrines/endocrin.htm Endocrine histology (anhb.uwa.edu.au)].

[[Category:Neuropathology]]

Pituitary gland

2022-09-30T10:58:05Z

Jensflorian: /* Pituitary neuroendocrine tumor (PitNET) */ Update on PitNET

The '''pituitary gland''' is known as the ''master gland''.

Divisions:<ref>[http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo.html http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo.html]</ref>
*Anterior pituitary ([[AKA]] adenohypophysis, pars distalis).
*Posterior pituitary (AKA neurohypophysis, neural pituitary, pars nervosa).

=Function=
===Anterior===
Hormones:<ref name=rcn_com>[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Pituitary.html http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Pituitary.html]</ref>
*Growth hormone (GH).
*Luteinizing hormone (LH)
*Follicle-stimulating hormone (FSH)
*Thyroid stimulating hormone (TSH)
*Adrenocorticotropic hormone (ACTH)
*Prolactin (PRL)

Mnemonic: "Go Look For The Adenoma Please" = GH, LH, FSH, TSH, ACTH, PRL.

===Intermedia===
* Originates from the posterior wall of the Rathke’s pouch.
* Hormones: MSH, ACTH precursor.
* Contains colloid cysts.

===Posterior===
Hormones:<ref name=rcn_com/>
*Oxytocin.
*Antidiuretic hormone (ADH).

=Anatomy and histology=
===Anatomy===
Basic anatomy (simplified):<ref name=bowen>URL: [http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo_pit.html http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo_pit.html]. Accessed on: 31 October 2010.</ref>
*Anterior:
**Pars distalis.
**Pars intermedia.
*Posterior:
**Pars nervosa.

Embryological origin:<ref name=bowen/>
*Anterior - Rathke's pouch (roof of mouth).
*Posterior - diencephalon (ventral aspect).

Images:
*[http://www.ouhsc.edu/histology/Glass%20slides/38_01.jpg Pituitary gland (ouhsc.edu)].
*[http://www.lab.anhb.uwa.edu.au/mb140/corepages/endocrines/Images/HypDevAni.gif Development of the pituitary - animation (anhb.uwa.edu)].

===Histology===
====Anterior====
*Acidophils (40% of cells) = red or orange.
**GH, PRL.
*Basophils (10% of cells) = basophilic (light blue).
**TSH, LH, FSH, ACTH.
*Chromophobes (50% of cells) = amphophilic (purplish/grey).

Notes:
*The cellular product (i.e. hormone produced) is not strictly correlated with the cell type.<ref name=Ref_PSNP26>{{Ref PSNP|26}}</ref>
*The cells can be typed using [[IHC]]; somatotrophs (GH), lactotrophs (PRL), corticotrophs (ACTH), thyrotrophs (TSH), gonadotrophs (FSH, LH).<ref>{{Ref PBoD8|1098-9}}</ref>

====Posterior====
Features:<ref name=Ref_PSNP26>{{Ref PSNP|26}}</ref>
*Herring bodies - '''key feature'''.
**Eosinophilic axonal dilations filled with lysosomes and neurosecretory granules.
*Less cellular.
**Usually more cellular in perivascular location.
Image: [http://www.ouhsc.edu/histology/Glass%20slides/38_09.jpg Herring bodies (ouhsc.edu)].

<gallery>
File:Pituitary gland histology 2014.jpg | Pituitary gland, low magnification (WC/Athikhun.suw)
</gallery>

=DDx for sella turcica lesions=
*[[Pituitary adenoma|PitNET]].
*[[Rathke cleft cyst]].
*[[Craniopharyngioma]].
*[[Germ cell tumour]].
*[[Meningioma]].

=Pituitary necrosis=
*Rare.

===Causes of pituitary necrosis===
*Sheehan syndrome - secondary to blood loss in childbirth.<ref>URL: [http://www.mayoclinic.com/health/sheehans-syndrome/DS00889 http://www.mayoclinic.com/health/sheehans-syndrome/DS00889]. Accessed on: 16 November 2010.</ref>
*[[Syphilis]] (fetal-maternal transmission).<ref>URL: [http://pediatrics.aappublications.org/cgi/content/full/104/1/e4 http://pediatrics.aappublications.org/cgi/content/full/104/1/e4]. Accessed on: 16 November 2010.</ref>
*Mollaret's meningitis - very rare.<ref name=pmid18715308>{{cite journal |author=Dancer CM, Woods ML, Henderson RD, Robertson T, Mungomery M, Allworth A |title=Mollaret's meningitis and pituitary failure associated with a Rathke's cleft cyst |journal=Intern Med J |volume=38 |issue=7 |pages=609–11 |year=2008 |month=July |pmid=18715308 |doi=10.1111/j.1445-5994.2008.01709.x |url=}}</ref> (???)
*Spontaneous necrosis of pituitary tumours - case reports.<ref>{{cite journal |author=Sachdev Y, Evered DC, Hall R |title=Spontaneous pituitary necrosis |journal=Br Med J |volume=1 |issue=6015 |pages=942 |year=1976 |month=April |pmid=1268492 |pmc=1639254 |doi= |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1639254/pdf/brmedj00512-0028a.pdf}}</ref>

Images:
*[http://path.upmc.edu/cases/case288.html Pituitary necrosis - several images (upmc.edu)].

=Specific entities=
==Pituitary neuroendocrine tumor (PitNET)==
Old terminology '''Pituitary adenoma''' is depreceated.
The WHO 2022 Classification of tumours of endocrine organs recoginizes following tumours:<ref>{{cite journal |vauthors=Asa SL, Mete O, Perry A, Osamura RY |title=Overview of the 2022 WHO Classification of Pituitary Tumors |journal=Endocr Pathol |volume=33 |issue=1 |pages=6–26 |date=March 2022 |pmid=35291028 |doi=10.1007/s12022-022-09703-7 |url=}}</ref>

{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! PitNET lineage
! PitNET type
! subtypes
! Hormone IHC
! Transcription factor IHC
|-
| PIT1
| Somatotroph tumor
| Densely and sparsely granulated tumor
| GH, a-subunit+/-, CK+
| PIT1
|-
| PIT1
| Lactotroph tumor
| Densely and sparsely granulated tumor
| PRL, CK-ve or weak
| PIT1, [[Estrogen receptor|ER]]
|-
| PIT1
| Mammosomatotroph tumor
|
| GH, PRL (usu. less), CK perinuclear +ve
| PIT1, [[Estrogen receptor|ER]]
|-
| PIT1
| Thyrotroph tumor
|
| TSH, CK-ve or weak
| PIT1, GATA3
|-
| PIT1
| Mature plurihormonal PIT1 lineage tumor
|
| GH, PRL, TSH, a-subunit +/-ve, CK perinuclear
| PIT1, [[Estrogen receptor|ER]], GATA3
|-
| PIT1
| Immature PIT1 lineage tumor
|
| Only focal GH, PRL, TSH, a-subunit +/-ve, CK variable
| PIT1, [[Estrogen receptor|ER]] +/-ve, GATA3 +/-ve
|-
| PIT1
| Acidophilic stem cell tumor
|
| PRL, GH (focal/variable), CK fibrous bodies
| PIT1, [[Estrogen receptor|ER]]
|-
| PIT1
| Mixed somatotroph and lactotroph tumor
|
| PRL, GH (in separate cells)
| PIT1, [[Estrogen receptor|ER]] (only in lactotroph component)
|-
| TPIT
| Corticotroph tumor
| Densely and sparsely granulated tumors, Crooke cell adenoma
| ACTH,CK+ve
| TPIT
|-
| SF1
| Gonadotroph tumor
|
| FSH, LH, a-Subunit or none
| SF1, ER, GATA3, CK+/-ve
|-
| None
| Plurihormonal tumor
|
| All combinations possible
| All combinations possible, CK+/-ve
|-
| None
| Null cell adenoma
|
| None (adenohypophyseal?)
| None
|}

Other tumours may be classified as plurhormonal or double adenomas or as adenomas with unusual IHC combination.

===General===
*Clinical:<ref>{{Ref PBoD8|1100}}</ref>
**Classically: visual field defects (bitemporal hemianopsia).
**Others (increased intracranial pressure): headache, nausea, vomiting.
**Tumor of adults.

Morphologic Classification:
#Microtumor <= 1 cm.
#Macrotumor 1-4 cm.
#Giant tumor > 4cm.

May be classified by what they secrete.
#Functional (endocrine hyperfunction).
#*Acromegaly/giantism.
#*Hyperprolactinemia.
#*Cushing disease.
#*Hyperthyroidism.
#*Significant elevation of FSH/LH.
#Clinically nonfunctioning.

Notes:
''Cushing disease'' is due to pituitary gland hypersecretion of ACTH (due to a pituitary adenoma ''or'' CRH hypersecretion from the hypothalamus).<ref name=Ref_PBoD8_1148>{{Ref PBoD8|1148}}</ref> [[Cushing syndrome]] is hypercortisolism ''not'' due to pituitary gland pathology.

Imaging:
*Sellar enlargement.
*Bone erosion, invasive growth esp. cavernous sinus (35-45%).
*Inhomogenous signal in T1w MRI.

====Familial pituitary adenomas====
A pituitary adenoma may be part of a familial syndrome:<ref name=pmid19564887>{{Cite journal | last1 = Elston | first1 = MS. | last2 = McDonald | first2 = KL. | last3 = Clifton-Bligh | first3 = RJ. | last4 = Robinson | first4 = BG. | title = Familial pituitary tumor syndromes. | journal = Nat Rev Endocrinol | volume = 5 | issue = 8 | pages = 453-61 | month = Aug | year = 2009 | doi = 10.1038/nrendo.2009.126 | PMID = 19564887 }}</ref><ref name=Ref_PCPBoD8|554>{{Ref PCPBoD8|554}}</ref>
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Syndrome
! Gene
! Notes
|-
| [[Multiple endocrine neoplasia]] I
| MEN1
| characterized by the 3 Ps: '''p'''ituitary adenoma, [[parathyroid adenoma|'''p'''arathyroid adenoma]], [[pancreatic neuroendocrine tumour|'''p'''ancreatic neuroendocrine tumour]]
|-
| MEN-1-like syndrome
| CDKN1B<ref name=omim600778>{{OMIM|600778}}</ref>
| also known as ''Multiple endocrine neoplasia IV'' <ref name=omim600778>{{OMIM|600778}}</ref>
|-
| [[Carney syndrome]]
| PRKAR1A
| other findings (mnemonic ''NAME''): nevi, [[atrial myxoma]], myxoid neurofibroma, ephelides (freckles)
|-
| Isolated pituitary adenoma<ref name=pmid22612670>{{Cite journal | last1 = Korbonits | first1 = M. | last2 = Storr | first2 = H. | last3 = Kumar | first3 = AV. | title = Familial pituitary adenomas - Who should be tested for AIP mutations? | journal = Clin Endocrinol (Oxf) | volume = | issue = | pages = | month = May | year = 2012 | doi = 10.1111/j.1365-2265.2012.04445.x | PMID = 22612670 }}</ref>
| AIP
| classically GH-producing adenoma - leads to acromegaly
|}

===Microscopic===
Features:<ref name=Ref_PSNP36>{{Ref PSNP|36}}</ref>
*Loss of fibrous stroma.
**The cells of a normal (anterior) pituitary are nested.
*Basophilic cells (corticotrophs).
*Eosinophilic cells(somatotrophs).

Notes:
*Smears very well.<ref>MUN. 24 November 2010.</ref>

====Images====
<gallery>
Image:Nonfunctioning_pituitary_adenoma_%281%29.jpg | Pituitary adenoma - non-functioning. (WC/KGH)
File:HE fibrosis pituitary adenoma.jpg | Extensive interstitial and perivascular fibrosis in a pituitary adenoma (WC/jensflorian)
File:PRL HE histology.jpg | Pituitary adenoma - PRL producing, HE. Note the basophilic appearance of the cells (WC/jensflorian)
File:PRL adenoma treatment HE.jpg | Pituitary adenoma - PRL producing, HE. Extensive regressive changes after after dopamine agonist treatment (WC/jensflorian)
File:PRL IHC pituitary adenoma.jpg | Pituitary adenoma - PRL producing, Prolactin IHC (WC/jensflorian)
File:Densely granulated HGH producing adenoma.jpg | Pituitary adenoma - HGH producing, HE. The cells have a slightly eosinophilic appearance (WC/jensflorian)
File:Sparsely granulated HGH adenoma.jpg | Sparsely granulated adenoma - HGH producing. Note the numerous fibrous bodies in HE stain (WC/jensflorian)
File:HGH adenoma CK8.jpg | Sparsely granulated adenoma - HGH producing. CK8 IHC highlighting fibrous bodies (WC/jensflorian)
File:TSHoma HE.jpg | Pituitary adenoma - TSH producing. HE stain showing pleomorphism (WC/jensflorian)
File:TSHoma IHC-TSH.jpg | Pituitary adenoma - TSH producing. TSH IHC can be heterogeneous (WC/jensflorian)
Image:Pituitary_adenoma_%281%29_GH_production.jpg | Pituitary adenoma - GH producing. (WC/KGH)
File:HE-GHoma.jpg | Pituitary adenoma , HE. This gonadotropin producing adenoma has a papillary architecture (WC/jensflorian)
File:FSH-GHoma.jpg | Pituitary adenoma, IHC for FSH (WC/jensflorian)
File:LH-GHoma.jpg | Pituitary adenoma, IHC for LH (WC/jensflorian)
File:ACTHoma-PAS-O-G.jpg | Pituitary adenoma , ACTH producing. PAS-O-G stain showing basophilic adenoma cells (WC/jensflorian)
File:ACTHoma-IHC.jpg | Pituitary adenoma , ACTH producing. Strong ACTH IHC in this basophilic adenoma (WC/jensflorian)
File:Pituitary_adenoma-nonfunctioning.jpg |Pituitary adenoma with vascular pseudorosettes, nonfunctioning (WC/jensflorian)
Crooke_HE_40x.jpg | Crooke cell adenoma, HE (WC/Marvin101)
File:Crooke Cytokeratins.jpg | Crooke cell adenoma, panCK (WC/Marvin101)
HE_fibrosis_pituitary_adenoma.jpg | Fibrosis in pituitary adenoma.
</gallery>

===Stains===
*Reticulin - loss of reticulin between tumour cells.

===IHC===
*LH.
*FSH.
*TSH - [[Hyperthyroidism]]
*GH - [[Acromegaly]].
*Prolactin -Galactorrhea, Amenorrhea, Gynecomastia. Golgi staining pattern in sparsely granulated cases.
*ACTH - [[Cushing syndrome]].
*PIT-1: stains somatotrophs, lactotrophs and thyrothrops.
*TPIT: stains corticotrophs.
*SF1: stains gonadotrophs.
*Chromogranin A +ve
*Synaptophysin strongly +ve (except lactotrophs)
*CAM5.2: fibrous bodies in sparsely granulated somatotroph adenoma, Ring-like staining in Crooke cell adenoma.
*MIB-1: Usu less than 3%.

Note:
Null-cell adenoma must be hormone immunonegative and negative for transcription factors.

===Variants===
*Corticotroph adenomas exhibiting Crooke's hyaline change: agressive course.<ref>{{Cite journal | last1 = George | first1 = DH. | last2 = Scheithauer | first2 = BW. | last3 = Kovacs | first3 = K. | last4 = Horvath | first4 = E. | last5 = Young | first5 = WF. | last6 = Lloyd | first6 = RV. | last7 = Meyer | first7 = FB. | title = Crooke's cell adenoma of the pituitary: an aggressive variant of corticotroph adenoma. | journal = Am J Surg Pathol | volume = 27 | issue = 10 | pages = 1330-6 | month = Oct | year = 2003 | doi = | PMID = 14508394 }}</ref>
*Acidophilic stem cell adenomas: large, locally invasive adenoma with low GH activity. <ref>{{Cite journal | last1 = Horvath | first1 = E. | last2 = Kovacs | first2 = K. | last3 = Singer | first3 = W. | last4 = Smyth | first4 = HS. | last5 = Killinger | first5 = DW. | last6 = Erzin | first6 = C. | last7 = Weiss | first7 = MH. | title = Acidophil stem cell adenoma of the human pituitary: clinicopathologic analysis of 15 cases. | journal = Cancer | volume = 47 | issue = 4 | pages = 761-71 | month = Feb | year = 1981 | doi = | PMID = 6261917 }}</ref>
*Sparsely granulated somatotroph adenomas are more invasive than other variants and respond less to medical treatment. <ref>{{Cite journal | last1 = Kato | first1 = M. | last2 = Inoshita | first2 = N. | last3 = Sugiyama | first3 = T. | last4 = Tani | first4 = Y. | last5 = Shichiri | first5 = M. | last6 = Sano | first6 = T. | last7 = Yamada | first7 = S. | last8 = Hirata | first8 = Y. | title = Differential expression of genes related to drug responsiveness between sparsely and densely granulated somatotroph adenomas. | journal = Endocr J | volume = 59 | issue = 3 | pages = 221-8 | month = | year = 2012 | doi = | PMID = 22200580 }}</ref>
* Lactotroph adenomas in men may show aggressive clinical behavior. <ref>{{Cite journal | last1 = Delgrange | first1 = E. | last2 = Vasiljevic | first2 = A. | last3 = Wierinckx | first3 = A. | last4 = François | first4 = P. | last5 = Jouanneau | first5 = E. | last6 = Raverot | first6 = G. | last7 = Trouillas | first7 = J. | title = Expression of estrogen receptor alpha is associated with prolactin pituitary tumor prognosis and supports the sex-related difference in tumor growth. | journal = Eur J Endocrinol | volume = 172 | issue = 6 | pages = 791-801 | month = Jun | year = 2015 | doi = 10.1530/EJE-14-0990 | PMID = 25792376 }}</ref>
*Poorly differentiated PIT-1 positive adenomas may show aggresive growth. <ref> {{Cite journal | last1 = Mete | first1 = O. | last2 = Gomez-Hernandez | first2 = K. | last3 = Kucharczyk | first3 = W. | last4 = Ridout | first4 = R. | last5 = Zadeh | first5 = G. | last6 = Gentili | first6 = F. | last7 = Ezzat | first7 = S. | last8 = Asa | first8 = SL. | title = Silent subtype 3 pituitary adenomas are not always silent and represent poorly differentiated monomorphous plurihormonal Pit-1 lineage adenomas. | journal = Mod Pathol | volume = 29 | issue = 2 | pages = 131-42 | month = Feb | year = 2016 | doi = 10.1038/modpathol.2015.151 | PMID = 26743473 }}</ref>

==Pituitary blastoma==
* New entity introduced in 2017<ref>{{Cite journal | last1 = Lopes | first1 = MBS. | title = The 2017 World Health Organization classification of tumors of the pituitary gland: a summary. | journal = Acta Neuropathol | volume = 134 | issue = 4 | pages = 521-535 | month = Oct | year = 2017 | doi = 10.1007/s00401-017-1769-8 | PMID = 28821944 }}</ref>
* Epithelial glands with rosette-like formations resembling immature Rathke epithelium.
* Synaptophysin +ve, usu. ACTH+ve
* DICER1 mutations<ref>{{Cite journal | last1 = de Kock | first1 = L. | last2 = Sabbaghian | first2 = N. | last3 = Plourde | first3 = F. | last4 = Srivastava | first4 = A. | last5 = Weber | first5 = E. | last6 = Bouron-Dal Soglio | first6 = D. | last7 = Hamel | first7 = N. | last8 = Choi | first8 = JH. | last9 = Park | first9 = SH. | title = Pituitary blastoma: a pathognomonic feature of germ-line DICER1 mutations. | journal = Acta Neuropathol | volume = 128 | issue = 1 | pages = 111-22 | month = Jul | year = 2014 | doi = 10.1007/s00401-014-1285-z | PMID = 24839956 }}</ref>

==Pituitary carcinoma==
* ICD-O: 8272/3
* Requires presence of cerebrospinal or systemic metastasis.
* Very rare.
* 75% are hormonally active (mostly PRL or ACTH).
* IHC: Synaptophysin, Chromogranin +ve

==Rathke cleft cyst==
===General===
*Benign counterpart of [[craniopharyngioma]].
*Arises from intermediate lobe of pituitary gland (''pars intermedia of pituitary gland'').

Radiology:
*Typically no calcifications.<ref name=emed_rcc>URL: [http://emedicine.medscape.com/article/343629-overview http://emedicine.medscape.com/article/343629-overview]. Accessed on: 14 November 2010.</ref>

Radiologic DDx:<ref name=emed_rcc>URL: [http://emedicine.medscape.com/article/343629-overview http://emedicine.medscape.com/article/343629-overview]. Accessed on: 14 November 2010.</ref>
*Arachnoid cyst.
*[[Craniopharyngioma]].
*[[Cysticercosis]].
*[[Pituitary adenoma]].
*Epidermoid of brain.

===Microscopic===
Features:
*Lined by a layer of cuboidal ''or'' columnar epithelial with cilia.
*+/-Goblet cells.<ref>URL: [http://www.endotext.org/neuroendo/neuroendo3/neuroendo3.html http://www.endotext.org/neuroendo/neuroendo3/neuroendo3.html]. Accessed on: 27 May 2010.</ref>
*+/-Squamous metaplasia ~ may be several layers thick.
**May be confused with ''[[papillary craniopharyngioma]]''.<ref name=Ref_PSNP408>{{Ref PSNP|408}}</ref>
*Cholesterol clefts may be seen in association with rupture.<ref>URL: [http://path.upmc.edu/cases/case177/dx.html http://path.upmc.edu/cases/case177/dx.html]. Accessed on: 8 January 2012.</ref>

DDx:
*[[Papillary craniopharyngioma]].

Images:
*[http://www.endotext.org/neuroendo/neuroendo3/figures/figure11.jpg Rathke cleft cyst (endotext.org)].
*[http://path.upmc.edu/cases/case177/micro.html Rathke cleft cyst (upmc.edu)].

==Craniopharyngioma==
{{Main|Craniopharyngioma}}

==Gangliocytoma==
* Neuronal cells in abundant neuropil.
* S-100, Synaptophysin +ve.
* Isolated sellar cases are very rare.

Image: [[https://twitter.com/sty_md/status/664676241111252992]]

==Mixed Gangliocytoma-adenoma==
AKA: ganglioneuroma, pituitary adenoma with neuronal choristoma (PANCH)
*Neuronal cells mixed with pituitary adenoma cells.
* Approx. 0.25% of all pituitary adenomas.
* Association with somatotroph adenomas (acromegaly).

==Pituicytoma==
{{Main|Pituicytoma}}

==Spindle cell oncocytoma==
*Origin: Neurohypophysis or infundibulum.
*Benign clinical course - WHO grade I.
*Elongated bipolar, spindle cells.
*Fascicular or storiform growth patterns.
*EMA: patchy, S-100+/-ve, GFAP+/-ve, TTF1+ve.

*It is thought that Spindle cell oncocytomas and Granular cell tumors of the neurohypophysis are variants of Pituicyoma.<ref>{{Cite journal | last1 = Mete | first1 = O. | last2 = Lopes | first2 = MB. | last3 = Asa | first3 = SL. | title = Spindle cell oncocytomas and granular cell tumors of the pituitary are variants of pituicytoma. | journal = Am J Surg Pathol | volume = 37 | issue = 11 | pages = 1694-9 | month = Nov | year = 2013 | doi = 10.1097/PAS.0b013e31829723e7 | PMID = 23887161 }}</ref>

==Granular cell tumor of the sellar region==
{{Main|Granular_cell_tumour}}

*Origin: Neurohypophysis or infundibulum.
*Benign clinical course - WHO grade I.
*Well circumscribed.
*Polygonal cells with abundant granular cytoplasm.
*CD68+ve, S-100+/-ve, GFAP+/-ve, TTF1+ve.

<gallery>
File:Granular_cell_tumor_pituitary.jpg | Granular cell tumor of the sellar region (HE).
</gallery>

==Autoimmune hypophysitis==
===General===
Features:<ref name=pmid18388197/>
*Rare.
*Autoantigens are unknown.
*May occur in pregnancy.
*May be misdiagnosed as a nonsecreting adenoma.

===Microscopic===
Features:<ref name=pmid18388197>{{cite journal |author=Tzou SC, Lupi I, Landek M, ''et al.'' |title=Autoimmune hypophysitis of SJL mice: clinical insights from a new animal model |journal=Endocrinology |volume=149 |issue=7 |pages=3461–9 |year=2008 |month=July |pmid=18388197 |pmc=2453094 |doi=10.1210/en.2007-1692 |url=}}</ref>
*Lymphocytic infiltration.

<gallery>
File:Lymphocytic_hypophysitis_CD3.jpg | Lymphocytic hypophysitis, CD3 IHC. (WC/jensflorian)
</gallery>

=See also=
*[[CNS cytopathology]].
*[[Neuropathology]].
*[[Brain tumours]].

=References=
{{reflist|2}}

=External links=
*[http://www.neuropathologyweb.org/ Neuropathology] - neuropathologyweb.org.
*[http://www.lab.anhb.uwa.edu.au/mb140/corepages/endocrines/endocrin.htm Endocrine histology (anhb.uwa.edu.au)].

[[Category:Neuropathology]]

Pituitary gland

2022-09-30T10:53:40Z

Jensflorian: /* Pituitary neuroendocrine tumor (PitNET) */ SF1 lineage

The '''pituitary gland''' is known as the ''master gland''.

Divisions:<ref>[http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo.html http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo.html]</ref>
*Anterior pituitary ([[AKA]] adenohypophysis, pars distalis).
*Posterior pituitary (AKA neurohypophysis, neural pituitary, pars nervosa).

=Function=
===Anterior===
Hormones:<ref name=rcn_com>[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Pituitary.html http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Pituitary.html]</ref>
*Growth hormone (GH).
*Luteinizing hormone (LH)
*Follicle-stimulating hormone (FSH)
*Thyroid stimulating hormone (TSH)
*Adrenocorticotropic hormone (ACTH)
*Prolactin (PRL)

Mnemonic: "Go Look For The Adenoma Please" = GH, LH, FSH, TSH, ACTH, PRL.

===Intermedia===
* Originates from the posterior wall of the Rathke’s pouch.
* Hormones: MSH, ACTH precursor.
* Contains colloid cysts.

===Posterior===
Hormones:<ref name=rcn_com/>
*Oxytocin.
*Antidiuretic hormone (ADH).

=Anatomy and histology=
===Anatomy===
Basic anatomy (simplified):<ref name=bowen>URL: [http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo_pit.html http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo_pit.html]. Accessed on: 31 October 2010.</ref>
*Anterior:
**Pars distalis.
**Pars intermedia.
*Posterior:
**Pars nervosa.

Embryological origin:<ref name=bowen/>
*Anterior - Rathke's pouch (roof of mouth).
*Posterior - diencephalon (ventral aspect).

Images:
*[http://www.ouhsc.edu/histology/Glass%20slides/38_01.jpg Pituitary gland (ouhsc.edu)].
*[http://www.lab.anhb.uwa.edu.au/mb140/corepages/endocrines/Images/HypDevAni.gif Development of the pituitary - animation (anhb.uwa.edu)].

===Histology===
====Anterior====
*Acidophils (40% of cells) = red or orange.
**GH, PRL.
*Basophils (10% of cells) = basophilic (light blue).
**TSH, LH, FSH, ACTH.
*Chromophobes (50% of cells) = amphophilic (purplish/grey).

Notes:
*The cellular product (i.e. hormone produced) is not strictly correlated with the cell type.<ref name=Ref_PSNP26>{{Ref PSNP|26}}</ref>
*The cells can be typed using [[IHC]]; somatotrophs (GH), lactotrophs (PRL), corticotrophs (ACTH), thyrotrophs (TSH), gonadotrophs (FSH, LH).<ref>{{Ref PBoD8|1098-9}}</ref>

====Posterior====
Features:<ref name=Ref_PSNP26>{{Ref PSNP|26}}</ref>
*Herring bodies - '''key feature'''.
**Eosinophilic axonal dilations filled with lysosomes and neurosecretory granules.
*Less cellular.
**Usually more cellular in perivascular location.
Image: [http://www.ouhsc.edu/histology/Glass%20slides/38_09.jpg Herring bodies (ouhsc.edu)].

<gallery>
File:Pituitary gland histology 2014.jpg | Pituitary gland, low magnification (WC/Athikhun.suw)
</gallery>

=DDx for sella turcica lesions=
*[[Pituitary adenoma|PitNET]].
*[[Rathke cleft cyst]].
*[[Craniopharyngioma]].
*[[Germ cell tumour]].
*[[Meningioma]].

=Pituitary necrosis=
*Rare.

===Causes of pituitary necrosis===
*Sheehan syndrome - secondary to blood loss in childbirth.<ref>URL: [http://www.mayoclinic.com/health/sheehans-syndrome/DS00889 http://www.mayoclinic.com/health/sheehans-syndrome/DS00889]. Accessed on: 16 November 2010.</ref>
*[[Syphilis]] (fetal-maternal transmission).<ref>URL: [http://pediatrics.aappublications.org/cgi/content/full/104/1/e4 http://pediatrics.aappublications.org/cgi/content/full/104/1/e4]. Accessed on: 16 November 2010.</ref>
*Mollaret's meningitis - very rare.<ref name=pmid18715308>{{cite journal |author=Dancer CM, Woods ML, Henderson RD, Robertson T, Mungomery M, Allworth A |title=Mollaret's meningitis and pituitary failure associated with a Rathke's cleft cyst |journal=Intern Med J |volume=38 |issue=7 |pages=609–11 |year=2008 |month=July |pmid=18715308 |doi=10.1111/j.1445-5994.2008.01709.x |url=}}</ref> (???)
*Spontaneous necrosis of pituitary tumours - case reports.<ref>{{cite journal |author=Sachdev Y, Evered DC, Hall R |title=Spontaneous pituitary necrosis |journal=Br Med J |volume=1 |issue=6015 |pages=942 |year=1976 |month=April |pmid=1268492 |pmc=1639254 |doi= |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1639254/pdf/brmedj00512-0028a.pdf}}</ref>

Images:
*[http://path.upmc.edu/cases/case288.html Pituitary necrosis - several images (upmc.edu)].

=Specific entities=
==Pituitary neuroendocrine tumor (PitNET)==
Old terminology '''Pituitary adenoma''' is depreceated.
The WHO 2022 Classification of tumours of endocrine organs recoginizes following tumours:<ref>{{cite journal |vauthors=Asa SL, Mete O, Perry A, Osamura RY |title=Overview of the 2022 WHO Classification of Pituitary Tumors |journal=Endocr Pathol |volume=33 |issue=1 |pages=6–26 |date=March 2022 |pmid=35291028 |doi=10.1007/s12022-022-09703-7 |url=}}</ref>

{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! PitNET lineage
! PitNET type
! subtypes
! Hormone IHC
! Transcription factor IHC
|-
| PIT1
| Somatotroph tumor
| Densely and sparsely granulated tumor
| GH, a-subunit+/-, CK+
| PIT1
|-
| PIT1
| Lactotroph tumor
| Densely and sparsely granulated tumor
| PRL, CK-ve or weak
| PIT1, [[Estrogen receptor|ER]]
|-
| PIT1
| Mammosomatotroph tumor
|
| GH, PRL (usu. less), CK perinuclear +ve
| PIT1, [[Estrogen receptor|ER]]
|-
| PIT1
| Thyrotroph tumor
|
| TSH, CK-ve or weak
| PIT1, GATA3
|-
| PIT1
| Mature plurihormonal PIT1 lineage tumor
|
| GH, PRL, TSH, a-subunit +/-ve, CK perinuclear
| PIT1, [[Estrogen receptor|ER]], GATA3
|-
| PIT1
| Immature PIT1 lineage tumor
|
| Only focal GH, PRL, TSH, a-subunit +/-ve, CK variable
| PIT1, [[Estrogen receptor|ER]] +/-ve, GATA3 +/-ve
|-
| PIT1
| Acidophilic stem cell tumor
|
| PRL, GH (focal/variable), CK fibrous bodies
| PIT1, [[Estrogen receptor|ER]]
|-
| PIT1
| Mixed somatotroph and lactotroph tumor
|
| PRL, GH (in separate cells)
| PIT1, [[Estrogen receptor|ER]] (only in lactotroph component)
|-
| TPIT
| Corticotroph tumor
| Densely and sparsely granulated tumors, Crooke cell adenoma
| ACTH,CK+ve
| TPIT
|-
| SF1
| Gonadotroph tumor
|
| FSH, LH or a-Subunit or none
| SF1, [[Estrogen receptor|ER]], GATA3, CK+/-ve
|-
|
| Null cell adenoma
|
| None
| None
|}

Other tumours may be classified as plurhormonal or double adenomas or as adenomas with unusual IHC combination.

===General===
*Clinical:<ref>{{Ref PBoD8|1100}}</ref>
**Classically: visual field defects (bitemporal hemianopsia).
**Others (increased intracranial pressure): headache, nausea, vomiting.
**Tumor of adults.

Morphologic Classification:
#Microadenoma <= 1 cm.
#Macroadenoma 1-4 cm.
#Giant adenoma > 4cm.

May be classified by what they secrete.
#Functional (endocrine hyperfunction).
#*Acromegaly/giantism.
#*Hyperprolactinemia.
#*Cushing disease.
#*Hyperthyroidism.
#*Significant elevation of FSH/LH.
#Clinically nonfunctioning.

Notes:
''Cushing disease'' is due to pituitary gland hypersecretion of ACTH (due to a pituitary adenoma ''or'' CRH hypersecretion from the hypothalamus).<ref name=Ref_PBoD8_1148>{{Ref PBoD8|1148}}</ref> [[Cushing syndrome]] is hypercortisolism ''not'' due to pituitary gland pathology.

Imaging:
*Sellar enlargement.
*Bone erosion, invasive growth esp. cavernous sinus (35-45%).
*Inhomogenous signal in T1w MRI.

====Familial pituitary adenomas====
A pituitary adenoma may be part of a familial syndrome:<ref name=pmid19564887>{{Cite journal | last1 = Elston | first1 = MS. | last2 = McDonald | first2 = KL. | last3 = Clifton-Bligh | first3 = RJ. | last4 = Robinson | first4 = BG. | title = Familial pituitary tumor syndromes. | journal = Nat Rev Endocrinol | volume = 5 | issue = 8 | pages = 453-61 | month = Aug | year = 2009 | doi = 10.1038/nrendo.2009.126 | PMID = 19564887 }}</ref><ref name=Ref_PCPBoD8|554>{{Ref PCPBoD8|554}}</ref>
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Syndrome
! Gene
! Notes
|-
| [[Multiple endocrine neoplasia]] I
| MEN1
| characterized by the 3 Ps: '''p'''ituitary adenoma, [[parathyroid adenoma|'''p'''arathyroid adenoma]], [[pancreatic neuroendocrine tumour|'''p'''ancreatic neuroendocrine tumour]]
|-
| MEN-1-like syndrome
| CDKN1B<ref name=omim600778>{{OMIM|600778}}</ref>
| also known as ''Multiple endocrine neoplasia IV'' <ref name=omim600778>{{OMIM|600778}}</ref>
|-
| [[Carney syndrome]]
| PRKAR1A
| other findings (mnemonic ''NAME''): nevi, [[atrial myxoma]], myxoid neurofibroma, ephelides (freckles)
|-
| Isolated pituitary adenoma<ref name=pmid22612670>{{Cite journal | last1 = Korbonits | first1 = M. | last2 = Storr | first2 = H. | last3 = Kumar | first3 = AV. | title = Familial pituitary adenomas - Who should be tested for AIP mutations? | journal = Clin Endocrinol (Oxf) | volume = | issue = | pages = | month = May | year = 2012 | doi = 10.1111/j.1365-2265.2012.04445.x | PMID = 22612670 }}</ref>
| AIP
| classically GH-producing adenoma - leads to acromegaly
|}

===Microscopic===
Features:<ref name=Ref_PSNP36>{{Ref PSNP|36}}</ref>
*Loss of fibrous stroma.
**The cells of a normal (anterior) pituitary are nested.
*Basophilic cells (corticotrophs).
*Eosinophilic cells(somatotrophs).

Notes:
*Smears very well.<ref>MUN. 24 November 2010.</ref>

====Images====
<gallery>
Image:Nonfunctioning_pituitary_adenoma_%281%29.jpg | Pituitary adenoma - non-functioning. (WC/KGH)
File:HE fibrosis pituitary adenoma.jpg | Extensive interstitial and perivascular fibrosis in a pituitary adenoma (WC/jensflorian)
File:PRL HE histology.jpg | Pituitary adenoma - PRL producing, HE. Note the basophilic appearance of the cells (WC/jensflorian)
File:PRL adenoma treatment HE.jpg | Pituitary adenoma - PRL producing, HE. Extensive regressive changes after after dopamine agonist treatment (WC/jensflorian)
File:PRL IHC pituitary adenoma.jpg | Pituitary adenoma - PRL producing, Prolactin IHC (WC/jensflorian)
File:Densely granulated HGH producing adenoma.jpg | Pituitary adenoma - HGH producing, HE. The cells have a slightly eosinophilic appearance (WC/jensflorian)
File:Sparsely granulated HGH adenoma.jpg | Sparsely granulated adenoma - HGH producing. Note the numerous fibrous bodies in HE stain (WC/jensflorian)
File:HGH adenoma CK8.jpg | Sparsely granulated adenoma - HGH producing. CK8 IHC highlighting fibrous bodies (WC/jensflorian)
File:TSHoma HE.jpg | Pituitary adenoma - TSH producing. HE stain showing pleomorphism (WC/jensflorian)
File:TSHoma IHC-TSH.jpg | Pituitary adenoma - TSH producing. TSH IHC can be heterogeneous (WC/jensflorian)
Image:Pituitary_adenoma_%281%29_GH_production.jpg | Pituitary adenoma - GH producing. (WC/KGH)
File:HE-GHoma.jpg | Pituitary adenoma , HE. This gonadotropin producing adenoma has a papillary architecture (WC/jensflorian)
File:FSH-GHoma.jpg | Pituitary adenoma, IHC for FSH (WC/jensflorian)
File:LH-GHoma.jpg | Pituitary adenoma, IHC for LH (WC/jensflorian)
File:ACTHoma-PAS-O-G.jpg | Pituitary adenoma , ACTH producing. PAS-O-G stain showing basophilic adenoma cells (WC/jensflorian)
File:ACTHoma-IHC.jpg | Pituitary adenoma , ACTH producing. Strong ACTH IHC in this basophilic adenoma (WC/jensflorian)
File:Pituitary_adenoma-nonfunctioning.jpg |Pituitary adenoma with vascular pseudorosettes, nonfunctioning (WC/jensflorian)
Crooke_HE_40x.jpg | Crooke cell adenoma, HE (WC/Marvin101)
File:Crooke Cytokeratins.jpg | Crooke cell adenoma, panCK (WC/Marvin101)
HE_fibrosis_pituitary_adenoma.jpg | Fibrosis in pituitary adenoma.
</gallery>

===Stains===
*Reticulin - loss of reticulin between tumour cells.

===IHC===
*LH.
*FSH.
*TSH - [[Hyperthyroidism]]
*GH - [[Acromegaly]].
*Prolactin -Galactorrhea, Amenorrhea, Gynecomastia. Golgi staining pattern in sparsely granulated cases.
*ACTH - [[Cushing syndrome]].
*PIT-1: stains somatotrophs, lactotrophs and thyrothrops.
*TPIT: stains corticotrophs.
*SF1: stains gonadotrophs.
*Chromogranin A +ve
*Synaptophysin strongly +ve (except lactotrophs)
*CAM5.2: fibrous bodies in sparsely granulated somatotroph adenoma, Ring-like staining in Crooke cell adenoma.
*MIB-1: Usu less than 3%.

Note:
Null-cell adenoma must be hormone immunonegative and negative for transcription factors.

===Variants===
*Corticotroph adenomas exhibiting Crooke's hyaline change: agressive course.<ref>{{Cite journal | last1 = George | first1 = DH. | last2 = Scheithauer | first2 = BW. | last3 = Kovacs | first3 = K. | last4 = Horvath | first4 = E. | last5 = Young | first5 = WF. | last6 = Lloyd | first6 = RV. | last7 = Meyer | first7 = FB. | title = Crooke's cell adenoma of the pituitary: an aggressive variant of corticotroph adenoma. | journal = Am J Surg Pathol | volume = 27 | issue = 10 | pages = 1330-6 | month = Oct | year = 2003 | doi = | PMID = 14508394 }}</ref>
*Acidophilic stem cell adenomas: large, locally invasive adenoma with low GH activity. <ref>{{Cite journal | last1 = Horvath | first1 = E. | last2 = Kovacs | first2 = K. | last3 = Singer | first3 = W. | last4 = Smyth | first4 = HS. | last5 = Killinger | first5 = DW. | last6 = Erzin | first6 = C. | last7 = Weiss | first7 = MH. | title = Acidophil stem cell adenoma of the human pituitary: clinicopathologic analysis of 15 cases. | journal = Cancer | volume = 47 | issue = 4 | pages = 761-71 | month = Feb | year = 1981 | doi = | PMID = 6261917 }}</ref>
*Sparsely granulated somatotroph adenomas are more invasive than other variants and respond less to medical treatment. <ref>{{Cite journal | last1 = Kato | first1 = M. | last2 = Inoshita | first2 = N. | last3 = Sugiyama | first3 = T. | last4 = Tani | first4 = Y. | last5 = Shichiri | first5 = M. | last6 = Sano | first6 = T. | last7 = Yamada | first7 = S. | last8 = Hirata | first8 = Y. | title = Differential expression of genes related to drug responsiveness between sparsely and densely granulated somatotroph adenomas. | journal = Endocr J | volume = 59 | issue = 3 | pages = 221-8 | month = | year = 2012 | doi = | PMID = 22200580 }}</ref>
* Lactotroph adenomas in men may show aggressive clinical behavior. <ref>{{Cite journal | last1 = Delgrange | first1 = E. | last2 = Vasiljevic | first2 = A. | last3 = Wierinckx | first3 = A. | last4 = François | first4 = P. | last5 = Jouanneau | first5 = E. | last6 = Raverot | first6 = G. | last7 = Trouillas | first7 = J. | title = Expression of estrogen receptor alpha is associated with prolactin pituitary tumor prognosis and supports the sex-related difference in tumor growth. | journal = Eur J Endocrinol | volume = 172 | issue = 6 | pages = 791-801 | month = Jun | year = 2015 | doi = 10.1530/EJE-14-0990 | PMID = 25792376 }}</ref>
*Poorly differentiated PIT-1 positive adenomas may show aggresive growth. <ref> {{Cite journal | last1 = Mete | first1 = O. | last2 = Gomez-Hernandez | first2 = K. | last3 = Kucharczyk | first3 = W. | last4 = Ridout | first4 = R. | last5 = Zadeh | first5 = G. | last6 = Gentili | first6 = F. | last7 = Ezzat | first7 = S. | last8 = Asa | first8 = SL. | title = Silent subtype 3 pituitary adenomas are not always silent and represent poorly differentiated monomorphous plurihormonal Pit-1 lineage adenomas. | journal = Mod Pathol | volume = 29 | issue = 2 | pages = 131-42 | month = Feb | year = 2016 | doi = 10.1038/modpathol.2015.151 | PMID = 26743473 }}</ref>

==Pituitary blastoma==
* New entity introduced in 2017<ref>{{Cite journal | last1 = Lopes | first1 = MBS. | title = The 2017 World Health Organization classification of tumors of the pituitary gland: a summary. | journal = Acta Neuropathol | volume = 134 | issue = 4 | pages = 521-535 | month = Oct | year = 2017 | doi = 10.1007/s00401-017-1769-8 | PMID = 28821944 }}</ref>
* Epithelial glands with rosette-like formations resembling immature Rathke epithelium.
* Synaptophysin +ve, usu. ACTH+ve
* DICER1 mutations<ref>{{Cite journal | last1 = de Kock | first1 = L. | last2 = Sabbaghian | first2 = N. | last3 = Plourde | first3 = F. | last4 = Srivastava | first4 = A. | last5 = Weber | first5 = E. | last6 = Bouron-Dal Soglio | first6 = D. | last7 = Hamel | first7 = N. | last8 = Choi | first8 = JH. | last9 = Park | first9 = SH. | title = Pituitary blastoma: a pathognomonic feature of germ-line DICER1 mutations. | journal = Acta Neuropathol | volume = 128 | issue = 1 | pages = 111-22 | month = Jul | year = 2014 | doi = 10.1007/s00401-014-1285-z | PMID = 24839956 }}</ref>

==Pituitary carcinoma==
* ICD-O: 8272/3
* Requires presence of cerebrospinal or systemic metastasis.
* Very rare.
* 75% are hormonally active (mostly PRL or ACTH).
* IHC: Synaptophysin, Chromogranin +ve

==Rathke cleft cyst==
===General===
*Benign counterpart of [[craniopharyngioma]].
*Arises from intermediate lobe of pituitary gland (''pars intermedia of pituitary gland'').

Radiology:
*Typically no calcifications.<ref name=emed_rcc>URL: [http://emedicine.medscape.com/article/343629-overview http://emedicine.medscape.com/article/343629-overview]. Accessed on: 14 November 2010.</ref>

Radiologic DDx:<ref name=emed_rcc>URL: [http://emedicine.medscape.com/article/343629-overview http://emedicine.medscape.com/article/343629-overview]. Accessed on: 14 November 2010.</ref>
*Arachnoid cyst.
*[[Craniopharyngioma]].
*[[Cysticercosis]].
*[[Pituitary adenoma]].
*Epidermoid of brain.

===Microscopic===
Features:
*Lined by a layer of cuboidal ''or'' columnar epithelial with cilia.
*+/-Goblet cells.<ref>URL: [http://www.endotext.org/neuroendo/neuroendo3/neuroendo3.html http://www.endotext.org/neuroendo/neuroendo3/neuroendo3.html]. Accessed on: 27 May 2010.</ref>
*+/-Squamous metaplasia ~ may be several layers thick.
**May be confused with ''[[papillary craniopharyngioma]]''.<ref name=Ref_PSNP408>{{Ref PSNP|408}}</ref>
*Cholesterol clefts may be seen in association with rupture.<ref>URL: [http://path.upmc.edu/cases/case177/dx.html http://path.upmc.edu/cases/case177/dx.html]. Accessed on: 8 January 2012.</ref>

DDx:
*[[Papillary craniopharyngioma]].

Images:
*[http://www.endotext.org/neuroendo/neuroendo3/figures/figure11.jpg Rathke cleft cyst (endotext.org)].
*[http://path.upmc.edu/cases/case177/micro.html Rathke cleft cyst (upmc.edu)].

==Craniopharyngioma==
{{Main|Craniopharyngioma}}

==Gangliocytoma==
* Neuronal cells in abundant neuropil.
* S-100, Synaptophysin +ve.
* Isolated sellar cases are very rare.

Image: [[https://twitter.com/sty_md/status/664676241111252992]]

==Mixed Gangliocytoma-adenoma==
AKA: ganglioneuroma, pituitary adenoma with neuronal choristoma (PANCH)
*Neuronal cells mixed with pituitary adenoma cells.
* Approx. 0.25% of all pituitary adenomas.
* Association with somatotroph adenomas (acromegaly).

==Pituicytoma==
{{Main|Pituicytoma}}

==Spindle cell oncocytoma==
*Origin: Neurohypophysis or infundibulum.
*Benign clinical course - WHO grade I.
*Elongated bipolar, spindle cells.
*Fascicular or storiform growth patterns.
*EMA: patchy, S-100+/-ve, GFAP+/-ve, TTF1+ve.

*It is thought that Spindle cell oncocytomas and Granular cell tumors of the neurohypophysis are variants of Pituicyoma.<ref>{{Cite journal | last1 = Mete | first1 = O. | last2 = Lopes | first2 = MB. | last3 = Asa | first3 = SL. | title = Spindle cell oncocytomas and granular cell tumors of the pituitary are variants of pituicytoma. | journal = Am J Surg Pathol | volume = 37 | issue = 11 | pages = 1694-9 | month = Nov | year = 2013 | doi = 10.1097/PAS.0b013e31829723e7 | PMID = 23887161 }}</ref>

==Granular cell tumor of the sellar region==
{{Main|Granular_cell_tumour}}

*Origin: Neurohypophysis or infundibulum.
*Benign clinical course - WHO grade I.
*Well circumscribed.
*Polygonal cells with abundant granular cytoplasm.
*CD68+ve, S-100+/-ve, GFAP+/-ve, TTF1+ve.

<gallery>
File:Granular_cell_tumor_pituitary.jpg | Granular cell tumor of the sellar region (HE).
</gallery>

==Autoimmune hypophysitis==
===General===
Features:<ref name=pmid18388197/>
*Rare.
*Autoantigens are unknown.
*May occur in pregnancy.
*May be misdiagnosed as a nonsecreting adenoma.

===Microscopic===
Features:<ref name=pmid18388197>{{cite journal |author=Tzou SC, Lupi I, Landek M, ''et al.'' |title=Autoimmune hypophysitis of SJL mice: clinical insights from a new animal model |journal=Endocrinology |volume=149 |issue=7 |pages=3461–9 |year=2008 |month=July |pmid=18388197 |pmc=2453094 |doi=10.1210/en.2007-1692 |url=}}</ref>
*Lymphocytic infiltration.

<gallery>
File:Lymphocytic_hypophysitis_CD3.jpg | Lymphocytic hypophysitis, CD3 IHC. (WC/jensflorian)
</gallery>

=See also=
*[[CNS cytopathology]].
*[[Neuropathology]].
*[[Brain tumours]].

=References=
{{reflist|2}}

=External links=
*[http://www.neuropathologyweb.org/ Neuropathology] - neuropathologyweb.org.
*[http://www.lab.anhb.uwa.edu.au/mb140/corepages/endocrines/endocrin.htm Endocrine histology (anhb.uwa.edu.au)].

[[Category:Neuropathology]]

Pituitary gland

2022-09-30T10:52:10Z

Jensflorian: /* Pituitary neuroendocrine tumor (PitNET) */ TPIT group

The '''pituitary gland''' is known as the ''master gland''.

Divisions:<ref>[http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo.html http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo.html]</ref>
*Anterior pituitary ([[AKA]] adenohypophysis, pars distalis).
*Posterior pituitary (AKA neurohypophysis, neural pituitary, pars nervosa).

=Function=
===Anterior===
Hormones:<ref name=rcn_com>[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Pituitary.html http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Pituitary.html]</ref>
*Growth hormone (GH).
*Luteinizing hormone (LH)
*Follicle-stimulating hormone (FSH)
*Thyroid stimulating hormone (TSH)
*Adrenocorticotropic hormone (ACTH)
*Prolactin (PRL)

Mnemonic: "Go Look For The Adenoma Please" = GH, LH, FSH, TSH, ACTH, PRL.

===Intermedia===
* Originates from the posterior wall of the Rathke’s pouch.
* Hormones: MSH, ACTH precursor.
* Contains colloid cysts.

===Posterior===
Hormones:<ref name=rcn_com/>
*Oxytocin.
*Antidiuretic hormone (ADH).

=Anatomy and histology=
===Anatomy===
Basic anatomy (simplified):<ref name=bowen>URL: [http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo_pit.html http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo_pit.html]. Accessed on: 31 October 2010.</ref>
*Anterior:
**Pars distalis.
**Pars intermedia.
*Posterior:
**Pars nervosa.

Embryological origin:<ref name=bowen/>
*Anterior - Rathke's pouch (roof of mouth).
*Posterior - diencephalon (ventral aspect).

Images:
*[http://www.ouhsc.edu/histology/Glass%20slides/38_01.jpg Pituitary gland (ouhsc.edu)].
*[http://www.lab.anhb.uwa.edu.au/mb140/corepages/endocrines/Images/HypDevAni.gif Development of the pituitary - animation (anhb.uwa.edu)].

===Histology===
====Anterior====
*Acidophils (40% of cells) = red or orange.
**GH, PRL.
*Basophils (10% of cells) = basophilic (light blue).
**TSH, LH, FSH, ACTH.
*Chromophobes (50% of cells) = amphophilic (purplish/grey).

Notes:
*The cellular product (i.e. hormone produced) is not strictly correlated with the cell type.<ref name=Ref_PSNP26>{{Ref PSNP|26}}</ref>
*The cells can be typed using [[IHC]]; somatotrophs (GH), lactotrophs (PRL), corticotrophs (ACTH), thyrotrophs (TSH), gonadotrophs (FSH, LH).<ref>{{Ref PBoD8|1098-9}}</ref>

====Posterior====
Features:<ref name=Ref_PSNP26>{{Ref PSNP|26}}</ref>
*Herring bodies - '''key feature'''.
**Eosinophilic axonal dilations filled with lysosomes and neurosecretory granules.
*Less cellular.
**Usually more cellular in perivascular location.
Image: [http://www.ouhsc.edu/histology/Glass%20slides/38_09.jpg Herring bodies (ouhsc.edu)].

<gallery>
File:Pituitary gland histology 2014.jpg | Pituitary gland, low magnification (WC/Athikhun.suw)
</gallery>

=DDx for sella turcica lesions=
*[[Pituitary adenoma|PitNET]].
*[[Rathke cleft cyst]].
*[[Craniopharyngioma]].
*[[Germ cell tumour]].
*[[Meningioma]].

=Pituitary necrosis=
*Rare.

===Causes of pituitary necrosis===
*Sheehan syndrome - secondary to blood loss in childbirth.<ref>URL: [http://www.mayoclinic.com/health/sheehans-syndrome/DS00889 http://www.mayoclinic.com/health/sheehans-syndrome/DS00889]. Accessed on: 16 November 2010.</ref>
*[[Syphilis]] (fetal-maternal transmission).<ref>URL: [http://pediatrics.aappublications.org/cgi/content/full/104/1/e4 http://pediatrics.aappublications.org/cgi/content/full/104/1/e4]. Accessed on: 16 November 2010.</ref>
*Mollaret's meningitis - very rare.<ref name=pmid18715308>{{cite journal |author=Dancer CM, Woods ML, Henderson RD, Robertson T, Mungomery M, Allworth A |title=Mollaret's meningitis and pituitary failure associated with a Rathke's cleft cyst |journal=Intern Med J |volume=38 |issue=7 |pages=609–11 |year=2008 |month=July |pmid=18715308 |doi=10.1111/j.1445-5994.2008.01709.x |url=}}</ref> (???)
*Spontaneous necrosis of pituitary tumours - case reports.<ref>{{cite journal |author=Sachdev Y, Evered DC, Hall R |title=Spontaneous pituitary necrosis |journal=Br Med J |volume=1 |issue=6015 |pages=942 |year=1976 |month=April |pmid=1268492 |pmc=1639254 |doi= |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1639254/pdf/brmedj00512-0028a.pdf}}</ref>

Images:
*[http://path.upmc.edu/cases/case288.html Pituitary necrosis - several images (upmc.edu)].

=Specific entities=
==Pituitary neuroendocrine tumor (PitNET)==
Old terminology '''Pituitary adenoma''' is depreceated.
The WHO 2022 Classification of tumours of endocrine organs recoginizes following tumours:<ref>{{cite journal |vauthors=Asa SL, Mete O, Perry A, Osamura RY |title=Overview of the 2022 WHO Classification of Pituitary Tumors |journal=Endocr Pathol |volume=33 |issue=1 |pages=6–26 |date=March 2022 |pmid=35291028 |doi=10.1007/s12022-022-09703-7 |url=}}</ref>

{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! PitNET lineage
! PitNET type
! subtypes
! Hormone secretion
! Transcription factor
|-
| PIT1
| Somatotroph tumor
| Densely and sparsely granulated tumor
| GH, a-subunit+/-, CK+
| PIT1
|-
| PIT1
| Lactotroph tumor
| Densely and sparsely granulated tumor
| PRL, CK-ve or weak
| PIT1, [[Estrogen receptor|ER]]
|-
| PIT1
| Mammosomatotroph tumor
|
| GH, PRL (usu. less), CK perinuclear +ve
| PIT1, [[Estrogen receptor|ER]]
|-
| PIT1
| Thyrotroph tumor
|
| TSH, CK-ve or weak
| PIT1, GATA3
|-
| PIT1
| Mature plurihormonal PIT1 lineage tumor
|
| GH, PRL, TSH, a-subunit +/-ve, CK perinuclear
| PIT1, [[Estrogen receptor|ER]], GATA3
|-
| PIT1
| Immature PIT1 lineage tumor
|
| Only focal GH, PRL, TSH, a-subunit +/-ve, CK variable
| PIT1, [[Estrogen receptor|ER]] +/-ve, GATA3 +/-ve
|-
| PIT1
| Acidophilic stem cell tumor
|
| PRL, GH (focal/variable), CK fibrous bodies
| PIT1, [[Estrogen receptor|ER]]
|-
| PIT1
| Mixed somatotroph and lactotroph tumor
|
| PRL, GH (in separate cells)
| PIT1, [[Estrogen receptor|ER]] (only in lactotroph component)
|-
| TPIT
| Corticotroph tumor
| Densely and sparsely granulated tumors, Crooke cell adenoma
| ACTH,CK+ve
| TPIT
|-
|
| Gonadotroph adenoma
| Sparsely granulated adenoma
| FSH, LH or a-Subunit
| SF1, [[Estrogen receptor|ER]], GATA2
|-
|
| Null cell adenoma
|
| None
| None
|}

Other tumours may be classified as plurhormonal or double adenomas or as adenomas with unusual IHC combination.

===General===
*Clinical:<ref>{{Ref PBoD8|1100}}</ref>
**Classically: visual field defects (bitemporal hemianopsia).
**Others (increased intracranial pressure): headache, nausea, vomiting.
**Tumor of adults.

Morphologic Classification:
#Microadenoma <= 1 cm.
#Macroadenoma 1-4 cm.
#Giant adenoma > 4cm.

May be classified by what they secrete.
#Functional (endocrine hyperfunction).
#*Acromegaly/giantism.
#*Hyperprolactinemia.
#*Cushing disease.
#*Hyperthyroidism.
#*Significant elevation of FSH/LH.
#Clinically nonfunctioning.

Notes:
''Cushing disease'' is due to pituitary gland hypersecretion of ACTH (due to a pituitary adenoma ''or'' CRH hypersecretion from the hypothalamus).<ref name=Ref_PBoD8_1148>{{Ref PBoD8|1148}}</ref> [[Cushing syndrome]] is hypercortisolism ''not'' due to pituitary gland pathology.

Imaging:
*Sellar enlargement.
*Bone erosion, invasive growth esp. cavernous sinus (35-45%).
*Inhomogenous signal in T1w MRI.

====Familial pituitary adenomas====
A pituitary adenoma may be part of a familial syndrome:<ref name=pmid19564887>{{Cite journal | last1 = Elston | first1 = MS. | last2 = McDonald | first2 = KL. | last3 = Clifton-Bligh | first3 = RJ. | last4 = Robinson | first4 = BG. | title = Familial pituitary tumor syndromes. | journal = Nat Rev Endocrinol | volume = 5 | issue = 8 | pages = 453-61 | month = Aug | year = 2009 | doi = 10.1038/nrendo.2009.126 | PMID = 19564887 }}</ref><ref name=Ref_PCPBoD8|554>{{Ref PCPBoD8|554}}</ref>
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Syndrome
! Gene
! Notes
|-
| [[Multiple endocrine neoplasia]] I
| MEN1
| characterized by the 3 Ps: '''p'''ituitary adenoma, [[parathyroid adenoma|'''p'''arathyroid adenoma]], [[pancreatic neuroendocrine tumour|'''p'''ancreatic neuroendocrine tumour]]
|-
| MEN-1-like syndrome
| CDKN1B<ref name=omim600778>{{OMIM|600778}}</ref>
| also known as ''Multiple endocrine neoplasia IV'' <ref name=omim600778>{{OMIM|600778}}</ref>
|-
| [[Carney syndrome]]
| PRKAR1A
| other findings (mnemonic ''NAME''): nevi, [[atrial myxoma]], myxoid neurofibroma, ephelides (freckles)
|-
| Isolated pituitary adenoma<ref name=pmid22612670>{{Cite journal | last1 = Korbonits | first1 = M. | last2 = Storr | first2 = H. | last3 = Kumar | first3 = AV. | title = Familial pituitary adenomas - Who should be tested for AIP mutations? | journal = Clin Endocrinol (Oxf) | volume = | issue = | pages = | month = May | year = 2012 | doi = 10.1111/j.1365-2265.2012.04445.x | PMID = 22612670 }}</ref>
| AIP
| classically GH-producing adenoma - leads to acromegaly
|}

===Microscopic===
Features:<ref name=Ref_PSNP36>{{Ref PSNP|36}}</ref>
*Loss of fibrous stroma.
**The cells of a normal (anterior) pituitary are nested.
*Basophilic cells (corticotrophs).
*Eosinophilic cells(somatotrophs).

Notes:
*Smears very well.<ref>MUN. 24 November 2010.</ref>

====Images====
<gallery>
Image:Nonfunctioning_pituitary_adenoma_%281%29.jpg | Pituitary adenoma - non-functioning. (WC/KGH)
File:HE fibrosis pituitary adenoma.jpg | Extensive interstitial and perivascular fibrosis in a pituitary adenoma (WC/jensflorian)
File:PRL HE histology.jpg | Pituitary adenoma - PRL producing, HE. Note the basophilic appearance of the cells (WC/jensflorian)
File:PRL adenoma treatment HE.jpg | Pituitary adenoma - PRL producing, HE. Extensive regressive changes after after dopamine agonist treatment (WC/jensflorian)
File:PRL IHC pituitary adenoma.jpg | Pituitary adenoma - PRL producing, Prolactin IHC (WC/jensflorian)
File:Densely granulated HGH producing adenoma.jpg | Pituitary adenoma - HGH producing, HE. The cells have a slightly eosinophilic appearance (WC/jensflorian)
File:Sparsely granulated HGH adenoma.jpg | Sparsely granulated adenoma - HGH producing. Note the numerous fibrous bodies in HE stain (WC/jensflorian)
File:HGH adenoma CK8.jpg | Sparsely granulated adenoma - HGH producing. CK8 IHC highlighting fibrous bodies (WC/jensflorian)
File:TSHoma HE.jpg | Pituitary adenoma - TSH producing. HE stain showing pleomorphism (WC/jensflorian)
File:TSHoma IHC-TSH.jpg | Pituitary adenoma - TSH producing. TSH IHC can be heterogeneous (WC/jensflorian)
Image:Pituitary_adenoma_%281%29_GH_production.jpg | Pituitary adenoma - GH producing. (WC/KGH)
File:HE-GHoma.jpg | Pituitary adenoma , HE. This gonadotropin producing adenoma has a papillary architecture (WC/jensflorian)
File:FSH-GHoma.jpg | Pituitary adenoma, IHC for FSH (WC/jensflorian)
File:LH-GHoma.jpg | Pituitary adenoma, IHC for LH (WC/jensflorian)
File:ACTHoma-PAS-O-G.jpg | Pituitary adenoma , ACTH producing. PAS-O-G stain showing basophilic adenoma cells (WC/jensflorian)
File:ACTHoma-IHC.jpg | Pituitary adenoma , ACTH producing. Strong ACTH IHC in this basophilic adenoma (WC/jensflorian)
File:Pituitary_adenoma-nonfunctioning.jpg |Pituitary adenoma with vascular pseudorosettes, nonfunctioning (WC/jensflorian)
Crooke_HE_40x.jpg | Crooke cell adenoma, HE (WC/Marvin101)
File:Crooke Cytokeratins.jpg | Crooke cell adenoma, panCK (WC/Marvin101)
HE_fibrosis_pituitary_adenoma.jpg | Fibrosis in pituitary adenoma.
</gallery>

===Stains===
*Reticulin - loss of reticulin between tumour cells.

===IHC===
*LH.
*FSH.
*TSH - [[Hyperthyroidism]]
*GH - [[Acromegaly]].
*Prolactin -Galactorrhea, Amenorrhea, Gynecomastia. Golgi staining pattern in sparsely granulated cases.
*ACTH - [[Cushing syndrome]].
*PIT-1: stains somatotrophs, lactotrophs and thyrothrops.
*TPIT: stains corticotrophs.
*SF1: stains gonadotrophs.
*Chromogranin A +ve
*Synaptophysin strongly +ve (except lactotrophs)
*CAM5.2: fibrous bodies in sparsely granulated somatotroph adenoma, Ring-like staining in Crooke cell adenoma.
*MIB-1: Usu less than 3%.

Note:
Null-cell adenoma must be hormone immunonegative and negative for transcription factors.

===Variants===
*Corticotroph adenomas exhibiting Crooke's hyaline change: agressive course.<ref>{{Cite journal | last1 = George | first1 = DH. | last2 = Scheithauer | first2 = BW. | last3 = Kovacs | first3 = K. | last4 = Horvath | first4 = E. | last5 = Young | first5 = WF. | last6 = Lloyd | first6 = RV. | last7 = Meyer | first7 = FB. | title = Crooke's cell adenoma of the pituitary: an aggressive variant of corticotroph adenoma. | journal = Am J Surg Pathol | volume = 27 | issue = 10 | pages = 1330-6 | month = Oct | year = 2003 | doi = | PMID = 14508394 }}</ref>
*Acidophilic stem cell adenomas: large, locally invasive adenoma with low GH activity. <ref>{{Cite journal | last1 = Horvath | first1 = E. | last2 = Kovacs | first2 = K. | last3 = Singer | first3 = W. | last4 = Smyth | first4 = HS. | last5 = Killinger | first5 = DW. | last6 = Erzin | first6 = C. | last7 = Weiss | first7 = MH. | title = Acidophil stem cell adenoma of the human pituitary: clinicopathologic analysis of 15 cases. | journal = Cancer | volume = 47 | issue = 4 | pages = 761-71 | month = Feb | year = 1981 | doi = | PMID = 6261917 }}</ref>
*Sparsely granulated somatotroph adenomas are more invasive than other variants and respond less to medical treatment. <ref>{{Cite journal | last1 = Kato | first1 = M. | last2 = Inoshita | first2 = N. | last3 = Sugiyama | first3 = T. | last4 = Tani | first4 = Y. | last5 = Shichiri | first5 = M. | last6 = Sano | first6 = T. | last7 = Yamada | first7 = S. | last8 = Hirata | first8 = Y. | title = Differential expression of genes related to drug responsiveness between sparsely and densely granulated somatotroph adenomas. | journal = Endocr J | volume = 59 | issue = 3 | pages = 221-8 | month = | year = 2012 | doi = | PMID = 22200580 }}</ref>
* Lactotroph adenomas in men may show aggressive clinical behavior. <ref>{{Cite journal | last1 = Delgrange | first1 = E. | last2 = Vasiljevic | first2 = A. | last3 = Wierinckx | first3 = A. | last4 = François | first4 = P. | last5 = Jouanneau | first5 = E. | last6 = Raverot | first6 = G. | last7 = Trouillas | first7 = J. | title = Expression of estrogen receptor alpha is associated with prolactin pituitary tumor prognosis and supports the sex-related difference in tumor growth. | journal = Eur J Endocrinol | volume = 172 | issue = 6 | pages = 791-801 | month = Jun | year = 2015 | doi = 10.1530/EJE-14-0990 | PMID = 25792376 }}</ref>
*Poorly differentiated PIT-1 positive adenomas may show aggresive growth. <ref> {{Cite journal | last1 = Mete | first1 = O. | last2 = Gomez-Hernandez | first2 = K. | last3 = Kucharczyk | first3 = W. | last4 = Ridout | first4 = R. | last5 = Zadeh | first5 = G. | last6 = Gentili | first6 = F. | last7 = Ezzat | first7 = S. | last8 = Asa | first8 = SL. | title = Silent subtype 3 pituitary adenomas are not always silent and represent poorly differentiated monomorphous plurihormonal Pit-1 lineage adenomas. | journal = Mod Pathol | volume = 29 | issue = 2 | pages = 131-42 | month = Feb | year = 2016 | doi = 10.1038/modpathol.2015.151 | PMID = 26743473 }}</ref>

==Pituitary blastoma==
* New entity introduced in 2017<ref>{{Cite journal | last1 = Lopes | first1 = MBS. | title = The 2017 World Health Organization classification of tumors of the pituitary gland: a summary. | journal = Acta Neuropathol | volume = 134 | issue = 4 | pages = 521-535 | month = Oct | year = 2017 | doi = 10.1007/s00401-017-1769-8 | PMID = 28821944 }}</ref>
* Epithelial glands with rosette-like formations resembling immature Rathke epithelium.
* Synaptophysin +ve, usu. ACTH+ve
* DICER1 mutations<ref>{{Cite journal | last1 = de Kock | first1 = L. | last2 = Sabbaghian | first2 = N. | last3 = Plourde | first3 = F. | last4 = Srivastava | first4 = A. | last5 = Weber | first5 = E. | last6 = Bouron-Dal Soglio | first6 = D. | last7 = Hamel | first7 = N. | last8 = Choi | first8 = JH. | last9 = Park | first9 = SH. | title = Pituitary blastoma: a pathognomonic feature of germ-line DICER1 mutations. | journal = Acta Neuropathol | volume = 128 | issue = 1 | pages = 111-22 | month = Jul | year = 2014 | doi = 10.1007/s00401-014-1285-z | PMID = 24839956 }}</ref>

==Pituitary carcinoma==
* ICD-O: 8272/3
* Requires presence of cerebrospinal or systemic metastasis.
* Very rare.
* 75% are hormonally active (mostly PRL or ACTH).
* IHC: Synaptophysin, Chromogranin +ve

==Rathke cleft cyst==
===General===
*Benign counterpart of [[craniopharyngioma]].
*Arises from intermediate lobe of pituitary gland (''pars intermedia of pituitary gland'').

Radiology:
*Typically no calcifications.<ref name=emed_rcc>URL: [http://emedicine.medscape.com/article/343629-overview http://emedicine.medscape.com/article/343629-overview]. Accessed on: 14 November 2010.</ref>

Radiologic DDx:<ref name=emed_rcc>URL: [http://emedicine.medscape.com/article/343629-overview http://emedicine.medscape.com/article/343629-overview]. Accessed on: 14 November 2010.</ref>
*Arachnoid cyst.
*[[Craniopharyngioma]].
*[[Cysticercosis]].
*[[Pituitary adenoma]].
*Epidermoid of brain.

===Microscopic===
Features:
*Lined by a layer of cuboidal ''or'' columnar epithelial with cilia.
*+/-Goblet cells.<ref>URL: [http://www.endotext.org/neuroendo/neuroendo3/neuroendo3.html http://www.endotext.org/neuroendo/neuroendo3/neuroendo3.html]. Accessed on: 27 May 2010.</ref>
*+/-Squamous metaplasia ~ may be several layers thick.
**May be confused with ''[[papillary craniopharyngioma]]''.<ref name=Ref_PSNP408>{{Ref PSNP|408}}</ref>
*Cholesterol clefts may be seen in association with rupture.<ref>URL: [http://path.upmc.edu/cases/case177/dx.html http://path.upmc.edu/cases/case177/dx.html]. Accessed on: 8 January 2012.</ref>

DDx:
*[[Papillary craniopharyngioma]].

Images:
*[http://www.endotext.org/neuroendo/neuroendo3/figures/figure11.jpg Rathke cleft cyst (endotext.org)].
*[http://path.upmc.edu/cases/case177/micro.html Rathke cleft cyst (upmc.edu)].

==Craniopharyngioma==
{{Main|Craniopharyngioma}}

==Gangliocytoma==
* Neuronal cells in abundant neuropil.
* S-100, Synaptophysin +ve.
* Isolated sellar cases are very rare.

Image: [[https://twitter.com/sty_md/status/664676241111252992]]

==Mixed Gangliocytoma-adenoma==
AKA: ganglioneuroma, pituitary adenoma with neuronal choristoma (PANCH)
*Neuronal cells mixed with pituitary adenoma cells.
* Approx. 0.25% of all pituitary adenomas.
* Association with somatotroph adenomas (acromegaly).

==Pituicytoma==
{{Main|Pituicytoma}}

==Spindle cell oncocytoma==
*Origin: Neurohypophysis or infundibulum.
*Benign clinical course - WHO grade I.
*Elongated bipolar, spindle cells.
*Fascicular or storiform growth patterns.
*EMA: patchy, S-100+/-ve, GFAP+/-ve, TTF1+ve.

*It is thought that Spindle cell oncocytomas and Granular cell tumors of the neurohypophysis are variants of Pituicyoma.<ref>{{Cite journal | last1 = Mete | first1 = O. | last2 = Lopes | first2 = MB. | last3 = Asa | first3 = SL. | title = Spindle cell oncocytomas and granular cell tumors of the pituitary are variants of pituicytoma. | journal = Am J Surg Pathol | volume = 37 | issue = 11 | pages = 1694-9 | month = Nov | year = 2013 | doi = 10.1097/PAS.0b013e31829723e7 | PMID = 23887161 }}</ref>

==Granular cell tumor of the sellar region==
{{Main|Granular_cell_tumour}}

*Origin: Neurohypophysis or infundibulum.
*Benign clinical course - WHO grade I.
*Well circumscribed.
*Polygonal cells with abundant granular cytoplasm.
*CD68+ve, S-100+/-ve, GFAP+/-ve, TTF1+ve.

<gallery>
File:Granular_cell_tumor_pituitary.jpg | Granular cell tumor of the sellar region (HE).
</gallery>

==Autoimmune hypophysitis==
===General===
Features:<ref name=pmid18388197/>
*Rare.
*Autoantigens are unknown.
*May occur in pregnancy.
*May be misdiagnosed as a nonsecreting adenoma.

===Microscopic===
Features:<ref name=pmid18388197>{{cite journal |author=Tzou SC, Lupi I, Landek M, ''et al.'' |title=Autoimmune hypophysitis of SJL mice: clinical insights from a new animal model |journal=Endocrinology |volume=149 |issue=7 |pages=3461–9 |year=2008 |month=July |pmid=18388197 |pmc=2453094 |doi=10.1210/en.2007-1692 |url=}}</ref>
*Lymphocytic infiltration.

<gallery>
File:Lymphocytic_hypophysitis_CD3.jpg | Lymphocytic hypophysitis, CD3 IHC. (WC/jensflorian)
</gallery>

=See also=
*[[CNS cytopathology]].
*[[Neuropathology]].
*[[Brain tumours]].

=References=
{{reflist|2}}

=External links=
*[http://www.neuropathologyweb.org/ Neuropathology] - neuropathologyweb.org.
*[http://www.lab.anhb.uwa.edu.au/mb140/corepages/endocrines/endocrin.htm Endocrine histology (anhb.uwa.edu.au)].

[[Category:Neuropathology]]

Pituitary adenoma

2022-09-30T10:37:59Z

Jensflorian: Update LINK

#redirect [[pituitary gland#Pituitary neuroendocrine tumor (PitNET)]]

[[Category:Diagnosis]]

Pituitary gland

2022-09-30T10:37:28Z

Jensflorian: /* DDx for sella turcica lesions */ PitNET is the new name!

The '''pituitary gland''' is known as the ''master gland''.

Divisions:<ref>[http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo.html http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo.html]</ref>
*Anterior pituitary ([[AKA]] adenohypophysis, pars distalis).
*Posterior pituitary (AKA neurohypophysis, neural pituitary, pars nervosa).

=Function=
===Anterior===
Hormones:<ref name=rcn_com>[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Pituitary.html http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Pituitary.html]</ref>
*Growth hormone (GH).
*Luteinizing hormone (LH)
*Follicle-stimulating hormone (FSH)
*Thyroid stimulating hormone (TSH)
*Adrenocorticotropic hormone (ACTH)
*Prolactin (PRL)

Mnemonic: "Go Look For The Adenoma Please" = GH, LH, FSH, TSH, ACTH, PRL.

===Intermedia===
* Originates from the posterior wall of the Rathke’s pouch.
* Hormones: MSH, ACTH precursor.
* Contains colloid cysts.

===Posterior===
Hormones:<ref name=rcn_com/>
*Oxytocin.
*Antidiuretic hormone (ADH).

=Anatomy and histology=
===Anatomy===
Basic anatomy (simplified):<ref name=bowen>URL: [http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo_pit.html http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo_pit.html]. Accessed on: 31 October 2010.</ref>
*Anterior:
**Pars distalis.
**Pars intermedia.
*Posterior:
**Pars nervosa.

Embryological origin:<ref name=bowen/>
*Anterior - Rathke's pouch (roof of mouth).
*Posterior - diencephalon (ventral aspect).

Images:
*[http://www.ouhsc.edu/histology/Glass%20slides/38_01.jpg Pituitary gland (ouhsc.edu)].
*[http://www.lab.anhb.uwa.edu.au/mb140/corepages/endocrines/Images/HypDevAni.gif Development of the pituitary - animation (anhb.uwa.edu)].

===Histology===
====Anterior====
*Acidophils (40% of cells) = red or orange.
**GH, PRL.
*Basophils (10% of cells) = basophilic (light blue).
**TSH, LH, FSH, ACTH.
*Chromophobes (50% of cells) = amphophilic (purplish/grey).

Notes:
*The cellular product (i.e. hormone produced) is not strictly correlated with the cell type.<ref name=Ref_PSNP26>{{Ref PSNP|26}}</ref>
*The cells can be typed using [[IHC]]; somatotrophs (GH), lactotrophs (PRL), corticotrophs (ACTH), thyrotrophs (TSH), gonadotrophs (FSH, LH).<ref>{{Ref PBoD8|1098-9}}</ref>

====Posterior====
Features:<ref name=Ref_PSNP26>{{Ref PSNP|26}}</ref>
*Herring bodies - '''key feature'''.
**Eosinophilic axonal dilations filled with lysosomes and neurosecretory granules.
*Less cellular.
**Usually more cellular in perivascular location.
Image: [http://www.ouhsc.edu/histology/Glass%20slides/38_09.jpg Herring bodies (ouhsc.edu)].

<gallery>
File:Pituitary gland histology 2014.jpg | Pituitary gland, low magnification (WC/Athikhun.suw)
</gallery>

=DDx for sella turcica lesions=
*[[Pituitary adenoma|PitNET]].
*[[Rathke cleft cyst]].
*[[Craniopharyngioma]].
*[[Germ cell tumour]].
*[[Meningioma]].

=Pituitary necrosis=
*Rare.

===Causes of pituitary necrosis===
*Sheehan syndrome - secondary to blood loss in childbirth.<ref>URL: [http://www.mayoclinic.com/health/sheehans-syndrome/DS00889 http://www.mayoclinic.com/health/sheehans-syndrome/DS00889]. Accessed on: 16 November 2010.</ref>
*[[Syphilis]] (fetal-maternal transmission).<ref>URL: [http://pediatrics.aappublications.org/cgi/content/full/104/1/e4 http://pediatrics.aappublications.org/cgi/content/full/104/1/e4]. Accessed on: 16 November 2010.</ref>
*Mollaret's meningitis - very rare.<ref name=pmid18715308>{{cite journal |author=Dancer CM, Woods ML, Henderson RD, Robertson T, Mungomery M, Allworth A |title=Mollaret's meningitis and pituitary failure associated with a Rathke's cleft cyst |journal=Intern Med J |volume=38 |issue=7 |pages=609–11 |year=2008 |month=July |pmid=18715308 |doi=10.1111/j.1445-5994.2008.01709.x |url=}}</ref> (???)
*Spontaneous necrosis of pituitary tumours - case reports.<ref>{{cite journal |author=Sachdev Y, Evered DC, Hall R |title=Spontaneous pituitary necrosis |journal=Br Med J |volume=1 |issue=6015 |pages=942 |year=1976 |month=April |pmid=1268492 |pmc=1639254 |doi= |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1639254/pdf/brmedj00512-0028a.pdf}}</ref>

Images:
*[http://path.upmc.edu/cases/case288.html Pituitary necrosis - several images (upmc.edu)].

=Specific entities=
==Pituitary neuroendocrine tumor (PitNET)==
Old terminology '''Pituitary adenoma''' is depreceated.
The WHO 2022 Classification of tumours of endocrine organs recoginizes following tumours:<ref>{{cite journal |vauthors=Asa SL, Mete O, Perry A, Osamura RY |title=Overview of the 2022 WHO Classification of Pituitary Tumors |journal=Endocr Pathol |volume=33 |issue=1 |pages=6–26 |date=March 2022 |pmid=35291028 |doi=10.1007/s12022-022-09703-7 |url=}}</ref>

{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! PitNET lineage
! PitNET type
! subtypes
! Hormone secretion
! Transcription factor
|-
| PIT1
| Somatotroph tumor
| Densely and sparsely granulated tumor
| GH, a-subunit+/-, CK+
| PIT1
|-
| PIT1
| Lactotroph tumor
| Densely and sparsely granulated tumor
| PRL, CK-ve or weak
| PIT1, [[Estrogen receptor|ER]]
|-
| PIT1
| Mammosomatotroph tumor
|
| GH, PRL (usu. less), CK perinuclear +ve
| PIT1, [[Estrogen receptor|ER]]
|-
| PIT1
| Thyrotroph tumor
|
| TSH, CK-ve or weak
| PIT1, GATA3
|-
| PIT1
| Mature plurihormonal PIT1 lineage tumor
|
| GH, PRL, TSH, a-subunit +/-ve, CK perinuclear
| PIT1, [[Estrogen receptor|ER]], GATA3
|-
| PIT1
| Immature PIT1 lineage tumor
|
| Only focal GH, PRL, TSH, a-subunit +/-ve, CK variable
| PIT1, [[Estrogen receptor|ER]] +/-ve, GATA3 +/-ve
|-
| PIT1
| Acidophilic stem cell tumor
|
| PRL, GH (focal/variable), CK fibrous bodies
| PIT1, [[Estrogen receptor|ER]]
|-
|
| Corticotroph adenoma
| Densely and sparsely granulated adenoma, Crooke cell adenoma
| ACTH,CAM 5.2
| TPIT
|-
|
| Gonadotroph adenoma
| Sparsely granulated adenoma
| FSH, LH or a-Subunit
| SF1, [[Estrogen receptor|ER]], GATA2
|-
|
| Null cell adenoma
|
| None
| None
|}

Other tumours may be classified as plurhormonal or double adenomas or as adenomas with unusual IHC combination.

===General===
*Clinical:<ref>{{Ref PBoD8|1100}}</ref>
**Classically: visual field defects (bitemporal hemianopsia).
**Others (increased intracranial pressure): headache, nausea, vomiting.
**Tumor of adults.

Morphologic Classification:
#Microadenoma <= 1 cm.
#Macroadenoma 1-4 cm.
#Giant adenoma > 4cm.

May be classified by what they secrete.
#Functional (endocrine hyperfunction).
#*Acromegaly/giantism.
#*Hyperprolactinemia.
#*Cushing disease.
#*Hyperthyroidism.
#*Significant elevation of FSH/LH.
#Clinically nonfunctioning.

Notes:
''Cushing disease'' is due to pituitary gland hypersecretion of ACTH (due to a pituitary adenoma ''or'' CRH hypersecretion from the hypothalamus).<ref name=Ref_PBoD8_1148>{{Ref PBoD8|1148}}</ref> [[Cushing syndrome]] is hypercortisolism ''not'' due to pituitary gland pathology.

Imaging:
*Sellar enlargement.
*Bone erosion, invasive growth esp. cavernous sinus (35-45%).
*Inhomogenous signal in T1w MRI.

====Familial pituitary adenomas====
A pituitary adenoma may be part of a familial syndrome:<ref name=pmid19564887>{{Cite journal | last1 = Elston | first1 = MS. | last2 = McDonald | first2 = KL. | last3 = Clifton-Bligh | first3 = RJ. | last4 = Robinson | first4 = BG. | title = Familial pituitary tumor syndromes. | journal = Nat Rev Endocrinol | volume = 5 | issue = 8 | pages = 453-61 | month = Aug | year = 2009 | doi = 10.1038/nrendo.2009.126 | PMID = 19564887 }}</ref><ref name=Ref_PCPBoD8|554>{{Ref PCPBoD8|554}}</ref>
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Syndrome
! Gene
! Notes
|-
| [[Multiple endocrine neoplasia]] I
| MEN1
| characterized by the 3 Ps: '''p'''ituitary adenoma, [[parathyroid adenoma|'''p'''arathyroid adenoma]], [[pancreatic neuroendocrine tumour|'''p'''ancreatic neuroendocrine tumour]]
|-
| MEN-1-like syndrome
| CDKN1B<ref name=omim600778>{{OMIM|600778}}</ref>
| also known as ''Multiple endocrine neoplasia IV'' <ref name=omim600778>{{OMIM|600778}}</ref>
|-
| [[Carney syndrome]]
| PRKAR1A
| other findings (mnemonic ''NAME''): nevi, [[atrial myxoma]], myxoid neurofibroma, ephelides (freckles)
|-
| Isolated pituitary adenoma<ref name=pmid22612670>{{Cite journal | last1 = Korbonits | first1 = M. | last2 = Storr | first2 = H. | last3 = Kumar | first3 = AV. | title = Familial pituitary adenomas - Who should be tested for AIP mutations? | journal = Clin Endocrinol (Oxf) | volume = | issue = | pages = | month = May | year = 2012 | doi = 10.1111/j.1365-2265.2012.04445.x | PMID = 22612670 }}</ref>
| AIP
| classically GH-producing adenoma - leads to acromegaly
|}

===Microscopic===
Features:<ref name=Ref_PSNP36>{{Ref PSNP|36}}</ref>
*Loss of fibrous stroma.
**The cells of a normal (anterior) pituitary are nested.
*Basophilic cells (corticotrophs).
*Eosinophilic cells(somatotrophs).

Notes:
*Smears very well.<ref>MUN. 24 November 2010.</ref>

====Images====
<gallery>
Image:Nonfunctioning_pituitary_adenoma_%281%29.jpg | Pituitary adenoma - non-functioning. (WC/KGH)
File:HE fibrosis pituitary adenoma.jpg | Extensive interstitial and perivascular fibrosis in a pituitary adenoma (WC/jensflorian)
File:PRL HE histology.jpg | Pituitary adenoma - PRL producing, HE. Note the basophilic appearance of the cells (WC/jensflorian)
File:PRL adenoma treatment HE.jpg | Pituitary adenoma - PRL producing, HE. Extensive regressive changes after after dopamine agonist treatment (WC/jensflorian)
File:PRL IHC pituitary adenoma.jpg | Pituitary adenoma - PRL producing, Prolactin IHC (WC/jensflorian)
File:Densely granulated HGH producing adenoma.jpg | Pituitary adenoma - HGH producing, HE. The cells have a slightly eosinophilic appearance (WC/jensflorian)
File:Sparsely granulated HGH adenoma.jpg | Sparsely granulated adenoma - HGH producing. Note the numerous fibrous bodies in HE stain (WC/jensflorian)
File:HGH adenoma CK8.jpg | Sparsely granulated adenoma - HGH producing. CK8 IHC highlighting fibrous bodies (WC/jensflorian)
File:TSHoma HE.jpg | Pituitary adenoma - TSH producing. HE stain showing pleomorphism (WC/jensflorian)
File:TSHoma IHC-TSH.jpg | Pituitary adenoma - TSH producing. TSH IHC can be heterogeneous (WC/jensflorian)
Image:Pituitary_adenoma_%281%29_GH_production.jpg | Pituitary adenoma - GH producing. (WC/KGH)
File:HE-GHoma.jpg | Pituitary adenoma , HE. This gonadotropin producing adenoma has a papillary architecture (WC/jensflorian)
File:FSH-GHoma.jpg | Pituitary adenoma, IHC for FSH (WC/jensflorian)
File:LH-GHoma.jpg | Pituitary adenoma, IHC for LH (WC/jensflorian)
File:ACTHoma-PAS-O-G.jpg | Pituitary adenoma , ACTH producing. PAS-O-G stain showing basophilic adenoma cells (WC/jensflorian)
File:ACTHoma-IHC.jpg | Pituitary adenoma , ACTH producing. Strong ACTH IHC in this basophilic adenoma (WC/jensflorian)
File:Pituitary_adenoma-nonfunctioning.jpg |Pituitary adenoma with vascular pseudorosettes, nonfunctioning (WC/jensflorian)
Crooke_HE_40x.jpg | Crooke cell adenoma, HE (WC/Marvin101)
File:Crooke Cytokeratins.jpg | Crooke cell adenoma, panCK (WC/Marvin101)
HE_fibrosis_pituitary_adenoma.jpg | Fibrosis in pituitary adenoma.
</gallery>

===Stains===
*Reticulin - loss of reticulin between tumour cells.

===IHC===
*LH.
*FSH.
*TSH - [[Hyperthyroidism]]
*GH - [[Acromegaly]].
*Prolactin -Galactorrhea, Amenorrhea, Gynecomastia. Golgi staining pattern in sparsely granulated cases.
*ACTH - [[Cushing syndrome]].
*PIT-1: stains somatotrophs, lactotrophs and thyrothrops.
*TPIT: stains corticotrophs.
*SF1: stains gonadotrophs.
*Chromogranin A +ve
*Synaptophysin strongly +ve (except lactotrophs)
*CAM5.2: fibrous bodies in sparsely granulated somatotroph adenoma, Ring-like staining in Crooke cell adenoma.
*MIB-1: Usu less than 3%.

Note:
Null-cell adenoma must be hormone immunonegative and negative for transcription factors.

===Variants===
*Corticotroph adenomas exhibiting Crooke's hyaline change: agressive course.<ref>{{Cite journal | last1 = George | first1 = DH. | last2 = Scheithauer | first2 = BW. | last3 = Kovacs | first3 = K. | last4 = Horvath | first4 = E. | last5 = Young | first5 = WF. | last6 = Lloyd | first6 = RV. | last7 = Meyer | first7 = FB. | title = Crooke's cell adenoma of the pituitary: an aggressive variant of corticotroph adenoma. | journal = Am J Surg Pathol | volume = 27 | issue = 10 | pages = 1330-6 | month = Oct | year = 2003 | doi = | PMID = 14508394 }}</ref>
*Acidophilic stem cell adenomas: large, locally invasive adenoma with low GH activity. <ref>{{Cite journal | last1 = Horvath | first1 = E. | last2 = Kovacs | first2 = K. | last3 = Singer | first3 = W. | last4 = Smyth | first4 = HS. | last5 = Killinger | first5 = DW. | last6 = Erzin | first6 = C. | last7 = Weiss | first7 = MH. | title = Acidophil stem cell adenoma of the human pituitary: clinicopathologic analysis of 15 cases. | journal = Cancer | volume = 47 | issue = 4 | pages = 761-71 | month = Feb | year = 1981 | doi = | PMID = 6261917 }}</ref>
*Sparsely granulated somatotroph adenomas are more invasive than other variants and respond less to medical treatment. <ref>{{Cite journal | last1 = Kato | first1 = M. | last2 = Inoshita | first2 = N. | last3 = Sugiyama | first3 = T. | last4 = Tani | first4 = Y. | last5 = Shichiri | first5 = M. | last6 = Sano | first6 = T. | last7 = Yamada | first7 = S. | last8 = Hirata | first8 = Y. | title = Differential expression of genes related to drug responsiveness between sparsely and densely granulated somatotroph adenomas. | journal = Endocr J | volume = 59 | issue = 3 | pages = 221-8 | month = | year = 2012 | doi = | PMID = 22200580 }}</ref>
* Lactotroph adenomas in men may show aggressive clinical behavior. <ref>{{Cite journal | last1 = Delgrange | first1 = E. | last2 = Vasiljevic | first2 = A. | last3 = Wierinckx | first3 = A. | last4 = François | first4 = P. | last5 = Jouanneau | first5 = E. | last6 = Raverot | first6 = G. | last7 = Trouillas | first7 = J. | title = Expression of estrogen receptor alpha is associated with prolactin pituitary tumor prognosis and supports the sex-related difference in tumor growth. | journal = Eur J Endocrinol | volume = 172 | issue = 6 | pages = 791-801 | month = Jun | year = 2015 | doi = 10.1530/EJE-14-0990 | PMID = 25792376 }}</ref>
*Poorly differentiated PIT-1 positive adenomas may show aggresive growth. <ref> {{Cite journal | last1 = Mete | first1 = O. | last2 = Gomez-Hernandez | first2 = K. | last3 = Kucharczyk | first3 = W. | last4 = Ridout | first4 = R. | last5 = Zadeh | first5 = G. | last6 = Gentili | first6 = F. | last7 = Ezzat | first7 = S. | last8 = Asa | first8 = SL. | title = Silent subtype 3 pituitary adenomas are not always silent and represent poorly differentiated monomorphous plurihormonal Pit-1 lineage adenomas. | journal = Mod Pathol | volume = 29 | issue = 2 | pages = 131-42 | month = Feb | year = 2016 | doi = 10.1038/modpathol.2015.151 | PMID = 26743473 }}</ref>

==Pituitary blastoma==
* New entity introduced in 2017<ref>{{Cite journal | last1 = Lopes | first1 = MBS. | title = The 2017 World Health Organization classification of tumors of the pituitary gland: a summary. | journal = Acta Neuropathol | volume = 134 | issue = 4 | pages = 521-535 | month = Oct | year = 2017 | doi = 10.1007/s00401-017-1769-8 | PMID = 28821944 }}</ref>
* Epithelial glands with rosette-like formations resembling immature Rathke epithelium.
* Synaptophysin +ve, usu. ACTH+ve
* DICER1 mutations<ref>{{Cite journal | last1 = de Kock | first1 = L. | last2 = Sabbaghian | first2 = N. | last3 = Plourde | first3 = F. | last4 = Srivastava | first4 = A. | last5 = Weber | first5 = E. | last6 = Bouron-Dal Soglio | first6 = D. | last7 = Hamel | first7 = N. | last8 = Choi | first8 = JH. | last9 = Park | first9 = SH. | title = Pituitary blastoma: a pathognomonic feature of germ-line DICER1 mutations. | journal = Acta Neuropathol | volume = 128 | issue = 1 | pages = 111-22 | month = Jul | year = 2014 | doi = 10.1007/s00401-014-1285-z | PMID = 24839956 }}</ref>

==Pituitary carcinoma==
* ICD-O: 8272/3
* Requires presence of cerebrospinal or systemic metastasis.
* Very rare.
* 75% are hormonally active (mostly PRL or ACTH).
* IHC: Synaptophysin, Chromogranin +ve

==Rathke cleft cyst==
===General===
*Benign counterpart of [[craniopharyngioma]].
*Arises from intermediate lobe of pituitary gland (''pars intermedia of pituitary gland'').

Radiology:
*Typically no calcifications.<ref name=emed_rcc>URL: [http://emedicine.medscape.com/article/343629-overview http://emedicine.medscape.com/article/343629-overview]. Accessed on: 14 November 2010.</ref>

Radiologic DDx:<ref name=emed_rcc>URL: [http://emedicine.medscape.com/article/343629-overview http://emedicine.medscape.com/article/343629-overview]. Accessed on: 14 November 2010.</ref>
*Arachnoid cyst.
*[[Craniopharyngioma]].
*[[Cysticercosis]].
*[[Pituitary adenoma]].
*Epidermoid of brain.

===Microscopic===
Features:
*Lined by a layer of cuboidal ''or'' columnar epithelial with cilia.
*+/-Goblet cells.<ref>URL: [http://www.endotext.org/neuroendo/neuroendo3/neuroendo3.html http://www.endotext.org/neuroendo/neuroendo3/neuroendo3.html]. Accessed on: 27 May 2010.</ref>
*+/-Squamous metaplasia ~ may be several layers thick.
**May be confused with ''[[papillary craniopharyngioma]]''.<ref name=Ref_PSNP408>{{Ref PSNP|408}}</ref>
*Cholesterol clefts may be seen in association with rupture.<ref>URL: [http://path.upmc.edu/cases/case177/dx.html http://path.upmc.edu/cases/case177/dx.html]. Accessed on: 8 January 2012.</ref>

DDx:
*[[Papillary craniopharyngioma]].

Images:
*[http://www.endotext.org/neuroendo/neuroendo3/figures/figure11.jpg Rathke cleft cyst (endotext.org)].
*[http://path.upmc.edu/cases/case177/micro.html Rathke cleft cyst (upmc.edu)].

==Craniopharyngioma==
{{Main|Craniopharyngioma}}

==Gangliocytoma==
* Neuronal cells in abundant neuropil.
* S-100, Synaptophysin +ve.
* Isolated sellar cases are very rare.

Image: [[https://twitter.com/sty_md/status/664676241111252992]]

==Mixed Gangliocytoma-adenoma==
AKA: ganglioneuroma, pituitary adenoma with neuronal choristoma (PANCH)
*Neuronal cells mixed with pituitary adenoma cells.
* Approx. 0.25% of all pituitary adenomas.
* Association with somatotroph adenomas (acromegaly).

==Pituicytoma==
{{Main|Pituicytoma}}

==Spindle cell oncocytoma==
*Origin: Neurohypophysis or infundibulum.
*Benign clinical course - WHO grade I.
*Elongated bipolar, spindle cells.
*Fascicular or storiform growth patterns.
*EMA: patchy, S-100+/-ve, GFAP+/-ve, TTF1+ve.

*It is thought that Spindle cell oncocytomas and Granular cell tumors of the neurohypophysis are variants of Pituicyoma.<ref>{{Cite journal | last1 = Mete | first1 = O. | last2 = Lopes | first2 = MB. | last3 = Asa | first3 = SL. | title = Spindle cell oncocytomas and granular cell tumors of the pituitary are variants of pituicytoma. | journal = Am J Surg Pathol | volume = 37 | issue = 11 | pages = 1694-9 | month = Nov | year = 2013 | doi = 10.1097/PAS.0b013e31829723e7 | PMID = 23887161 }}</ref>

==Granular cell tumor of the sellar region==
{{Main|Granular_cell_tumour}}

*Origin: Neurohypophysis or infundibulum.
*Benign clinical course - WHO grade I.
*Well circumscribed.
*Polygonal cells with abundant granular cytoplasm.
*CD68+ve, S-100+/-ve, GFAP+/-ve, TTF1+ve.

<gallery>
File:Granular_cell_tumor_pituitary.jpg | Granular cell tumor of the sellar region (HE).
</gallery>

==Autoimmune hypophysitis==
===General===
Features:<ref name=pmid18388197/>
*Rare.
*Autoantigens are unknown.
*May occur in pregnancy.
*May be misdiagnosed as a nonsecreting adenoma.

===Microscopic===
Features:<ref name=pmid18388197>{{cite journal |author=Tzou SC, Lupi I, Landek M, ''et al.'' |title=Autoimmune hypophysitis of SJL mice: clinical insights from a new animal model |journal=Endocrinology |volume=149 |issue=7 |pages=3461–9 |year=2008 |month=July |pmid=18388197 |pmc=2453094 |doi=10.1210/en.2007-1692 |url=}}</ref>
*Lymphocytic infiltration.

<gallery>
File:Lymphocytic_hypophysitis_CD3.jpg | Lymphocytic hypophysitis, CD3 IHC. (WC/jensflorian)
</gallery>

=See also=
*[[CNS cytopathology]].
*[[Neuropathology]].
*[[Brain tumours]].

=References=
{{reflist|2}}

=External links=
*[http://www.neuropathologyweb.org/ Neuropathology] - neuropathologyweb.org.
*[http://www.lab.anhb.uwa.edu.au/mb140/corepages/endocrines/endocrin.htm Endocrine histology (anhb.uwa.edu.au)].

[[Category:Neuropathology]]

Pituitary gland

2022-09-30T10:29:30Z

Jensflorian: /* Pituitary neuroendocrine tumor (PitNET) */ Update

The '''pituitary gland''' is known as the ''master gland''.

Divisions:<ref>[http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo.html http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo.html]</ref>
*Anterior pituitary ([[AKA]] adenohypophysis, pars distalis).
*Posterior pituitary (AKA neurohypophysis, neural pituitary, pars nervosa).

=Function=
===Anterior===
Hormones:<ref name=rcn_com>[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Pituitary.html http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Pituitary.html]</ref>
*Growth hormone (GH).
*Luteinizing hormone (LH)
*Follicle-stimulating hormone (FSH)
*Thyroid stimulating hormone (TSH)
*Adrenocorticotropic hormone (ACTH)
*Prolactin (PRL)

Mnemonic: "Go Look For The Adenoma Please" = GH, LH, FSH, TSH, ACTH, PRL.

===Intermedia===
* Originates from the posterior wall of the Rathke’s pouch.
* Hormones: MSH, ACTH precursor.
* Contains colloid cysts.

===Posterior===
Hormones:<ref name=rcn_com/>
*Oxytocin.
*Antidiuretic hormone (ADH).

=Anatomy and histology=
===Anatomy===
Basic anatomy (simplified):<ref name=bowen>URL: [http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo_pit.html http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo_pit.html]. Accessed on: 31 October 2010.</ref>
*Anterior:
**Pars distalis.
**Pars intermedia.
*Posterior:
**Pars nervosa.

Embryological origin:<ref name=bowen/>
*Anterior - Rathke's pouch (roof of mouth).
*Posterior - diencephalon (ventral aspect).

Images:
*[http://www.ouhsc.edu/histology/Glass%20slides/38_01.jpg Pituitary gland (ouhsc.edu)].
*[http://www.lab.anhb.uwa.edu.au/mb140/corepages/endocrines/Images/HypDevAni.gif Development of the pituitary - animation (anhb.uwa.edu)].

===Histology===
====Anterior====
*Acidophils (40% of cells) = red or orange.
**GH, PRL.
*Basophils (10% of cells) = basophilic (light blue).
**TSH, LH, FSH, ACTH.
*Chromophobes (50% of cells) = amphophilic (purplish/grey).

Notes:
*The cellular product (i.e. hormone produced) is not strictly correlated with the cell type.<ref name=Ref_PSNP26>{{Ref PSNP|26}}</ref>
*The cells can be typed using [[IHC]]; somatotrophs (GH), lactotrophs (PRL), corticotrophs (ACTH), thyrotrophs (TSH), gonadotrophs (FSH, LH).<ref>{{Ref PBoD8|1098-9}}</ref>

====Posterior====
Features:<ref name=Ref_PSNP26>{{Ref PSNP|26}}</ref>
*Herring bodies - '''key feature'''.
**Eosinophilic axonal dilations filled with lysosomes and neurosecretory granules.
*Less cellular.
**Usually more cellular in perivascular location.
Image: [http://www.ouhsc.edu/histology/Glass%20slides/38_09.jpg Herring bodies (ouhsc.edu)].

<gallery>
File:Pituitary gland histology 2014.jpg | Pituitary gland, low magnification (WC/Athikhun.suw)
</gallery>

=DDx for sella turcica lesions=
*[[Pituitary adenoma]].
*[[Rathke cleft cyst]].
*[[Craniopharyngioma]].
*[[Germ cell tumour]].
*[[Meningioma]].

=Pituitary necrosis=
*Rare.

===Causes of pituitary necrosis===
*Sheehan syndrome - secondary to blood loss in childbirth.<ref>URL: [http://www.mayoclinic.com/health/sheehans-syndrome/DS00889 http://www.mayoclinic.com/health/sheehans-syndrome/DS00889]. Accessed on: 16 November 2010.</ref>
*[[Syphilis]] (fetal-maternal transmission).<ref>URL: [http://pediatrics.aappublications.org/cgi/content/full/104/1/e4 http://pediatrics.aappublications.org/cgi/content/full/104/1/e4]. Accessed on: 16 November 2010.</ref>
*Mollaret's meningitis - very rare.<ref name=pmid18715308>{{cite journal |author=Dancer CM, Woods ML, Henderson RD, Robertson T, Mungomery M, Allworth A |title=Mollaret's meningitis and pituitary failure associated with a Rathke's cleft cyst |journal=Intern Med J |volume=38 |issue=7 |pages=609–11 |year=2008 |month=July |pmid=18715308 |doi=10.1111/j.1445-5994.2008.01709.x |url=}}</ref> (???)
*Spontaneous necrosis of pituitary tumours - case reports.<ref>{{cite journal |author=Sachdev Y, Evered DC, Hall R |title=Spontaneous pituitary necrosis |journal=Br Med J |volume=1 |issue=6015 |pages=942 |year=1976 |month=April |pmid=1268492 |pmc=1639254 |doi= |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1639254/pdf/brmedj00512-0028a.pdf}}</ref>

Images:
*[http://path.upmc.edu/cases/case288.html Pituitary necrosis - several images (upmc.edu)].

=Specific entities=
==Pituitary neuroendocrine tumor (PitNET)==
Old terminology '''Pituitary adenoma''' is depreceated.
The WHO 2022 Classification of tumours of endocrine organs recoginizes following tumours:<ref>{{cite journal |vauthors=Asa SL, Mete O, Perry A, Osamura RY |title=Overview of the 2022 WHO Classification of Pituitary Tumors |journal=Endocr Pathol |volume=33 |issue=1 |pages=6–26 |date=March 2022 |pmid=35291028 |doi=10.1007/s12022-022-09703-7 |url=}}</ref>

{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! PitNET lineage
! PitNET type
! subtypes
! Hormone secretion
! Transcription factor
|-
| PIT1
| Somatotroph tumor
| Densely and sparsely granulated tumor
| GH, a-subunit+/-, CK+
| PIT1
|-
| PIT1
| Lactotroph tumor
| Densely and sparsely granulated tumor
| PRL, CK-ve or weak
| PIT1, [[Estrogen receptor|ER]]
|-
| PIT1
| Mammosomatotroph tumor
|
| GH, PRL (usu. less), CK perinuclear +ve
| PIT1, [[Estrogen receptor|ER]]
|-
| PIT1
| Thyrotroph tumor
|
| TSH, CK-ve or weak
| PIT1, GATA3
|-
| PIT1
| Mature plurihormonal PIT1 lineage tumor
|
| GH, PRL, TSH, a-subunit +/-ve, CK perinuclear
| PIT1, [[Estrogen receptor|ER]], GATA3
|-
| PIT1
| Immature PIT1 lineage tumor
|
| Only focal GH, PRL, TSH, a-subunit +/-ve, CK variable
| PIT1, [[Estrogen receptor|ER]] +/-ve, GATA3 +/-ve
|-
| PIT1
| Acidophilic stem cell tumor
|
| PRL, GH (focal/variable), CK fibrous bodies
| PIT1, [[Estrogen receptor|ER]]
|-
|
| Corticotroph adenoma
| Densely and sparsely granulated adenoma, Crooke cell adenoma
| ACTH,CAM 5.2
| TPIT
|-
|
| Gonadotroph adenoma
| Sparsely granulated adenoma
| FSH, LH or a-Subunit
| SF1, [[Estrogen receptor|ER]], GATA2
|-
|
| Null cell adenoma
|
| None
| None
|}

Other tumours may be classified as plurhormonal or double adenomas or as adenomas with unusual IHC combination.

===General===
*Clinical:<ref>{{Ref PBoD8|1100}}</ref>
**Classically: visual field defects (bitemporal hemianopsia).
**Others (increased intracranial pressure): headache, nausea, vomiting.
**Tumor of adults.

Morphologic Classification:
#Microadenoma <= 1 cm.
#Macroadenoma 1-4 cm.
#Giant adenoma > 4cm.

May be classified by what they secrete.
#Functional (endocrine hyperfunction).
#*Acromegaly/giantism.
#*Hyperprolactinemia.
#*Cushing disease.
#*Hyperthyroidism.
#*Significant elevation of FSH/LH.
#Clinically nonfunctioning.

Notes:
''Cushing disease'' is due to pituitary gland hypersecretion of ACTH (due to a pituitary adenoma ''or'' CRH hypersecretion from the hypothalamus).<ref name=Ref_PBoD8_1148>{{Ref PBoD8|1148}}</ref> [[Cushing syndrome]] is hypercortisolism ''not'' due to pituitary gland pathology.

Imaging:
*Sellar enlargement.
*Bone erosion, invasive growth esp. cavernous sinus (35-45%).
*Inhomogenous signal in T1w MRI.

====Familial pituitary adenomas====
A pituitary adenoma may be part of a familial syndrome:<ref name=pmid19564887>{{Cite journal | last1 = Elston | first1 = MS. | last2 = McDonald | first2 = KL. | last3 = Clifton-Bligh | first3 = RJ. | last4 = Robinson | first4 = BG. | title = Familial pituitary tumor syndromes. | journal = Nat Rev Endocrinol | volume = 5 | issue = 8 | pages = 453-61 | month = Aug | year = 2009 | doi = 10.1038/nrendo.2009.126 | PMID = 19564887 }}</ref><ref name=Ref_PCPBoD8|554>{{Ref PCPBoD8|554}}</ref>
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Syndrome
! Gene
! Notes
|-
| [[Multiple endocrine neoplasia]] I
| MEN1
| characterized by the 3 Ps: '''p'''ituitary adenoma, [[parathyroid adenoma|'''p'''arathyroid adenoma]], [[pancreatic neuroendocrine tumour|'''p'''ancreatic neuroendocrine tumour]]
|-
| MEN-1-like syndrome
| CDKN1B<ref name=omim600778>{{OMIM|600778}}</ref>
| also known as ''Multiple endocrine neoplasia IV'' <ref name=omim600778>{{OMIM|600778}}</ref>
|-
| [[Carney syndrome]]
| PRKAR1A
| other findings (mnemonic ''NAME''): nevi, [[atrial myxoma]], myxoid neurofibroma, ephelides (freckles)
|-
| Isolated pituitary adenoma<ref name=pmid22612670>{{Cite journal | last1 = Korbonits | first1 = M. | last2 = Storr | first2 = H. | last3 = Kumar | first3 = AV. | title = Familial pituitary adenomas - Who should be tested for AIP mutations? | journal = Clin Endocrinol (Oxf) | volume = | issue = | pages = | month = May | year = 2012 | doi = 10.1111/j.1365-2265.2012.04445.x | PMID = 22612670 }}</ref>
| AIP
| classically GH-producing adenoma - leads to acromegaly
|}

===Microscopic===
Features:<ref name=Ref_PSNP36>{{Ref PSNP|36}}</ref>
*Loss of fibrous stroma.
**The cells of a normal (anterior) pituitary are nested.
*Basophilic cells (corticotrophs).
*Eosinophilic cells(somatotrophs).

Notes:
*Smears very well.<ref>MUN. 24 November 2010.</ref>

====Images====
<gallery>
Image:Nonfunctioning_pituitary_adenoma_%281%29.jpg | Pituitary adenoma - non-functioning. (WC/KGH)
File:HE fibrosis pituitary adenoma.jpg | Extensive interstitial and perivascular fibrosis in a pituitary adenoma (WC/jensflorian)
File:PRL HE histology.jpg | Pituitary adenoma - PRL producing, HE. Note the basophilic appearance of the cells (WC/jensflorian)
File:PRL adenoma treatment HE.jpg | Pituitary adenoma - PRL producing, HE. Extensive regressive changes after after dopamine agonist treatment (WC/jensflorian)
File:PRL IHC pituitary adenoma.jpg | Pituitary adenoma - PRL producing, Prolactin IHC (WC/jensflorian)
File:Densely granulated HGH producing adenoma.jpg | Pituitary adenoma - HGH producing, HE. The cells have a slightly eosinophilic appearance (WC/jensflorian)
File:Sparsely granulated HGH adenoma.jpg | Sparsely granulated adenoma - HGH producing. Note the numerous fibrous bodies in HE stain (WC/jensflorian)
File:HGH adenoma CK8.jpg | Sparsely granulated adenoma - HGH producing. CK8 IHC highlighting fibrous bodies (WC/jensflorian)
File:TSHoma HE.jpg | Pituitary adenoma - TSH producing. HE stain showing pleomorphism (WC/jensflorian)
File:TSHoma IHC-TSH.jpg | Pituitary adenoma - TSH producing. TSH IHC can be heterogeneous (WC/jensflorian)
Image:Pituitary_adenoma_%281%29_GH_production.jpg | Pituitary adenoma - GH producing. (WC/KGH)
File:HE-GHoma.jpg | Pituitary adenoma , HE. This gonadotropin producing adenoma has a papillary architecture (WC/jensflorian)
File:FSH-GHoma.jpg | Pituitary adenoma, IHC for FSH (WC/jensflorian)
File:LH-GHoma.jpg | Pituitary adenoma, IHC for LH (WC/jensflorian)
File:ACTHoma-PAS-O-G.jpg | Pituitary adenoma , ACTH producing. PAS-O-G stain showing basophilic adenoma cells (WC/jensflorian)
File:ACTHoma-IHC.jpg | Pituitary adenoma , ACTH producing. Strong ACTH IHC in this basophilic adenoma (WC/jensflorian)
File:Pituitary_adenoma-nonfunctioning.jpg |Pituitary adenoma with vascular pseudorosettes, nonfunctioning (WC/jensflorian)
Crooke_HE_40x.jpg | Crooke cell adenoma, HE (WC/Marvin101)
File:Crooke Cytokeratins.jpg | Crooke cell adenoma, panCK (WC/Marvin101)
HE_fibrosis_pituitary_adenoma.jpg | Fibrosis in pituitary adenoma.
</gallery>

===Stains===
*Reticulin - loss of reticulin between tumour cells.

===IHC===
*LH.
*FSH.
*TSH - [[Hyperthyroidism]]
*GH - [[Acromegaly]].
*Prolactin -Galactorrhea, Amenorrhea, Gynecomastia. Golgi staining pattern in sparsely granulated cases.
*ACTH - [[Cushing syndrome]].
*PIT-1: stains somatotrophs, lactotrophs and thyrothrops.
*TPIT: stains corticotrophs.
*SF1: stains gonadotrophs.
*Chromogranin A +ve
*Synaptophysin strongly +ve (except lactotrophs)
*CAM5.2: fibrous bodies in sparsely granulated somatotroph adenoma, Ring-like staining in Crooke cell adenoma.
*MIB-1: Usu less than 3%.

Note:
Null-cell adenoma must be hormone immunonegative and negative for transcription factors.

===Variants===
*Corticotroph adenomas exhibiting Crooke's hyaline change: agressive course.<ref>{{Cite journal | last1 = George | first1 = DH. | last2 = Scheithauer | first2 = BW. | last3 = Kovacs | first3 = K. | last4 = Horvath | first4 = E. | last5 = Young | first5 = WF. | last6 = Lloyd | first6 = RV. | last7 = Meyer | first7 = FB. | title = Crooke's cell adenoma of the pituitary: an aggressive variant of corticotroph adenoma. | journal = Am J Surg Pathol | volume = 27 | issue = 10 | pages = 1330-6 | month = Oct | year = 2003 | doi = | PMID = 14508394 }}</ref>
*Acidophilic stem cell adenomas: large, locally invasive adenoma with low GH activity. <ref>{{Cite journal | last1 = Horvath | first1 = E. | last2 = Kovacs | first2 = K. | last3 = Singer | first3 = W. | last4 = Smyth | first4 = HS. | last5 = Killinger | first5 = DW. | last6 = Erzin | first6 = C. | last7 = Weiss | first7 = MH. | title = Acidophil stem cell adenoma of the human pituitary: clinicopathologic analysis of 15 cases. | journal = Cancer | volume = 47 | issue = 4 | pages = 761-71 | month = Feb | year = 1981 | doi = | PMID = 6261917 }}</ref>
*Sparsely granulated somatotroph adenomas are more invasive than other variants and respond less to medical treatment. <ref>{{Cite journal | last1 = Kato | first1 = M. | last2 = Inoshita | first2 = N. | last3 = Sugiyama | first3 = T. | last4 = Tani | first4 = Y. | last5 = Shichiri | first5 = M. | last6 = Sano | first6 = T. | last7 = Yamada | first7 = S. | last8 = Hirata | first8 = Y. | title = Differential expression of genes related to drug responsiveness between sparsely and densely granulated somatotroph adenomas. | journal = Endocr J | volume = 59 | issue = 3 | pages = 221-8 | month = | year = 2012 | doi = | PMID = 22200580 }}</ref>
* Lactotroph adenomas in men may show aggressive clinical behavior. <ref>{{Cite journal | last1 = Delgrange | first1 = E. | last2 = Vasiljevic | first2 = A. | last3 = Wierinckx | first3 = A. | last4 = François | first4 = P. | last5 = Jouanneau | first5 = E. | last6 = Raverot | first6 = G. | last7 = Trouillas | first7 = J. | title = Expression of estrogen receptor alpha is associated with prolactin pituitary tumor prognosis and supports the sex-related difference in tumor growth. | journal = Eur J Endocrinol | volume = 172 | issue = 6 | pages = 791-801 | month = Jun | year = 2015 | doi = 10.1530/EJE-14-0990 | PMID = 25792376 }}</ref>
*Poorly differentiated PIT-1 positive adenomas may show aggresive growth. <ref> {{Cite journal | last1 = Mete | first1 = O. | last2 = Gomez-Hernandez | first2 = K. | last3 = Kucharczyk | first3 = W. | last4 = Ridout | first4 = R. | last5 = Zadeh | first5 = G. | last6 = Gentili | first6 = F. | last7 = Ezzat | first7 = S. | last8 = Asa | first8 = SL. | title = Silent subtype 3 pituitary adenomas are not always silent and represent poorly differentiated monomorphous plurihormonal Pit-1 lineage adenomas. | journal = Mod Pathol | volume = 29 | issue = 2 | pages = 131-42 | month = Feb | year = 2016 | doi = 10.1038/modpathol.2015.151 | PMID = 26743473 }}</ref>

==Pituitary blastoma==
* New entity introduced in 2017<ref>{{Cite journal | last1 = Lopes | first1 = MBS. | title = The 2017 World Health Organization classification of tumors of the pituitary gland: a summary. | journal = Acta Neuropathol | volume = 134 | issue = 4 | pages = 521-535 | month = Oct | year = 2017 | doi = 10.1007/s00401-017-1769-8 | PMID = 28821944 }}</ref>
* Epithelial glands with rosette-like formations resembling immature Rathke epithelium.
* Synaptophysin +ve, usu. ACTH+ve
* DICER1 mutations<ref>{{Cite journal | last1 = de Kock | first1 = L. | last2 = Sabbaghian | first2 = N. | last3 = Plourde | first3 = F. | last4 = Srivastava | first4 = A. | last5 = Weber | first5 = E. | last6 = Bouron-Dal Soglio | first6 = D. | last7 = Hamel | first7 = N. | last8 = Choi | first8 = JH. | last9 = Park | first9 = SH. | title = Pituitary blastoma: a pathognomonic feature of germ-line DICER1 mutations. | journal = Acta Neuropathol | volume = 128 | issue = 1 | pages = 111-22 | month = Jul | year = 2014 | doi = 10.1007/s00401-014-1285-z | PMID = 24839956 }}</ref>

==Pituitary carcinoma==
* ICD-O: 8272/3
* Requires presence of cerebrospinal or systemic metastasis.
* Very rare.
* 75% are hormonally active (mostly PRL or ACTH).
* IHC: Synaptophysin, Chromogranin +ve

==Rathke cleft cyst==
===General===
*Benign counterpart of [[craniopharyngioma]].
*Arises from intermediate lobe of pituitary gland (''pars intermedia of pituitary gland'').

Radiology:
*Typically no calcifications.<ref name=emed_rcc>URL: [http://emedicine.medscape.com/article/343629-overview http://emedicine.medscape.com/article/343629-overview]. Accessed on: 14 November 2010.</ref>

Radiologic DDx:<ref name=emed_rcc>URL: [http://emedicine.medscape.com/article/343629-overview http://emedicine.medscape.com/article/343629-overview]. Accessed on: 14 November 2010.</ref>
*Arachnoid cyst.
*[[Craniopharyngioma]].
*[[Cysticercosis]].
*[[Pituitary adenoma]].
*Epidermoid of brain.

===Microscopic===
Features:
*Lined by a layer of cuboidal ''or'' columnar epithelial with cilia.
*+/-Goblet cells.<ref>URL: [http://www.endotext.org/neuroendo/neuroendo3/neuroendo3.html http://www.endotext.org/neuroendo/neuroendo3/neuroendo3.html]. Accessed on: 27 May 2010.</ref>
*+/-Squamous metaplasia ~ may be several layers thick.
**May be confused with ''[[papillary craniopharyngioma]]''.<ref name=Ref_PSNP408>{{Ref PSNP|408}}</ref>
*Cholesterol clefts may be seen in association with rupture.<ref>URL: [http://path.upmc.edu/cases/case177/dx.html http://path.upmc.edu/cases/case177/dx.html]. Accessed on: 8 January 2012.</ref>

DDx:
*[[Papillary craniopharyngioma]].

Images:
*[http://www.endotext.org/neuroendo/neuroendo3/figures/figure11.jpg Rathke cleft cyst (endotext.org)].
*[http://path.upmc.edu/cases/case177/micro.html Rathke cleft cyst (upmc.edu)].

==Craniopharyngioma==
{{Main|Craniopharyngioma}}

==Gangliocytoma==
* Neuronal cells in abundant neuropil.
* S-100, Synaptophysin +ve.
* Isolated sellar cases are very rare.

Image: [[https://twitter.com/sty_md/status/664676241111252992]]

==Mixed Gangliocytoma-adenoma==
AKA: ganglioneuroma, pituitary adenoma with neuronal choristoma (PANCH)
*Neuronal cells mixed with pituitary adenoma cells.
* Approx. 0.25% of all pituitary adenomas.
* Association with somatotroph adenomas (acromegaly).

==Pituicytoma==
{{Main|Pituicytoma}}

==Spindle cell oncocytoma==
*Origin: Neurohypophysis or infundibulum.
*Benign clinical course - WHO grade I.
*Elongated bipolar, spindle cells.
*Fascicular or storiform growth patterns.
*EMA: patchy, S-100+/-ve, GFAP+/-ve, TTF1+ve.

*It is thought that Spindle cell oncocytomas and Granular cell tumors of the neurohypophysis are variants of Pituicyoma.<ref>{{Cite journal | last1 = Mete | first1 = O. | last2 = Lopes | first2 = MB. | last3 = Asa | first3 = SL. | title = Spindle cell oncocytomas and granular cell tumors of the pituitary are variants of pituicytoma. | journal = Am J Surg Pathol | volume = 37 | issue = 11 | pages = 1694-9 | month = Nov | year = 2013 | doi = 10.1097/PAS.0b013e31829723e7 | PMID = 23887161 }}</ref>

==Granular cell tumor of the sellar region==
{{Main|Granular_cell_tumour}}

*Origin: Neurohypophysis or infundibulum.
*Benign clinical course - WHO grade I.
*Well circumscribed.
*Polygonal cells with abundant granular cytoplasm.
*CD68+ve, S-100+/-ve, GFAP+/-ve, TTF1+ve.

<gallery>
File:Granular_cell_tumor_pituitary.jpg | Granular cell tumor of the sellar region (HE).
</gallery>

==Autoimmune hypophysitis==
===General===
Features:<ref name=pmid18388197/>
*Rare.
*Autoantigens are unknown.
*May occur in pregnancy.
*May be misdiagnosed as a nonsecreting adenoma.

===Microscopic===
Features:<ref name=pmid18388197>{{cite journal |author=Tzou SC, Lupi I, Landek M, ''et al.'' |title=Autoimmune hypophysitis of SJL mice: clinical insights from a new animal model |journal=Endocrinology |volume=149 |issue=7 |pages=3461–9 |year=2008 |month=July |pmid=18388197 |pmc=2453094 |doi=10.1210/en.2007-1692 |url=}}</ref>
*Lymphocytic infiltration.

<gallery>
File:Lymphocytic_hypophysitis_CD3.jpg | Lymphocytic hypophysitis, CD3 IHC. (WC/jensflorian)
</gallery>

=See also=
*[[CNS cytopathology]].
*[[Neuropathology]].
*[[Brain tumours]].

=References=
{{reflist|2}}

=External links=
*[http://www.neuropathologyweb.org/ Neuropathology] - neuropathologyweb.org.
*[http://www.lab.anhb.uwa.edu.au/mb140/corepages/endocrines/endocrin.htm Endocrine histology (anhb.uwa.edu.au)].

[[Category:Neuropathology]]

Pituitary gland

2022-09-30T10:24:52Z

Jensflorian: /* Pituitary neuroendocrine tumor (PitNET) */ PIT1 lineage update

The '''pituitary gland''' is known as the ''master gland''.

Divisions:<ref>[http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo.html http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo.html]</ref>
*Anterior pituitary ([[AKA]] adenohypophysis, pars distalis).
*Posterior pituitary (AKA neurohypophysis, neural pituitary, pars nervosa).

=Function=
===Anterior===
Hormones:<ref name=rcn_com>[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Pituitary.html http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Pituitary.html]</ref>
*Growth hormone (GH).
*Luteinizing hormone (LH)
*Follicle-stimulating hormone (FSH)
*Thyroid stimulating hormone (TSH)
*Adrenocorticotropic hormone (ACTH)
*Prolactin (PRL)

Mnemonic: "Go Look For The Adenoma Please" = GH, LH, FSH, TSH, ACTH, PRL.

===Intermedia===
* Originates from the posterior wall of the Rathke’s pouch.
* Hormones: MSH, ACTH precursor.
* Contains colloid cysts.

===Posterior===
Hormones:<ref name=rcn_com/>
*Oxytocin.
*Antidiuretic hormone (ADH).

=Anatomy and histology=
===Anatomy===
Basic anatomy (simplified):<ref name=bowen>URL: [http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo_pit.html http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo_pit.html]. Accessed on: 31 October 2010.</ref>
*Anterior:
**Pars distalis.
**Pars intermedia.
*Posterior:
**Pars nervosa.

Embryological origin:<ref name=bowen/>
*Anterior - Rathke's pouch (roof of mouth).
*Posterior - diencephalon (ventral aspect).

Images:
*[http://www.ouhsc.edu/histology/Glass%20slides/38_01.jpg Pituitary gland (ouhsc.edu)].
*[http://www.lab.anhb.uwa.edu.au/mb140/corepages/endocrines/Images/HypDevAni.gif Development of the pituitary - animation (anhb.uwa.edu)].

===Histology===
====Anterior====
*Acidophils (40% of cells) = red or orange.
**GH, PRL.
*Basophils (10% of cells) = basophilic (light blue).
**TSH, LH, FSH, ACTH.
*Chromophobes (50% of cells) = amphophilic (purplish/grey).

Notes:
*The cellular product (i.e. hormone produced) is not strictly correlated with the cell type.<ref name=Ref_PSNP26>{{Ref PSNP|26}}</ref>
*The cells can be typed using [[IHC]]; somatotrophs (GH), lactotrophs (PRL), corticotrophs (ACTH), thyrotrophs (TSH), gonadotrophs (FSH, LH).<ref>{{Ref PBoD8|1098-9}}</ref>

====Posterior====
Features:<ref name=Ref_PSNP26>{{Ref PSNP|26}}</ref>
*Herring bodies - '''key feature'''.
**Eosinophilic axonal dilations filled with lysosomes and neurosecretory granules.
*Less cellular.
**Usually more cellular in perivascular location.
Image: [http://www.ouhsc.edu/histology/Glass%20slides/38_09.jpg Herring bodies (ouhsc.edu)].

<gallery>
File:Pituitary gland histology 2014.jpg | Pituitary gland, low magnification (WC/Athikhun.suw)
</gallery>

=DDx for sella turcica lesions=
*[[Pituitary adenoma]].
*[[Rathke cleft cyst]].
*[[Craniopharyngioma]].
*[[Germ cell tumour]].
*[[Meningioma]].

=Pituitary necrosis=
*Rare.

===Causes of pituitary necrosis===
*Sheehan syndrome - secondary to blood loss in childbirth.<ref>URL: [http://www.mayoclinic.com/health/sheehans-syndrome/DS00889 http://www.mayoclinic.com/health/sheehans-syndrome/DS00889]. Accessed on: 16 November 2010.</ref>
*[[Syphilis]] (fetal-maternal transmission).<ref>URL: [http://pediatrics.aappublications.org/cgi/content/full/104/1/e4 http://pediatrics.aappublications.org/cgi/content/full/104/1/e4]. Accessed on: 16 November 2010.</ref>
*Mollaret's meningitis - very rare.<ref name=pmid18715308>{{cite journal |author=Dancer CM, Woods ML, Henderson RD, Robertson T, Mungomery M, Allworth A |title=Mollaret's meningitis and pituitary failure associated with a Rathke's cleft cyst |journal=Intern Med J |volume=38 |issue=7 |pages=609–11 |year=2008 |month=July |pmid=18715308 |doi=10.1111/j.1445-5994.2008.01709.x |url=}}</ref> (???)
*Spontaneous necrosis of pituitary tumours - case reports.<ref>{{cite journal |author=Sachdev Y, Evered DC, Hall R |title=Spontaneous pituitary necrosis |journal=Br Med J |volume=1 |issue=6015 |pages=942 |year=1976 |month=April |pmid=1268492 |pmc=1639254 |doi= |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1639254/pdf/brmedj00512-0028a.pdf}}</ref>

Images:
*[http://path.upmc.edu/cases/case288.html Pituitary necrosis - several images (upmc.edu)].

=Specific entities=
==Pituitary neuroendocrine tumor (PitNET)==
Old terminology '''Pituitary adenoma''' is depreceated
===General===
*Clinical:<ref>{{Ref PBoD8|1100}}</ref>
**Classically: visual field defects (bitemporal hemianopsia).
**Others (increased intracranial pressure): headache, nausea, vomiting.
**Tumor of adults.

Morphologic Classification:
#Microadenoma <= 1 cm.
#Macroadenoma 1-4 cm.
#Giant adenoma > 4cm.

May be classified by what they secrete.
#Functional (endocrine hyperfunction).
#*Acromegaly/giantism.
#*Hyperprolactinemia.
#*Cushing disease.
#*Hyperthyroidism.
#*Significant elevation of FSH/LH.
#Clinically nonfunctioning.

Notes:
''Cushing disease'' is due to pituitary gland hypersecretion of ACTH (due to a pituitary adenoma ''or'' CRH hypersecretion from the hypothalamus).<ref name=Ref_PBoD8_1148>{{Ref PBoD8|1148}}</ref> [[Cushing syndrome]] is hypercortisolism ''not'' due to pituitary gland pathology.

Imaging:
*Sellar enlargement.
*Bone erosion, invasive growth esp. cavernous sinus (35-45%).
*Inhomogenous signal in T1w MRI.

====Familial pituitary adenomas====
A pituitary adenoma may be part of a familial syndrome:<ref name=pmid19564887>{{Cite journal | last1 = Elston | first1 = MS. | last2 = McDonald | first2 = KL. | last3 = Clifton-Bligh | first3 = RJ. | last4 = Robinson | first4 = BG. | title = Familial pituitary tumor syndromes. | journal = Nat Rev Endocrinol | volume = 5 | issue = 8 | pages = 453-61 | month = Aug | year = 2009 | doi = 10.1038/nrendo.2009.126 | PMID = 19564887 }}</ref><ref name=Ref_PCPBoD8|554>{{Ref PCPBoD8|554}}</ref>
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Syndrome
! Gene
! Notes
|-
| [[Multiple endocrine neoplasia]] I
| MEN1
| characterized by the 3 Ps: '''p'''ituitary adenoma, [[parathyroid adenoma|'''p'''arathyroid adenoma]], [[pancreatic neuroendocrine tumour|'''p'''ancreatic neuroendocrine tumour]]
|-
| MEN-1-like syndrome
| CDKN1B<ref name=omim600778>{{OMIM|600778}}</ref>
| also known as ''Multiple endocrine neoplasia IV'' <ref name=omim600778>{{OMIM|600778}}</ref>
|-
| [[Carney syndrome]]
| PRKAR1A
| other findings (mnemonic ''NAME''): nevi, [[atrial myxoma]], myxoid neurofibroma, ephelides (freckles)
|-
| Isolated pituitary adenoma<ref name=pmid22612670>{{Cite journal | last1 = Korbonits | first1 = M. | last2 = Storr | first2 = H. | last3 = Kumar | first3 = AV. | title = Familial pituitary adenomas - Who should be tested for AIP mutations? | journal = Clin Endocrinol (Oxf) | volume = | issue = | pages = | month = May | year = 2012 | doi = 10.1111/j.1365-2265.2012.04445.x | PMID = 22612670 }}</ref>
| AIP
| classically GH-producing adenoma - leads to acromegaly
|}

===Microscopic===
Features:<ref name=Ref_PSNP36>{{Ref PSNP|36}}</ref>
*Loss of fibrous stroma.
**The cells of a normal (anterior) pituitary are nested.
*Basophilic cells (corticotrophs).
*Eosinophilic cells(somatotrophs).

Notes:
*Smears very well.<ref>MUN. 24 November 2010.</ref>

The WHO 2022 Classification of tumours of endocrine organs recoginizes following tumours:<ref>{{cite journal |vauthors=Asa SL, Mete O, Perry A, Osamura RY |title=Overview of the 2022 WHO Classification of Pituitary Tumors |journal=Endocr Pathol |volume=33 |issue=1 |pages=6–26 |date=March 2022 |pmid=35291028 |doi=10.1007/s12022-022-09703-7 |url=}}</ref>

{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! PitNET lineage
! PitNET type
! subtypes
! Hormone secretion
! Transcription factor
|-
| PIT1
| Somatotroph tumor
| Densely and sparsely granulated tumor
| GH, a-subunit+/-, CK+
| PIT1
|-
| PIT1
| Lactotroph tumor
| Densely and sparsely granulated tumor
| PRL, CK-ve or weak
| PIT1, [[Estrogen receptor|ER]]
|-
| PIT1
| Mammosomatotroph tumor
|
| GH, PRL (usu. less), CK perinuclear +ve
| PIT1, [[Estrogen receptor|ER]]
|-
| PIT1
| Thyrotroph tumor
|
| TSH, CK-ve or weak
| PIT1, GATA3
|-
| PIT1
| Mature plurihormonal PIT1 lineage tumor
|
| GH, PRL, TSH, a-subunit +/-ve
| PIT1, [[Estrogen receptor|ER]], GATA3

|-
|
| Corticotroph adenoma
| Densely and sparsely granulated adenoma, Crooke cell adenoma
| ACTH,CAM 5.2
| TPIT
|-
|
| Gonadotroph adenoma
| Sparsely granulated adenoma
| FSH, LH or a-Subunit
| SF1, [[Estrogen receptor|ER]], GATA2
|-
|
| Null cell adenoma
|
| None
| None
|}

Other tumours may be classified as plurhormonal or double adenomas or as adenomas with unusual IHC combination.

====Images====
<gallery>
Image:Nonfunctioning_pituitary_adenoma_%281%29.jpg | Pituitary adenoma - non-functioning. (WC/KGH)
File:HE fibrosis pituitary adenoma.jpg | Extensive interstitial and perivascular fibrosis in a pituitary adenoma (WC/jensflorian)
File:PRL HE histology.jpg | Pituitary adenoma - PRL producing, HE. Note the basophilic appearance of the cells (WC/jensflorian)
File:PRL adenoma treatment HE.jpg | Pituitary adenoma - PRL producing, HE. Extensive regressive changes after after dopamine agonist treatment (WC/jensflorian)
File:PRL IHC pituitary adenoma.jpg | Pituitary adenoma - PRL producing, Prolactin IHC (WC/jensflorian)
File:Densely granulated HGH producing adenoma.jpg | Pituitary adenoma - HGH producing, HE. The cells have a slightly eosinophilic appearance (WC/jensflorian)
File:Sparsely granulated HGH adenoma.jpg | Sparsely granulated adenoma - HGH producing. Note the numerous fibrous bodies in HE stain (WC/jensflorian)
File:HGH adenoma CK8.jpg | Sparsely granulated adenoma - HGH producing. CK8 IHC highlighting fibrous bodies (WC/jensflorian)
File:TSHoma HE.jpg | Pituitary adenoma - TSH producing. HE stain showing pleomorphism (WC/jensflorian)
File:TSHoma IHC-TSH.jpg | Pituitary adenoma - TSH producing. TSH IHC can be heterogeneous (WC/jensflorian)
Image:Pituitary_adenoma_%281%29_GH_production.jpg | Pituitary adenoma - GH producing. (WC/KGH)
File:HE-GHoma.jpg | Pituitary adenoma , HE. This gonadotropin producing adenoma has a papillary architecture (WC/jensflorian)
File:FSH-GHoma.jpg | Pituitary adenoma, IHC for FSH (WC/jensflorian)
File:LH-GHoma.jpg | Pituitary adenoma, IHC for LH (WC/jensflorian)
File:ACTHoma-PAS-O-G.jpg | Pituitary adenoma , ACTH producing. PAS-O-G stain showing basophilic adenoma cells (WC/jensflorian)
File:ACTHoma-IHC.jpg | Pituitary adenoma , ACTH producing. Strong ACTH IHC in this basophilic adenoma (WC/jensflorian)
File:Pituitary_adenoma-nonfunctioning.jpg |Pituitary adenoma with vascular pseudorosettes, nonfunctioning (WC/jensflorian)
Crooke_HE_40x.jpg | Crooke cell adenoma, HE (WC/Marvin101)
File:Crooke Cytokeratins.jpg | Crooke cell adenoma, panCK (WC/Marvin101)
HE_fibrosis_pituitary_adenoma.jpg | Fibrosis in pituitary adenoma.
</gallery>

===Stains===
*Reticulin - loss of reticulin between tumour cells.

===IHC===
*LH.
*FSH.
*TSH - [[Hyperthyroidism]]
*GH - [[Acromegaly]].
*Prolactin -Galactorrhea, Amenorrhea, Gynecomastia. Golgi staining pattern in sparsely granulated cases.
*ACTH - [[Cushing syndrome]].
*PIT-1: stains somatotrophs, lactotrophs and thyrothrops.
*TPIT: stains corticotrophs.
*SF1: stains gonadotrophs.
*Chromogranin A +ve
*Synaptophysin strongly +ve (except lactotrophs)
*CAM5.2: fibrous bodies in sparsely granulated somatotroph adenoma, Ring-like staining in Crooke cell adenoma.
*MIB-1: Usu less than 3%.

Note:
Null-cell adenoma must be hormone immunonegative and negative for transcription factors.

===Variants===
*Corticotroph adenomas exhibiting Crooke's hyaline change: agressive course.<ref>{{Cite journal | last1 = George | first1 = DH. | last2 = Scheithauer | first2 = BW. | last3 = Kovacs | first3 = K. | last4 = Horvath | first4 = E. | last5 = Young | first5 = WF. | last6 = Lloyd | first6 = RV. | last7 = Meyer | first7 = FB. | title = Crooke's cell adenoma of the pituitary: an aggressive variant of corticotroph adenoma. | journal = Am J Surg Pathol | volume = 27 | issue = 10 | pages = 1330-6 | month = Oct | year = 2003 | doi = | PMID = 14508394 }}</ref>
*Acidophilic stem cell adenomas: large, locally invasive adenoma with low GH activity. <ref>{{Cite journal | last1 = Horvath | first1 = E. | last2 = Kovacs | first2 = K. | last3 = Singer | first3 = W. | last4 = Smyth | first4 = HS. | last5 = Killinger | first5 = DW. | last6 = Erzin | first6 = C. | last7 = Weiss | first7 = MH. | title = Acidophil stem cell adenoma of the human pituitary: clinicopathologic analysis of 15 cases. | journal = Cancer | volume = 47 | issue = 4 | pages = 761-71 | month = Feb | year = 1981 | doi = | PMID = 6261917 }}</ref>
*Sparsely granulated somatotroph adenomas are more invasive than other variants and respond less to medical treatment. <ref>{{Cite journal | last1 = Kato | first1 = M. | last2 = Inoshita | first2 = N. | last3 = Sugiyama | first3 = T. | last4 = Tani | first4 = Y. | last5 = Shichiri | first5 = M. | last6 = Sano | first6 = T. | last7 = Yamada | first7 = S. | last8 = Hirata | first8 = Y. | title = Differential expression of genes related to drug responsiveness between sparsely and densely granulated somatotroph adenomas. | journal = Endocr J | volume = 59 | issue = 3 | pages = 221-8 | month = | year = 2012 | doi = | PMID = 22200580 }}</ref>
* Lactotroph adenomas in men may show aggressive clinical behavior. <ref>{{Cite journal | last1 = Delgrange | first1 = E. | last2 = Vasiljevic | first2 = A. | last3 = Wierinckx | first3 = A. | last4 = François | first4 = P. | last5 = Jouanneau | first5 = E. | last6 = Raverot | first6 = G. | last7 = Trouillas | first7 = J. | title = Expression of estrogen receptor alpha is associated with prolactin pituitary tumor prognosis and supports the sex-related difference in tumor growth. | journal = Eur J Endocrinol | volume = 172 | issue = 6 | pages = 791-801 | month = Jun | year = 2015 | doi = 10.1530/EJE-14-0990 | PMID = 25792376 }}</ref>
*Poorly differentiated PIT-1 positive adenomas may show aggresive growth. <ref> {{Cite journal | last1 = Mete | first1 = O. | last2 = Gomez-Hernandez | first2 = K. | last3 = Kucharczyk | first3 = W. | last4 = Ridout | first4 = R. | last5 = Zadeh | first5 = G. | last6 = Gentili | first6 = F. | last7 = Ezzat | first7 = S. | last8 = Asa | first8 = SL. | title = Silent subtype 3 pituitary adenomas are not always silent and represent poorly differentiated monomorphous plurihormonal Pit-1 lineage adenomas. | journal = Mod Pathol | volume = 29 | issue = 2 | pages = 131-42 | month = Feb | year = 2016 | doi = 10.1038/modpathol.2015.151 | PMID = 26743473 }}</ref>

==Pituitary blastoma==
* New entity introduced in 2017<ref>{{Cite journal | last1 = Lopes | first1 = MBS. | title = The 2017 World Health Organization classification of tumors of the pituitary gland: a summary. | journal = Acta Neuropathol | volume = 134 | issue = 4 | pages = 521-535 | month = Oct | year = 2017 | doi = 10.1007/s00401-017-1769-8 | PMID = 28821944 }}</ref>
* Epithelial glands with rosette-like formations resembling immature Rathke epithelium.
* Synaptophysin +ve, usu. ACTH+ve
* DICER1 mutations<ref>{{Cite journal | last1 = de Kock | first1 = L. | last2 = Sabbaghian | first2 = N. | last3 = Plourde | first3 = F. | last4 = Srivastava | first4 = A. | last5 = Weber | first5 = E. | last6 = Bouron-Dal Soglio | first6 = D. | last7 = Hamel | first7 = N. | last8 = Choi | first8 = JH. | last9 = Park | first9 = SH. | title = Pituitary blastoma: a pathognomonic feature of germ-line DICER1 mutations. | journal = Acta Neuropathol | volume = 128 | issue = 1 | pages = 111-22 | month = Jul | year = 2014 | doi = 10.1007/s00401-014-1285-z | PMID = 24839956 }}</ref>

==Pituitary carcinoma==
* ICD-O: 8272/3
* Requires presence of cerebrospinal or systemic metastasis.
* Very rare.
* 75% are hormonally active (mostly PRL or ACTH).
* IHC: Synaptophysin, Chromogranin +ve

==Rathke cleft cyst==
===General===
*Benign counterpart of [[craniopharyngioma]].
*Arises from intermediate lobe of pituitary gland (''pars intermedia of pituitary gland'').

Radiology:
*Typically no calcifications.<ref name=emed_rcc>URL: [http://emedicine.medscape.com/article/343629-overview http://emedicine.medscape.com/article/343629-overview]. Accessed on: 14 November 2010.</ref>

Radiologic DDx:<ref name=emed_rcc>URL: [http://emedicine.medscape.com/article/343629-overview http://emedicine.medscape.com/article/343629-overview]. Accessed on: 14 November 2010.</ref>
*Arachnoid cyst.
*[[Craniopharyngioma]].
*[[Cysticercosis]].
*[[Pituitary adenoma]].
*Epidermoid of brain.

===Microscopic===
Features:
*Lined by a layer of cuboidal ''or'' columnar epithelial with cilia.
*+/-Goblet cells.<ref>URL: [http://www.endotext.org/neuroendo/neuroendo3/neuroendo3.html http://www.endotext.org/neuroendo/neuroendo3/neuroendo3.html]. Accessed on: 27 May 2010.</ref>
*+/-Squamous metaplasia ~ may be several layers thick.
**May be confused with ''[[papillary craniopharyngioma]]''.<ref name=Ref_PSNP408>{{Ref PSNP|408}}</ref>
*Cholesterol clefts may be seen in association with rupture.<ref>URL: [http://path.upmc.edu/cases/case177/dx.html http://path.upmc.edu/cases/case177/dx.html]. Accessed on: 8 January 2012.</ref>

DDx:
*[[Papillary craniopharyngioma]].

Images:
*[http://www.endotext.org/neuroendo/neuroendo3/figures/figure11.jpg Rathke cleft cyst (endotext.org)].
*[http://path.upmc.edu/cases/case177/micro.html Rathke cleft cyst (upmc.edu)].

==Craniopharyngioma==
{{Main|Craniopharyngioma}}

==Gangliocytoma==
* Neuronal cells in abundant neuropil.
* S-100, Synaptophysin +ve.
* Isolated sellar cases are very rare.

Image: [[https://twitter.com/sty_md/status/664676241111252992]]

==Mixed Gangliocytoma-adenoma==
AKA: ganglioneuroma, pituitary adenoma with neuronal choristoma (PANCH)
*Neuronal cells mixed with pituitary adenoma cells.
* Approx. 0.25% of all pituitary adenomas.
* Association with somatotroph adenomas (acromegaly).

==Pituicytoma==
{{Main|Pituicytoma}}

==Spindle cell oncocytoma==
*Origin: Neurohypophysis or infundibulum.
*Benign clinical course - WHO grade I.
*Elongated bipolar, spindle cells.
*Fascicular or storiform growth patterns.
*EMA: patchy, S-100+/-ve, GFAP+/-ve, TTF1+ve.

*It is thought that Spindle cell oncocytomas and Granular cell tumors of the neurohypophysis are variants of Pituicyoma.<ref>{{Cite journal | last1 = Mete | first1 = O. | last2 = Lopes | first2 = MB. | last3 = Asa | first3 = SL. | title = Spindle cell oncocytomas and granular cell tumors of the pituitary are variants of pituicytoma. | journal = Am J Surg Pathol | volume = 37 | issue = 11 | pages = 1694-9 | month = Nov | year = 2013 | doi = 10.1097/PAS.0b013e31829723e7 | PMID = 23887161 }}</ref>

==Granular cell tumor of the sellar region==
{{Main|Granular_cell_tumour}}

*Origin: Neurohypophysis or infundibulum.
*Benign clinical course - WHO grade I.
*Well circumscribed.
*Polygonal cells with abundant granular cytoplasm.
*CD68+ve, S-100+/-ve, GFAP+/-ve, TTF1+ve.

<gallery>
File:Granular_cell_tumor_pituitary.jpg | Granular cell tumor of the sellar region (HE).
</gallery>

==Autoimmune hypophysitis==
===General===
Features:<ref name=pmid18388197/>
*Rare.
*Autoantigens are unknown.
*May occur in pregnancy.
*May be misdiagnosed as a nonsecreting adenoma.

===Microscopic===
Features:<ref name=pmid18388197>{{cite journal |author=Tzou SC, Lupi I, Landek M, ''et al.'' |title=Autoimmune hypophysitis of SJL mice: clinical insights from a new animal model |journal=Endocrinology |volume=149 |issue=7 |pages=3461–9 |year=2008 |month=July |pmid=18388197 |pmc=2453094 |doi=10.1210/en.2007-1692 |url=}}</ref>
*Lymphocytic infiltration.

<gallery>
File:Lymphocytic_hypophysitis_CD3.jpg | Lymphocytic hypophysitis, CD3 IHC. (WC/jensflorian)
</gallery>

=See also=
*[[CNS cytopathology]].
*[[Neuropathology]].
*[[Brain tumours]].

=References=
{{reflist|2}}

=External links=
*[http://www.neuropathologyweb.org/ Neuropathology] - neuropathologyweb.org.
*[http://www.lab.anhb.uwa.edu.au/mb140/corepages/endocrines/endocrin.htm Endocrine histology (anhb.uwa.edu.au)].

[[Category:Neuropathology]]

Pituitary gland

2022-09-30T10:15:33Z

Jensflorian: /* Pituitary adenoma */ Starting Update on 2022 WHO classification

The '''pituitary gland''' is known as the ''master gland''.

Divisions:<ref>[http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo.html http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo.html]</ref>
*Anterior pituitary ([[AKA]] adenohypophysis, pars distalis).
*Posterior pituitary (AKA neurohypophysis, neural pituitary, pars nervosa).

=Function=
===Anterior===
Hormones:<ref name=rcn_com>[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Pituitary.html http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Pituitary.html]</ref>
*Growth hormone (GH).
*Luteinizing hormone (LH)
*Follicle-stimulating hormone (FSH)
*Thyroid stimulating hormone (TSH)
*Adrenocorticotropic hormone (ACTH)
*Prolactin (PRL)

Mnemonic: "Go Look For The Adenoma Please" = GH, LH, FSH, TSH, ACTH, PRL.

===Intermedia===
* Originates from the posterior wall of the Rathke’s pouch.
* Hormones: MSH, ACTH precursor.
* Contains colloid cysts.

===Posterior===
Hormones:<ref name=rcn_com/>
*Oxytocin.
*Antidiuretic hormone (ADH).

=Anatomy and histology=
===Anatomy===
Basic anatomy (simplified):<ref name=bowen>URL: [http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo_pit.html http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo_pit.html]. Accessed on: 31 October 2010.</ref>
*Anterior:
**Pars distalis.
**Pars intermedia.
*Posterior:
**Pars nervosa.

Embryological origin:<ref name=bowen/>
*Anterior - Rathke's pouch (roof of mouth).
*Posterior - diencephalon (ventral aspect).

Images:
*[http://www.ouhsc.edu/histology/Glass%20slides/38_01.jpg Pituitary gland (ouhsc.edu)].
*[http://www.lab.anhb.uwa.edu.au/mb140/corepages/endocrines/Images/HypDevAni.gif Development of the pituitary - animation (anhb.uwa.edu)].

===Histology===
====Anterior====
*Acidophils (40% of cells) = red or orange.
**GH, PRL.
*Basophils (10% of cells) = basophilic (light blue).
**TSH, LH, FSH, ACTH.
*Chromophobes (50% of cells) = amphophilic (purplish/grey).

Notes:
*The cellular product (i.e. hormone produced) is not strictly correlated with the cell type.<ref name=Ref_PSNP26>{{Ref PSNP|26}}</ref>
*The cells can be typed using [[IHC]]; somatotrophs (GH), lactotrophs (PRL), corticotrophs (ACTH), thyrotrophs (TSH), gonadotrophs (FSH, LH).<ref>{{Ref PBoD8|1098-9}}</ref>

====Posterior====
Features:<ref name=Ref_PSNP26>{{Ref PSNP|26}}</ref>
*Herring bodies - '''key feature'''.
**Eosinophilic axonal dilations filled with lysosomes and neurosecretory granules.
*Less cellular.
**Usually more cellular in perivascular location.
Image: [http://www.ouhsc.edu/histology/Glass%20slides/38_09.jpg Herring bodies (ouhsc.edu)].

<gallery>
File:Pituitary gland histology 2014.jpg | Pituitary gland, low magnification (WC/Athikhun.suw)
</gallery>

=DDx for sella turcica lesions=
*[[Pituitary adenoma]].
*[[Rathke cleft cyst]].
*[[Craniopharyngioma]].
*[[Germ cell tumour]].
*[[Meningioma]].

=Pituitary necrosis=
*Rare.

===Causes of pituitary necrosis===
*Sheehan syndrome - secondary to blood loss in childbirth.<ref>URL: [http://www.mayoclinic.com/health/sheehans-syndrome/DS00889 http://www.mayoclinic.com/health/sheehans-syndrome/DS00889]. Accessed on: 16 November 2010.</ref>
*[[Syphilis]] (fetal-maternal transmission).<ref>URL: [http://pediatrics.aappublications.org/cgi/content/full/104/1/e4 http://pediatrics.aappublications.org/cgi/content/full/104/1/e4]. Accessed on: 16 November 2010.</ref>
*Mollaret's meningitis - very rare.<ref name=pmid18715308>{{cite journal |author=Dancer CM, Woods ML, Henderson RD, Robertson T, Mungomery M, Allworth A |title=Mollaret's meningitis and pituitary failure associated with a Rathke's cleft cyst |journal=Intern Med J |volume=38 |issue=7 |pages=609–11 |year=2008 |month=July |pmid=18715308 |doi=10.1111/j.1445-5994.2008.01709.x |url=}}</ref> (???)
*Spontaneous necrosis of pituitary tumours - case reports.<ref>{{cite journal |author=Sachdev Y, Evered DC, Hall R |title=Spontaneous pituitary necrosis |journal=Br Med J |volume=1 |issue=6015 |pages=942 |year=1976 |month=April |pmid=1268492 |pmc=1639254 |doi= |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1639254/pdf/brmedj00512-0028a.pdf}}</ref>

Images:
*[http://path.upmc.edu/cases/case288.html Pituitary necrosis - several images (upmc.edu)].

=Specific entities=
==Pituitary neuroendocrine tumor (PitNET)==
Old terminology '''Pituitary adenoma''' is depreceated
===General===
*Clinical:<ref>{{Ref PBoD8|1100}}</ref>
**Classically: visual field defects (bitemporal hemianopsia).
**Others (increased intracranial pressure): headache, nausea, vomiting.
**Tumor of adults.

Morphologic Classification:
#Microadenoma <= 1 cm.
#Macroadenoma 1-4 cm.
#Giant adenoma > 4cm.

May be classified by what they secrete.
#Functional (endocrine hyperfunction).
#*Acromegaly/giantism.
#*Hyperprolactinemia.
#*Cushing disease.
#*Hyperthyroidism.
#*Significant elevation of FSH/LH.
#Clinically nonfunctioning.

Notes:
''Cushing disease'' is due to pituitary gland hypersecretion of ACTH (due to a pituitary adenoma ''or'' CRH hypersecretion from the hypothalamus).<ref name=Ref_PBoD8_1148>{{Ref PBoD8|1148}}</ref> [[Cushing syndrome]] is hypercortisolism ''not'' due to pituitary gland pathology.

Imaging:
*Sellar enlargement.
*Bone erosion, invasive growth esp. cavernous sinus (35-45%).
*Inhomogenous signal in T1w MRI.

====Familial pituitary adenomas====
A pituitary adenoma may be part of a familial syndrome:<ref name=pmid19564887>{{Cite journal | last1 = Elston | first1 = MS. | last2 = McDonald | first2 = KL. | last3 = Clifton-Bligh | first3 = RJ. | last4 = Robinson | first4 = BG. | title = Familial pituitary tumor syndromes. | journal = Nat Rev Endocrinol | volume = 5 | issue = 8 | pages = 453-61 | month = Aug | year = 2009 | doi = 10.1038/nrendo.2009.126 | PMID = 19564887 }}</ref><ref name=Ref_PCPBoD8|554>{{Ref PCPBoD8|554}}</ref>
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Syndrome
! Gene
! Notes
|-
| [[Multiple endocrine neoplasia]] I
| MEN1
| characterized by the 3 Ps: '''p'''ituitary adenoma, [[parathyroid adenoma|'''p'''arathyroid adenoma]], [[pancreatic neuroendocrine tumour|'''p'''ancreatic neuroendocrine tumour]]
|-
| MEN-1-like syndrome
| CDKN1B<ref name=omim600778>{{OMIM|600778}}</ref>
| also known as ''Multiple endocrine neoplasia IV'' <ref name=omim600778>{{OMIM|600778}}</ref>
|-
| [[Carney syndrome]]
| PRKAR1A
| other findings (mnemonic ''NAME''): nevi, [[atrial myxoma]], myxoid neurofibroma, ephelides (freckles)
|-
| Isolated pituitary adenoma<ref name=pmid22612670>{{Cite journal | last1 = Korbonits | first1 = M. | last2 = Storr | first2 = H. | last3 = Kumar | first3 = AV. | title = Familial pituitary adenomas - Who should be tested for AIP mutations? | journal = Clin Endocrinol (Oxf) | volume = | issue = | pages = | month = May | year = 2012 | doi = 10.1111/j.1365-2265.2012.04445.x | PMID = 22612670 }}</ref>
| AIP
| classically GH-producing adenoma - leads to acromegaly
|}

===Microscopic===
Features:<ref name=Ref_PSNP36>{{Ref PSNP|36}}</ref>
*Loss of fibrous stroma.
**The cells of a normal (anterior) pituitary are nested.
*Basophilic cells (corticotrophs).
*Eosinophilic cells(somatotrophs).

Notes:
*Smears very well.<ref>MUN. 24 November 2010.</ref>

The WHO 2022 Classification of tumours of endocrine organs recoginizes following tumours:<ref>{{cite journal |vauthors=Asa SL, Mete O, Perry A, Osamura RY |title=Overview of the 2022 WHO Classification of Pituitary Tumors |journal=Endocr Pathol |volume=33 |issue=1 |pages=6–26 |date=March 2022 |pmid=35291028 |doi=10.1007/s12022-022-09703-7 |url=}}</ref>

{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! PitNET lineage
! PitNET type
! subtypes
! Hormone secretion
! Transcription factor
|-
|
| Somatotroph adenoma
| Densely and sparsely granulated adenoma, Mammosomatotroph adenoma, Mixed GH and PRL adenoma
| GH +/- PRL
| PIT1
|-
|
| Lactotroph adenoma
| Densely and sparsely granulated adenoma, Acidophilic stem cell adenoma
| PRL
| PIT1, [[Estrogen receptor|ER]]
|-
|
| Thyrotroph adenoma
|
| TSH
| PIT1, [[Estrogen receptor|ER]]
|-
|
| Corticotroph adenoma
| Densely and sparsely granulated adenoma, Crooke cell adenoma
| ACTH,CAM 5.2
| TPIT
|-
|
| Gonadotroph adenoma
| Sparsely granulated adenoma
| FSH, LH or a-Subunit
| SF1, [[Estrogen receptor|ER]], GATA2
|-
|
| Null cell adenoma
|
| None
| None
|}

Other tumours may be classified as plurhormonal or double adenomas or as adenomas with unusual IHC combination.

====Images====
<gallery>
Image:Nonfunctioning_pituitary_adenoma_%281%29.jpg | Pituitary adenoma - non-functioning. (WC/KGH)
File:HE fibrosis pituitary adenoma.jpg | Extensive interstitial and perivascular fibrosis in a pituitary adenoma (WC/jensflorian)
File:PRL HE histology.jpg | Pituitary adenoma - PRL producing, HE. Note the basophilic appearance of the cells (WC/jensflorian)
File:PRL adenoma treatment HE.jpg | Pituitary adenoma - PRL producing, HE. Extensive regressive changes after after dopamine agonist treatment (WC/jensflorian)
File:PRL IHC pituitary adenoma.jpg | Pituitary adenoma - PRL producing, Prolactin IHC (WC/jensflorian)
File:Densely granulated HGH producing adenoma.jpg | Pituitary adenoma - HGH producing, HE. The cells have a slightly eosinophilic appearance (WC/jensflorian)
File:Sparsely granulated HGH adenoma.jpg | Sparsely granulated adenoma - HGH producing. Note the numerous fibrous bodies in HE stain (WC/jensflorian)
File:HGH adenoma CK8.jpg | Sparsely granulated adenoma - HGH producing. CK8 IHC highlighting fibrous bodies (WC/jensflorian)
File:TSHoma HE.jpg | Pituitary adenoma - TSH producing. HE stain showing pleomorphism (WC/jensflorian)
File:TSHoma IHC-TSH.jpg | Pituitary adenoma - TSH producing. TSH IHC can be heterogeneous (WC/jensflorian)
Image:Pituitary_adenoma_%281%29_GH_production.jpg | Pituitary adenoma - GH producing. (WC/KGH)
File:HE-GHoma.jpg | Pituitary adenoma , HE. This gonadotropin producing adenoma has a papillary architecture (WC/jensflorian)
File:FSH-GHoma.jpg | Pituitary adenoma, IHC for FSH (WC/jensflorian)
File:LH-GHoma.jpg | Pituitary adenoma, IHC for LH (WC/jensflorian)
File:ACTHoma-PAS-O-G.jpg | Pituitary adenoma , ACTH producing. PAS-O-G stain showing basophilic adenoma cells (WC/jensflorian)
File:ACTHoma-IHC.jpg | Pituitary adenoma , ACTH producing. Strong ACTH IHC in this basophilic adenoma (WC/jensflorian)
File:Pituitary_adenoma-nonfunctioning.jpg |Pituitary adenoma with vascular pseudorosettes, nonfunctioning (WC/jensflorian)
Crooke_HE_40x.jpg | Crooke cell adenoma, HE (WC/Marvin101)
File:Crooke Cytokeratins.jpg | Crooke cell adenoma, panCK (WC/Marvin101)
HE_fibrosis_pituitary_adenoma.jpg | Fibrosis in pituitary adenoma.
</gallery>

===Stains===
*Reticulin - loss of reticulin between tumour cells.

===IHC===
*LH.
*FSH.
*TSH - [[Hyperthyroidism]]
*GH - [[Acromegaly]].
*Prolactin -Galactorrhea, Amenorrhea, Gynecomastia. Golgi staining pattern in sparsely granulated cases.
*ACTH - [[Cushing syndrome]].
*PIT-1: stains somatotrophs, lactotrophs and thyrothrops.
*TPIT: stains corticotrophs.
*SF1: stains gonadotrophs.
*Chromogranin A +ve
*Synaptophysin strongly +ve (except lactotrophs)
*CAM5.2: fibrous bodies in sparsely granulated somatotroph adenoma, Ring-like staining in Crooke cell adenoma.
*MIB-1: Usu less than 3%.

Note:
Null-cell adenoma must be hormone immunonegative and negative for transcription factors.

===Variants===
*Corticotroph adenomas exhibiting Crooke's hyaline change: agressive course.<ref>{{Cite journal | last1 = George | first1 = DH. | last2 = Scheithauer | first2 = BW. | last3 = Kovacs | first3 = K. | last4 = Horvath | first4 = E. | last5 = Young | first5 = WF. | last6 = Lloyd | first6 = RV. | last7 = Meyer | first7 = FB. | title = Crooke's cell adenoma of the pituitary: an aggressive variant of corticotroph adenoma. | journal = Am J Surg Pathol | volume = 27 | issue = 10 | pages = 1330-6 | month = Oct | year = 2003 | doi = | PMID = 14508394 }}</ref>
*Acidophilic stem cell adenomas: large, locally invasive adenoma with low GH activity. <ref>{{Cite journal | last1 = Horvath | first1 = E. | last2 = Kovacs | first2 = K. | last3 = Singer | first3 = W. | last4 = Smyth | first4 = HS. | last5 = Killinger | first5 = DW. | last6 = Erzin | first6 = C. | last7 = Weiss | first7 = MH. | title = Acidophil stem cell adenoma of the human pituitary: clinicopathologic analysis of 15 cases. | journal = Cancer | volume = 47 | issue = 4 | pages = 761-71 | month = Feb | year = 1981 | doi = | PMID = 6261917 }}</ref>
*Sparsely granulated somatotroph adenomas are more invasive than other variants and respond less to medical treatment. <ref>{{Cite journal | last1 = Kato | first1 = M. | last2 = Inoshita | first2 = N. | last3 = Sugiyama | first3 = T. | last4 = Tani | first4 = Y. | last5 = Shichiri | first5 = M. | last6 = Sano | first6 = T. | last7 = Yamada | first7 = S. | last8 = Hirata | first8 = Y. | title = Differential expression of genes related to drug responsiveness between sparsely and densely granulated somatotroph adenomas. | journal = Endocr J | volume = 59 | issue = 3 | pages = 221-8 | month = | year = 2012 | doi = | PMID = 22200580 }}</ref>
* Lactotroph adenomas in men may show aggressive clinical behavior. <ref>{{Cite journal | last1 = Delgrange | first1 = E. | last2 = Vasiljevic | first2 = A. | last3 = Wierinckx | first3 = A. | last4 = François | first4 = P. | last5 = Jouanneau | first5 = E. | last6 = Raverot | first6 = G. | last7 = Trouillas | first7 = J. | title = Expression of estrogen receptor alpha is associated with prolactin pituitary tumor prognosis and supports the sex-related difference in tumor growth. | journal = Eur J Endocrinol | volume = 172 | issue = 6 | pages = 791-801 | month = Jun | year = 2015 | doi = 10.1530/EJE-14-0990 | PMID = 25792376 }}</ref>
*Poorly differentiated PIT-1 positive adenomas may show aggresive growth. <ref> {{Cite journal | last1 = Mete | first1 = O. | last2 = Gomez-Hernandez | first2 = K. | last3 = Kucharczyk | first3 = W. | last4 = Ridout | first4 = R. | last5 = Zadeh | first5 = G. | last6 = Gentili | first6 = F. | last7 = Ezzat | first7 = S. | last8 = Asa | first8 = SL. | title = Silent subtype 3 pituitary adenomas are not always silent and represent poorly differentiated monomorphous plurihormonal Pit-1 lineage adenomas. | journal = Mod Pathol | volume = 29 | issue = 2 | pages = 131-42 | month = Feb | year = 2016 | doi = 10.1038/modpathol.2015.151 | PMID = 26743473 }}</ref>

==Pituitary blastoma==
* New entity introduced in 2017<ref>{{Cite journal | last1 = Lopes | first1 = MBS. | title = The 2017 World Health Organization classification of tumors of the pituitary gland: a summary. | journal = Acta Neuropathol | volume = 134 | issue = 4 | pages = 521-535 | month = Oct | year = 2017 | doi = 10.1007/s00401-017-1769-8 | PMID = 28821944 }}</ref>
* Epithelial glands with rosette-like formations resembling immature Rathke epithelium.
* Synaptophysin +ve, usu. ACTH+ve
* DICER1 mutations<ref>{{Cite journal | last1 = de Kock | first1 = L. | last2 = Sabbaghian | first2 = N. | last3 = Plourde | first3 = F. | last4 = Srivastava | first4 = A. | last5 = Weber | first5 = E. | last6 = Bouron-Dal Soglio | first6 = D. | last7 = Hamel | first7 = N. | last8 = Choi | first8 = JH. | last9 = Park | first9 = SH. | title = Pituitary blastoma: a pathognomonic feature of germ-line DICER1 mutations. | journal = Acta Neuropathol | volume = 128 | issue = 1 | pages = 111-22 | month = Jul | year = 2014 | doi = 10.1007/s00401-014-1285-z | PMID = 24839956 }}</ref>

==Pituitary carcinoma==
* ICD-O: 8272/3
* Requires presence of cerebrospinal or systemic metastasis.
* Very rare.
* 75% are hormonally active (mostly PRL or ACTH).
* IHC: Synaptophysin, Chromogranin +ve

==Rathke cleft cyst==
===General===
*Benign counterpart of [[craniopharyngioma]].
*Arises from intermediate lobe of pituitary gland (''pars intermedia of pituitary gland'').

Radiology:
*Typically no calcifications.<ref name=emed_rcc>URL: [http://emedicine.medscape.com/article/343629-overview http://emedicine.medscape.com/article/343629-overview]. Accessed on: 14 November 2010.</ref>

Radiologic DDx:<ref name=emed_rcc>URL: [http://emedicine.medscape.com/article/343629-overview http://emedicine.medscape.com/article/343629-overview]. Accessed on: 14 November 2010.</ref>
*Arachnoid cyst.
*[[Craniopharyngioma]].
*[[Cysticercosis]].
*[[Pituitary adenoma]].
*Epidermoid of brain.

===Microscopic===
Features:
*Lined by a layer of cuboidal ''or'' columnar epithelial with cilia.
*+/-Goblet cells.<ref>URL: [http://www.endotext.org/neuroendo/neuroendo3/neuroendo3.html http://www.endotext.org/neuroendo/neuroendo3/neuroendo3.html]. Accessed on: 27 May 2010.</ref>
*+/-Squamous metaplasia ~ may be several layers thick.
**May be confused with ''[[papillary craniopharyngioma]]''.<ref name=Ref_PSNP408>{{Ref PSNP|408}}</ref>
*Cholesterol clefts may be seen in association with rupture.<ref>URL: [http://path.upmc.edu/cases/case177/dx.html http://path.upmc.edu/cases/case177/dx.html]. Accessed on: 8 January 2012.</ref>

DDx:
*[[Papillary craniopharyngioma]].

Images:
*[http://www.endotext.org/neuroendo/neuroendo3/figures/figure11.jpg Rathke cleft cyst (endotext.org)].
*[http://path.upmc.edu/cases/case177/micro.html Rathke cleft cyst (upmc.edu)].

==Craniopharyngioma==
{{Main|Craniopharyngioma}}

==Gangliocytoma==
* Neuronal cells in abundant neuropil.
* S-100, Synaptophysin +ve.
* Isolated sellar cases are very rare.

Image: [[https://twitter.com/sty_md/status/664676241111252992]]

==Mixed Gangliocytoma-adenoma==
AKA: ganglioneuroma, pituitary adenoma with neuronal choristoma (PANCH)
*Neuronal cells mixed with pituitary adenoma cells.
* Approx. 0.25% of all pituitary adenomas.
* Association with somatotroph adenomas (acromegaly).

==Pituicytoma==
{{Main|Pituicytoma}}

==Spindle cell oncocytoma==
*Origin: Neurohypophysis or infundibulum.
*Benign clinical course - WHO grade I.
*Elongated bipolar, spindle cells.
*Fascicular or storiform growth patterns.
*EMA: patchy, S-100+/-ve, GFAP+/-ve, TTF1+ve.

*It is thought that Spindle cell oncocytomas and Granular cell tumors of the neurohypophysis are variants of Pituicyoma.<ref>{{Cite journal | last1 = Mete | first1 = O. | last2 = Lopes | first2 = MB. | last3 = Asa | first3 = SL. | title = Spindle cell oncocytomas and granular cell tumors of the pituitary are variants of pituicytoma. | journal = Am J Surg Pathol | volume = 37 | issue = 11 | pages = 1694-9 | month = Nov | year = 2013 | doi = 10.1097/PAS.0b013e31829723e7 | PMID = 23887161 }}</ref>

==Granular cell tumor of the sellar region==
{{Main|Granular_cell_tumour}}

*Origin: Neurohypophysis or infundibulum.
*Benign clinical course - WHO grade I.
*Well circumscribed.
*Polygonal cells with abundant granular cytoplasm.
*CD68+ve, S-100+/-ve, GFAP+/-ve, TTF1+ve.

<gallery>
File:Granular_cell_tumor_pituitary.jpg | Granular cell tumor of the sellar region (HE).
</gallery>

==Autoimmune hypophysitis==
===General===
Features:<ref name=pmid18388197/>
*Rare.
*Autoantigens are unknown.
*May occur in pregnancy.
*May be misdiagnosed as a nonsecreting adenoma.

===Microscopic===
Features:<ref name=pmid18388197>{{cite journal |author=Tzou SC, Lupi I, Landek M, ''et al.'' |title=Autoimmune hypophysitis of SJL mice: clinical insights from a new animal model |journal=Endocrinology |volume=149 |issue=7 |pages=3461–9 |year=2008 |month=July |pmid=18388197 |pmc=2453094 |doi=10.1210/en.2007-1692 |url=}}</ref>
*Lymphocytic infiltration.

<gallery>
File:Lymphocytic_hypophysitis_CD3.jpg | Lymphocytic hypophysitis, CD3 IHC. (WC/jensflorian)
</gallery>

=See also=
*[[CNS cytopathology]].
*[[Neuropathology]].
*[[Brain tumours]].

=References=
{{reflist|2}}

=External links=
*[http://www.neuropathologyweb.org/ Neuropathology] - neuropathologyweb.org.
*[http://www.lab.anhb.uwa.edu.au/mb140/corepages/endocrines/endocrin.htm Endocrine histology (anhb.uwa.edu.au)].

[[Category:Neuropathology]]

Meningioma

2022-09-19T14:13:57Z

Jensflorian: /* IHC */ update

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Meningioma_high_mag.jpg
| Width =
| Caption = Meningioma. [[HPS stain]].
| Synonyms =
| Micro = whorled appearance, calcification - [[psammoma bodies|psammomatous]], +/-[[nuclear pseudoinclusions]]
| Subtypes = Grade I (meningothelial, fibrous, transistional, psammomatous, angiomatous, microcystic, secretory, lymphoplasmacyte-rich, metaplastic), Grade II (invasive, clear cell, chordoid), Grade III (papillary, rhabdoid)
| LMDDx = [[schwannoma]], [[solitary fibrous tumour]], [[hemangiopericytoma]], others
| Stains =
| IHC = EMA +ve, [[keratins]] usu. -ve, CD34 -ve/+ve, S-100 -ve (usu.), PR +ve (-ve in more aggressive ones)
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site = see ''[[CNS tumours]]''
| Assdx =
| Syndromes = [[Neurofibromatosis|neurofibromatosis 2]], [[nevoid basal cell carcinoma syndrome]]
| Clinicalhx = +/-radiation
| Signs =
| Symptoms =
| Prevalence = common
| Bloodwork =
| Rads = extra-axial, intradural lesion, dural tail sign (on MRI)
| Endoscopy =
| Prognosis = usually benign, dependent on grade
| Other =
| ClinDDx = dependent on site - see ''[[CNS tumours]]''
| Tx = surgical removal
}}
'''Meningioma''' a very common [[CNS tumours|tumour]] in [[neuropathology]].

==General==
===Prevalence===
*Most common primary brain tumour.<ref name=pmid25343186>{{Cite journal | last1 = Rogers | first1 = L. | last2 = Barani | first2 = I. | last3 = Chamberlain | first3 = M. | last4 = Kaley | first4 = TJ. | last5 = McDermott | first5 = M. | last6 = Raizer | first6 = J. | last7 = Schiff | first7 = D. | last8 = Weber | first8 = DC. | last9 = Wen | first9 = PY. | title = Meningiomas: knowledge base, treatment outcomes, and uncertainties. A RANO review. | journal = J Neurosurg | volume = | issue = | pages = 1-20 | month = Oct | year = 2014 | doi = 10.3171/2014.7.JNS131644 | PMID = 25343186 }}</ref>
*May be caused by prior radiation.<ref name=pmid25249493>{{Cite journal | last1 = Baldi | first1 = I. | last2 = Engelhardt | first2 = J. | last3 = Bonnet | first3 = C. | last4 = Bauchet | first4 = L. | last5 = Berteaud | first5 = E. | last6 = Grüber | first6 = A. | last7 = Loiseau | first7 = H. | title = Epidemiology of meningiomas. | journal = Neurochirurgie | volume = | issue = | pages = | month = Sep | year = 2014 | doi = 10.1016/j.neuchi.2014.05.006 | PMID = 25249493 }}</ref>
*Women develop meningioma twice as likely as men.<ref>{{Cite journal | last1 = Wiemels | first1 = J. | last2 = Wrensch | first2 = M. | last3 = Claus | first3 = EB. | title = Epidemiology and etiology of meningioma. | journal = J Neurooncol | volume = 99 | issue = 3 | pages = 307-14 | month = Sep | year = 2010 | doi = 10.1007/s11060-010-0386-3 | PMID = 20821343 }}</ref>
*More than 90% are solitary.

===Prognosis===
*Most are benign - usu. a good prognosis.
**Even benign tumors may show extensive local spread - considerable morbidity and mortality.
**Metastases are rare and then usu. after surgery.
*May be malignant - bad prognosis.

*Factors associated with unfavourable prognosis:
**BAP1 mutations.<ref>{{Cite journal | last1 = Shankar | first1 = GM. | last2 = Abedalthagafi | first2 = M. | last3 = Vaubel | first3 = RA. | last4 = Merrill | first4 = PH. | last5 = Nayyar | first5 = N. | last6 = Gill | first6 = CM. | last7 = Brewster | first7 = R. | last8 = Bi | first8 = WL. | last9 = Agarwalla | first9 = PK. | title = Germline and somatic BAP1 mutations in high-grade rhabdoid meningiomas. | journal = Neuro Oncol | volume = 19 | issue = 4 | pages = 535-545 | month = 04 | year = 2017 | doi = 10.1093/neuonc/now235 | PMID = 28170043 }}</ref>
**Presence of TERT promotor mutation.<ref>{{Cite journal | last1 = Sahm | first1 = F. | last2 = Schrimpf | first2 = D. | last3 = Olar | first3 = A. | last4 = Koelsche | first4 = C. | last5 = Reuss | first5 = D. | last6 = Bissel | first6 = J. | last7 = Kratz | first7 = A. | last8 = Capper | first8 = D. | last9 = Schefzyk | first9 = S. | title = TERT Promoter Mutations and Risk of Recurrence in Meningioma. | journal = J Natl Cancer Inst | volume = 108 | issue = 5 | pages = | month = May | year = 2016 | doi = 10.1093/jnci/djv377 | PMID = 26668184 }}</ref>
**Loss of H3K27me3.<ref>{{Cite journal | last1 = Katz | first1 = LM. | last2 = Hielscher | first2 = T. | last3 = Liechty | first3 = B. | last4 = Silverman | first4 = J. | last5 = Zagzag | first5 = D. | last6 = Sen | first6 = R. | last7 = Wu | first7 = P. | last8 = Golfinos | first8 = JG. | last9 = Reuss | first9 = D. | title = Loss of histone H3K27me3 identifies a subset of meningiomas with increased risk of recurrence. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Apr | year = 2018 | doi = 10.1007/s00401-018-1844-9 | PMID = 29627952 }}</ref>

===Genetics===
*May be seen in genetic disorders such as:
**[[Neurofibromatosis|Neurofibromatosis 2 (NF2)]].<Ref>URL: [http://moon.ouhsc.edu/kfung/jty1/neurotest/Q13-Ans.htm http://moon.ouhsc.edu/kfung/jty1/neurotest/Q13-Ans.htm]. Accessed on: 26 October 2010.</ref>
**[[Nevoid basal cell carcinoma syndrome]] (Gorlin syndrome).<ref name=pmid15545745>{{Cite journal | last1 = Kimonis | first1 = VE. | last2 = Mehta | first2 = SG. | last3 = Digiovanna | first3 = JJ. | last4 = Bale | first4 = SJ. | last5 = Pastakia | first5 = B. | title = Radiological features in 82 patients with nevoid basal cell carcinoma (NBCC or Gorlin) syndrome. | journal = Genet Med | volume = 6 | issue = 6 | pages = 495-502 | month = | year = | doi = 10.109701.GIM.0000145045.17711.1C | PMID = 15545745 }}</ref><ref>{{Cite journal | last1 = Lee | first1 = CW. | last2 = Tan | first2 = TC. | title = Meningioma associated with Gorlin's syndrome. | journal = J Clin Neurosci | volume = 21 | issue = 2 | pages = 349-50 | month = Feb | year = 2014 | doi = 10.1016/j.jocn.2013.02.033 | PMID = 24100109 }}</ref>

===Quick overview===
{| class="wikitable sortable"
! Name
! Histologic criteria
! Subtypes
! Image
|-
| Classic, WHO I
| less then 4 mit/10 HPF and no atypia
| meningeothelial, fibroblastic, transitional, psammomatous, angiomatous, microcytsic, secretory, lymphoplasmacyte-rich, metaplastic
| [[File:Miningioma_(1)_transitional_type.jpg|thumb|center|150px]]
|-
| Atypical, WHO II
| brain invasion, 4 or more mit/10 HPF, or 3 of the following: necrosis, increased cellularity, high nuc:cyto ratio, nucleoli, sheeting
| chordoid, clear cell
| [[File:Brain_invasion_meningioma.jpg|thumb|center|150px]]
|-
| Anaplastic, WHO III
| 20 or more mitoses/10 HPF, morphologiy similiar to carcinoma or sarcoma
| rhabdoid, papillary
| [[File:Mitoses_anaplastic_meningioma.jpg|thumb|center|150px]]
|}

==Gross/Radiology==
*Extra-axial, intradural.
**Can be extradural - very rare.<ref name=upmc_case702>URL: [http://path.upmc.edu/cases/case702.html http://path.upmc.edu/cases/case702.html]. Accessed on: 2 February 2012.</ref>
*[[Dural tail sign]] (DTS) on MRI.<ref name=pmid22839655>{{Cite journal | last1 = Ikeda | first1 = D. | last2 = Chiocca | first2 = EA. | title = Editorial: dural tail sign. | journal = J Neurosurg | volume = 117 | issue = 4 | pages = 643-4 | month = Oct | year = 2012 | doi = 10.3171/2012.2.JNS12266 | PMID = 22839655 }}</ref><ref name=pmid25238986>{{Cite journal | last1 = Wen | first1 = M. | last2 = Jung | first2 = S. | last3 = Moon | first3 = KS. | last4 = Pei | first4 = J. | last5 = Lee | first5 = KH. | last6 = Jin | first6 = SG. | last7 = Li | first7 = SY. | last8 = Ryu | first8 = HH. | title = Immunohistochemical profile of the dural tail in intracranial meningiomas. | journal = Acta Neurochir (Wien) | volume = 156 | issue = 12 | pages = 2263-73 | month = Dec | year = 2014 | doi = 10.1007/s00701-014-2216-4 | PMID = 25238986 }}</ref>
**Enhancement of dura adjacent to the mass lesion - commonly seen (~70% of cases).<ref name=pmid2120998>{{Cite journal | last1 = Aoki | first1 = S. | last2 = Sasaki | first2 = Y. | last3 = Machida | first3 = T. | last4 = Tanioka | first4 = H. | title = Contrast-enhanced MR images in patients with meningioma: importance of enhancement of the dura adjacent to the tumor. | journal = AJNR Am J Neuroradiol | volume = 11 | issue = 5 | pages = 935-8 | month = | year = | doi = | PMID = 2120998 }}</ref>
**May be subclassified radiologically - predictive of grading.<ref name=pmid22839654>{{Cite journal | last1 = Qi | first1 = ST. | last2 = Liu | first2 = Y. | last3 = Pan | first3 = J. | last4 = Chotai | first4 = S. | last5 = Fang | first5 = LX. | title = A radiopathological classification of dural tail sign of meningiomas. | journal = J Neurosurg | volume = 117 | issue = 4 | pages = 645-53 | month = Oct | year = 2012 | doi = 10.3171/2012.6.JNS111987 | PMID = 22839654 }}</ref>
*+/-Hyperostosis.
**Associated with invasion into the skull in ~20% of cases.<ref name=pmid22406780>{{Cite journal | last1 = Goyal | first1 = N. | last2 = Kakkar | first2 = A. | last3 = Sarkar | first3 = C. | last4 = Agrawal | first4 = D. | title = Does bony hyperostosis in intracranial meningioma signify tumor invasion? A radio-pathologic study. | journal = Neurol India | volume = 60 | issue = 1 | pages = 50-4 | month = | year = | doi = 10.4103/0028-3886.93589 | PMID = 22406780 }}</ref>

<gallery>
File:Keilbeinmeningeom MRT T1KMax.jpg | Sphenoid wing meningioma (WC/Hellerhoff)
File:Meningioma.jpg | Brain displacement by meningioma (AFIP)
File:Meningioma-1.jpg | Macroscopy (Всеволод Лучанский (vvray))
</gallery>

==Microscopic==
Features (memory device ''WCN''):
*Whorled appearance - '''key feature'''.
*Calcification, [[psammoma bodies|psammomatous]] (target-like appearance; (tight) onion skin).
*+/-[[Nuclear pseudoinclusions]] - focal nuclear clearing with a sharp interface to unremarkable chromatin.

Notes:
*May involute into benign sclerotic tissue.<ref>URL: [http://radiographics.rsna.org/content/23/3/785.long http://radiographics.rsna.org/content/23/3/785.long]. Accessed on: 3 November 2010.</ref>
*Thick-walled blood vessels -> think [[schwannoma]].

DDx:
*[[Schwannoma]] - especially at [[CP angle]].
*[[Solitary fibrous tumour]].
*[[Hemangiopericytoma]].
*Others - see subtypes.

===Images===
<Gallery>
Image:Meningioma_high_mag.jpg | Meningioma - high mag. (WC)
Image:Meningioma_intermed_mag.jpg | Meningioma - intermed. mag. (WC)
Image:Meningioma_-_brain_invasion_-_intermed_mag.jpg | Meningioma with brain invasion - intermed. mag. (WC)
Image:Meningioma_-_brain_invasion_-_high_mag.jpg | Meningioma with brain invasion - high mag. (WC)
File:Meningeotheliomatous_meningeoma_whorl_formations.jpg | Whorls in meningioma. (WC)
File:Image NP T1c 0001.JPG | Whorls in meningioma. (WC)
File:Image NP T1c 0004.JPG | Meningioma annotated. (WC)
</gallery>
www:
*[http://www.neuropathologyweb.org/chapter7/chapter7dMiscellaneous.html Meningioma (neuropathologyweb.org)].
*[http://path.upmc.edu/cases/case702.html Extra-dural meningioma (upmc.edu)].

===Morphologic subtypes===
*Many subtypes exist.<ref name=Ref_PSNP194>{{Ref PSNP|194}}</ref>
*The histologic subtypes generally don't have much prognostic significance.
**Some subtypes are high grade by definition; also see ''histologic grading''.

====Grade I====
=====Meningothelial meningioma=====
*Most common.

Microscopic:
*Syncytial, nuclear clearing ([[pseudoinclusions]]).
*Whorls, Onion bulb formations.
*Few psammoma bodies.

Molecular:
*AKT E17K mutations.<ref>{{Cite journal | last1 = Sahm | first1 = F. | last2 = Bissel | first2 = J. | last3 = Koelsche | first3 = C. | last4 = Schweizer | first4 = L. | last5 = Capper | first5 = D. | last6 = Reuss | first6 = D. | last7 = Böhmer | first7 = K. | last8 = Lass | first8 = U. | last9 = Göck | first9 = T. | title = AKT1E17K mutations cluster with meningothelial and transitional meningiomas and can be detected by SFRP1 immunohistochemistry. | journal = Acta Neuropathol | volume = 126 | issue = 5 | pages = 757-62 | month = Nov | year = 2013 | doi = 10.1007/s00401-013-1187-5 | PMID = 24096618 }}</ref>

<gallery>
Meningeotheliomatous_meningeoma_whorl_formations.jpg | Syncytial appearance, whorl formations (WC/jensflorian)
File:Meningioma_showing_Psammoma_body.jpg | Psammoma body (WC/Netha Hussain)
File:Meningioma_cytologie.jpg | Onion bulb formation in smear (WC/jensflorian)
File:Meningioma_intermed_mag.jpg | Meningioma HPS stain (WC/Nephron)
</gallery>

=====Fibrous meningioma=====
*[[AKA]] ''fibroblastic meningioma''.
*'''Not''' collagen... but looks like it.
**It is really laminin or fibronectin.
*Spindle cells in parallel bundles.
*Few to none whorl formations.

<gallery>
File:Meningioma_fibromatous_variant.jpg | Fibrous meingioma (WC)
File:Miningioma_(4)_EMA.JPG | EMA staining (WC/marvin 101)
</gallery>

=====Transitional meningioma=====
*AKA mixed.
*Common.
*Lobular and fasicular growth patterns coexist.
*Usu. a mixture of meningeothelial and fibromatous meningioma

<gallery>
File:Miningioma_(1)_transitional_type.jpg | Low power (WC/KGH)
File:Miningioma_(2)_transitional_type.jpg | Intermed magnification (WC/KGH)
File:Prominent mitosis meningioma.jpg | Mitosis in a transitional meningioma (WC/jensflorian)
</gallery>

=====Psammomatous meningioma=====
Microscopic:
*[[Psammoma bodies]] dominate over tumor cells.
**Irregular calcifications (confluent psammoma bodies).
*Usually found in spinal cord.

<gallery>
File:Psammomatous_meningioma.jpg | Numerous psammoma bodies (WC/jensflorian)
File:NP psammomatous meningioma 0002.jpg | Psammomatous meningioma after EDTA treatment (WC)
</gallery>

=====Angiomatous meningioma=====
*AKA vascular.
*May bleed like stink.
*May show extensive edema.
*Hyalinized vessels dominate over tumor cells.
*Degenerative nuclear atypia.

DDx:
*Vascular malformatons
*Hemangioblastoma

<gallery>
File:Angiomatous_meningioma_HE_x100.jpg | Angiomatous meningioma (WC/jensflorian)
</gallery>

=====Microcystic meningioma=====
Microscopic:
*Cystic appearance.
*Increased cytologic pleomorphism of the elongated cells.

DDx:
*Clear cell meningioma
*Hemangioblastoma

<gallery>
File:Microcystic_meningeoma_HE_x100.jpg | Microcyts (WC/jensflorian)
</gallery>

=====Secretory meningioma=====
*Associated with brain edema; may have a worse outcome.

Microscopic:<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/Com04/Com405-1-Diss.htm http://moon.ouhsc.edu/kfung/jty1/Com04/Com405-1-Diss.htm]. Accessed on: 12 October 2011.</ref>
*Eosinophilic intracytoplasmic inclusions that are [[CEA]] +ve and [[PAS]] +ve.

Molecular:
* Combined KLF4 K409Q and TRAF7 mutations.<ref>{{Cite journal | last1 = Reuss | first1 = DE. | last2 = Piro | first2 = RM. | last3 = Jones | first3 = DT. | last4 = Simon | first4 = M. | last5 = Ketter | first5 = R. | last6 = Kool | first6 = M. | last7 = Becker | first7 = A. | last8 = Sahm | first8 = F. | last9 = Pusch | first9 = S. | title = Secretory meningiomas are defined by combined KLF4 K409Q and TRAF7 mutations. | journal = Acta Neuropathol | volume = 125 | issue = 3 | pages = 351-8 | month = Mar | year = 2013 | doi = 10.1007/s00401-013-1093-x | PMID = 23404370 }}</ref>

DDx:
*Metastatic [[mucinous adenocarcinoma]].
*Pituitary adenoma

<gallery>
File:Secretory_meningioma_HE_x200.jpg | Secretory granules (WC/jensflorian)
File:Secretory_meningioma_PAS.jpg | PAS-positive secretory granules (WC/jensflorian)
File:Secretory_meningioma_HE_smear.jpg | Smear with secretory granules (WC/jensflorian)
</gallery>

Images:
*[http://moon.ouhsc.edu/kfung/jty1/Com04/Com04Image/Com405-1-8.gif Secretory meningioma (ouhsc.edu)].<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/Com04/Com405-1-Diss.htm http://moon.ouhsc.edu/kfung/jty1/Com04/Com405-1-Diss.htm]. Accessed on: 3 January 2012.</ref>
*[http://path.upmc.edu/cases/case370.html Secretory meningioma - several images (upmc.edu)].

=====Lymphoplasmacyte-rich meningioma=====
Microscopic:
*Lymphocytes.
*Plasma cells.

Images:
*[http://path.upmc.edu/cases/case225/micro.html Lymphoplasmacyte-rich meningioma - case 1 - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case247/micro.html Lymphoplasmacyte-rich meningioma - case 2 - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case528.html Lymphoplasmacyte-rich meningioma - case 3 - several images (upmc.edu)].

=====Metaplastic meningioma=====
*No clinical significance.
*Probably do not represent true metaplasia in all cases.
*Clincal information is rquired to distinguish between bone invasion and meningiomas with bone formation.

Microscopic:
*Cartilage or bone formation.
*Myxoid or xanthomatous changes.

<gallery>
File:Metaplastic_osseous_meningioma.jpg | Ossified meningioma, HE stain. (WC/jensflorian)
File:Metaplastic_xanthomatous_meningioma.jpg | Metaplastic meningioma with xanthomatous changes. (WC/jensflorian)
</gallery>

====Grade II====
=====Brain invasive meningioma=====
*Invades the brain (irregular, tongue-like).
*Absence of leptomeningeal layer.
*Brain invasion can be present in grade I tumors, these are then classified as "atypical", ie. as grade II tumors.
*The prognostic significance of brain invasion is still unclear, some studies do not show a course similiar to grade II meningiomas.<ref>{{Cite journal | last1 = Baumgarten | first1 = P. | last2 = Gessler | first2 = F. | last3 = Schittenhelm | first3 = J. | last4 = Skardelly | first4 = M. | last5 = Tews | first5 = DS. | last6 = Senft | first6 = C. | last7 = Dunst | first7 = M. | last8 = Imoehl | first8 = L. | last9 = Plate | first9 = KH. | title = Brain invasion in otherwise benign meningiomas does not predict tumor recurrence. | journal = Acta Neuropathol | volume = 132 | issue = 3 | pages = 479-81 | month = Sep | year = 2016 | doi = 10.1007/s00401-016-1598-1 | PMID = 27464983 }}</ref><ref>{{Cite journal | last1 = Brokinkel | first1 = B. | last2 = Hess | first2 = K. | last3 = Mawrin | first3 = C. | title = Brain invasion in Meningiomas - Clinical considerations and impact of neuropathological evaluation: A systematic Review. | journal = Neuro Oncol | volume = | issue = | pages = | month = Apr | year = 2017 | doi = 10.1093/neuonc/nox071 | PMID = 28419308 }}</ref><ref>{{Cite journal | last1 = Pizem | first1 = J. | last2 = Velnar | first2 = T. | last3 = Prestor | first3 = B. | last4 = Mlakar | first4 = J. | last5 = Popovic | first5 = M. | title = Brain invasion assessability in meningiomas is related to meningioma size and grade, and can be improved by extensive sampling of the surgically removed meningioma specimen. | journal = Clin Neuropathol | volume = 33 | issue = 5 | pages = 354-63 | month = | year = | doi = 10.5414/NP300750 | PMID = 25034703 }}</ref>

Images:
*[http://moon.ouhsc.edu/kfung/jty1/Composites/FNA0IE18-Meningioma-Invasion.htm Meningioma with brain invasion (ouhsc.edu)].

<gallery>
File:Brain invasion meningioma.jpg | Finger-like protrusions, HE (WC/jensflorian)
File:Meningioma - brain invasion - very high mag.jpg | Brain invasive meningooma (WC/Nephron)
</gallery>

=====Clear cell meningioma=====
Epidemiology:
*Usu. spinal cord.<ref>{{Ref PSNP|200}}</ref>

Microscopic:
*Clear cells - contain glycogen (PAS +ve).

<gallery>
File:HE_clear_cell_meningioma.jpg | Clear cell meningioma, HE (WC/jensflorian)
</gallery>

Molecular:
*SMARCE1 mutations.<ref>{{Cite journal | last1 = Smith | first1 = MJ. | last2 = Wallace | first2 = AJ. | last3 = Bennett | first3 = C. | last4 = Hasselblatt | first4 = M. | last5 = Elert-Dobkowska | first5 = E. | last6 = Evans | first6 = LT. | last7 = Hickey | first7 = WF. | last8 = van Hoff | first8 = J. | last9 = Bauer | first9 = D. | title = Germline SMARCE1 mutations predispose to both spinal and cranial clear cell meningiomas. | journal = J Pathol | volume = 234 | issue = 4 | pages = 436-40 | month = Dec | year = 2014 | doi = 10.1002/path.4427 | PMID = 25143307 }}</ref>

Images:
*[http://www.surgicalpathologyatlas.com/glfusion/mediagallery/media.php?f=0&sort=0&s=20080802174938386 Clear cell meningioma (surgicalpathologyatlas.com)].
*[http://blog.lib.umn.edu/santa013/neuropathology/2009/10/meningioma-with-clear-cell-features.html Clear cell meningioma (umn.edu)].

=====Chordoid meningioma=====
*Chordoma-like.

Microscopic:
*[[Myxoid]] appearance.

<gallery>
File:Chordoid meningoma HE x200.jpg | Chordoid meningioma - HE (WC/jensflorian)
File:Alcian blue chordoid meningioma.jpg | Chordoid meningioma - alcian blue (WC/jensflorian)
</gallery>

Image:
*[http://frontalcortex.com/?page=oll&topic=24&qid=914 Chordoid meningioma (frontalcortex.com)].

====Grade III====
=====Papillary meningioma=====
Microscopic:
*discohesive meningothelial tumour cells around a fibrovascular core.
*perivascular pseudorosettes.

<gallery>
File:Papillary meningioma HE.jpg | Papillary meningioma (WC/jensflorian)
File:Pap meningioma.jpg | Papillary meningioma (WC)
</gallery>

=====Rhabdoid meningioma=====
Microscopic:
*Rhabdoid appearance (abundant cytoplasm).
**Cross-striations.

<gallery>
Image:Rhabdoid Meningioma Histopathology.jpg | Rhabdoid meningioma. (WC/Marvin 101)
File:Rhabdoid meningioma frozen section HE.jpg | Frozen section (WC/jensflorian)
</gallery>
www:
*[http://path.upmc.edu/cases/case373.html Rhabdoid meningioma - case 1 - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case393.html Rhabdoid meningioma - case 2 - several images (upmc.edu)].

====Other morphological variants====
These are currently not listed in the WHO as separate entities.
*Oncocytic.<ref>{{Cite journal | last1 = Zunarelli | first1 = E. | last2 = Tallarico | first2 = E. | last3 = Valentini | first3 = A. | last4 = Maiorana | first4 = A. | title = Oncocytic meningioma: study of eight new cases and analysis of 13 reported cases. | journal = Pathology | volume = 42 | issue = 6 | pages = 587-9 | month = | year = 2010 | doi = 10.3109/00313025.2010.508740 | PMID = 20854082 }}</ref>
*Whorling-sclerosing.<ref>{{Cite journal | last1 = Haberler | first1 = C. | last2 = Jarius | first2 = C. | last3 = Lang | first3 = S. | last4 = Rössler | first4 = K. | last5 = Gruber | first5 = A. | last6 = Hainfellner | first6 = JA. | last7 = Budka | first7 = H. | title = Fibrous meningeal tumours with extensive non-calcifying collagenous whorls and glial fibrillary acidic protein expression: the whorling-sclerosing variant of meningioma. | journal = Neuropathol Appl Neurobiol | volume = 28 | issue = 1 | pages = 42-7 | month = Feb | year = 2002 | doi = | PMID = 11849562 }}</ref>
*Rosette-forming.<ref>{{Cite journal | last1 = Liverman | first1 = C. | last2 = Mafra | first2 = M. | last3 = Chuang | first3 = SS. | last4 = Shivane | first4 = A. | last5 = Chakrabarty | first5 = A. | last6 = Highley | first6 = R. | last7 = Hilton | first7 = DA. | last8 = Byrne | first8 = NP. | last9 = Wesseling | first9 = P. | title = A clinicopathologic study of 11 rosette-forming meningiomas: a rare and potentially confusing pattern. | journal = Acta Neuropathol | volume = 130 | issue = 2 | pages = 311-3 | month = Aug | year = 2015 | doi = 10.1007/s00401-015-1456-6 | PMID = 26106026 }}</ref>

<gallery>
File:Meningioma_Whorling_sclerosing.jpg | Whorling-sclerosing features in meningioma (HE/jensflorian)
File:Meningioma_pseudorosettes.jpg | Meningioma with rosette-forming features (HE/jensflorian)
</gallery>

===Histologic grading===
Grading:<ref name=Ref_PSNP194>{{Ref PSNP|194}}</ref>
*Grade 1:
**Low mitotic rate (< 4 mitoses/10 HPF - for whatever HPF means, see [[HPFitis]]).
**Excludes ''clear cell'', ''chordoid'', ''papillary'', and ''rhabdoid'' subtypes.
*Grade 2 (either #1, #2 or #3):
*#Brain-invasive meningioma.
*#*Invasion of meningioma into brain.
*#**Meninogioma with entraped GFAP +ve tissue.
*#Atypical meningioma (by histomorphology) - either ''A'' or ''B''.
*#* A. Intermediate mitotic rate (>= 4 mitoses/10 HPF - for whatever ''HPF'' means, see [[HPFitis]].)
*#* B. Three of the following five features:
*#*#Sheeting architecture.
*#*#High [[NC ratio]] clusters; clusters of "lymphocyte-like" cells.
*#*#Hypercellularity.
*#*#Macronucleoli.
*#*#[[Necrosis]] not caused by treatment, e.g. radiation or embolization.
*#''Clear cell'' or ''chordoid'' subtype.
*Grade 3 (either of the following):
**High mitotic rate (>=20 mitoses/10 HPF - for whatever ''HPF'' means, see [[HPFitis]].)
**"Frank anaplasia"; marked nuclear atypia.
**''Papillary'' or ''rhabdoid'' subtype.

Notes:
*Grade II soft criteria memory device ''HMNs'': hypercellular, macronucleoli, NC ratio increased, necrosis, sheeting.

==IHC==
*EMA +ve (approx. 90%).<ref name=Ref_PSNP13>{{Ref PSNP|13}}</ref>
*PR +ve (approx. 75%, expression decreases from grade I to III).
*SSTR2A +ve (approx. 95%).
*S100 variable (up to 35% cases, usually patchy).<ref>{{cite journal |vauthors=Behling F, Fodi C, Skardelly M, Paulsen F, Tabatabai G, Honegger J, Tatagiba M, Schittenhelm J |title=The prognostic role of the immunohistochemical expression of S100 in meningiomas |journal=J Cancer Res Clin Oncol |volume= |issue= |pages= |date=July 2022 |pmid=35838837 |doi=10.1007/s00432-022-04186-9 |url=}}</ref>
*SOX10 -ve.
*GFAP -ve.
*CD34 usu. -ve (approx 8% cases positive).
*CD13 +ve.<ref>{{cite journal |vauthors=Marletta S, Luchini C, Sperandio N, Torresani E, Sorio A, Girolami I, Scarpa A, Eccher A, Ghimenton C |title=CD13 is a useful tool in the differential diagnosis of meningiomas with potential biological and prognostic implications |journal=Virchows Arch |volume=480 |issue=6 |pages=1223–1230 |date=June 2022 |pmid=35212813 |pmc=9184408 |doi=10.1007/s00428-022-03304-9 |url=}}</ref>
*Other CKs usually -ve (approx 6% cases positive, mostly secretory meningiomas).

==Molecular==
Non-syndromal meningiomas may show AKT1/TRAF7, SMO, KLF4/TRAF7, and PIK3CA mutations (1/3 of cases).<ref>{{Cite journal | last1 = Clark | first1 = VE. | last2 = Erson-Omay | first2 = EZ. | last3 = Serin | first3 = A. | last4 = Yin | first4 = J. | last5 = Cotney | first5 = J. | last6 = Ozduman | first6 = K. | last7 = Avşar | first7 = T. | last8 = Li | first8 = J. | last9 = Murray | first9 = PB. | title = Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO. | journal = Science | volume = 339 | issue = 6123 | pages = 1077-80 | month = Mar | year = 2013 | doi = 10.1126/science.1233009 | PMID = 23348505 }}</ref>
*AKT/TRAF7 mutations are usually basal and associated with meningothelial histology.
*KLF4/TRAF7 mutations are highly specific for secretory histology.
*TRAF7 mutations are the first step and occur thorughout the WD40 domain. <ref>{{cite journal |vauthors=Dogan H, Blume C, Patel A, Jungwirth G, Sogerer L, Ratliff M, Ketter R, Herold-Mende C, Jones DTW, Wick W, Vollmuth P, Zweckberger K, Reuss D, von Deimling A, Sahm F |title=Single-cell DNA sequencing reveals order of mutational acquisition in TRAF7/AKT1 and TRAF7/KLF4 mutant meningiomas |journal=Acta Neuropathol |volume=144 |issue=4 |pages=799–802 |date=October 2022 |pmid=35984495 |doi=10.1007/s00401-022-02485-6 |url=}}</ref>

Intraventricular meningiomas have NF2 mutations.
<ref>{{cite journal |vauthors=Jungwirth G, Warta R, Beynon C, Sahm F, von Deimling A, Unterberg A, Herold-Mende C, Jungk C |title=Intraventricular meningiomas frequently harbor NF2 mutations but lack common genetic alterations in TRAF7, AKT1, SMO, KLF4, PIK3CA, and TERT |journal=Acta Neuropathol Commun |volume=7 |issue=1 |pages=140 |date=August 2019 |pmid=31470906 |pmc=6716845 |doi=10.1186/s40478-019-0793-4 |url=}}</ref>

Several inherited diseases are associated with meningiomas:
*[[Neurofibromatosis]] type II<ref>{{Cite journal | last1 = Fontaine | first1 = B. | last2 = Rouleau | first2 = GA. | last3 = Seizinger | first3 = BR. | last4 = Menon | first4 = AG. | last5 = Jewell | first5 = AF. | last6 = Martuza | first6 = RL. | last7 = Gusella | first7 = JF. | title = Molecular genetics of neurofibromatosis 2 and related tumors (acoustic neuroma and meningioma). | journal = Ann N Y Acad Sci | volume = 615 | issue = | pages = 338-43 | month = | year = 1991 | doi = | PMID = 2039155 }}</ref>
*Germline SMARCE1 and SMARCB1 mutations<ref>{{Cite journal | last1 = Smith | first1 = MJ. | last2 = O'Sullivan | first2 = J. | last3 = Bhaskar | first3 = SS. | last4 = Hadfield | first4 = KD. | last5 = Poke | first5 = G. | last6 = Caird | first6 = J. | last7 = Sharif | first7 = S. | last8 = Eccles | first8 = D. | last9 = Fitzpatrick | first9 = D. | title = Loss-of-function mutations in SMARCE1 cause an inherited disorder of multiple spinal meningiomas. | journal = Nat Genet | volume = 45 | issue = 3 | pages = 295-8 | month = Mar | year = 2013 | doi = 10.1038/ng.2552 | PMID = 23377182 }}</ref><ref>{{Cite journal | last1 = van den Munckhof | first1 = P. | last2 = Christiaans | first2 = I. | last3 = Kenter | first3 = SB. | last4 = Baas | first4 = F. | last5 = Hulsebos | first5 = TJ. | title = Germline SMARCB1 mutation predisposes to multiple meningiomas and schwannomas with preferential location of cranial meningiomas at the falx cerebri. | journal = Neurogenetics | volume = 13 | issue = 1 | pages = 1-7 | month = Feb | year = 2012 | doi = 10.1007/s10048-011-0300-y | PMID = 22038540 }}</ref>
*Loss of SUFU (SHH-Pathway).<ref>{{Cite journal | last1 = Aavikko | first1 = M. | last2 = Li | first2 = SP. | last3 = Saarinen | first3 = S. | last4 = Alhopuro | first4 = P. | last5 = Kaasinen | first5 = E. | last6 = Morgunova | first6 = E. | last7 = Li | first7 = Y. | last8 = Vesanen | first8 = K. | last9 = Smith | first9 = MJ. | title = Loss of SUFU function in familial multiple meningioma. | journal = Am J Hum Genet | volume = 91 | issue = 3 | pages = 520-6 | month = Sep | year = 2012 | doi = 10.1016/j.ajhg.2012.07.015 | PMID = 22958902 }}</ref>
*Rare YAP1 fusions in a subset of pediatric meningioma (HIPPO pathyway).<ref>{{Cite journal | last1 = Sievers | first1 = P. | last2 = Chiang | first2 = J. | last3 = Schrimpf | first3 = D. | last4 = Stichel | first4 = D. | last5 = Paramasivam | first5 = N. | last6 = Sill | first6 = M. | last7 = Gayden | first7 = T. | last8 = Casalini | first8 = B. | last9 = Reuss | first9 = DE. | title = YAP1-fusions in pediatric NF2-wildtype meningioma. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Nov | year = 2019 | doi = 10.1007/s00401-019-02095-9 | PMID = 31734728 }}</ref>

Methylation profiling distinguishes two major groups with six distinct clinically relevant methylation classes.<ref>{{Cite journal | last1 = Sahm | first1 = F. | last2 = Schrimpf | first2 = D. | last3 = Stichel | first3 = D. | last4 = Jones | first4 = DT. | last5 = Hielscher | first5 = T. | last6 = Schefzyk | first6 = S. | last7 = Okonechnikov | first7 = K. | last8 = Koelsche | first8 = C. | last9 = Reuss | first9 = DE. | title = DNA methylation-based classification and grading system for meningioma: a multicentre, retrospective analysis. | journal = Lancet Oncol | volume = | issue = | pages = | month = Mar | year = 2017 | doi = 10.1016/S1470-2045(17)30155-9 | PMID = 28314689 }}</ref>

===DDx of meningioma & IHC<ref name=pmid16393681>{{cite journal |author=Hahn HP, Bundock EA, Hornick JL |title=Immunohistochemical staining for claudin-1 can help distinguish meningiomas from histologic mimics |journal=Am. J. Clin. Pathol. |volume=125 |issue=2 |pages=203–8 |year=2006 |month=February |pmid=16393681 |doi=10.1309/G659-FVVB-MG7U-4RPQ |url=http://ajcp.ascpjournals.org/content/125/2/203.full.pdf}}</ref>===
*S-100 strong +ve - [[schwannoma]].
**+ve in ~80% of fibrous meningiomas.
*CD34 +ve - [[solitary fibrous tumour]].
**+ve in ~60% of [[fibrous meningioma]]s.
*STAT6 nuclear +ve: [[solitary fibrous tumour]].
*[[EMA]] +ve in ~30% of [[solitary fibrous tumour]]/[[hemangiopericytoma]].
*Claudin-1 - new kid on the block: +ve in meningioma, but low [[sensitivity]].
*SSTR2A +ve in meningioma, usu. -ve in [[Perineurioma]] <ref>{{Cite journal | last1 = Agaimy | first1 = A. | last2 = Buslei | first2 = R. | last3 = Coras | first3 = R. | last4 = Rubin | first4 = BP. | last5 = Mentzel | first5 = T. | title = Comparative study of soft tissue perineurioma and meningioma using a five-marker immunohistochemical panel. | journal = Histopathology | volume = 65 | issue = 1 | pages = 60-70 | month = Jul | year = 2014 | doi = 10.1111/his.12366 | PMID = 24393170 }}</ref>
* Progesterone receptor: +ve in mostly grade I and meningeothelial tumors.<ref>{{Cite journal | last1 = Grunberg | first1 = SM. | title = The role of progesterone receptors in meningioma. | journal = Cancer Treat Res | volume = 58 | issue = | pages = 127-37 | month = | year = 1991 | doi = | PMID = 1683782 }}</ref>
* [[Pulmonary meningothelial-like nodule]]

===A standard work-up===
*Ki-67 >5-10% - predicts re-occurrence.<ref>Croul, SE. 8 November 2010.</ref>
*PR (progesterone receptor) +ve in > 80% of meningiomas.<ref>{{Cite journal | last1 = Takei | first1 = H. | last2 = Buckleair | first2 = LW. | last3 = Powell | first3 = SZ. | title = Immunohistochemical expression of apoptosis regulating proteins and sex hormone receptors in meningiomas. | journal = Neuropathology | volume = 28 | issue = 1 | pages = 62-8 | month = Feb | year = 2008 | doi = 10.1111/j.1440-1789.2007.00852.x | PMID = 18021195 }}</ref>
**Loss of PR staining predicts recurrence.
**Strong association with tumour grade:<ref name=pmid22616825>{{Cite journal | last1 = Tao | first1 = Y. | last2 = Liang | first2 = G. | last3 = Li | first3 = Z. | last4 = Wang | first4 = Y. | last5 = Wu | first5 = A. | last6 = Wang | first6 = H. | last7 = Lu | first7 = Y. | last8 = Liu | first8 = Z. | last9 = Hu | first9 = G. | title = Clinical features and immunohistochemical expression levels of androgen, estrogen, progesterone and Ki-67 receptors in relationship with gross-total resected meningiomas relapse. | journal = Br J Neurosurg | volume = | issue = | pages = | month = May | year = 2012 | doi = 10.3109/02688697.2012.685780 | PMID = 22616825 }}</ref>
***Low WHO grade tumours usu. +ve.
***High WHO grade tumours usu. -ve.

==See also==
*[[Neuropathology]].
*[[Neurohistology]].
*[[CNS tumours]].
*[[Pulmonary meningothelial-like nodule]].

==References==
{{Reflist|2}}

[[Category:Neuropathology tumours]]
[[Category:Diagnosis]]

Meningioma

2022-09-19T14:06:49Z

Jensflorian: /* Molecular */ update

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Meningioma_high_mag.jpg
| Width =
| Caption = Meningioma. [[HPS stain]].
| Synonyms =
| Micro = whorled appearance, calcification - [[psammoma bodies|psammomatous]], +/-[[nuclear pseudoinclusions]]
| Subtypes = Grade I (meningothelial, fibrous, transistional, psammomatous, angiomatous, microcystic, secretory, lymphoplasmacyte-rich, metaplastic), Grade II (invasive, clear cell, chordoid), Grade III (papillary, rhabdoid)
| LMDDx = [[schwannoma]], [[solitary fibrous tumour]], [[hemangiopericytoma]], others
| Stains =
| IHC = EMA +ve, [[keratins]] usu. -ve, CD34 -ve/+ve, S-100 -ve (usu.), PR +ve (-ve in more aggressive ones)
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site = see ''[[CNS tumours]]''
| Assdx =
| Syndromes = [[Neurofibromatosis|neurofibromatosis 2]], [[nevoid basal cell carcinoma syndrome]]
| Clinicalhx = +/-radiation
| Signs =
| Symptoms =
| Prevalence = common
| Bloodwork =
| Rads = extra-axial, intradural lesion, dural tail sign (on MRI)
| Endoscopy =
| Prognosis = usually benign, dependent on grade
| Other =
| ClinDDx = dependent on site - see ''[[CNS tumours]]''
| Tx = surgical removal
}}
'''Meningioma''' a very common [[CNS tumours|tumour]] in [[neuropathology]].

==General==
===Prevalence===
*Most common primary brain tumour.<ref name=pmid25343186>{{Cite journal | last1 = Rogers | first1 = L. | last2 = Barani | first2 = I. | last3 = Chamberlain | first3 = M. | last4 = Kaley | first4 = TJ. | last5 = McDermott | first5 = M. | last6 = Raizer | first6 = J. | last7 = Schiff | first7 = D. | last8 = Weber | first8 = DC. | last9 = Wen | first9 = PY. | title = Meningiomas: knowledge base, treatment outcomes, and uncertainties. A RANO review. | journal = J Neurosurg | volume = | issue = | pages = 1-20 | month = Oct | year = 2014 | doi = 10.3171/2014.7.JNS131644 | PMID = 25343186 }}</ref>
*May be caused by prior radiation.<ref name=pmid25249493>{{Cite journal | last1 = Baldi | first1 = I. | last2 = Engelhardt | first2 = J. | last3 = Bonnet | first3 = C. | last4 = Bauchet | first4 = L. | last5 = Berteaud | first5 = E. | last6 = Grüber | first6 = A. | last7 = Loiseau | first7 = H. | title = Epidemiology of meningiomas. | journal = Neurochirurgie | volume = | issue = | pages = | month = Sep | year = 2014 | doi = 10.1016/j.neuchi.2014.05.006 | PMID = 25249493 }}</ref>
*Women develop meningioma twice as likely as men.<ref>{{Cite journal | last1 = Wiemels | first1 = J. | last2 = Wrensch | first2 = M. | last3 = Claus | first3 = EB. | title = Epidemiology and etiology of meningioma. | journal = J Neurooncol | volume = 99 | issue = 3 | pages = 307-14 | month = Sep | year = 2010 | doi = 10.1007/s11060-010-0386-3 | PMID = 20821343 }}</ref>
*More than 90% are solitary.

===Prognosis===
*Most are benign - usu. a good prognosis.
**Even benign tumors may show extensive local spread - considerable morbidity and mortality.
**Metastases are rare and then usu. after surgery.
*May be malignant - bad prognosis.

*Factors associated with unfavourable prognosis:
**BAP1 mutations.<ref>{{Cite journal | last1 = Shankar | first1 = GM. | last2 = Abedalthagafi | first2 = M. | last3 = Vaubel | first3 = RA. | last4 = Merrill | first4 = PH. | last5 = Nayyar | first5 = N. | last6 = Gill | first6 = CM. | last7 = Brewster | first7 = R. | last8 = Bi | first8 = WL. | last9 = Agarwalla | first9 = PK. | title = Germline and somatic BAP1 mutations in high-grade rhabdoid meningiomas. | journal = Neuro Oncol | volume = 19 | issue = 4 | pages = 535-545 | month = 04 | year = 2017 | doi = 10.1093/neuonc/now235 | PMID = 28170043 }}</ref>
**Presence of TERT promotor mutation.<ref>{{Cite journal | last1 = Sahm | first1 = F. | last2 = Schrimpf | first2 = D. | last3 = Olar | first3 = A. | last4 = Koelsche | first4 = C. | last5 = Reuss | first5 = D. | last6 = Bissel | first6 = J. | last7 = Kratz | first7 = A. | last8 = Capper | first8 = D. | last9 = Schefzyk | first9 = S. | title = TERT Promoter Mutations and Risk of Recurrence in Meningioma. | journal = J Natl Cancer Inst | volume = 108 | issue = 5 | pages = | month = May | year = 2016 | doi = 10.1093/jnci/djv377 | PMID = 26668184 }}</ref>
**Loss of H3K27me3.<ref>{{Cite journal | last1 = Katz | first1 = LM. | last2 = Hielscher | first2 = T. | last3 = Liechty | first3 = B. | last4 = Silverman | first4 = J. | last5 = Zagzag | first5 = D. | last6 = Sen | first6 = R. | last7 = Wu | first7 = P. | last8 = Golfinos | first8 = JG. | last9 = Reuss | first9 = D. | title = Loss of histone H3K27me3 identifies a subset of meningiomas with increased risk of recurrence. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Apr | year = 2018 | doi = 10.1007/s00401-018-1844-9 | PMID = 29627952 }}</ref>

===Genetics===
*May be seen in genetic disorders such as:
**[[Neurofibromatosis|Neurofibromatosis 2 (NF2)]].<Ref>URL: [http://moon.ouhsc.edu/kfung/jty1/neurotest/Q13-Ans.htm http://moon.ouhsc.edu/kfung/jty1/neurotest/Q13-Ans.htm]. Accessed on: 26 October 2010.</ref>
**[[Nevoid basal cell carcinoma syndrome]] (Gorlin syndrome).<ref name=pmid15545745>{{Cite journal | last1 = Kimonis | first1 = VE. | last2 = Mehta | first2 = SG. | last3 = Digiovanna | first3 = JJ. | last4 = Bale | first4 = SJ. | last5 = Pastakia | first5 = B. | title = Radiological features in 82 patients with nevoid basal cell carcinoma (NBCC or Gorlin) syndrome. | journal = Genet Med | volume = 6 | issue = 6 | pages = 495-502 | month = | year = | doi = 10.109701.GIM.0000145045.17711.1C | PMID = 15545745 }}</ref><ref>{{Cite journal | last1 = Lee | first1 = CW. | last2 = Tan | first2 = TC. | title = Meningioma associated with Gorlin's syndrome. | journal = J Clin Neurosci | volume = 21 | issue = 2 | pages = 349-50 | month = Feb | year = 2014 | doi = 10.1016/j.jocn.2013.02.033 | PMID = 24100109 }}</ref>

===Quick overview===
{| class="wikitable sortable"
! Name
! Histologic criteria
! Subtypes
! Image
|-
| Classic, WHO I
| less then 4 mit/10 HPF and no atypia
| meningeothelial, fibroblastic, transitional, psammomatous, angiomatous, microcytsic, secretory, lymphoplasmacyte-rich, metaplastic
| [[File:Miningioma_(1)_transitional_type.jpg|thumb|center|150px]]
|-
| Atypical, WHO II
| brain invasion, 4 or more mit/10 HPF, or 3 of the following: necrosis, increased cellularity, high nuc:cyto ratio, nucleoli, sheeting
| chordoid, clear cell
| [[File:Brain_invasion_meningioma.jpg|thumb|center|150px]]
|-
| Anaplastic, WHO III
| 20 or more mitoses/10 HPF, morphologiy similiar to carcinoma or sarcoma
| rhabdoid, papillary
| [[File:Mitoses_anaplastic_meningioma.jpg|thumb|center|150px]]
|}

==Gross/Radiology==
*Extra-axial, intradural.
**Can be extradural - very rare.<ref name=upmc_case702>URL: [http://path.upmc.edu/cases/case702.html http://path.upmc.edu/cases/case702.html]. Accessed on: 2 February 2012.</ref>
*[[Dural tail sign]] (DTS) on MRI.<ref name=pmid22839655>{{Cite journal | last1 = Ikeda | first1 = D. | last2 = Chiocca | first2 = EA. | title = Editorial: dural tail sign. | journal = J Neurosurg | volume = 117 | issue = 4 | pages = 643-4 | month = Oct | year = 2012 | doi = 10.3171/2012.2.JNS12266 | PMID = 22839655 }}</ref><ref name=pmid25238986>{{Cite journal | last1 = Wen | first1 = M. | last2 = Jung | first2 = S. | last3 = Moon | first3 = KS. | last4 = Pei | first4 = J. | last5 = Lee | first5 = KH. | last6 = Jin | first6 = SG. | last7 = Li | first7 = SY. | last8 = Ryu | first8 = HH. | title = Immunohistochemical profile of the dural tail in intracranial meningiomas. | journal = Acta Neurochir (Wien) | volume = 156 | issue = 12 | pages = 2263-73 | month = Dec | year = 2014 | doi = 10.1007/s00701-014-2216-4 | PMID = 25238986 }}</ref>
**Enhancement of dura adjacent to the mass lesion - commonly seen (~70% of cases).<ref name=pmid2120998>{{Cite journal | last1 = Aoki | first1 = S. | last2 = Sasaki | first2 = Y. | last3 = Machida | first3 = T. | last4 = Tanioka | first4 = H. | title = Contrast-enhanced MR images in patients with meningioma: importance of enhancement of the dura adjacent to the tumor. | journal = AJNR Am J Neuroradiol | volume = 11 | issue = 5 | pages = 935-8 | month = | year = | doi = | PMID = 2120998 }}</ref>
**May be subclassified radiologically - predictive of grading.<ref name=pmid22839654>{{Cite journal | last1 = Qi | first1 = ST. | last2 = Liu | first2 = Y. | last3 = Pan | first3 = J. | last4 = Chotai | first4 = S. | last5 = Fang | first5 = LX. | title = A radiopathological classification of dural tail sign of meningiomas. | journal = J Neurosurg | volume = 117 | issue = 4 | pages = 645-53 | month = Oct | year = 2012 | doi = 10.3171/2012.6.JNS111987 | PMID = 22839654 }}</ref>
*+/-Hyperostosis.
**Associated with invasion into the skull in ~20% of cases.<ref name=pmid22406780>{{Cite journal | last1 = Goyal | first1 = N. | last2 = Kakkar | first2 = A. | last3 = Sarkar | first3 = C. | last4 = Agrawal | first4 = D. | title = Does bony hyperostosis in intracranial meningioma signify tumor invasion? A radio-pathologic study. | journal = Neurol India | volume = 60 | issue = 1 | pages = 50-4 | month = | year = | doi = 10.4103/0028-3886.93589 | PMID = 22406780 }}</ref>

<gallery>
File:Keilbeinmeningeom MRT T1KMax.jpg | Sphenoid wing meningioma (WC/Hellerhoff)
File:Meningioma.jpg | Brain displacement by meningioma (AFIP)
File:Meningioma-1.jpg | Macroscopy (Всеволод Лучанский (vvray))
</gallery>

==Microscopic==
Features (memory device ''WCN''):
*Whorled appearance - '''key feature'''.
*Calcification, [[psammoma bodies|psammomatous]] (target-like appearance; (tight) onion skin).
*+/-[[Nuclear pseudoinclusions]] - focal nuclear clearing with a sharp interface to unremarkable chromatin.

Notes:
*May involute into benign sclerotic tissue.<ref>URL: [http://radiographics.rsna.org/content/23/3/785.long http://radiographics.rsna.org/content/23/3/785.long]. Accessed on: 3 November 2010.</ref>
*Thick-walled blood vessels -> think [[schwannoma]].

DDx:
*[[Schwannoma]] - especially at [[CP angle]].
*[[Solitary fibrous tumour]].
*[[Hemangiopericytoma]].
*Others - see subtypes.

===Images===
<Gallery>
Image:Meningioma_high_mag.jpg | Meningioma - high mag. (WC)
Image:Meningioma_intermed_mag.jpg | Meningioma - intermed. mag. (WC)
Image:Meningioma_-_brain_invasion_-_intermed_mag.jpg | Meningioma with brain invasion - intermed. mag. (WC)
Image:Meningioma_-_brain_invasion_-_high_mag.jpg | Meningioma with brain invasion - high mag. (WC)
File:Meningeotheliomatous_meningeoma_whorl_formations.jpg | Whorls in meningioma. (WC)
File:Image NP T1c 0001.JPG | Whorls in meningioma. (WC)
File:Image NP T1c 0004.JPG | Meningioma annotated. (WC)
</gallery>
www:
*[http://www.neuropathologyweb.org/chapter7/chapter7dMiscellaneous.html Meningioma (neuropathologyweb.org)].
*[http://path.upmc.edu/cases/case702.html Extra-dural meningioma (upmc.edu)].

===Morphologic subtypes===
*Many subtypes exist.<ref name=Ref_PSNP194>{{Ref PSNP|194}}</ref>
*The histologic subtypes generally don't have much prognostic significance.
**Some subtypes are high grade by definition; also see ''histologic grading''.

====Grade I====
=====Meningothelial meningioma=====
*Most common.

Microscopic:
*Syncytial, nuclear clearing ([[pseudoinclusions]]).
*Whorls, Onion bulb formations.
*Few psammoma bodies.

Molecular:
*AKT E17K mutations.<ref>{{Cite journal | last1 = Sahm | first1 = F. | last2 = Bissel | first2 = J. | last3 = Koelsche | first3 = C. | last4 = Schweizer | first4 = L. | last5 = Capper | first5 = D. | last6 = Reuss | first6 = D. | last7 = Böhmer | first7 = K. | last8 = Lass | first8 = U. | last9 = Göck | first9 = T. | title = AKT1E17K mutations cluster with meningothelial and transitional meningiomas and can be detected by SFRP1 immunohistochemistry. | journal = Acta Neuropathol | volume = 126 | issue = 5 | pages = 757-62 | month = Nov | year = 2013 | doi = 10.1007/s00401-013-1187-5 | PMID = 24096618 }}</ref>

<gallery>
Meningeotheliomatous_meningeoma_whorl_formations.jpg | Syncytial appearance, whorl formations (WC/jensflorian)
File:Meningioma_showing_Psammoma_body.jpg | Psammoma body (WC/Netha Hussain)
File:Meningioma_cytologie.jpg | Onion bulb formation in smear (WC/jensflorian)
File:Meningioma_intermed_mag.jpg | Meningioma HPS stain (WC/Nephron)
</gallery>

=====Fibrous meningioma=====
*[[AKA]] ''fibroblastic meningioma''.
*'''Not''' collagen... but looks like it.
**It is really laminin or fibronectin.
*Spindle cells in parallel bundles.
*Few to none whorl formations.

<gallery>
File:Meningioma_fibromatous_variant.jpg | Fibrous meingioma (WC)
File:Miningioma_(4)_EMA.JPG | EMA staining (WC/marvin 101)
</gallery>

=====Transitional meningioma=====
*AKA mixed.
*Common.
*Lobular and fasicular growth patterns coexist.
*Usu. a mixture of meningeothelial and fibromatous meningioma

<gallery>
File:Miningioma_(1)_transitional_type.jpg | Low power (WC/KGH)
File:Miningioma_(2)_transitional_type.jpg | Intermed magnification (WC/KGH)
File:Prominent mitosis meningioma.jpg | Mitosis in a transitional meningioma (WC/jensflorian)
</gallery>

=====Psammomatous meningioma=====
Microscopic:
*[[Psammoma bodies]] dominate over tumor cells.
**Irregular calcifications (confluent psammoma bodies).
*Usually found in spinal cord.

<gallery>
File:Psammomatous_meningioma.jpg | Numerous psammoma bodies (WC/jensflorian)
File:NP psammomatous meningioma 0002.jpg | Psammomatous meningioma after EDTA treatment (WC)
</gallery>

=====Angiomatous meningioma=====
*AKA vascular.
*May bleed like stink.
*May show extensive edema.
*Hyalinized vessels dominate over tumor cells.
*Degenerative nuclear atypia.

DDx:
*Vascular malformatons
*Hemangioblastoma

<gallery>
File:Angiomatous_meningioma_HE_x100.jpg | Angiomatous meningioma (WC/jensflorian)
</gallery>

=====Microcystic meningioma=====
Microscopic:
*Cystic appearance.
*Increased cytologic pleomorphism of the elongated cells.

DDx:
*Clear cell meningioma
*Hemangioblastoma

<gallery>
File:Microcystic_meningeoma_HE_x100.jpg | Microcyts (WC/jensflorian)
</gallery>

=====Secretory meningioma=====
*Associated with brain edema; may have a worse outcome.

Microscopic:<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/Com04/Com405-1-Diss.htm http://moon.ouhsc.edu/kfung/jty1/Com04/Com405-1-Diss.htm]. Accessed on: 12 October 2011.</ref>
*Eosinophilic intracytoplasmic inclusions that are [[CEA]] +ve and [[PAS]] +ve.

Molecular:
* Combined KLF4 K409Q and TRAF7 mutations.<ref>{{Cite journal | last1 = Reuss | first1 = DE. | last2 = Piro | first2 = RM. | last3 = Jones | first3 = DT. | last4 = Simon | first4 = M. | last5 = Ketter | first5 = R. | last6 = Kool | first6 = M. | last7 = Becker | first7 = A. | last8 = Sahm | first8 = F. | last9 = Pusch | first9 = S. | title = Secretory meningiomas are defined by combined KLF4 K409Q and TRAF7 mutations. | journal = Acta Neuropathol | volume = 125 | issue = 3 | pages = 351-8 | month = Mar | year = 2013 | doi = 10.1007/s00401-013-1093-x | PMID = 23404370 }}</ref>

DDx:
*Metastatic [[mucinous adenocarcinoma]].
*Pituitary adenoma

<gallery>
File:Secretory_meningioma_HE_x200.jpg | Secretory granules (WC/jensflorian)
File:Secretory_meningioma_PAS.jpg | PAS-positive secretory granules (WC/jensflorian)
File:Secretory_meningioma_HE_smear.jpg | Smear with secretory granules (WC/jensflorian)
</gallery>

Images:
*[http://moon.ouhsc.edu/kfung/jty1/Com04/Com04Image/Com405-1-8.gif Secretory meningioma (ouhsc.edu)].<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/Com04/Com405-1-Diss.htm http://moon.ouhsc.edu/kfung/jty1/Com04/Com405-1-Diss.htm]. Accessed on: 3 January 2012.</ref>
*[http://path.upmc.edu/cases/case370.html Secretory meningioma - several images (upmc.edu)].

=====Lymphoplasmacyte-rich meningioma=====
Microscopic:
*Lymphocytes.
*Plasma cells.

Images:
*[http://path.upmc.edu/cases/case225/micro.html Lymphoplasmacyte-rich meningioma - case 1 - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case247/micro.html Lymphoplasmacyte-rich meningioma - case 2 - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case528.html Lymphoplasmacyte-rich meningioma - case 3 - several images (upmc.edu)].

=====Metaplastic meningioma=====
*No clinical significance.
*Probably do not represent true metaplasia in all cases.
*Clincal information is rquired to distinguish between bone invasion and meningiomas with bone formation.

Microscopic:
*Cartilage or bone formation.
*Myxoid or xanthomatous changes.

<gallery>
File:Metaplastic_osseous_meningioma.jpg | Ossified meningioma, HE stain. (WC/jensflorian)
File:Metaplastic_xanthomatous_meningioma.jpg | Metaplastic meningioma with xanthomatous changes. (WC/jensflorian)
</gallery>

====Grade II====
=====Brain invasive meningioma=====
*Invades the brain (irregular, tongue-like).
*Absence of leptomeningeal layer.
*Brain invasion can be present in grade I tumors, these are then classified as "atypical", ie. as grade II tumors.
*The prognostic significance of brain invasion is still unclear, some studies do not show a course similiar to grade II meningiomas.<ref>{{Cite journal | last1 = Baumgarten | first1 = P. | last2 = Gessler | first2 = F. | last3 = Schittenhelm | first3 = J. | last4 = Skardelly | first4 = M. | last5 = Tews | first5 = DS. | last6 = Senft | first6 = C. | last7 = Dunst | first7 = M. | last8 = Imoehl | first8 = L. | last9 = Plate | first9 = KH. | title = Brain invasion in otherwise benign meningiomas does not predict tumor recurrence. | journal = Acta Neuropathol | volume = 132 | issue = 3 | pages = 479-81 | month = Sep | year = 2016 | doi = 10.1007/s00401-016-1598-1 | PMID = 27464983 }}</ref><ref>{{Cite journal | last1 = Brokinkel | first1 = B. | last2 = Hess | first2 = K. | last3 = Mawrin | first3 = C. | title = Brain invasion in Meningiomas - Clinical considerations and impact of neuropathological evaluation: A systematic Review. | journal = Neuro Oncol | volume = | issue = | pages = | month = Apr | year = 2017 | doi = 10.1093/neuonc/nox071 | PMID = 28419308 }}</ref><ref>{{Cite journal | last1 = Pizem | first1 = J. | last2 = Velnar | first2 = T. | last3 = Prestor | first3 = B. | last4 = Mlakar | first4 = J. | last5 = Popovic | first5 = M. | title = Brain invasion assessability in meningiomas is related to meningioma size and grade, and can be improved by extensive sampling of the surgically removed meningioma specimen. | journal = Clin Neuropathol | volume = 33 | issue = 5 | pages = 354-63 | month = | year = | doi = 10.5414/NP300750 | PMID = 25034703 }}</ref>

Images:
*[http://moon.ouhsc.edu/kfung/jty1/Composites/FNA0IE18-Meningioma-Invasion.htm Meningioma with brain invasion (ouhsc.edu)].

<gallery>
File:Brain invasion meningioma.jpg | Finger-like protrusions, HE (WC/jensflorian)
File:Meningioma - brain invasion - very high mag.jpg | Brain invasive meningooma (WC/Nephron)
</gallery>

=====Clear cell meningioma=====
Epidemiology:
*Usu. spinal cord.<ref>{{Ref PSNP|200}}</ref>

Microscopic:
*Clear cells - contain glycogen (PAS +ve).

<gallery>
File:HE_clear_cell_meningioma.jpg | Clear cell meningioma, HE (WC/jensflorian)
</gallery>

Molecular:
*SMARCE1 mutations.<ref>{{Cite journal | last1 = Smith | first1 = MJ. | last2 = Wallace | first2 = AJ. | last3 = Bennett | first3 = C. | last4 = Hasselblatt | first4 = M. | last5 = Elert-Dobkowska | first5 = E. | last6 = Evans | first6 = LT. | last7 = Hickey | first7 = WF. | last8 = van Hoff | first8 = J. | last9 = Bauer | first9 = D. | title = Germline SMARCE1 mutations predispose to both spinal and cranial clear cell meningiomas. | journal = J Pathol | volume = 234 | issue = 4 | pages = 436-40 | month = Dec | year = 2014 | doi = 10.1002/path.4427 | PMID = 25143307 }}</ref>

Images:
*[http://www.surgicalpathologyatlas.com/glfusion/mediagallery/media.php?f=0&sort=0&s=20080802174938386 Clear cell meningioma (surgicalpathologyatlas.com)].
*[http://blog.lib.umn.edu/santa013/neuropathology/2009/10/meningioma-with-clear-cell-features.html Clear cell meningioma (umn.edu)].

=====Chordoid meningioma=====
*Chordoma-like.

Microscopic:
*[[Myxoid]] appearance.

<gallery>
File:Chordoid meningoma HE x200.jpg | Chordoid meningioma - HE (WC/jensflorian)
File:Alcian blue chordoid meningioma.jpg | Chordoid meningioma - alcian blue (WC/jensflorian)
</gallery>

Image:
*[http://frontalcortex.com/?page=oll&topic=24&qid=914 Chordoid meningioma (frontalcortex.com)].

====Grade III====
=====Papillary meningioma=====
Microscopic:
*discohesive meningothelial tumour cells around a fibrovascular core.
*perivascular pseudorosettes.

<gallery>
File:Papillary meningioma HE.jpg | Papillary meningioma (WC/jensflorian)
File:Pap meningioma.jpg | Papillary meningioma (WC)
</gallery>

=====Rhabdoid meningioma=====
Microscopic:
*Rhabdoid appearance (abundant cytoplasm).
**Cross-striations.

<gallery>
Image:Rhabdoid Meningioma Histopathology.jpg | Rhabdoid meningioma. (WC/Marvin 101)
File:Rhabdoid meningioma frozen section HE.jpg | Frozen section (WC/jensflorian)
</gallery>
www:
*[http://path.upmc.edu/cases/case373.html Rhabdoid meningioma - case 1 - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case393.html Rhabdoid meningioma - case 2 - several images (upmc.edu)].

====Other morphological variants====
These are currently not listed in the WHO as separate entities.
*Oncocytic.<ref>{{Cite journal | last1 = Zunarelli | first1 = E. | last2 = Tallarico | first2 = E. | last3 = Valentini | first3 = A. | last4 = Maiorana | first4 = A. | title = Oncocytic meningioma: study of eight new cases and analysis of 13 reported cases. | journal = Pathology | volume = 42 | issue = 6 | pages = 587-9 | month = | year = 2010 | doi = 10.3109/00313025.2010.508740 | PMID = 20854082 }}</ref>
*Whorling-sclerosing.<ref>{{Cite journal | last1 = Haberler | first1 = C. | last2 = Jarius | first2 = C. | last3 = Lang | first3 = S. | last4 = Rössler | first4 = K. | last5 = Gruber | first5 = A. | last6 = Hainfellner | first6 = JA. | last7 = Budka | first7 = H. | title = Fibrous meningeal tumours with extensive non-calcifying collagenous whorls and glial fibrillary acidic protein expression: the whorling-sclerosing variant of meningioma. | journal = Neuropathol Appl Neurobiol | volume = 28 | issue = 1 | pages = 42-7 | month = Feb | year = 2002 | doi = | PMID = 11849562 }}</ref>
*Rosette-forming.<ref>{{Cite journal | last1 = Liverman | first1 = C. | last2 = Mafra | first2 = M. | last3 = Chuang | first3 = SS. | last4 = Shivane | first4 = A. | last5 = Chakrabarty | first5 = A. | last6 = Highley | first6 = R. | last7 = Hilton | first7 = DA. | last8 = Byrne | first8 = NP. | last9 = Wesseling | first9 = P. | title = A clinicopathologic study of 11 rosette-forming meningiomas: a rare and potentially confusing pattern. | journal = Acta Neuropathol | volume = 130 | issue = 2 | pages = 311-3 | month = Aug | year = 2015 | doi = 10.1007/s00401-015-1456-6 | PMID = 26106026 }}</ref>

<gallery>
File:Meningioma_Whorling_sclerosing.jpg | Whorling-sclerosing features in meningioma (HE/jensflorian)
File:Meningioma_pseudorosettes.jpg | Meningioma with rosette-forming features (HE/jensflorian)
</gallery>

===Histologic grading===
Grading:<ref name=Ref_PSNP194>{{Ref PSNP|194}}</ref>
*Grade 1:
**Low mitotic rate (< 4 mitoses/10 HPF - for whatever HPF means, see [[HPFitis]]).
**Excludes ''clear cell'', ''chordoid'', ''papillary'', and ''rhabdoid'' subtypes.
*Grade 2 (either #1, #2 or #3):
*#Brain-invasive meningioma.
*#*Invasion of meningioma into brain.
*#**Meninogioma with entraped GFAP +ve tissue.
*#Atypical meningioma (by histomorphology) - either ''A'' or ''B''.
*#* A. Intermediate mitotic rate (>= 4 mitoses/10 HPF - for whatever ''HPF'' means, see [[HPFitis]].)
*#* B. Three of the following five features:
*#*#Sheeting architecture.
*#*#High [[NC ratio]] clusters; clusters of "lymphocyte-like" cells.
*#*#Hypercellularity.
*#*#Macronucleoli.
*#*#[[Necrosis]] not caused by treatment, e.g. radiation or embolization.
*#''Clear cell'' or ''chordoid'' subtype.
*Grade 3 (either of the following):
**High mitotic rate (>=20 mitoses/10 HPF - for whatever ''HPF'' means, see [[HPFitis]].)
**"Frank anaplasia"; marked nuclear atypia.
**''Papillary'' or ''rhabdoid'' subtype.

Notes:
*Grade II soft criteria memory device ''HMNs'': hypercellular, macronucleoli, NC ratio increased, necrosis, sheeting.

==IHC==
*EMA +ve (approx. 90%).<ref name=Ref_PSNP13>{{Ref PSNP|13}}</ref>
*PR +ve (approx. 75%, expression decreases from grade I to III).
*SSTR2A +ve (approx. 95%).
*S100 variable (up to 35% cases, usually patchy).
*SOX10 -ve.
*GFAP -ve.
*CD34 usu. -ve (approx 8% cases positive).
*Other CKs usually -ve (approx 6% cases positive, mostly secretory meningiomas).

==Molecular==
Non-syndromal meningiomas may show AKT1/TRAF7, SMO, KLF4/TRAF7, and PIK3CA mutations (1/3 of cases).<ref>{{Cite journal | last1 = Clark | first1 = VE. | last2 = Erson-Omay | first2 = EZ. | last3 = Serin | first3 = A. | last4 = Yin | first4 = J. | last5 = Cotney | first5 = J. | last6 = Ozduman | first6 = K. | last7 = Avşar | first7 = T. | last8 = Li | first8 = J. | last9 = Murray | first9 = PB. | title = Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO. | journal = Science | volume = 339 | issue = 6123 | pages = 1077-80 | month = Mar | year = 2013 | doi = 10.1126/science.1233009 | PMID = 23348505 }}</ref>
*AKT/TRAF7 mutations are usually basal and associated with meningothelial histology.
*KLF4/TRAF7 mutations are highly specific for secretory histology.
*TRAF7 mutations are the first step and occur thorughout the WD40 domain. <ref>{{cite journal |vauthors=Dogan H, Blume C, Patel A, Jungwirth G, Sogerer L, Ratliff M, Ketter R, Herold-Mende C, Jones DTW, Wick W, Vollmuth P, Zweckberger K, Reuss D, von Deimling A, Sahm F |title=Single-cell DNA sequencing reveals order of mutational acquisition in TRAF7/AKT1 and TRAF7/KLF4 mutant meningiomas |journal=Acta Neuropathol |volume=144 |issue=4 |pages=799–802 |date=October 2022 |pmid=35984495 |doi=10.1007/s00401-022-02485-6 |url=}}</ref>

Intraventricular meningiomas have NF2 mutations.
<ref>{{cite journal |vauthors=Jungwirth G, Warta R, Beynon C, Sahm F, von Deimling A, Unterberg A, Herold-Mende C, Jungk C |title=Intraventricular meningiomas frequently harbor NF2 mutations but lack common genetic alterations in TRAF7, AKT1, SMO, KLF4, PIK3CA, and TERT |journal=Acta Neuropathol Commun |volume=7 |issue=1 |pages=140 |date=August 2019 |pmid=31470906 |pmc=6716845 |doi=10.1186/s40478-019-0793-4 |url=}}</ref>

Several inherited diseases are associated with meningiomas:
*[[Neurofibromatosis]] type II<ref>{{Cite journal | last1 = Fontaine | first1 = B. | last2 = Rouleau | first2 = GA. | last3 = Seizinger | first3 = BR. | last4 = Menon | first4 = AG. | last5 = Jewell | first5 = AF. | last6 = Martuza | first6 = RL. | last7 = Gusella | first7 = JF. | title = Molecular genetics of neurofibromatosis 2 and related tumors (acoustic neuroma and meningioma). | journal = Ann N Y Acad Sci | volume = 615 | issue = | pages = 338-43 | month = | year = 1991 | doi = | PMID = 2039155 }}</ref>
*Germline SMARCE1 and SMARCB1 mutations<ref>{{Cite journal | last1 = Smith | first1 = MJ. | last2 = O'Sullivan | first2 = J. | last3 = Bhaskar | first3 = SS. | last4 = Hadfield | first4 = KD. | last5 = Poke | first5 = G. | last6 = Caird | first6 = J. | last7 = Sharif | first7 = S. | last8 = Eccles | first8 = D. | last9 = Fitzpatrick | first9 = D. | title = Loss-of-function mutations in SMARCE1 cause an inherited disorder of multiple spinal meningiomas. | journal = Nat Genet | volume = 45 | issue = 3 | pages = 295-8 | month = Mar | year = 2013 | doi = 10.1038/ng.2552 | PMID = 23377182 }}</ref><ref>{{Cite journal | last1 = van den Munckhof | first1 = P. | last2 = Christiaans | first2 = I. | last3 = Kenter | first3 = SB. | last4 = Baas | first4 = F. | last5 = Hulsebos | first5 = TJ. | title = Germline SMARCB1 mutation predisposes to multiple meningiomas and schwannomas with preferential location of cranial meningiomas at the falx cerebri. | journal = Neurogenetics | volume = 13 | issue = 1 | pages = 1-7 | month = Feb | year = 2012 | doi = 10.1007/s10048-011-0300-y | PMID = 22038540 }}</ref>
*Loss of SUFU (SHH-Pathway).<ref>{{Cite journal | last1 = Aavikko | first1 = M. | last2 = Li | first2 = SP. | last3 = Saarinen | first3 = S. | last4 = Alhopuro | first4 = P. | last5 = Kaasinen | first5 = E. | last6 = Morgunova | first6 = E. | last7 = Li | first7 = Y. | last8 = Vesanen | first8 = K. | last9 = Smith | first9 = MJ. | title = Loss of SUFU function in familial multiple meningioma. | journal = Am J Hum Genet | volume = 91 | issue = 3 | pages = 520-6 | month = Sep | year = 2012 | doi = 10.1016/j.ajhg.2012.07.015 | PMID = 22958902 }}</ref>
*Rare YAP1 fusions in a subset of pediatric meningioma (HIPPO pathyway).<ref>{{Cite journal | last1 = Sievers | first1 = P. | last2 = Chiang | first2 = J. | last3 = Schrimpf | first3 = D. | last4 = Stichel | first4 = D. | last5 = Paramasivam | first5 = N. | last6 = Sill | first6 = M. | last7 = Gayden | first7 = T. | last8 = Casalini | first8 = B. | last9 = Reuss | first9 = DE. | title = YAP1-fusions in pediatric NF2-wildtype meningioma. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Nov | year = 2019 | doi = 10.1007/s00401-019-02095-9 | PMID = 31734728 }}</ref>

Methylation profiling distinguishes two major groups with six distinct clinically relevant methylation classes.<ref>{{Cite journal | last1 = Sahm | first1 = F. | last2 = Schrimpf | first2 = D. | last3 = Stichel | first3 = D. | last4 = Jones | first4 = DT. | last5 = Hielscher | first5 = T. | last6 = Schefzyk | first6 = S. | last7 = Okonechnikov | first7 = K. | last8 = Koelsche | first8 = C. | last9 = Reuss | first9 = DE. | title = DNA methylation-based classification and grading system for meningioma: a multicentre, retrospective analysis. | journal = Lancet Oncol | volume = | issue = | pages = | month = Mar | year = 2017 | doi = 10.1016/S1470-2045(17)30155-9 | PMID = 28314689 }}</ref>

===DDx of meningioma & IHC<ref name=pmid16393681>{{cite journal |author=Hahn HP, Bundock EA, Hornick JL |title=Immunohistochemical staining for claudin-1 can help distinguish meningiomas from histologic mimics |journal=Am. J. Clin. Pathol. |volume=125 |issue=2 |pages=203–8 |year=2006 |month=February |pmid=16393681 |doi=10.1309/G659-FVVB-MG7U-4RPQ |url=http://ajcp.ascpjournals.org/content/125/2/203.full.pdf}}</ref>===
*S-100 strong +ve - [[schwannoma]].
**+ve in ~80% of fibrous meningiomas.
*CD34 +ve - [[solitary fibrous tumour]].
**+ve in ~60% of [[fibrous meningioma]]s.
*STAT6 nuclear +ve: [[solitary fibrous tumour]].
*[[EMA]] +ve in ~30% of [[solitary fibrous tumour]]/[[hemangiopericytoma]].
*Claudin-1 - new kid on the block: +ve in meningioma, but low [[sensitivity]].
*SSTR2A +ve in meningioma, usu. -ve in [[Perineurioma]] <ref>{{Cite journal | last1 = Agaimy | first1 = A. | last2 = Buslei | first2 = R. | last3 = Coras | first3 = R. | last4 = Rubin | first4 = BP. | last5 = Mentzel | first5 = T. | title = Comparative study of soft tissue perineurioma and meningioma using a five-marker immunohistochemical panel. | journal = Histopathology | volume = 65 | issue = 1 | pages = 60-70 | month = Jul | year = 2014 | doi = 10.1111/his.12366 | PMID = 24393170 }}</ref>
* Progesterone receptor: +ve in mostly grade I and meningeothelial tumors.<ref>{{Cite journal | last1 = Grunberg | first1 = SM. | title = The role of progesterone receptors in meningioma. | journal = Cancer Treat Res | volume = 58 | issue = | pages = 127-37 | month = | year = 1991 | doi = | PMID = 1683782 }}</ref>
* [[Pulmonary meningothelial-like nodule]]

===A standard work-up===
*Ki-67 >5-10% - predicts re-occurrence.<ref>Croul, SE. 8 November 2010.</ref>
*PR (progesterone receptor) +ve in > 80% of meningiomas.<ref>{{Cite journal | last1 = Takei | first1 = H. | last2 = Buckleair | first2 = LW. | last3 = Powell | first3 = SZ. | title = Immunohistochemical expression of apoptosis regulating proteins and sex hormone receptors in meningiomas. | journal = Neuropathology | volume = 28 | issue = 1 | pages = 62-8 | month = Feb | year = 2008 | doi = 10.1111/j.1440-1789.2007.00852.x | PMID = 18021195 }}</ref>
**Loss of PR staining predicts recurrence.
**Strong association with tumour grade:<ref name=pmid22616825>{{Cite journal | last1 = Tao | first1 = Y. | last2 = Liang | first2 = G. | last3 = Li | first3 = Z. | last4 = Wang | first4 = Y. | last5 = Wu | first5 = A. | last6 = Wang | first6 = H. | last7 = Lu | first7 = Y. | last8 = Liu | first8 = Z. | last9 = Hu | first9 = G. | title = Clinical features and immunohistochemical expression levels of androgen, estrogen, progesterone and Ki-67 receptors in relationship with gross-total resected meningiomas relapse. | journal = Br J Neurosurg | volume = | issue = | pages = | month = May | year = 2012 | doi = 10.3109/02688697.2012.685780 | PMID = 22616825 }}</ref>
***Low WHO grade tumours usu. +ve.
***High WHO grade tumours usu. -ve.

==See also==
*[[Neuropathology]].
*[[Neurohistology]].
*[[CNS tumours]].
*[[Pulmonary meningothelial-like nodule]].

==References==
{{Reflist|2}}

[[Category:Neuropathology tumours]]
[[Category:Diagnosis]]

Ependymoma

2022-09-19T13:20:31Z

Jensflorian: /* Microscopic */ Spinal ependymoma

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Ependymoma_H%26E.jpg
| Width =
| Caption = Ependymoma grade II WHO. [[H&E stain]]
| Synonyms =
| Micro = Perivascular pseudorosettes, ependymal rosettes
| Subtypes = Tanycytic, Clear cell, Papillary, Cellular
| LMDDx = [[Subependymoma]], [[Glioblastoma]], [[Pilocytic astrocytoma]], [[Oligodendroglioma]]
| Stains =
| IHC = GFAP +ve
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site =
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence =
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis = intermediate to poor (WHO Grades II & III)
| Other =
| ClinDDx =
| Tx =
}}

'''Ependymoma''' is a [[neuropathology tumour]].

==General==
*Called the forgotten glial tumour.
*Anatomic location and molecular data is essential for tumor diagnosis.

Epidemiology:<ref name=Ref_PBoD8_1334>{{Ref PBoD8|1334}}</ref>
*Usual site:
**Adults: usually spinal cord.
**Children: usually posterior fossa.
*May be associated with [[neurofibromatosis type 2]].

There are currently ten main ependymal tumors:<ref name=Ref_WHOCNS_74>{{Ref WHOCNS|74}}</ref>
#Supratentorial [[Subependymoma]]
#Supratentorial ependymoma, ZFTA-fusion positive
#Supratentorial ependymoma, YAP1-fusion positive
#Posterior fossa [[Subependymoma]]
#Posterior fossa ependymoma group A
#Posterior fossa ependymoma group B
#Spinal [[Subependymoma]]
#Spinal ependymoma
#Spinal ependymoma, MYCN-amplified
#[[Myxopapillary ependymoma]]

Ependymoma, NOS (not otherwise specified): Molecular analysis still missing.
Ependymoma, NEC (not elsewhere classfied): Tumor cannot assigned to any of the defined entities.

Note: Molecularly defined ependymomas can be still graded as CNS grade 2 or 3 depending on histological features.

*Depreceated terminologies:
**Papillary ependymoma.
**Clear cell ependymoma.
**Tanycytic ependymoma.
**Cellular ependymoma.
**Ependymoma, RELA fusion-positive.<ref>{{Cite journal | last1 = Parker | first1 = M. | last2 = Mohankumar | first2 = KM. | last3 = Punchihewa | first3 = C. | last4 = Weinlich | first4 = R. | last5 = Dalton | first5 = JD. | last6 = Li | first6 = Y. | last7 = Lee | first7 = R. | last8 = Tatevossian | first8 = RG. | last9 = Phoenix | first9 = TN. | title = C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. | journal = Nature | volume = 506 | issue = 7489 | pages = 451-5 | month = Feb | year = 2014 | doi = 10.1038/nature13109 | PMID = 24553141 }}</ref><ref>{{Cite journal | last1 = Pietsch | first1 = T. | last2 = Wohlers | first2 = I. | last3 = Goschzik | first3 = T. | last4 = Dreschmann | first4 = V. | last5 = Denkhaus | first5 = D. | last6 = Dörner | first6 = E. | last7 = Rahmann | first7 = S. | last8 = Klein-Hitpass | first8 = L. | title = Supratentorial ependymomas of childhood carry C11orf95-RELA fusions leading to pathological activation of the NF-κB signaling pathway. | journal = Acta Neuropathol | volume = 127 | issue = 4 | pages = 609-11 | month = Apr | year = 2014 | doi = 10.1007/s00401-014-1264-4 | PMID = 24562983 }}</ref> This is now called Supratentorial ependymoma, ZFTA-fusion positive.
**Anaplastic ependymoma. This is now called CNS grade 3 ependymoma.

==Gross==
*Usually discrete and enhancing.
*Ventricular location, but also within the spinal cord.
*Dissemination possible.
*[[Myxopapillary ependymoma]] classically at [[filum terminale]].
*[[Subependymoma]] typically seen in IVth ventricle.
<gallery>
File:AFIP405711R-EPENDYMOMA.jpg | Radiology (AFIP)
File:AFIP405713G-EPENDYMOMA.jpg | Ependymoma in the fourth ventricle (AFIP)
File:Ependymoma in the fourth ventricle.jpg | Gross (AFIP)
</gallery>

==Microscopic==
==="Classic" ependymoma===
*Come in two CNS WHO grades: 2 and 3.
*Usu. sharply demarcated from surrounding brain parenchyma.
Features:
*Cells have a "tadpole-like" morphology.
**May also be described as ''ice cream cone-shaped''.<ref>[http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html]</ref>
*'''Rosettes''' = circular nuclear free zones/cells arranged in a pseudoglandular fashion; comes in two flavours in ependymoma:
**''Perivascular pseudorosettes'' = (tumour) cells arranged around a blood vessel; nuclei of cells distant from the blood vessel, i.e. rim of cytoplasm (from tumour cells) surround blood vessel (nucleus-free zone); more common than ependymal rosette... but less specific.
**''Ependymal rosette'' ([[AKA]] ''true ependymal rosette'') = rosette has an empty space at the centre - '''key feature'''.
*Nuclear features monotonous, i.e. "boring".<ref>MUN. 6 Oct 2009.</ref>
**There is little variation in size, shape and staining.
*Hyalinized vessels.
*Calcification.
*Rare cases with cartilagineous metaplasia.<ref>{{Cite journal | last1 = Wang | first1 = X. | last2 = Zhang | first2 = S. | last3 = Ye | first3 = Y. | last4 = Chen | first4 = Y. | last5 = Liu | first5 = X. | title = Ependymoma with cartilaginous metaplasia might have more aggressive behavior: a case report and literature review. | journal = Brain Tumor Pathol | volume = 29 | issue = 3 | pages = 172-6 | month = Jul | year = 2012 | doi = 10.1007/s10014-011-0079-4 | PMID = 22228122 }}</ref>
*Branching capillaries usu. only in supratentorial ependymomas.

===Supratentorial ependymoma===
*Usu. connected to the ventricles.
*Mostly frontal or temporal lobe.
*Approx. 1/3 of all ependymal tumours (41% in children).
*Irregular CM enhancement.
*YAP1-fused tumors in children oft large at time of diagnosis.
*Cysts and/or calcification possible.
*Sharply demarcated from adjacent brain parenchyma.
*True ependymal rosettes are rare.
*Occasionally branching capillary vessels.
*Clear cell phenotypes more common than in other locations.
*Complete surgical resection is the best predictor.
*CSF spread in up to 15% of tumours.

===Posterior fossa ependymoma===
*Usu. 4th ventricle, less common in CPA.
*Most frequent in children.
*May contain tumour nodules with increased cell density.
*Micocysts, vascular hyalinization and calcification can be present.
*No morphologic differences between Group A and B tumours.
*Perivascular pseudorosettes almost always present.
*Rare papillary or tanicytic patterns.

DDx (supratentorial and posterior fossa ependymoma):
*[[Subependymoma]].
*[[Glioblastoma]] (GBM).
*Gliomas with BCOR internal tandem duplication.
*[[Astroblastoma]], MN1-altered.
**Invasive border = GBM; circumscribed border of lesion = ependymoma.
*[[Oligodendroglioma]] (Clear cell ependymoma))
*CNS embryonal tumour with BCOR internal tandem duplication.

===Spinal ependymoma===
*Isomorphic nuclei.
*Mitotic activity usu. very low.
*Calcification, hemorrhage, cystic and/or metaplastic changes may be seen.
*Most tumours show CNS grade 2 histology.
**CNS grade 3 tumours should be examined for MYCN amplification.
*Outcome usu. good, extent of resection is prognostic.

DDx (spinal ependymoma):
*[[Pilocytic astrocytoma]] (Tanycytic ependymoma)
*Diffuse midline glioma, H3 K27-altered
*Small cell glioblastoma (MYCN-amplified spinal ependymoma)

===Images===
www:
*[http://www.flickr.com/photos/ckrishnan/3862487821/in/photostream Ependymoma (flickr.com)].
*[http://www.ajnr.org/cgi/content-nw/full/27/3/488/F10 Ependymoma - ependymal rosettes (ajnr.org)].
*[http://path.upmc.edu/cases/case95/micro.html Anaplastic ependymoma - case 1 (upmc.edu)].
*[http://path.upmc.edu/cases/case324.html Anaplastic ependymoma - case 2 (upmc.edu)].
<gallery>
File:AFIP405736M-EPENDYMOMA.jpg | Ependymoma smear. (AFIP)
File:AFIP405715M-EPENDYMOMA.jpg | Perivascular pseudorosettes in a ependymoma. (AFIP)
Image:Ependymoma_intermed_mag.jpg | Ependymoma - intermed. mag. (WC)
Image:Ependymoma_low_intermed_mag.jpg | Ependymoma - low mag. (WC)
File:Ependymoma_H%26E.jpg | Ependymoma - high mag. (WC/Sbrandner)
File:Ependymoma_true_ependymal_rosettes_and_pseudorosettes.jpg | True ependymal and pseudorosettes in a ependymoma. (WC/jensflorian)
File:Ependymal_linings_ependymoma_HE.jpg | Ependymal linings in a ependymoma. (WC/jensflorian)
File:Ependymoma_GFAP.jpg| GFAP IHC in a ependymoma. (WC/Sbrandner)
File:EMA_ependymoma_periluminal.jpg | Periluminal EMA positivity in a ependymoma. (WC/jensflorian)
File:Ependymoma_EMA.jpg | Dot-like EMA immunreactivity n a ependymoma. (WC/Marvin101)
File:Tanycytic ependymoma HE.jpg | Tanycytic morphology in ependymoma must not confused with [[pilocytic astrocytoma]]. (WC/jensflorian)
File:Tanicytic_ependymoma_x10.jpg | Tanycytic morphology in ependymoma - low mag. (WC/jensflorian)
File:Papillary_Ependymoma.jpg | Papillary morphology in ependymoma - low mag. (WC/jensflorian)
File:Papillary_ependymoma_HE_x40.jpg | Papillary morphology in ependymoma - intermed. mag. (WC/jensflorian)
File:Clear_cell_ependymoma_HE.jpg | Clear cell morphology in ependymoma may mimic [[oligodendroglioma]]. (WC/jensflorian)
File:HE_anaplastic_epedymomas_mitoses_pleomorphism.jpg | Brisk mitotic activity in a anaplastic ependymoma. (WC/jensflorian)
File:Cartilaginous metaplasia ependymoma.jpg|Metaplastic transformation in an anaplastic ependymoma. (WC/jensflorian)
File:Ependymoma_L1CAM_IHC.jpg | L1CAM immunohistochemistry indicates presence of ZFTA-fusion.
File:Ependymoma_NFkappaB_IHC.jpg | Nuclear NFkappaB IHC indicates presence of ZFTA-fusion.
</gallery>

===Grading===
Easy:
*Subependymoma = CNS WHO grade 1.
*Myxopapillary ependymoma = CNS WHO grade 2.

Not so easy:
All other ependymomas: WHO CNS Grade 2 vs. Grade 3 depends on:
*Cellular density.
*Mitoses (no clear cut-off).
*Necrosis (not prognostic).
*Microvascular proliferation.
*Poor interobserver reliability<ref>{{Cite journal | last1 = Ellison | first1 = DW. | last2 = Kocak | first2 = M. | last3 = Figarella-Branger | first3 = D. | last4 = Felice | first4 = G. | last5 = Catherine | first5 = G. | last6 = Pietsch | first6 = T. | last7 = Frappaz | first7 = D. | last8 = Massimino | first8 = M. | last9 = Grill | first9 = J. | title = Histopathological grading of pediatric ependymoma: reproducibility and clinical relevance in European trial cohorts. | journal = J Negat Results Biomed | volume = 10 | issue = | pages = 7 | month = May | year = 2011 | doi = 10.1186/1477-5751-10-7 | PMID = 21627842 }}</ref>

Notes:
*Many tumours fall between grade 2 and grade 3.
*Rare cases with sarcomatous or cartilaginous components.<ref>{{Cite journal | last1 = Vajtai | first1 = I. | last2 = Kuhlen | first2 = D. | last3 = Kappeler | first3 = A. | last4 = Mariani | first4 = L. | last5 = Zimmermann | first5 = A. | last6 = Paulus | first6 = W. | title = Rapid spontaneous malignant progression of supratentorial tanycytic ependymoma with sarcomatous features - "Ependymosarcoma". | journal = Pathol Res Pract | volume = 206 | issue = 7 | pages = 493-8 | month = Jul | year = 2010 | doi = 10.1016/j.prp.2009.07.013 | PMID = 19853384 }}</ref><ref>{{Cite journal | last1 = Boukas | first1 = A. | last2 = Joshi | first2 = A. | last3 = Jenkins | first3 = A. | last4 = Holliman | first4 = D. | title = Extensive cartilaginous metaplasia of recurrent posterior fossa ependymoma: case report and review of the literature. | journal = Pediatr Neurosurg | volume = 49 | issue = 2 | pages = 93-8 | month = | year = 2013 | doi = 10.1159/000356931 | PMID = 24401698 }}</ref>

==IHC==
*Reticulin-ve.
*GFAP+ve.
*MIB1 (usu low).
*[[IDH-1]]-ve.
*EMA (dots and rings).<ref>{{Cite journal | last1 = Hasselblatt | first1 = M. | last2 = Paulus | first2 = W. | title = Sensitivity and specificity of epithelial membrane antigen staining patterns in ependymomas. | journal = Acta Neuropathol | volume = 106 | issue = 4 | pages = 385-8 | month = Oct | year = 2003 | doi = 10.1007/s00401-003-0752-8 | PMID = 12898159 }}</ref>
**Widespread and strong EMA expression is indicative of YAP1-fused ependymoma.
*Olig2-ve.<ref>{{Cite journal | last1 = Švajdler | first1 = M. | last2 = Rychlý | first2 = B. | last3 = Mezencev | first3 = R. | last4 = Fröhlichová | first4 = L. | last5 = Bednárová | first5 = A. | last6 = Pataky | first6 = F. | last7 = Daum | first7 = O. | title = SOX10 and Olig2 as negative markers for the diagnosis of ependymomas: An immunohistochemical study of 98 glial tumors. | journal = Histol Histopathol | volume = 31 | issue = 1 | pages = 95-102 | month = Jan | year = 2016 | doi = 10.14670/HH-11-654 | PMID = 26287936 }}</ref>
*H3K27me3 nuclear loss in Posterior fossa group A ependymoma (nuclear loss is diagnostic).<ref>{{Cite journal | last1 = Panwalkar | first1 = P. | last2 = Clark | first2 = J. | last3 = Ramaswamy | first3 = V. | last4 = Hawes | first4 = D. | last5 = Yang | first5 = F. | last6 = Dunham | first6 = C. | last7 = Yip | first7 = S. | last8 = Hukin | first8 = J. | last9 = Sun | first9 = Y. | title = Immunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Jul | year = 2017 | doi = 10.1007/s00401-017-1752-4 | PMID = 28733933 }}</ref>
*L1CAM in supratentorial tumors (expression indicates ZFTA fusion).<ref>{{Cite journal | last1 = Parker | first1 = M. | last2 = Mohankumar | first2 = KM. | last3 = Punchihewa | first3 = C. | last4 = Weinlich | first4 = R. | last5 = Dalton | first5 = JD. | last6 = Li | first6 = Y. | last7 = Lee | first7 = R. | last8 = Tatevossian | first8 = RG. | last9 = Phoenix | first9 = TN. | title = C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. | journal = Nature | volume = 506 | issue = 7489 | pages = 451-5 | month = Feb | year = 2014 | doi = 10.1038/nature13109 | PMID = 24553141 }}</ref>
*p65 nuclear +ve in ZFTA-fused ependymoma.

==Molecular==
'''Supratentorial Ependymoma'''
*SE, ZFTA-fusion positive: Adults and children (up to 80% of cases).<ref>{{Cite journal | last1 = Parker | first1 = M. | last2 = Mohankumar | first2 = KM. | last3 = Punchihewa | first3 = C. | last4 = Weinlich | first4 = R. | last5 = Dalton | first5 = JD. | last6 = Li | first6 = Y. | last7 = Lee | first7 = R. | last8 = Tatevossian | first8 = RG. | last9 = Phoenix | first9 = TN. | title = C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. | journal = Nature | volume = 506 | issue = 7489 | pages = 451-5 | month = Feb | year = 2014 | doi = 10.1038/nature13109 | PMID = 24553141 }}</ref>
**ZFTA-RELA fusion most common alteration.
**Chromothripsis.
**EPHB2 amplifications and CDKN2A deletions in a subset of these tumors<ref>{{Cite journal | last1 = Philip-Hollingsworth | first1 = S. | last2 = Hollingsworth | first2 = RI. | last3 = Dazzo | first3 = FB. | title = Host-range related structural features of the acidic extracellular polysaccharides of Rhizobium trifolii and Rhizobium leguminosarum. | journal = J Biol Chem | volume = 264 | issue = 3 | pages = 1461-6 | month = Jan | year = 1989 | doi = | PMID = 2912966 }}</ref>
*SE, YAP-fusion positive.
**Restricted to children (6-7% of all supratentorial ependymomas).
**YAP-MAMLD fusion most common alteration.
'''Posterior fossa Ependymoma'''
Two distinct molecular subgroups exist in the posterior fossa:<ref>{{Cite journal | last1 = Witt | first1 = H. | last2 = Mack | first2 = SC. | last3 = Ryzhova | first3 = M. | last4 = Bender | first4 = S. | last5 = Sill | first5 = M. | last6 = Isserlin | first6 = R. | last7 = Benner | first7 = A. | last8 = Hielscher | first8 = T. | last9 = Milde | first9 = T. | title = Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma. | journal = Cancer Cell | volume = 20 | issue = 2 | pages = 143-57 | month = Aug | year = 2011 | doi = 10.1016/j.ccr.2011.07.007 | PMID = 21840481 }}</ref>
* Group A ependymomas:
**typically found in children.
**laterally.
**relatively unfavorable clinical outcome.
**CpG island methylator phenotype.<ref>{{Cite journal | last1 = Mack | first1 = SC. | last2 = Witt | first2 = H. | last3 = Piro | first3 = RM. | last4 = Gu | first4 = L. | last5 = Zuyderduyn | first5 = S. | last6 = Stütz | first6 = AM. | last7 = Wang | first7 = X. | last8 = Gallo | first8 = M. | last9 = Garzia | first9 = L. | title = Epigenomic alterations define lethal CIMP-positive ependymomas of infancy. | journal = Nature | volume = 506 | issue = 7489 | pages = 445-50 | month = Feb | year = 2014 | doi = 10.1038/nature13108 | PMID = 24553142 }}</ref>
**Loss of H3K27me.<ref>{{Cite journal | last1 = Panwalkar | first1 = P. | last2 = Clark | first2 = J. | last3 = Ramaswamy | first3 = V. | last4 = Hawes | first4 = D. | last5 = Yang | first5 = F. | last6 = Dunham | first6 = C. | last7 = Yip | first7 = S. | last8 = Hukin | first8 = J. | last9 = Sun | first9 = Y. | title = Immunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Jul | year = 2017 | doi = 10.1007/s00401-017-1752-4 | PMID = 28733933 }}</ref>
* Group B ependymomas:
**typically adults.
**midline.
**relatively favorable clinical outcomes.
**gene expression profiles similar to that of spinal cord ependymomas.
**increased Chromosomal 1q gains. <ref>{{Cite journal | last1 = Korshunov | first1 = A. | last2 = Witt | first2 = H. | last3 = Hielscher | first3 = T. | last4 = Benner | first4 = A. | last5 = Remke | first5 = M. | last6 = Ryzhova | first6 = M. | last7 = Milde | first7 = T. | last8 = Bender | first8 = S. | last9 = Wittmann | first9 = A. | title = Molecular staging of intracranial ependymoma in children and adults. | journal = J Clin Oncol | volume = 28 | issue = 19 | pages = 3182-90 | month = Jul | year = 2010 | doi = 10.1200/JCO.2009.27.3359 | PMID = 20516456 }}</ref>

==See also==
*[[Subependymoma]].
*[[Myxopapillary ependymoma]].
*[[Neuropathology tumours]].

==References==
{{Reflist|1}}

[[Category:Diagnosis]]
[[Category:Neuropathology tumours]]

Ependymoma

2022-09-19T13:16:23Z

Jensflorian: /* Microscopic */ PF

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Ependymoma_H%26E.jpg
| Width =
| Caption = Ependymoma grade II WHO. [[H&E stain]]
| Synonyms =
| Micro = Perivascular pseudorosettes, ependymal rosettes
| Subtypes = Tanycytic, Clear cell, Papillary, Cellular
| LMDDx = [[Subependymoma]], [[Glioblastoma]], [[Pilocytic astrocytoma]], [[Oligodendroglioma]]
| Stains =
| IHC = GFAP +ve
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site =
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence =
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis = intermediate to poor (WHO Grades II & III)
| Other =
| ClinDDx =
| Tx =
}}

'''Ependymoma''' is a [[neuropathology tumour]].

==General==
*Called the forgotten glial tumour.
*Anatomic location and molecular data is essential for tumor diagnosis.

Epidemiology:<ref name=Ref_PBoD8_1334>{{Ref PBoD8|1334}}</ref>
*Usual site:
**Adults: usually spinal cord.
**Children: usually posterior fossa.
*May be associated with [[neurofibromatosis type 2]].

There are currently ten main ependymal tumors:<ref name=Ref_WHOCNS_74>{{Ref WHOCNS|74}}</ref>
#Supratentorial [[Subependymoma]]
#Supratentorial ependymoma, ZFTA-fusion positive
#Supratentorial ependymoma, YAP1-fusion positive
#Posterior fossa [[Subependymoma]]
#Posterior fossa ependymoma group A
#Posterior fossa ependymoma group B
#Spinal [[Subependymoma]]
#Spinal ependymoma
#Spinal ependymoma, MYCN-amplified
#[[Myxopapillary ependymoma]]

Ependymoma, NOS (not otherwise specified): Molecular analysis still missing.
Ependymoma, NEC (not elsewhere classfied): Tumor cannot assigned to any of the defined entities.

Note: Molecularly defined ependymomas can be still graded as CNS grade 2 or 3 depending on histological features.

*Depreceated terminologies:
**Papillary ependymoma.
**Clear cell ependymoma.
**Tanycytic ependymoma.
**Cellular ependymoma.
**Ependymoma, RELA fusion-positive.<ref>{{Cite journal | last1 = Parker | first1 = M. | last2 = Mohankumar | first2 = KM. | last3 = Punchihewa | first3 = C. | last4 = Weinlich | first4 = R. | last5 = Dalton | first5 = JD. | last6 = Li | first6 = Y. | last7 = Lee | first7 = R. | last8 = Tatevossian | first8 = RG. | last9 = Phoenix | first9 = TN. | title = C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. | journal = Nature | volume = 506 | issue = 7489 | pages = 451-5 | month = Feb | year = 2014 | doi = 10.1038/nature13109 | PMID = 24553141 }}</ref><ref>{{Cite journal | last1 = Pietsch | first1 = T. | last2 = Wohlers | first2 = I. | last3 = Goschzik | first3 = T. | last4 = Dreschmann | first4 = V. | last5 = Denkhaus | first5 = D. | last6 = Dörner | first6 = E. | last7 = Rahmann | first7 = S. | last8 = Klein-Hitpass | first8 = L. | title = Supratentorial ependymomas of childhood carry C11orf95-RELA fusions leading to pathological activation of the NF-κB signaling pathway. | journal = Acta Neuropathol | volume = 127 | issue = 4 | pages = 609-11 | month = Apr | year = 2014 | doi = 10.1007/s00401-014-1264-4 | PMID = 24562983 }}</ref> This is now called Supratentorial ependymoma, ZFTA-fusion positive.
**Anaplastic ependymoma. This is now called CNS grade 3 ependymoma.

==Gross==
*Usually discrete and enhancing.
*Ventricular location, but also within the spinal cord.
*Dissemination possible.
*[[Myxopapillary ependymoma]] classically at [[filum terminale]].
*[[Subependymoma]] typically seen in IVth ventricle.
<gallery>
File:AFIP405711R-EPENDYMOMA.jpg | Radiology (AFIP)
File:AFIP405713G-EPENDYMOMA.jpg | Ependymoma in the fourth ventricle (AFIP)
File:Ependymoma in the fourth ventricle.jpg | Gross (AFIP)
</gallery>

==Microscopic==
==="Classic" ependymoma===
*Come in two CNS WHO grades: 2 and 3.
*Usu. sharply demarcated from surrounding brain parenchyma.
Features:
*Cells have a "tadpole-like" morphology.
**May also be described as ''ice cream cone-shaped''.<ref>[http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html]</ref>
*'''Rosettes''' = circular nuclear free zones/cells arranged in a pseudoglandular fashion; comes in two flavours in ependymoma:
**''Perivascular pseudorosettes'' = (tumour) cells arranged around a blood vessel; nuclei of cells distant from the blood vessel, i.e. rim of cytoplasm (from tumour cells) surround blood vessel (nucleus-free zone); more common than ependymal rosette... but less specific.
**''Ependymal rosette'' ([[AKA]] ''true ependymal rosette'') = rosette has an empty space at the centre - '''key feature'''.
*Nuclear features monotonous, i.e. "boring".<ref>MUN. 6 Oct 2009.</ref>
**There is little variation in size, shape and staining.
*Hyalinized vessels.
*Calcification.
*Rare cases with cartilagineous metaplasia.<ref>{{Cite journal | last1 = Wang | first1 = X. | last2 = Zhang | first2 = S. | last3 = Ye | first3 = Y. | last4 = Chen | first4 = Y. | last5 = Liu | first5 = X. | title = Ependymoma with cartilaginous metaplasia might have more aggressive behavior: a case report and literature review. | journal = Brain Tumor Pathol | volume = 29 | issue = 3 | pages = 172-6 | month = Jul | year = 2012 | doi = 10.1007/s10014-011-0079-4 | PMID = 22228122 }}</ref>
*Branching capillaries usu. only in supratentorial ependymomas.

===Supratentorial ependymoma===
*Usu. connected to the ventricles.
*Mostly frontal or temporal lobe.
*Approx. 1/3 of all ependymal tumours (41% in children).
*Irregular CM enhancement.
*YAP1-fused tumors in children oft large at time of diagnosis.
*Cysts and/or calcification possible.
*Sharply demarcated from adjacent brain parenchyma.
*True ependymal rosettes are rare.
*Occasionally branching capillary vessels.
*Clear cell phenotypes more common than in other locations.
*Complete surgical resection is the best predictor.
*CSF spread in up to 15% of tumours.

===Posterior fossa ependymoma===
*Usu. 4th ventricle, less common in CPA.
*Most frequent in children.
*May contain tumour nodules with increased cell density.
*Micocysts, vascular hyalinization and calcification can be present.
*No morphologic differences between Group A and B tumours.
*Perivascular pseudorosettes almost always present.
*Rare papillary or tanicytic patterns.

DDx (supratentorial and posterior fossa ependymoma):
*[[Subependymoma]].
*[[Glioblastoma]] (GBM).
*Gliomas with BCOR internal tandem duplication.
*[[Astroblastoma]], MN1-altered.
**Invasive border = GBM; circumscribed border of lesion = ependymoma.
*[[Oligodendroglioma]] (Clear cell ependymoma))
*CNS embryonal tumour with BCOR internal tandem duplication.

DDx (spinal ependymoma):
*[[Pilocytic astrocytoma]] (Tanycytic ependymoma)
*Diffuse midline glioma, H3 K27-altered
*Small cell glioblastoma (MYCN-amplified spinal ependymoma)

===Images===
www:
*[http://www.flickr.com/photos/ckrishnan/3862487821/in/photostream Ependymoma (flickr.com)].
*[http://www.ajnr.org/cgi/content-nw/full/27/3/488/F10 Ependymoma - ependymal rosettes (ajnr.org)].
*[http://path.upmc.edu/cases/case95/micro.html Anaplastic ependymoma - case 1 (upmc.edu)].
*[http://path.upmc.edu/cases/case324.html Anaplastic ependymoma - case 2 (upmc.edu)].
<gallery>
File:AFIP405736M-EPENDYMOMA.jpg | Ependymoma smear. (AFIP)
File:AFIP405715M-EPENDYMOMA.jpg | Perivascular pseudorosettes in a ependymoma. (AFIP)
Image:Ependymoma_intermed_mag.jpg | Ependymoma - intermed. mag. (WC)
Image:Ependymoma_low_intermed_mag.jpg | Ependymoma - low mag. (WC)
File:Ependymoma_H%26E.jpg | Ependymoma - high mag. (WC/Sbrandner)
File:Ependymoma_true_ependymal_rosettes_and_pseudorosettes.jpg | True ependymal and pseudorosettes in a ependymoma. (WC/jensflorian)
File:Ependymal_linings_ependymoma_HE.jpg | Ependymal linings in a ependymoma. (WC/jensflorian)
File:Ependymoma_GFAP.jpg| GFAP IHC in a ependymoma. (WC/Sbrandner)
File:EMA_ependymoma_periluminal.jpg | Periluminal EMA positivity in a ependymoma. (WC/jensflorian)
File:Ependymoma_EMA.jpg | Dot-like EMA immunreactivity n a ependymoma. (WC/Marvin101)
File:Tanycytic ependymoma HE.jpg | Tanycytic morphology in ependymoma must not confused with [[pilocytic astrocytoma]]. (WC/jensflorian)
File:Tanicytic_ependymoma_x10.jpg | Tanycytic morphology in ependymoma - low mag. (WC/jensflorian)
File:Papillary_Ependymoma.jpg | Papillary morphology in ependymoma - low mag. (WC/jensflorian)
File:Papillary_ependymoma_HE_x40.jpg | Papillary morphology in ependymoma - intermed. mag. (WC/jensflorian)
File:Clear_cell_ependymoma_HE.jpg | Clear cell morphology in ependymoma may mimic [[oligodendroglioma]]. (WC/jensflorian)
File:HE_anaplastic_epedymomas_mitoses_pleomorphism.jpg | Brisk mitotic activity in a anaplastic ependymoma. (WC/jensflorian)
File:Cartilaginous metaplasia ependymoma.jpg|Metaplastic transformation in an anaplastic ependymoma. (WC/jensflorian)
File:Ependymoma_L1CAM_IHC.jpg | L1CAM immunohistochemistry indicates presence of ZFTA-fusion.
File:Ependymoma_NFkappaB_IHC.jpg | Nuclear NFkappaB IHC indicates presence of ZFTA-fusion.
</gallery>

===Grading===
Easy:
*Subependymoma = CNS WHO grade 1.
*Myxopapillary ependymoma = CNS WHO grade 2.

Not so easy:
All other ependymomas: WHO CNS Grade 2 vs. Grade 3 depends on:
*Cellular density.
*Mitoses (no clear cut-off).
*Necrosis (not prognostic).
*Microvascular proliferation.
*Poor interobserver reliability<ref>{{Cite journal | last1 = Ellison | first1 = DW. | last2 = Kocak | first2 = M. | last3 = Figarella-Branger | first3 = D. | last4 = Felice | first4 = G. | last5 = Catherine | first5 = G. | last6 = Pietsch | first6 = T. | last7 = Frappaz | first7 = D. | last8 = Massimino | first8 = M. | last9 = Grill | first9 = J. | title = Histopathological grading of pediatric ependymoma: reproducibility and clinical relevance in European trial cohorts. | journal = J Negat Results Biomed | volume = 10 | issue = | pages = 7 | month = May | year = 2011 | doi = 10.1186/1477-5751-10-7 | PMID = 21627842 }}</ref>

Notes:
*Many tumours fall between grade 2 and grade 3.
*Rare cases with sarcomatous or cartilaginous components.<ref>{{Cite journal | last1 = Vajtai | first1 = I. | last2 = Kuhlen | first2 = D. | last3 = Kappeler | first3 = A. | last4 = Mariani | first4 = L. | last5 = Zimmermann | first5 = A. | last6 = Paulus | first6 = W. | title = Rapid spontaneous malignant progression of supratentorial tanycytic ependymoma with sarcomatous features - "Ependymosarcoma". | journal = Pathol Res Pract | volume = 206 | issue = 7 | pages = 493-8 | month = Jul | year = 2010 | doi = 10.1016/j.prp.2009.07.013 | PMID = 19853384 }}</ref><ref>{{Cite journal | last1 = Boukas | first1 = A. | last2 = Joshi | first2 = A. | last3 = Jenkins | first3 = A. | last4 = Holliman | first4 = D. | title = Extensive cartilaginous metaplasia of recurrent posterior fossa ependymoma: case report and review of the literature. | journal = Pediatr Neurosurg | volume = 49 | issue = 2 | pages = 93-8 | month = | year = 2013 | doi = 10.1159/000356931 | PMID = 24401698 }}</ref>

==IHC==
*Reticulin-ve.
*GFAP+ve.
*MIB1 (usu low).
*[[IDH-1]]-ve.
*EMA (dots and rings).<ref>{{Cite journal | last1 = Hasselblatt | first1 = M. | last2 = Paulus | first2 = W. | title = Sensitivity and specificity of epithelial membrane antigen staining patterns in ependymomas. | journal = Acta Neuropathol | volume = 106 | issue = 4 | pages = 385-8 | month = Oct | year = 2003 | doi = 10.1007/s00401-003-0752-8 | PMID = 12898159 }}</ref>
**Widespread and strong EMA expression is indicative of YAP1-fused ependymoma.
*Olig2-ve.<ref>{{Cite journal | last1 = Švajdler | first1 = M. | last2 = Rychlý | first2 = B. | last3 = Mezencev | first3 = R. | last4 = Fröhlichová | first4 = L. | last5 = Bednárová | first5 = A. | last6 = Pataky | first6 = F. | last7 = Daum | first7 = O. | title = SOX10 and Olig2 as negative markers for the diagnosis of ependymomas: An immunohistochemical study of 98 glial tumors. | journal = Histol Histopathol | volume = 31 | issue = 1 | pages = 95-102 | month = Jan | year = 2016 | doi = 10.14670/HH-11-654 | PMID = 26287936 }}</ref>
*H3K27me3 nuclear loss in Posterior fossa group A ependymoma (nuclear loss is diagnostic).<ref>{{Cite journal | last1 = Panwalkar | first1 = P. | last2 = Clark | first2 = J. | last3 = Ramaswamy | first3 = V. | last4 = Hawes | first4 = D. | last5 = Yang | first5 = F. | last6 = Dunham | first6 = C. | last7 = Yip | first7 = S. | last8 = Hukin | first8 = J. | last9 = Sun | first9 = Y. | title = Immunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Jul | year = 2017 | doi = 10.1007/s00401-017-1752-4 | PMID = 28733933 }}</ref>
*L1CAM in supratentorial tumors (expression indicates ZFTA fusion).<ref>{{Cite journal | last1 = Parker | first1 = M. | last2 = Mohankumar | first2 = KM. | last3 = Punchihewa | first3 = C. | last4 = Weinlich | first4 = R. | last5 = Dalton | first5 = JD. | last6 = Li | first6 = Y. | last7 = Lee | first7 = R. | last8 = Tatevossian | first8 = RG. | last9 = Phoenix | first9 = TN. | title = C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. | journal = Nature | volume = 506 | issue = 7489 | pages = 451-5 | month = Feb | year = 2014 | doi = 10.1038/nature13109 | PMID = 24553141 }}</ref>
*p65 nuclear +ve in ZFTA-fused ependymoma.

==Molecular==
'''Supratentorial Ependymoma'''
*SE, ZFTA-fusion positive: Adults and children (up to 80% of cases).<ref>{{Cite journal | last1 = Parker | first1 = M. | last2 = Mohankumar | first2 = KM. | last3 = Punchihewa | first3 = C. | last4 = Weinlich | first4 = R. | last5 = Dalton | first5 = JD. | last6 = Li | first6 = Y. | last7 = Lee | first7 = R. | last8 = Tatevossian | first8 = RG. | last9 = Phoenix | first9 = TN. | title = C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. | journal = Nature | volume = 506 | issue = 7489 | pages = 451-5 | month = Feb | year = 2014 | doi = 10.1038/nature13109 | PMID = 24553141 }}</ref>
**ZFTA-RELA fusion most common alteration.
**Chromothripsis.
**EPHB2 amplifications and CDKN2A deletions in a subset of these tumors<ref>{{Cite journal | last1 = Philip-Hollingsworth | first1 = S. | last2 = Hollingsworth | first2 = RI. | last3 = Dazzo | first3 = FB. | title = Host-range related structural features of the acidic extracellular polysaccharides of Rhizobium trifolii and Rhizobium leguminosarum. | journal = J Biol Chem | volume = 264 | issue = 3 | pages = 1461-6 | month = Jan | year = 1989 | doi = | PMID = 2912966 }}</ref>
*SE, YAP-fusion positive.
**Restricted to children (6-7% of all supratentorial ependymomas).
**YAP-MAMLD fusion most common alteration.
'''Posterior fossa Ependymoma'''
Two distinct molecular subgroups exist in the posterior fossa:<ref>{{Cite journal | last1 = Witt | first1 = H. | last2 = Mack | first2 = SC. | last3 = Ryzhova | first3 = M. | last4 = Bender | first4 = S. | last5 = Sill | first5 = M. | last6 = Isserlin | first6 = R. | last7 = Benner | first7 = A. | last8 = Hielscher | first8 = T. | last9 = Milde | first9 = T. | title = Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma. | journal = Cancer Cell | volume = 20 | issue = 2 | pages = 143-57 | month = Aug | year = 2011 | doi = 10.1016/j.ccr.2011.07.007 | PMID = 21840481 }}</ref>
* Group A ependymomas:
**typically found in children.
**laterally.
**relatively unfavorable clinical outcome.
**CpG island methylator phenotype.<ref>{{Cite journal | last1 = Mack | first1 = SC. | last2 = Witt | first2 = H. | last3 = Piro | first3 = RM. | last4 = Gu | first4 = L. | last5 = Zuyderduyn | first5 = S. | last6 = Stütz | first6 = AM. | last7 = Wang | first7 = X. | last8 = Gallo | first8 = M. | last9 = Garzia | first9 = L. | title = Epigenomic alterations define lethal CIMP-positive ependymomas of infancy. | journal = Nature | volume = 506 | issue = 7489 | pages = 445-50 | month = Feb | year = 2014 | doi = 10.1038/nature13108 | PMID = 24553142 }}</ref>
**Loss of H3K27me.<ref>{{Cite journal | last1 = Panwalkar | first1 = P. | last2 = Clark | first2 = J. | last3 = Ramaswamy | first3 = V. | last4 = Hawes | first4 = D. | last5 = Yang | first5 = F. | last6 = Dunham | first6 = C. | last7 = Yip | first7 = S. | last8 = Hukin | first8 = J. | last9 = Sun | first9 = Y. | title = Immunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Jul | year = 2017 | doi = 10.1007/s00401-017-1752-4 | PMID = 28733933 }}</ref>
* Group B ependymomas:
**typically adults.
**midline.
**relatively favorable clinical outcomes.
**gene expression profiles similar to that of spinal cord ependymomas.
**increased Chromosomal 1q gains. <ref>{{Cite journal | last1 = Korshunov | first1 = A. | last2 = Witt | first2 = H. | last3 = Hielscher | first3 = T. | last4 = Benner | first4 = A. | last5 = Remke | first5 = M. | last6 = Ryzhova | first6 = M. | last7 = Milde | first7 = T. | last8 = Bender | first8 = S. | last9 = Wittmann | first9 = A. | title = Molecular staging of intracranial ependymoma in children and adults. | journal = J Clin Oncol | volume = 28 | issue = 19 | pages = 3182-90 | month = Jul | year = 2010 | doi = 10.1200/JCO.2009.27.3359 | PMID = 20516456 }}</ref>

==See also==
*[[Subependymoma]].
*[[Myxopapillary ependymoma]].
*[[Neuropathology tumours]].

==References==
{{Reflist|1}}

[[Category:Diagnosis]]
[[Category:Neuropathology tumours]]

Ependymoma

2022-09-19T12:51:00Z

Jensflorian: /* Supratentorial ependymoma */ children

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Ependymoma_H%26E.jpg
| Width =
| Caption = Ependymoma grade II WHO. [[H&E stain]]
| Synonyms =
| Micro = Perivascular pseudorosettes, ependymal rosettes
| Subtypes = Tanycytic, Clear cell, Papillary, Cellular
| LMDDx = [[Subependymoma]], [[Glioblastoma]], [[Pilocytic astrocytoma]], [[Oligodendroglioma]]
| Stains =
| IHC = GFAP +ve
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site =
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence =
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis = intermediate to poor (WHO Grades II & III)
| Other =
| ClinDDx =
| Tx =
}}

'''Ependymoma''' is a [[neuropathology tumour]].

==General==
*Called the forgotten glial tumour.
*Anatomic location and molecular data is essential for tumor diagnosis.

Epidemiology:<ref name=Ref_PBoD8_1334>{{Ref PBoD8|1334}}</ref>
*Usual site:
**Adults: usually spinal cord.
**Children: usually posterior fossa.
*May be associated with [[neurofibromatosis type 2]].

There are currently ten main ependymal tumors:<ref name=Ref_WHOCNS_74>{{Ref WHOCNS|74}}</ref>
#Supratentorial [[Subependymoma]]
#Supratentorial ependymoma, ZFTA-fusion positive
#Supratentorial ependymoma, YAP1-fusion positive
#Posterior fossa [[Subependymoma]]
#Posterior fossa ependymoma group A
#Posterior fossa ependymoma group B
#Spinal [[Subependymoma]]
#Spinal ependymoma
#Spinal ependymoma, MYCN-amplified
#[[Myxopapillary ependymoma]]

Ependymoma, NOS (not otherwise specified): Molecular analysis still missing.
Ependymoma, NEC (not elsewhere classfied): Tumor cannot assigned to any of the defined entities.

Note: Molecularly defined ependymomas can be still graded as CNS grade 2 or 3 depending on histological features.

*Depreceated terminologies:
**Papillary ependymoma.
**Clear cell ependymoma.
**Tanycytic ependymoma.
**Cellular ependymoma.
**Ependymoma, RELA fusion-positive.<ref>{{Cite journal | last1 = Parker | first1 = M. | last2 = Mohankumar | first2 = KM. | last3 = Punchihewa | first3 = C. | last4 = Weinlich | first4 = R. | last5 = Dalton | first5 = JD. | last6 = Li | first6 = Y. | last7 = Lee | first7 = R. | last8 = Tatevossian | first8 = RG. | last9 = Phoenix | first9 = TN. | title = C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. | journal = Nature | volume = 506 | issue = 7489 | pages = 451-5 | month = Feb | year = 2014 | doi = 10.1038/nature13109 | PMID = 24553141 }}</ref><ref>{{Cite journal | last1 = Pietsch | first1 = T. | last2 = Wohlers | first2 = I. | last3 = Goschzik | first3 = T. | last4 = Dreschmann | first4 = V. | last5 = Denkhaus | first5 = D. | last6 = Dörner | first6 = E. | last7 = Rahmann | first7 = S. | last8 = Klein-Hitpass | first8 = L. | title = Supratentorial ependymomas of childhood carry C11orf95-RELA fusions leading to pathological activation of the NF-κB signaling pathway. | journal = Acta Neuropathol | volume = 127 | issue = 4 | pages = 609-11 | month = Apr | year = 2014 | doi = 10.1007/s00401-014-1264-4 | PMID = 24562983 }}</ref> This is now called Supratentorial ependymoma, ZFTA-fusion positive.
**Anaplastic ependymoma. This is now called CNS grade 3 ependymoma.

==Gross==
*Usually discrete and enhancing.
*Ventricular location, but also within the spinal cord.
*Dissemination possible.
*[[Myxopapillary ependymoma]] classically at [[filum terminale]].
*[[Subependymoma]] typically seen in IVth ventricle.
<gallery>
File:AFIP405711R-EPENDYMOMA.jpg | Radiology (AFIP)
File:AFIP405713G-EPENDYMOMA.jpg | Ependymoma in the fourth ventricle (AFIP)
File:Ependymoma in the fourth ventricle.jpg | Gross (AFIP)
</gallery>

==Microscopic==
==="Classic" ependymoma===
*Come in two CNS WHO grades: 2 and 3.
*Usu. sharply demarcated from surrounding brain parenchyma.
Features:
*Cells have a "tadpole-like" morphology.
**May also be described as ''ice cream cone-shaped''.<ref>[http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html]</ref>
*'''Rosettes''' = circular nuclear free zones/cells arranged in a pseudoglandular fashion; comes in two flavours in ependymoma:
**''Perivascular pseudorosettes'' = (tumour) cells arranged around a blood vessel; nuclei of cells distant from the blood vessel, i.e. rim of cytoplasm (from tumour cells) surround blood vessel (nucleus-free zone); more common than ependymal rosette... but less specific.
**''Ependymal rosette'' ([[AKA]] ''true ependymal rosette'') = rosette has an empty space at the centre - '''key feature'''.
*Nuclear features monotonous, i.e. "boring".<ref>MUN. 6 Oct 2009.</ref>
**There is little variation in size, shape and staining.
*Hyalinized vessels.
*Calcification.
*Rare cases with cartilagineous metaplasia.<ref>{{Cite journal | last1 = Wang | first1 = X. | last2 = Zhang | first2 = S. | last3 = Ye | first3 = Y. | last4 = Chen | first4 = Y. | last5 = Liu | first5 = X. | title = Ependymoma with cartilaginous metaplasia might have more aggressive behavior: a case report and literature review. | journal = Brain Tumor Pathol | volume = 29 | issue = 3 | pages = 172-6 | month = Jul | year = 2012 | doi = 10.1007/s10014-011-0079-4 | PMID = 22228122 }}</ref>
*Branching capillaries usu. only in supratentorial ependymomas.

===Supratentorial ependymoma===
*Usu. connected to the ventricles.
*Mostly frontal or temporal lobe.
*Approx. 1/3 of all ependymal tumours (41% in children).
*Irregular CM enhancement.
*YAP1-fused tumors in children oft large at time of diagnosis.
*Cysts and/or calcification possible.
*Sharply demarcated from adjacent brain parenchyma.
*True ependymal rosettes are rare.
*Occasionally branching capillary vessels.
*Clear cell phenotypes more common than in other locations.
*Complete surgical resection is the best predictor.
*CSF spread in up to 15% of tumours.

DDx (supratentorial and posterior fossa ependymoma):
*[[Subependymoma]].
*[[Glioblastoma]] (GBM).
*Gliomas with BCOR internal tandem duplication.
*[[Astroblastoma]], MN1-altered.
**Invasive border = GBM; circumscribed border of lesion = ependymoma.
*[[Oligodendroglioma]] (Clear cell ependymoma))
*CNS embryonal tumour with BCOR internal tandem duplication.

DDx (spinal ependymoma):
*[[Pilocytic astrocytoma]] (Tanycytic ependymoma)
*Diffuse midline glioma, H3 K27-altered
*Small cell glioblastoma (MYCN-amplified spinal ependymoma)

====Images====
www:
*[http://www.flickr.com/photos/ckrishnan/3862487821/in/photostream Ependymoma (flickr.com)].
*[http://www.ajnr.org/cgi/content-nw/full/27/3/488/F10 Ependymoma - ependymal rosettes (ajnr.org)].
*[http://path.upmc.edu/cases/case95/micro.html Anaplastic ependymoma - case 1 (upmc.edu)].
*[http://path.upmc.edu/cases/case324.html Anaplastic ependymoma - case 2 (upmc.edu)].
<gallery>
File:AFIP405736M-EPENDYMOMA.jpg | Ependymoma smear. (AFIP)
File:AFIP405715M-EPENDYMOMA.jpg | Perivascular pseudorosettes in a ependymoma. (AFIP)
Image:Ependymoma_intermed_mag.jpg | Ependymoma - intermed. mag. (WC)
Image:Ependymoma_low_intermed_mag.jpg | Ependymoma - low mag. (WC)
File:Ependymoma_H%26E.jpg | Ependymoma - high mag. (WC/Sbrandner)
File:Ependymoma_true_ependymal_rosettes_and_pseudorosettes.jpg | True ependymal and pseudorosettes in a ependymoma. (WC/jensflorian)
File:Ependymal_linings_ependymoma_HE.jpg | Ependymal linings in a ependymoma. (WC/jensflorian)
File:Ependymoma_GFAP.jpg| GFAP IHC in a ependymoma. (WC/Sbrandner)
File:EMA_ependymoma_periluminal.jpg | Periluminal EMA positivity in a ependymoma. (WC/jensflorian)
File:Ependymoma_EMA.jpg | Dot-like EMA immunreactivity n a ependymoma. (WC/Marvin101)
File:Tanycytic ependymoma HE.jpg | Tanycytic morphology in ependymoma must not confused with [[pilocytic astrocytoma]]. (WC/jensflorian)
File:Tanicytic_ependymoma_x10.jpg | Tanycytic morphology in ependymoma - low mag. (WC/jensflorian)
File:Papillary_Ependymoma.jpg | Papillary morphology in ependymoma - low mag. (WC/jensflorian)
File:Papillary_ependymoma_HE_x40.jpg | Papillary morphology in ependymoma - intermed. mag. (WC/jensflorian)
File:Clear_cell_ependymoma_HE.jpg | Clear cell morphology in ependymoma may mimic [[oligodendroglioma]]. (WC/jensflorian)
File:HE_anaplastic_epedymomas_mitoses_pleomorphism.jpg | Brisk mitotic activity in a anaplastic ependymoma. (WC/jensflorian)
File:Cartilaginous metaplasia ependymoma.jpg|Metaplastic transformation in an anaplastic ependymoma. (WC/jensflorian)
File:Ependymoma_L1CAM_IHC.jpg | L1CAM immunohistochemistry indicates presence of ZFTA-fusion.
File:Ependymoma_NFkappaB_IHC.jpg | Nuclear NFkappaB IHC indicates presence of ZFTA-fusion.
</gallery>

===Grading===
Easy:
*Subependymoma = CNS WHO grade 1.
*Myxopapillary ependymoma = CNS WHO grade 2.

Not so easy:
All other ependymomas: WHO CNS Grade 2 vs. Grade 3 depends on:
*Cellular density.
*Mitoses (no clear cut-off).
*Necrosis (not prognostic).
*Microvascular proliferation.
*Poor interobserver reliability<ref>{{Cite journal | last1 = Ellison | first1 = DW. | last2 = Kocak | first2 = M. | last3 = Figarella-Branger | first3 = D. | last4 = Felice | first4 = G. | last5 = Catherine | first5 = G. | last6 = Pietsch | first6 = T. | last7 = Frappaz | first7 = D. | last8 = Massimino | first8 = M. | last9 = Grill | first9 = J. | title = Histopathological grading of pediatric ependymoma: reproducibility and clinical relevance in European trial cohorts. | journal = J Negat Results Biomed | volume = 10 | issue = | pages = 7 | month = May | year = 2011 | doi = 10.1186/1477-5751-10-7 | PMID = 21627842 }}</ref>

Notes:
*Many tumours fall between grade 2 and grade 3.
*Rare cases with sarcomatous or cartilaginous components.<ref>{{Cite journal | last1 = Vajtai | first1 = I. | last2 = Kuhlen | first2 = D. | last3 = Kappeler | first3 = A. | last4 = Mariani | first4 = L. | last5 = Zimmermann | first5 = A. | last6 = Paulus | first6 = W. | title = Rapid spontaneous malignant progression of supratentorial tanycytic ependymoma with sarcomatous features - "Ependymosarcoma". | journal = Pathol Res Pract | volume = 206 | issue = 7 | pages = 493-8 | month = Jul | year = 2010 | doi = 10.1016/j.prp.2009.07.013 | PMID = 19853384 }}</ref><ref>{{Cite journal | last1 = Boukas | first1 = A. | last2 = Joshi | first2 = A. | last3 = Jenkins | first3 = A. | last4 = Holliman | first4 = D. | title = Extensive cartilaginous metaplasia of recurrent posterior fossa ependymoma: case report and review of the literature. | journal = Pediatr Neurosurg | volume = 49 | issue = 2 | pages = 93-8 | month = | year = 2013 | doi = 10.1159/000356931 | PMID = 24401698 }}</ref>

==IHC==
*Reticulin-ve.
*GFAP+ve.
*MIB1 (usu low).
*[[IDH-1]]-ve.
*EMA (dots and rings).<ref>{{Cite journal | last1 = Hasselblatt | first1 = M. | last2 = Paulus | first2 = W. | title = Sensitivity and specificity of epithelial membrane antigen staining patterns in ependymomas. | journal = Acta Neuropathol | volume = 106 | issue = 4 | pages = 385-8 | month = Oct | year = 2003 | doi = 10.1007/s00401-003-0752-8 | PMID = 12898159 }}</ref>
**Widespread and strong EMA expression is indicative of YAP1-fused ependymoma.
*Olig2-ve.<ref>{{Cite journal | last1 = Švajdler | first1 = M. | last2 = Rychlý | first2 = B. | last3 = Mezencev | first3 = R. | last4 = Fröhlichová | first4 = L. | last5 = Bednárová | first5 = A. | last6 = Pataky | first6 = F. | last7 = Daum | first7 = O. | title = SOX10 and Olig2 as negative markers for the diagnosis of ependymomas: An immunohistochemical study of 98 glial tumors. | journal = Histol Histopathol | volume = 31 | issue = 1 | pages = 95-102 | month = Jan | year = 2016 | doi = 10.14670/HH-11-654 | PMID = 26287936 }}</ref>
*H3K27me3 nuclear loss in Posterior fossa group A ependymoma (nuclear loss is diagnostic).<ref>{{Cite journal | last1 = Panwalkar | first1 = P. | last2 = Clark | first2 = J. | last3 = Ramaswamy | first3 = V. | last4 = Hawes | first4 = D. | last5 = Yang | first5 = F. | last6 = Dunham | first6 = C. | last7 = Yip | first7 = S. | last8 = Hukin | first8 = J. | last9 = Sun | first9 = Y. | title = Immunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Jul | year = 2017 | doi = 10.1007/s00401-017-1752-4 | PMID = 28733933 }}</ref>
*L1CAM in supratentorial tumors (expression indicates ZFTA fusion).<ref>{{Cite journal | last1 = Parker | first1 = M. | last2 = Mohankumar | first2 = KM. | last3 = Punchihewa | first3 = C. | last4 = Weinlich | first4 = R. | last5 = Dalton | first5 = JD. | last6 = Li | first6 = Y. | last7 = Lee | first7 = R. | last8 = Tatevossian | first8 = RG. | last9 = Phoenix | first9 = TN. | title = C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. | journal = Nature | volume = 506 | issue = 7489 | pages = 451-5 | month = Feb | year = 2014 | doi = 10.1038/nature13109 | PMID = 24553141 }}</ref>
*p65 nuclear +ve in ZFTA-fused ependymoma.

==Molecular==
'''Supratentorial Ependymoma'''
*SE, ZFTA-fusion positive: Adults and children (up to 80% of cases).<ref>{{Cite journal | last1 = Parker | first1 = M. | last2 = Mohankumar | first2 = KM. | last3 = Punchihewa | first3 = C. | last4 = Weinlich | first4 = R. | last5 = Dalton | first5 = JD. | last6 = Li | first6 = Y. | last7 = Lee | first7 = R. | last8 = Tatevossian | first8 = RG. | last9 = Phoenix | first9 = TN. | title = C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. | journal = Nature | volume = 506 | issue = 7489 | pages = 451-5 | month = Feb | year = 2014 | doi = 10.1038/nature13109 | PMID = 24553141 }}</ref>
**ZFTA-RELA fusion most common alteration.
**Chromothripsis.
**EPHB2 amplifications and CDKN2A deletions in a subset of these tumors<ref>{{Cite journal | last1 = Philip-Hollingsworth | first1 = S. | last2 = Hollingsworth | first2 = RI. | last3 = Dazzo | first3 = FB. | title = Host-range related structural features of the acidic extracellular polysaccharides of Rhizobium trifolii and Rhizobium leguminosarum. | journal = J Biol Chem | volume = 264 | issue = 3 | pages = 1461-6 | month = Jan | year = 1989 | doi = | PMID = 2912966 }}</ref>
*SE, YAP-fusion positive.
**Restricted to children (6-7% of all supratentorial ependymomas).
**YAP-MAMLD fusion most common alteration.
'''Posterior fossa Ependymoma'''
Two distinct molecular subgroups exist in the posterior fossa:<ref>{{Cite journal | last1 = Witt | first1 = H. | last2 = Mack | first2 = SC. | last3 = Ryzhova | first3 = M. | last4 = Bender | first4 = S. | last5 = Sill | first5 = M. | last6 = Isserlin | first6 = R. | last7 = Benner | first7 = A. | last8 = Hielscher | first8 = T. | last9 = Milde | first9 = T. | title = Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma. | journal = Cancer Cell | volume = 20 | issue = 2 | pages = 143-57 | month = Aug | year = 2011 | doi = 10.1016/j.ccr.2011.07.007 | PMID = 21840481 }}</ref>
* Group A ependymomas:
**typically found in children.
**laterally.
**relatively unfavorable clinical outcome.
**CpG island methylator phenotype.<ref>{{Cite journal | last1 = Mack | first1 = SC. | last2 = Witt | first2 = H. | last3 = Piro | first3 = RM. | last4 = Gu | first4 = L. | last5 = Zuyderduyn | first5 = S. | last6 = Stütz | first6 = AM. | last7 = Wang | first7 = X. | last8 = Gallo | first8 = M. | last9 = Garzia | first9 = L. | title = Epigenomic alterations define lethal CIMP-positive ependymomas of infancy. | journal = Nature | volume = 506 | issue = 7489 | pages = 445-50 | month = Feb | year = 2014 | doi = 10.1038/nature13108 | PMID = 24553142 }}</ref>
**Loss of H3K27me.<ref>{{Cite journal | last1 = Panwalkar | first1 = P. | last2 = Clark | first2 = J. | last3 = Ramaswamy | first3 = V. | last4 = Hawes | first4 = D. | last5 = Yang | first5 = F. | last6 = Dunham | first6 = C. | last7 = Yip | first7 = S. | last8 = Hukin | first8 = J. | last9 = Sun | first9 = Y. | title = Immunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Jul | year = 2017 | doi = 10.1007/s00401-017-1752-4 | PMID = 28733933 }}</ref>
* Group B ependymomas:
**typically adults.
**midline.
**relatively favorable clinical outcomes.
**gene expression profiles similar to that of spinal cord ependymomas.
**increased Chromosomal 1q gains. <ref>{{Cite journal | last1 = Korshunov | first1 = A. | last2 = Witt | first2 = H. | last3 = Hielscher | first3 = T. | last4 = Benner | first4 = A. | last5 = Remke | first5 = M. | last6 = Ryzhova | first6 = M. | last7 = Milde | first7 = T. | last8 = Bender | first8 = S. | last9 = Wittmann | first9 = A. | title = Molecular staging of intracranial ependymoma in children and adults. | journal = J Clin Oncol | volume = 28 | issue = 19 | pages = 3182-90 | month = Jul | year = 2010 | doi = 10.1200/JCO.2009.27.3359 | PMID = 20516456 }}</ref>

==See also==
*[[Subependymoma]].
*[[Myxopapillary ependymoma]].
*[[Neuropathology tumours]].

==References==
{{Reflist|1}}

[[Category:Diagnosis]]
[[Category:Neuropathology tumours]]

Ependymoma

2022-09-19T12:50:01Z

Jensflorian: /* Molecular */ Update

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Ependymoma_H%26E.jpg
| Width =
| Caption = Ependymoma grade II WHO. [[H&E stain]]
| Synonyms =
| Micro = Perivascular pseudorosettes, ependymal rosettes
| Subtypes = Tanycytic, Clear cell, Papillary, Cellular
| LMDDx = [[Subependymoma]], [[Glioblastoma]], [[Pilocytic astrocytoma]], [[Oligodendroglioma]]
| Stains =
| IHC = GFAP +ve
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site =
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence =
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis = intermediate to poor (WHO Grades II & III)
| Other =
| ClinDDx =
| Tx =
}}

'''Ependymoma''' is a [[neuropathology tumour]].

==General==
*Called the forgotten glial tumour.
*Anatomic location and molecular data is essential for tumor diagnosis.

Epidemiology:<ref name=Ref_PBoD8_1334>{{Ref PBoD8|1334}}</ref>
*Usual site:
**Adults: usually spinal cord.
**Children: usually posterior fossa.
*May be associated with [[neurofibromatosis type 2]].

There are currently ten main ependymal tumors:<ref name=Ref_WHOCNS_74>{{Ref WHOCNS|74}}</ref>
#Supratentorial [[Subependymoma]]
#Supratentorial ependymoma, ZFTA-fusion positive
#Supratentorial ependymoma, YAP1-fusion positive
#Posterior fossa [[Subependymoma]]
#Posterior fossa ependymoma group A
#Posterior fossa ependymoma group B
#Spinal [[Subependymoma]]
#Spinal ependymoma
#Spinal ependymoma, MYCN-amplified
#[[Myxopapillary ependymoma]]

Ependymoma, NOS (not otherwise specified): Molecular analysis still missing.
Ependymoma, NEC (not elsewhere classfied): Tumor cannot assigned to any of the defined entities.

Note: Molecularly defined ependymomas can be still graded as CNS grade 2 or 3 depending on histological features.

*Depreceated terminologies:
**Papillary ependymoma.
**Clear cell ependymoma.
**Tanycytic ependymoma.
**Cellular ependymoma.
**Ependymoma, RELA fusion-positive.<ref>{{Cite journal | last1 = Parker | first1 = M. | last2 = Mohankumar | first2 = KM. | last3 = Punchihewa | first3 = C. | last4 = Weinlich | first4 = R. | last5 = Dalton | first5 = JD. | last6 = Li | first6 = Y. | last7 = Lee | first7 = R. | last8 = Tatevossian | first8 = RG. | last9 = Phoenix | first9 = TN. | title = C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. | journal = Nature | volume = 506 | issue = 7489 | pages = 451-5 | month = Feb | year = 2014 | doi = 10.1038/nature13109 | PMID = 24553141 }}</ref><ref>{{Cite journal | last1 = Pietsch | first1 = T. | last2 = Wohlers | first2 = I. | last3 = Goschzik | first3 = T. | last4 = Dreschmann | first4 = V. | last5 = Denkhaus | first5 = D. | last6 = Dörner | first6 = E. | last7 = Rahmann | first7 = S. | last8 = Klein-Hitpass | first8 = L. | title = Supratentorial ependymomas of childhood carry C11orf95-RELA fusions leading to pathological activation of the NF-κB signaling pathway. | journal = Acta Neuropathol | volume = 127 | issue = 4 | pages = 609-11 | month = Apr | year = 2014 | doi = 10.1007/s00401-014-1264-4 | PMID = 24562983 }}</ref> This is now called Supratentorial ependymoma, ZFTA-fusion positive.
**Anaplastic ependymoma. This is now called CNS grade 3 ependymoma.

==Gross==
*Usually discrete and enhancing.
*Ventricular location, but also within the spinal cord.
*Dissemination possible.
*[[Myxopapillary ependymoma]] classically at [[filum terminale]].
*[[Subependymoma]] typically seen in IVth ventricle.
<gallery>
File:AFIP405711R-EPENDYMOMA.jpg | Radiology (AFIP)
File:AFIP405713G-EPENDYMOMA.jpg | Ependymoma in the fourth ventricle (AFIP)
File:Ependymoma in the fourth ventricle.jpg | Gross (AFIP)
</gallery>

==Microscopic==
==="Classic" ependymoma===
*Come in two CNS WHO grades: 2 and 3.
*Usu. sharply demarcated from surrounding brain parenchyma.
Features:
*Cells have a "tadpole-like" morphology.
**May also be described as ''ice cream cone-shaped''.<ref>[http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html]</ref>
*'''Rosettes''' = circular nuclear free zones/cells arranged in a pseudoglandular fashion; comes in two flavours in ependymoma:
**''Perivascular pseudorosettes'' = (tumour) cells arranged around a blood vessel; nuclei of cells distant from the blood vessel, i.e. rim of cytoplasm (from tumour cells) surround blood vessel (nucleus-free zone); more common than ependymal rosette... but less specific.
**''Ependymal rosette'' ([[AKA]] ''true ependymal rosette'') = rosette has an empty space at the centre - '''key feature'''.
*Nuclear features monotonous, i.e. "boring".<ref>MUN. 6 Oct 2009.</ref>
**There is little variation in size, shape and staining.
*Hyalinized vessels.
*Calcification.
*Rare cases with cartilagineous metaplasia.<ref>{{Cite journal | last1 = Wang | first1 = X. | last2 = Zhang | first2 = S. | last3 = Ye | first3 = Y. | last4 = Chen | first4 = Y. | last5 = Liu | first5 = X. | title = Ependymoma with cartilaginous metaplasia might have more aggressive behavior: a case report and literature review. | journal = Brain Tumor Pathol | volume = 29 | issue = 3 | pages = 172-6 | month = Jul | year = 2012 | doi = 10.1007/s10014-011-0079-4 | PMID = 22228122 }}</ref>
*Branching capillaries usu. only in supratentorial ependymomas.

===Supratentorial ependymoma===
*Usu. connected to the ventricles.
*Mostly frontal or temporal lobe.
*Approx. 1/3 of all ependymal tumours (41% in children).
*Irregular CM enhancement.
*Cysts and/or calcification possible.
*Sharply demarcated from adjacent brain parenchyma.
*True ependymal rosettes are rare.
*Occasionally branching capillary vessels.
*Clear cell phenotypes more common than in other locations.
*Complete surgical resection is the best predictor.
*CSF spread in up to 15% of tumours.

DDx (supratentorial and posterior fossa ependymoma):
*[[Subependymoma]].
*[[Glioblastoma]] (GBM).
*Gliomas with BCOR internal tandem duplication.
*[[Astroblastoma]], MN1-altered.
**Invasive border = GBM; circumscribed border of lesion = ependymoma.
*[[Oligodendroglioma]] (Clear cell ependymoma))
*CNS embryonal tumour with BCOR internal tandem duplication.

DDx (spinal ependymoma):
*[[Pilocytic astrocytoma]] (Tanycytic ependymoma)
*Diffuse midline glioma, H3 K27-altered
*Small cell glioblastoma (MYCN-amplified spinal ependymoma)

====Images====
www:
*[http://www.flickr.com/photos/ckrishnan/3862487821/in/photostream Ependymoma (flickr.com)].
*[http://www.ajnr.org/cgi/content-nw/full/27/3/488/F10 Ependymoma - ependymal rosettes (ajnr.org)].
*[http://path.upmc.edu/cases/case95/micro.html Anaplastic ependymoma - case 1 (upmc.edu)].
*[http://path.upmc.edu/cases/case324.html Anaplastic ependymoma - case 2 (upmc.edu)].
<gallery>
File:AFIP405736M-EPENDYMOMA.jpg | Ependymoma smear. (AFIP)
File:AFIP405715M-EPENDYMOMA.jpg | Perivascular pseudorosettes in a ependymoma. (AFIP)
Image:Ependymoma_intermed_mag.jpg | Ependymoma - intermed. mag. (WC)
Image:Ependymoma_low_intermed_mag.jpg | Ependymoma - low mag. (WC)
File:Ependymoma_H%26E.jpg | Ependymoma - high mag. (WC/Sbrandner)
File:Ependymoma_true_ependymal_rosettes_and_pseudorosettes.jpg | True ependymal and pseudorosettes in a ependymoma. (WC/jensflorian)
File:Ependymal_linings_ependymoma_HE.jpg | Ependymal linings in a ependymoma. (WC/jensflorian)
File:Ependymoma_GFAP.jpg| GFAP IHC in a ependymoma. (WC/Sbrandner)
File:EMA_ependymoma_periluminal.jpg | Periluminal EMA positivity in a ependymoma. (WC/jensflorian)
File:Ependymoma_EMA.jpg | Dot-like EMA immunreactivity n a ependymoma. (WC/Marvin101)
File:Tanycytic ependymoma HE.jpg | Tanycytic morphology in ependymoma must not confused with [[pilocytic astrocytoma]]. (WC/jensflorian)
File:Tanicytic_ependymoma_x10.jpg | Tanycytic morphology in ependymoma - low mag. (WC/jensflorian)
File:Papillary_Ependymoma.jpg | Papillary morphology in ependymoma - low mag. (WC/jensflorian)
File:Papillary_ependymoma_HE_x40.jpg | Papillary morphology in ependymoma - intermed. mag. (WC/jensflorian)
File:Clear_cell_ependymoma_HE.jpg | Clear cell morphology in ependymoma may mimic [[oligodendroglioma]]. (WC/jensflorian)
File:HE_anaplastic_epedymomas_mitoses_pleomorphism.jpg | Brisk mitotic activity in a anaplastic ependymoma. (WC/jensflorian)
File:Cartilaginous metaplasia ependymoma.jpg|Metaplastic transformation in an anaplastic ependymoma. (WC/jensflorian)
File:Ependymoma_L1CAM_IHC.jpg | L1CAM immunohistochemistry indicates presence of ZFTA-fusion.
File:Ependymoma_NFkappaB_IHC.jpg | Nuclear NFkappaB IHC indicates presence of ZFTA-fusion.
</gallery>

===Grading===
Easy:
*Subependymoma = CNS WHO grade 1.
*Myxopapillary ependymoma = CNS WHO grade 2.

Not so easy:
All other ependymomas: WHO CNS Grade 2 vs. Grade 3 depends on:
*Cellular density.
*Mitoses (no clear cut-off).
*Necrosis (not prognostic).
*Microvascular proliferation.
*Poor interobserver reliability<ref>{{Cite journal | last1 = Ellison | first1 = DW. | last2 = Kocak | first2 = M. | last3 = Figarella-Branger | first3 = D. | last4 = Felice | first4 = G. | last5 = Catherine | first5 = G. | last6 = Pietsch | first6 = T. | last7 = Frappaz | first7 = D. | last8 = Massimino | first8 = M. | last9 = Grill | first9 = J. | title = Histopathological grading of pediatric ependymoma: reproducibility and clinical relevance in European trial cohorts. | journal = J Negat Results Biomed | volume = 10 | issue = | pages = 7 | month = May | year = 2011 | doi = 10.1186/1477-5751-10-7 | PMID = 21627842 }}</ref>

Notes:
*Many tumours fall between grade 2 and grade 3.
*Rare cases with sarcomatous or cartilaginous components.<ref>{{Cite journal | last1 = Vajtai | first1 = I. | last2 = Kuhlen | first2 = D. | last3 = Kappeler | first3 = A. | last4 = Mariani | first4 = L. | last5 = Zimmermann | first5 = A. | last6 = Paulus | first6 = W. | title = Rapid spontaneous malignant progression of supratentorial tanycytic ependymoma with sarcomatous features - "Ependymosarcoma". | journal = Pathol Res Pract | volume = 206 | issue = 7 | pages = 493-8 | month = Jul | year = 2010 | doi = 10.1016/j.prp.2009.07.013 | PMID = 19853384 }}</ref><ref>{{Cite journal | last1 = Boukas | first1 = A. | last2 = Joshi | first2 = A. | last3 = Jenkins | first3 = A. | last4 = Holliman | first4 = D. | title = Extensive cartilaginous metaplasia of recurrent posterior fossa ependymoma: case report and review of the literature. | journal = Pediatr Neurosurg | volume = 49 | issue = 2 | pages = 93-8 | month = | year = 2013 | doi = 10.1159/000356931 | PMID = 24401698 }}</ref>

==IHC==
*Reticulin-ve.
*GFAP+ve.
*MIB1 (usu low).
*[[IDH-1]]-ve.
*EMA (dots and rings).<ref>{{Cite journal | last1 = Hasselblatt | first1 = M. | last2 = Paulus | first2 = W. | title = Sensitivity and specificity of epithelial membrane antigen staining patterns in ependymomas. | journal = Acta Neuropathol | volume = 106 | issue = 4 | pages = 385-8 | month = Oct | year = 2003 | doi = 10.1007/s00401-003-0752-8 | PMID = 12898159 }}</ref>
**Widespread and strong EMA expression is indicative of YAP1-fused ependymoma.
*Olig2-ve.<ref>{{Cite journal | last1 = Švajdler | first1 = M. | last2 = Rychlý | first2 = B. | last3 = Mezencev | first3 = R. | last4 = Fröhlichová | first4 = L. | last5 = Bednárová | first5 = A. | last6 = Pataky | first6 = F. | last7 = Daum | first7 = O. | title = SOX10 and Olig2 as negative markers for the diagnosis of ependymomas: An immunohistochemical study of 98 glial tumors. | journal = Histol Histopathol | volume = 31 | issue = 1 | pages = 95-102 | month = Jan | year = 2016 | doi = 10.14670/HH-11-654 | PMID = 26287936 }}</ref>
*H3K27me3 nuclear loss in Posterior fossa group A ependymoma (nuclear loss is diagnostic).<ref>{{Cite journal | last1 = Panwalkar | first1 = P. | last2 = Clark | first2 = J. | last3 = Ramaswamy | first3 = V. | last4 = Hawes | first4 = D. | last5 = Yang | first5 = F. | last6 = Dunham | first6 = C. | last7 = Yip | first7 = S. | last8 = Hukin | first8 = J. | last9 = Sun | first9 = Y. | title = Immunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Jul | year = 2017 | doi = 10.1007/s00401-017-1752-4 | PMID = 28733933 }}</ref>
*L1CAM in supratentorial tumors (expression indicates ZFTA fusion).<ref>{{Cite journal | last1 = Parker | first1 = M. | last2 = Mohankumar | first2 = KM. | last3 = Punchihewa | first3 = C. | last4 = Weinlich | first4 = R. | last5 = Dalton | first5 = JD. | last6 = Li | first6 = Y. | last7 = Lee | first7 = R. | last8 = Tatevossian | first8 = RG. | last9 = Phoenix | first9 = TN. | title = C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. | journal = Nature | volume = 506 | issue = 7489 | pages = 451-5 | month = Feb | year = 2014 | doi = 10.1038/nature13109 | PMID = 24553141 }}</ref>
*p65 nuclear +ve in ZFTA-fused ependymoma.

==Molecular==
'''Supratentorial Ependymoma'''
*SE, ZFTA-fusion positive: Adults and children (up to 80% of cases).<ref>{{Cite journal | last1 = Parker | first1 = M. | last2 = Mohankumar | first2 = KM. | last3 = Punchihewa | first3 = C. | last4 = Weinlich | first4 = R. | last5 = Dalton | first5 = JD. | last6 = Li | first6 = Y. | last7 = Lee | first7 = R. | last8 = Tatevossian | first8 = RG. | last9 = Phoenix | first9 = TN. | title = C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. | journal = Nature | volume = 506 | issue = 7489 | pages = 451-5 | month = Feb | year = 2014 | doi = 10.1038/nature13109 | PMID = 24553141 }}</ref>
**ZFTA-RELA fusion most common alteration.
**Chromothripsis.
**EPHB2 amplifications and CDKN2A deletions in a subset of these tumors<ref>{{Cite journal | last1 = Philip-Hollingsworth | first1 = S. | last2 = Hollingsworth | first2 = RI. | last3 = Dazzo | first3 = FB. | title = Host-range related structural features of the acidic extracellular polysaccharides of Rhizobium trifolii and Rhizobium leguminosarum. | journal = J Biol Chem | volume = 264 | issue = 3 | pages = 1461-6 | month = Jan | year = 1989 | doi = | PMID = 2912966 }}</ref>
*SE, YAP-fusion positive.
**Restricted to children (6-7% of all supratentorial ependymomas).
**YAP-MAMLD fusion most common alteration.
'''Posterior fossa Ependymoma'''
Two distinct molecular subgroups exist in the posterior fossa:<ref>{{Cite journal | last1 = Witt | first1 = H. | last2 = Mack | first2 = SC. | last3 = Ryzhova | first3 = M. | last4 = Bender | first4 = S. | last5 = Sill | first5 = M. | last6 = Isserlin | first6 = R. | last7 = Benner | first7 = A. | last8 = Hielscher | first8 = T. | last9 = Milde | first9 = T. | title = Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma. | journal = Cancer Cell | volume = 20 | issue = 2 | pages = 143-57 | month = Aug | year = 2011 | doi = 10.1016/j.ccr.2011.07.007 | PMID = 21840481 }}</ref>
* Group A ependymomas:
**typically found in children.
**laterally.
**relatively unfavorable clinical outcome.
**CpG island methylator phenotype.<ref>{{Cite journal | last1 = Mack | first1 = SC. | last2 = Witt | first2 = H. | last3 = Piro | first3 = RM. | last4 = Gu | first4 = L. | last5 = Zuyderduyn | first5 = S. | last6 = Stütz | first6 = AM. | last7 = Wang | first7 = X. | last8 = Gallo | first8 = M. | last9 = Garzia | first9 = L. | title = Epigenomic alterations define lethal CIMP-positive ependymomas of infancy. | journal = Nature | volume = 506 | issue = 7489 | pages = 445-50 | month = Feb | year = 2014 | doi = 10.1038/nature13108 | PMID = 24553142 }}</ref>
**Loss of H3K27me.<ref>{{Cite journal | last1 = Panwalkar | first1 = P. | last2 = Clark | first2 = J. | last3 = Ramaswamy | first3 = V. | last4 = Hawes | first4 = D. | last5 = Yang | first5 = F. | last6 = Dunham | first6 = C. | last7 = Yip | first7 = S. | last8 = Hukin | first8 = J. | last9 = Sun | first9 = Y. | title = Immunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Jul | year = 2017 | doi = 10.1007/s00401-017-1752-4 | PMID = 28733933 }}</ref>
* Group B ependymomas:
**typically adults.
**midline.
**relatively favorable clinical outcomes.
**gene expression profiles similar to that of spinal cord ependymomas.
**increased Chromosomal 1q gains. <ref>{{Cite journal | last1 = Korshunov | first1 = A. | last2 = Witt | first2 = H. | last3 = Hielscher | first3 = T. | last4 = Benner | first4 = A. | last5 = Remke | first5 = M. | last6 = Ryzhova | first6 = M. | last7 = Milde | first7 = T. | last8 = Bender | first8 = S. | last9 = Wittmann | first9 = A. | title = Molecular staging of intracranial ependymoma in children and adults. | journal = J Clin Oncol | volume = 28 | issue = 19 | pages = 3182-90 | month = Jul | year = 2010 | doi = 10.1200/JCO.2009.27.3359 | PMID = 20516456 }}</ref>

==See also==
*[[Subependymoma]].
*[[Myxopapillary ependymoma]].
*[[Neuropathology tumours]].

==References==
{{Reflist|1}}

[[Category:Diagnosis]]
[[Category:Neuropathology tumours]]

Ependymoma

2022-09-19T12:43:25Z

Jensflorian: /* Microscopic */ Supratentorial ependymoma

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Ependymoma_H%26E.jpg
| Width =
| Caption = Ependymoma grade II WHO. [[H&E stain]]
| Synonyms =
| Micro = Perivascular pseudorosettes, ependymal rosettes
| Subtypes = Tanycytic, Clear cell, Papillary, Cellular
| LMDDx = [[Subependymoma]], [[Glioblastoma]], [[Pilocytic astrocytoma]], [[Oligodendroglioma]]
| Stains =
| IHC = GFAP +ve
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site =
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence =
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis = intermediate to poor (WHO Grades II & III)
| Other =
| ClinDDx =
| Tx =
}}

'''Ependymoma''' is a [[neuropathology tumour]].

==General==
*Called the forgotten glial tumour.
*Anatomic location and molecular data is essential for tumor diagnosis.

Epidemiology:<ref name=Ref_PBoD8_1334>{{Ref PBoD8|1334}}</ref>
*Usual site:
**Adults: usually spinal cord.
**Children: usually posterior fossa.
*May be associated with [[neurofibromatosis type 2]].

There are currently ten main ependymal tumors:<ref name=Ref_WHOCNS_74>{{Ref WHOCNS|74}}</ref>
#Supratentorial [[Subependymoma]]
#Supratentorial ependymoma, ZFTA-fusion positive
#Supratentorial ependymoma, YAP1-fusion positive
#Posterior fossa [[Subependymoma]]
#Posterior fossa ependymoma group A
#Posterior fossa ependymoma group B
#Spinal [[Subependymoma]]
#Spinal ependymoma
#Spinal ependymoma, MYCN-amplified
#[[Myxopapillary ependymoma]]

Ependymoma, NOS (not otherwise specified): Molecular analysis still missing.
Ependymoma, NEC (not elsewhere classfied): Tumor cannot assigned to any of the defined entities.

Note: Molecularly defined ependymomas can be still graded as CNS grade 2 or 3 depending on histological features.

*Depreceated terminologies:
**Papillary ependymoma.
**Clear cell ependymoma.
**Tanycytic ependymoma.
**Cellular ependymoma.
**Ependymoma, RELA fusion-positive.<ref>{{Cite journal | last1 = Parker | first1 = M. | last2 = Mohankumar | first2 = KM. | last3 = Punchihewa | first3 = C. | last4 = Weinlich | first4 = R. | last5 = Dalton | first5 = JD. | last6 = Li | first6 = Y. | last7 = Lee | first7 = R. | last8 = Tatevossian | first8 = RG. | last9 = Phoenix | first9 = TN. | title = C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. | journal = Nature | volume = 506 | issue = 7489 | pages = 451-5 | month = Feb | year = 2014 | doi = 10.1038/nature13109 | PMID = 24553141 }}</ref><ref>{{Cite journal | last1 = Pietsch | first1 = T. | last2 = Wohlers | first2 = I. | last3 = Goschzik | first3 = T. | last4 = Dreschmann | first4 = V. | last5 = Denkhaus | first5 = D. | last6 = Dörner | first6 = E. | last7 = Rahmann | first7 = S. | last8 = Klein-Hitpass | first8 = L. | title = Supratentorial ependymomas of childhood carry C11orf95-RELA fusions leading to pathological activation of the NF-κB signaling pathway. | journal = Acta Neuropathol | volume = 127 | issue = 4 | pages = 609-11 | month = Apr | year = 2014 | doi = 10.1007/s00401-014-1264-4 | PMID = 24562983 }}</ref> This is now called Supratentorial ependymoma, ZFTA-fusion positive.
**Anaplastic ependymoma. This is now called CNS grade 3 ependymoma.

==Gross==
*Usually discrete and enhancing.
*Ventricular location, but also within the spinal cord.
*Dissemination possible.
*[[Myxopapillary ependymoma]] classically at [[filum terminale]].
*[[Subependymoma]] typically seen in IVth ventricle.
<gallery>
File:AFIP405711R-EPENDYMOMA.jpg | Radiology (AFIP)
File:AFIP405713G-EPENDYMOMA.jpg | Ependymoma in the fourth ventricle (AFIP)
File:Ependymoma in the fourth ventricle.jpg | Gross (AFIP)
</gallery>

==Microscopic==
==="Classic" ependymoma===
*Come in two CNS WHO grades: 2 and 3.
*Usu. sharply demarcated from surrounding brain parenchyma.
Features:
*Cells have a "tadpole-like" morphology.
**May also be described as ''ice cream cone-shaped''.<ref>[http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html]</ref>
*'''Rosettes''' = circular nuclear free zones/cells arranged in a pseudoglandular fashion; comes in two flavours in ependymoma:
**''Perivascular pseudorosettes'' = (tumour) cells arranged around a blood vessel; nuclei of cells distant from the blood vessel, i.e. rim of cytoplasm (from tumour cells) surround blood vessel (nucleus-free zone); more common than ependymal rosette... but less specific.
**''Ependymal rosette'' ([[AKA]] ''true ependymal rosette'') = rosette has an empty space at the centre - '''key feature'''.
*Nuclear features monotonous, i.e. "boring".<ref>MUN. 6 Oct 2009.</ref>
**There is little variation in size, shape and staining.
*Hyalinized vessels.
*Calcification.
*Rare cases with cartilagineous metaplasia.<ref>{{Cite journal | last1 = Wang | first1 = X. | last2 = Zhang | first2 = S. | last3 = Ye | first3 = Y. | last4 = Chen | first4 = Y. | last5 = Liu | first5 = X. | title = Ependymoma with cartilaginous metaplasia might have more aggressive behavior: a case report and literature review. | journal = Brain Tumor Pathol | volume = 29 | issue = 3 | pages = 172-6 | month = Jul | year = 2012 | doi = 10.1007/s10014-011-0079-4 | PMID = 22228122 }}</ref>
*Branching capillaries usu. only in supratentorial ependymomas.

===Supratentorial ependymoma===
*Usu. connected to the ventricles.
*Mostly frontal or temporal lobe.
*Approx. 1/3 of all ependymal tumours (41% in children).
*Irregular CM enhancement.
*Cysts and/or calcification possible.
*Sharply demarcated from adjacent brain parenchyma.
*True ependymal rosettes are rare.
*Occasionally branching capillary vessels.
*Clear cell phenotypes more common than in other locations.
*Complete surgical resection is the best predictor.
*CSF spread in up to 15% of tumours.

DDx (supratentorial and posterior fossa ependymoma):
*[[Subependymoma]].
*[[Glioblastoma]] (GBM).
*Gliomas with BCOR internal tandem duplication.
*[[Astroblastoma]], MN1-altered.
**Invasive border = GBM; circumscribed border of lesion = ependymoma.
*[[Oligodendroglioma]] (Clear cell ependymoma))
*CNS embryonal tumour with BCOR internal tandem duplication.

DDx (spinal ependymoma):
*[[Pilocytic astrocytoma]] (Tanycytic ependymoma)
*Diffuse midline glioma, H3 K27-altered
*Small cell glioblastoma (MYCN-amplified spinal ependymoma)

====Images====
www:
*[http://www.flickr.com/photos/ckrishnan/3862487821/in/photostream Ependymoma (flickr.com)].
*[http://www.ajnr.org/cgi/content-nw/full/27/3/488/F10 Ependymoma - ependymal rosettes (ajnr.org)].
*[http://path.upmc.edu/cases/case95/micro.html Anaplastic ependymoma - case 1 (upmc.edu)].
*[http://path.upmc.edu/cases/case324.html Anaplastic ependymoma - case 2 (upmc.edu)].
<gallery>
File:AFIP405736M-EPENDYMOMA.jpg | Ependymoma smear. (AFIP)
File:AFIP405715M-EPENDYMOMA.jpg | Perivascular pseudorosettes in a ependymoma. (AFIP)
Image:Ependymoma_intermed_mag.jpg | Ependymoma - intermed. mag. (WC)
Image:Ependymoma_low_intermed_mag.jpg | Ependymoma - low mag. (WC)
File:Ependymoma_H%26E.jpg | Ependymoma - high mag. (WC/Sbrandner)
File:Ependymoma_true_ependymal_rosettes_and_pseudorosettes.jpg | True ependymal and pseudorosettes in a ependymoma. (WC/jensflorian)
File:Ependymal_linings_ependymoma_HE.jpg | Ependymal linings in a ependymoma. (WC/jensflorian)
File:Ependymoma_GFAP.jpg| GFAP IHC in a ependymoma. (WC/Sbrandner)
File:EMA_ependymoma_periluminal.jpg | Periluminal EMA positivity in a ependymoma. (WC/jensflorian)
File:Ependymoma_EMA.jpg | Dot-like EMA immunreactivity n a ependymoma. (WC/Marvin101)
File:Tanycytic ependymoma HE.jpg | Tanycytic morphology in ependymoma must not confused with [[pilocytic astrocytoma]]. (WC/jensflorian)
File:Tanicytic_ependymoma_x10.jpg | Tanycytic morphology in ependymoma - low mag. (WC/jensflorian)
File:Papillary_Ependymoma.jpg | Papillary morphology in ependymoma - low mag. (WC/jensflorian)
File:Papillary_ependymoma_HE_x40.jpg | Papillary morphology in ependymoma - intermed. mag. (WC/jensflorian)
File:Clear_cell_ependymoma_HE.jpg | Clear cell morphology in ependymoma may mimic [[oligodendroglioma]]. (WC/jensflorian)
File:HE_anaplastic_epedymomas_mitoses_pleomorphism.jpg | Brisk mitotic activity in a anaplastic ependymoma. (WC/jensflorian)
File:Cartilaginous metaplasia ependymoma.jpg|Metaplastic transformation in an anaplastic ependymoma. (WC/jensflorian)
File:Ependymoma_L1CAM_IHC.jpg | L1CAM immunohistochemistry indicates presence of ZFTA-fusion.
File:Ependymoma_NFkappaB_IHC.jpg | Nuclear NFkappaB IHC indicates presence of ZFTA-fusion.
</gallery>

===Grading===
Easy:
*Subependymoma = CNS WHO grade 1.
*Myxopapillary ependymoma = CNS WHO grade 2.

Not so easy:
All other ependymomas: WHO CNS Grade 2 vs. Grade 3 depends on:
*Cellular density.
*Mitoses (no clear cut-off).
*Necrosis (not prognostic).
*Microvascular proliferation.
*Poor interobserver reliability<ref>{{Cite journal | last1 = Ellison | first1 = DW. | last2 = Kocak | first2 = M. | last3 = Figarella-Branger | first3 = D. | last4 = Felice | first4 = G. | last5 = Catherine | first5 = G. | last6 = Pietsch | first6 = T. | last7 = Frappaz | first7 = D. | last8 = Massimino | first8 = M. | last9 = Grill | first9 = J. | title = Histopathological grading of pediatric ependymoma: reproducibility and clinical relevance in European trial cohorts. | journal = J Negat Results Biomed | volume = 10 | issue = | pages = 7 | month = May | year = 2011 | doi = 10.1186/1477-5751-10-7 | PMID = 21627842 }}</ref>

Notes:
*Many tumours fall between grade 2 and grade 3.
*Rare cases with sarcomatous or cartilaginous components.<ref>{{Cite journal | last1 = Vajtai | first1 = I. | last2 = Kuhlen | first2 = D. | last3 = Kappeler | first3 = A. | last4 = Mariani | first4 = L. | last5 = Zimmermann | first5 = A. | last6 = Paulus | first6 = W. | title = Rapid spontaneous malignant progression of supratentorial tanycytic ependymoma with sarcomatous features - "Ependymosarcoma". | journal = Pathol Res Pract | volume = 206 | issue = 7 | pages = 493-8 | month = Jul | year = 2010 | doi = 10.1016/j.prp.2009.07.013 | PMID = 19853384 }}</ref><ref>{{Cite journal | last1 = Boukas | first1 = A. | last2 = Joshi | first2 = A. | last3 = Jenkins | first3 = A. | last4 = Holliman | first4 = D. | title = Extensive cartilaginous metaplasia of recurrent posterior fossa ependymoma: case report and review of the literature. | journal = Pediatr Neurosurg | volume = 49 | issue = 2 | pages = 93-8 | month = | year = 2013 | doi = 10.1159/000356931 | PMID = 24401698 }}</ref>

==IHC==
*Reticulin-ve.
*GFAP+ve.
*MIB1 (usu low).
*[[IDH-1]]-ve.
*EMA (dots and rings).<ref>{{Cite journal | last1 = Hasselblatt | first1 = M. | last2 = Paulus | first2 = W. | title = Sensitivity and specificity of epithelial membrane antigen staining patterns in ependymomas. | journal = Acta Neuropathol | volume = 106 | issue = 4 | pages = 385-8 | month = Oct | year = 2003 | doi = 10.1007/s00401-003-0752-8 | PMID = 12898159 }}</ref>
**Widespread and strong EMA expression is indicative of YAP1-fused ependymoma.
*Olig2-ve.<ref>{{Cite journal | last1 = Švajdler | first1 = M. | last2 = Rychlý | first2 = B. | last3 = Mezencev | first3 = R. | last4 = Fröhlichová | first4 = L. | last5 = Bednárová | first5 = A. | last6 = Pataky | first6 = F. | last7 = Daum | first7 = O. | title = SOX10 and Olig2 as negative markers for the diagnosis of ependymomas: An immunohistochemical study of 98 glial tumors. | journal = Histol Histopathol | volume = 31 | issue = 1 | pages = 95-102 | month = Jan | year = 2016 | doi = 10.14670/HH-11-654 | PMID = 26287936 }}</ref>
*H3K27me3 nuclear loss in Posterior fossa group A ependymoma (nuclear loss is diagnostic).<ref>{{Cite journal | last1 = Panwalkar | first1 = P. | last2 = Clark | first2 = J. | last3 = Ramaswamy | first3 = V. | last4 = Hawes | first4 = D. | last5 = Yang | first5 = F. | last6 = Dunham | first6 = C. | last7 = Yip | first7 = S. | last8 = Hukin | first8 = J. | last9 = Sun | first9 = Y. | title = Immunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Jul | year = 2017 | doi = 10.1007/s00401-017-1752-4 | PMID = 28733933 }}</ref>
*L1CAM in supratentorial tumors (expression indicates ZFTA fusion).<ref>{{Cite journal | last1 = Parker | first1 = M. | last2 = Mohankumar | first2 = KM. | last3 = Punchihewa | first3 = C. | last4 = Weinlich | first4 = R. | last5 = Dalton | first5 = JD. | last6 = Li | first6 = Y. | last7 = Lee | first7 = R. | last8 = Tatevossian | first8 = RG. | last9 = Phoenix | first9 = TN. | title = C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. | journal = Nature | volume = 506 | issue = 7489 | pages = 451-5 | month = Feb | year = 2014 | doi = 10.1038/nature13109 | PMID = 24553141 }}</ref>
*p65 nuclear +ve in ZFTA-fused ependymoma.

==Molecular==
Two distinct molecular subgroups exist in the posterior fossa:<ref>{{Cite journal | last1 = Witt | first1 = H. | last2 = Mack | first2 = SC. | last3 = Ryzhova | first3 = M. | last4 = Bender | first4 = S. | last5 = Sill | first5 = M. | last6 = Isserlin | first6 = R. | last7 = Benner | first7 = A. | last8 = Hielscher | first8 = T. | last9 = Milde | first9 = T. | title = Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma. | journal = Cancer Cell | volume = 20 | issue = 2 | pages = 143-57 | month = Aug | year = 2011 | doi = 10.1016/j.ccr.2011.07.007 | PMID = 21840481 }}</ref>
* Group A ependymomas:
**typically found in children.
**laterally.
**relatively unfavorable clinical outcome.
**CpG island methylator phenotype.<ref>{{Cite journal | last1 = Mack | first1 = SC. | last2 = Witt | first2 = H. | last3 = Piro | first3 = RM. | last4 = Gu | first4 = L. | last5 = Zuyderduyn | first5 = S. | last6 = Stütz | first6 = AM. | last7 = Wang | first7 = X. | last8 = Gallo | first8 = M. | last9 = Garzia | first9 = L. | title = Epigenomic alterations define lethal CIMP-positive ependymomas of infancy. | journal = Nature | volume = 506 | issue = 7489 | pages = 445-50 | month = Feb | year = 2014 | doi = 10.1038/nature13108 | PMID = 24553142 }}</ref>
**Loss of H3K27me.<ref>{{Cite journal | last1 = Panwalkar | first1 = P. | last2 = Clark | first2 = J. | last3 = Ramaswamy | first3 = V. | last4 = Hawes | first4 = D. | last5 = Yang | first5 = F. | last6 = Dunham | first6 = C. | last7 = Yip | first7 = S. | last8 = Hukin | first8 = J. | last9 = Sun | first9 = Y. | title = Immunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Jul | year = 2017 | doi = 10.1007/s00401-017-1752-4 | PMID = 28733933 }}</ref>
* Group B ependymomas:
**typically adults.
**midline.
**relatively favorable clinical outcomes.
**gene expression profiles similar to that of spinal cord ependymomas.
**increased Chromosomal 1q gains. <ref>{{Cite journal | last1 = Korshunov | first1 = A. | last2 = Witt | first2 = H. | last3 = Hielscher | first3 = T. | last4 = Benner | first4 = A. | last5 = Remke | first5 = M. | last6 = Ryzhova | first6 = M. | last7 = Milde | first7 = T. | last8 = Bender | first8 = S. | last9 = Wittmann | first9 = A. | title = Molecular staging of intracranial ependymoma in children and adults. | journal = J Clin Oncol | volume = 28 | issue = 19 | pages = 3182-90 | month = Jul | year = 2010 | doi = 10.1200/JCO.2009.27.3359 | PMID = 20516456 }}</ref>

Supratentorial ependymomas have also a distinct profile:
*70 % of these ependymomas are ZFTA-fusion positive and have recurrent gene fusions mostly involving RELA<ref>{{Cite journal | last1 = Parker | first1 = M. | last2 = Mohankumar | first2 = KM. | last3 = Punchihewa | first3 = C. | last4 = Weinlich | first4 = R. | last5 = Dalton | first5 = JD. | last6 = Li | first6 = Y. | last7 = Lee | first7 = R. | last8 = Tatevossian | first8 = RG. | last9 = Phoenix | first9 = TN. | title = C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. | journal = Nature | volume = 506 | issue = 7489 | pages = 451-5 | month = Feb | year = 2014 | doi = 10.1038/nature13109 | PMID = 24553141 }}</ref>
**EPHB2 amplifications and CDKN2A deletions in a subset of these tumors<ref>{{Cite journal | last1 = Philip-Hollingsworth | first1 = S. | last2 = Hollingsworth | first2 = RI. | last3 = Dazzo | first3 = FB. | title = Host-range related structural features of the acidic extracellular polysaccharides of Rhizobium trifolii and Rhizobium leguminosarum. | journal = J Biol Chem | volume = 264 | issue = 3 | pages = 1461-6 | month = Jan | year = 1989 | doi = | PMID = 2912966 }}</ref>
*6-8% are YAP1-fusion positive, mostly MAMLD1 as fusion partner.
Note: Molecular subgroups have no treatment implications (at the moment).

==See also==
*[[Subependymoma]].
*[[Myxopapillary ependymoma]].
*[[Neuropathology tumours]].

==References==
{{Reflist|1}}

[[Category:Diagnosis]]
[[Category:Neuropathology tumours]]

Ependymoma

2022-09-19T12:32:46Z

Jensflorian: Update molecular classes.

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Ependymoma_H%26E.jpg
| Width =
| Caption = Ependymoma grade II WHO. [[H&E stain]]
| Synonyms =
| Micro = Perivascular pseudorosettes, ependymal rosettes
| Subtypes = Tanycytic, Clear cell, Papillary, Cellular
| LMDDx = [[Subependymoma]], [[Glioblastoma]], [[Pilocytic astrocytoma]], [[Oligodendroglioma]]
| Stains =
| IHC = GFAP +ve
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site =
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence =
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis = intermediate to poor (WHO Grades II & III)
| Other =
| ClinDDx =
| Tx =
}}

'''Ependymoma''' is a [[neuropathology tumour]].

==General==
*Called the forgotten glial tumour.
*Anatomic location and molecular data is essential for tumor diagnosis.

Epidemiology:<ref name=Ref_PBoD8_1334>{{Ref PBoD8|1334}}</ref>
*Usual site:
**Adults: usually spinal cord.
**Children: usually posterior fossa.
*May be associated with [[neurofibromatosis type 2]].

There are currently ten main ependymal tumors:<ref name=Ref_WHOCNS_74>{{Ref WHOCNS|74}}</ref>
#Supratentorial [[Subependymoma]]
#Supratentorial ependymoma, ZFTA-fusion positive
#Supratentorial ependymoma, YAP1-fusion positive
#Posterior fossa [[Subependymoma]]
#Posterior fossa ependymoma group A
#Posterior fossa ependymoma group B
#Spinal [[Subependymoma]]
#Spinal ependymoma
#Spinal ependymoma, MYCN-amplified
#[[Myxopapillary ependymoma]]

Ependymoma, NOS (not otherwise specified): Molecular analysis still missing.
Ependymoma, NEC (not elsewhere classfied): Tumor cannot assigned to any of the defined entities.

Note: Molecularly defined ependymomas can be still graded as CNS grade 2 or 3 depending on histological features.

*Depreceated terminologies:
**Papillary ependymoma.
**Clear cell ependymoma.
**Tanycytic ependymoma.
**Cellular ependymoma.
**Ependymoma, RELA fusion-positive.<ref>{{Cite journal | last1 = Parker | first1 = M. | last2 = Mohankumar | first2 = KM. | last3 = Punchihewa | first3 = C. | last4 = Weinlich | first4 = R. | last5 = Dalton | first5 = JD. | last6 = Li | first6 = Y. | last7 = Lee | first7 = R. | last8 = Tatevossian | first8 = RG. | last9 = Phoenix | first9 = TN. | title = C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. | journal = Nature | volume = 506 | issue = 7489 | pages = 451-5 | month = Feb | year = 2014 | doi = 10.1038/nature13109 | PMID = 24553141 }}</ref><ref>{{Cite journal | last1 = Pietsch | first1 = T. | last2 = Wohlers | first2 = I. | last3 = Goschzik | first3 = T. | last4 = Dreschmann | first4 = V. | last5 = Denkhaus | first5 = D. | last6 = Dörner | first6 = E. | last7 = Rahmann | first7 = S. | last8 = Klein-Hitpass | first8 = L. | title = Supratentorial ependymomas of childhood carry C11orf95-RELA fusions leading to pathological activation of the NF-κB signaling pathway. | journal = Acta Neuropathol | volume = 127 | issue = 4 | pages = 609-11 | month = Apr | year = 2014 | doi = 10.1007/s00401-014-1264-4 | PMID = 24562983 }}</ref> This is now called Supratentorial ependymoma, ZFTA-fusion positive.
**Anaplastic ependymoma. This is now called CNS grade 3 ependymoma.

==Gross==
*Usually discrete and enhancing.
*Ventricular location, but also within the spinal cord.
*Dissemination possible.
*[[Myxopapillary ependymoma]] classically at [[filum terminale]].
*[[Subependymoma]] typically seen in IVth ventricle.
<gallery>
File:AFIP405711R-EPENDYMOMA.jpg | Radiology (AFIP)
File:AFIP405713G-EPENDYMOMA.jpg | Ependymoma in the fourth ventricle (AFIP)
File:Ependymoma in the fourth ventricle.jpg | Gross (AFIP)
</gallery>

==Microscopic==
==="Classic" ependymoma===
*Come in two CNS WHO grades: 2 and 3.
*Usu. sharply demarcated from surrounding brain parenchyma.
Features:
*Cells have a "tadpole-like" morphology.
**May also be described as ''ice cream cone-shaped''.<ref>[http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html]</ref>
*'''Rosettes''' = circular nuclear free zones/cells arranged in a pseudoglandular fashion; comes in two flavours in ependymoma:
**''Perivascular pseudorosettes'' = (tumour) cells arranged around a blood vessel; nuclei of cells distant from the blood vessel, i.e. rim of cytoplasm (from tumour cells) surround blood vessel (nucleus-free zone); more common than ependymal rosette... but less specific.
**''Ependymal rosette'' ([[AKA]] ''true ependymal rosette'') = rosette has an empty space at the centre - '''key feature'''.
*Nuclear features monotonous, i.e. "boring".<ref>MUN. 6 Oct 2009.</ref>
**There is little variation in size, shape and staining.
*Hyalinized vessels.
*Calcification.
*Rare cases with cartilagineous metaplasia.<ref>{{Cite journal | last1 = Wang | first1 = X. | last2 = Zhang | first2 = S. | last3 = Ye | first3 = Y. | last4 = Chen | first4 = Y. | last5 = Liu | first5 = X. | title = Ependymoma with cartilaginous metaplasia might have more aggressive behavior: a case report and literature review. | journal = Brain Tumor Pathol | volume = 29 | issue = 3 | pages = 172-6 | month = Jul | year = 2012 | doi = 10.1007/s10014-011-0079-4 | PMID = 22228122 }}</ref>
*Branching capillaries usu. only in supratentorial ependymomas.

DDx (supratentorial and posterior fossa ependymoma):
*[[Subependymoma]].
*[[Glioblastoma]] (GBM).
*Gliomas with BCOR internal tandem duplication.
*[[Astroblastoma]], MN1-altered.
**Invasive border = GBM; circumscribed border of lesion = ependymoma.
*[[Oligodendroglioma]] (Clear cell ependymoma))

DDx (spinal ependymoma):
*[[Pilocytic astrocytoma]] (Tanycytic ependymoma)
*Diffuse midline glioma, H3 K27-altered
*Small cell glioblastoma (MYCN-amplified spinal ependymoma)

====Images====
www:
*[http://www.flickr.com/photos/ckrishnan/3862487821/in/photostream Ependymoma (flickr.com)].
*[http://www.ajnr.org/cgi/content-nw/full/27/3/488/F10 Ependymoma - ependymal rosettes (ajnr.org)].
*[http://path.upmc.edu/cases/case95/micro.html Anaplastic ependymoma - case 1 (upmc.edu)].
*[http://path.upmc.edu/cases/case324.html Anaplastic ependymoma - case 2 (upmc.edu)].
<gallery>
File:AFIP405736M-EPENDYMOMA.jpg | Ependymoma smear. (AFIP)
File:AFIP405715M-EPENDYMOMA.jpg | Perivascular pseudorosettes in a ependymoma. (AFIP)
Image:Ependymoma_intermed_mag.jpg | Ependymoma - intermed. mag. (WC)
Image:Ependymoma_low_intermed_mag.jpg | Ependymoma - low mag. (WC)
File:Ependymoma_H%26E.jpg | Ependymoma - high mag. (WC/Sbrandner)
File:Ependymoma_true_ependymal_rosettes_and_pseudorosettes.jpg | True ependymal and pseudorosettes in a ependymoma. (WC/jensflorian)
File:Ependymal_linings_ependymoma_HE.jpg | Ependymal linings in a ependymoma. (WC/jensflorian)
File:Ependymoma_GFAP.jpg| GFAP IHC in a ependymoma. (WC/Sbrandner)
File:EMA_ependymoma_periluminal.jpg | Periluminal EMA positivity in a ependymoma. (WC/jensflorian)
File:Ependymoma_EMA.jpg | Dot-like EMA immunreactivity n a ependymoma. (WC/Marvin101)
File:Tanycytic ependymoma HE.jpg | Tanycytic morphology in ependymoma must not confused with [[pilocytic astrocytoma]]. (WC/jensflorian)
File:Tanicytic_ependymoma_x10.jpg | Tanycytic morphology in ependymoma - low mag. (WC/jensflorian)
File:Papillary_Ependymoma.jpg | Papillary morphology in ependymoma - low mag. (WC/jensflorian)
File:Papillary_ependymoma_HE_x40.jpg | Papillary morphology in ependymoma - intermed. mag. (WC/jensflorian)
File:Clear_cell_ependymoma_HE.jpg | Clear cell morphology in ependymoma may mimic [[oligodendroglioma]]. (WC/jensflorian)
File:HE_anaplastic_epedymomas_mitoses_pleomorphism.jpg | Brisk mitotic activity in a anaplastic ependymoma. (WC/jensflorian)
File:Cartilaginous metaplasia ependymoma.jpg|Metaplastic transformation in an anaplastic ependymoma. (WC/jensflorian)
File:Ependymoma_L1CAM_IHC.jpg | L1CAM immunohistochemistry indicates presence of ZFTA-fusion.
File:Ependymoma_NFkappaB_IHC.jpg | Nuclear NFkappaB IHC indicates presence of ZFTA-fusion.
</gallery>

===Grading===
Easy:
*Subependymoma = CNS WHO grade 1.
*Myxopapillary ependymoma = CNS WHO grade 2.

Not so easy:
All other ependymomas: WHO CNS Grade 2 vs. Grade 3 depends on:
*Cellular density.
*Mitoses (no clear cut-off).
*Necrosis (not prognostic).
*Microvascular proliferation.
*Poor interobserver reliability<ref>{{Cite journal | last1 = Ellison | first1 = DW. | last2 = Kocak | first2 = M. | last3 = Figarella-Branger | first3 = D. | last4 = Felice | first4 = G. | last5 = Catherine | first5 = G. | last6 = Pietsch | first6 = T. | last7 = Frappaz | first7 = D. | last8 = Massimino | first8 = M. | last9 = Grill | first9 = J. | title = Histopathological grading of pediatric ependymoma: reproducibility and clinical relevance in European trial cohorts. | journal = J Negat Results Biomed | volume = 10 | issue = | pages = 7 | month = May | year = 2011 | doi = 10.1186/1477-5751-10-7 | PMID = 21627842 }}</ref>

Notes:
*Many tumours fall between grade 2 and grade 3.
*Rare cases with sarcomatous or cartilaginous components.<ref>{{Cite journal | last1 = Vajtai | first1 = I. | last2 = Kuhlen | first2 = D. | last3 = Kappeler | first3 = A. | last4 = Mariani | first4 = L. | last5 = Zimmermann | first5 = A. | last6 = Paulus | first6 = W. | title = Rapid spontaneous malignant progression of supratentorial tanycytic ependymoma with sarcomatous features - "Ependymosarcoma". | journal = Pathol Res Pract | volume = 206 | issue = 7 | pages = 493-8 | month = Jul | year = 2010 | doi = 10.1016/j.prp.2009.07.013 | PMID = 19853384 }}</ref><ref>{{Cite journal | last1 = Boukas | first1 = A. | last2 = Joshi | first2 = A. | last3 = Jenkins | first3 = A. | last4 = Holliman | first4 = D. | title = Extensive cartilaginous metaplasia of recurrent posterior fossa ependymoma: case report and review of the literature. | journal = Pediatr Neurosurg | volume = 49 | issue = 2 | pages = 93-8 | month = | year = 2013 | doi = 10.1159/000356931 | PMID = 24401698 }}</ref>

==IHC==
*Reticulin-ve.
*GFAP+ve.
*MIB1 (usu low).
*[[IDH-1]]-ve.
*EMA (dots and rings).<ref>{{Cite journal | last1 = Hasselblatt | first1 = M. | last2 = Paulus | first2 = W. | title = Sensitivity and specificity of epithelial membrane antigen staining patterns in ependymomas. | journal = Acta Neuropathol | volume = 106 | issue = 4 | pages = 385-8 | month = Oct | year = 2003 | doi = 10.1007/s00401-003-0752-8 | PMID = 12898159 }}</ref>
**Widespread and strong EMA expression is indicative of YAP1-fused ependymoma.
*Olig2-ve.<ref>{{Cite journal | last1 = Švajdler | first1 = M. | last2 = Rychlý | first2 = B. | last3 = Mezencev | first3 = R. | last4 = Fröhlichová | first4 = L. | last5 = Bednárová | first5 = A. | last6 = Pataky | first6 = F. | last7 = Daum | first7 = O. | title = SOX10 and Olig2 as negative markers for the diagnosis of ependymomas: An immunohistochemical study of 98 glial tumors. | journal = Histol Histopathol | volume = 31 | issue = 1 | pages = 95-102 | month = Jan | year = 2016 | doi = 10.14670/HH-11-654 | PMID = 26287936 }}</ref>
*H3K27me3 nuclear loss in Posterior fossa group A ependymoma (nuclear loss is diagnostic).<ref>{{Cite journal | last1 = Panwalkar | first1 = P. | last2 = Clark | first2 = J. | last3 = Ramaswamy | first3 = V. | last4 = Hawes | first4 = D. | last5 = Yang | first5 = F. | last6 = Dunham | first6 = C. | last7 = Yip | first7 = S. | last8 = Hukin | first8 = J. | last9 = Sun | first9 = Y. | title = Immunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Jul | year = 2017 | doi = 10.1007/s00401-017-1752-4 | PMID = 28733933 }}</ref>
*L1CAM in supratentorial tumors (expression indicates ZFTA fusion).<ref>{{Cite journal | last1 = Parker | first1 = M. | last2 = Mohankumar | first2 = KM. | last3 = Punchihewa | first3 = C. | last4 = Weinlich | first4 = R. | last5 = Dalton | first5 = JD. | last6 = Li | first6 = Y. | last7 = Lee | first7 = R. | last8 = Tatevossian | first8 = RG. | last9 = Phoenix | first9 = TN. | title = C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. | journal = Nature | volume = 506 | issue = 7489 | pages = 451-5 | month = Feb | year = 2014 | doi = 10.1038/nature13109 | PMID = 24553141 }}</ref>
*p65 nuclear +ve in ZFTA-fused ependymoma.

==Molecular==
Two distinct molecular subgroups exist in the posterior fossa:<ref>{{Cite journal | last1 = Witt | first1 = H. | last2 = Mack | first2 = SC. | last3 = Ryzhova | first3 = M. | last4 = Bender | first4 = S. | last5 = Sill | first5 = M. | last6 = Isserlin | first6 = R. | last7 = Benner | first7 = A. | last8 = Hielscher | first8 = T. | last9 = Milde | first9 = T. | title = Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma. | journal = Cancer Cell | volume = 20 | issue = 2 | pages = 143-57 | month = Aug | year = 2011 | doi = 10.1016/j.ccr.2011.07.007 | PMID = 21840481 }}</ref>
* Group A ependymomas:
**typically found in children.
**laterally.
**relatively unfavorable clinical outcome.
**CpG island methylator phenotype.<ref>{{Cite journal | last1 = Mack | first1 = SC. | last2 = Witt | first2 = H. | last3 = Piro | first3 = RM. | last4 = Gu | first4 = L. | last5 = Zuyderduyn | first5 = S. | last6 = Stütz | first6 = AM. | last7 = Wang | first7 = X. | last8 = Gallo | first8 = M. | last9 = Garzia | first9 = L. | title = Epigenomic alterations define lethal CIMP-positive ependymomas of infancy. | journal = Nature | volume = 506 | issue = 7489 | pages = 445-50 | month = Feb | year = 2014 | doi = 10.1038/nature13108 | PMID = 24553142 }}</ref>
**Loss of H3K27me.<ref>{{Cite journal | last1 = Panwalkar | first1 = P. | last2 = Clark | first2 = J. | last3 = Ramaswamy | first3 = V. | last4 = Hawes | first4 = D. | last5 = Yang | first5 = F. | last6 = Dunham | first6 = C. | last7 = Yip | first7 = S. | last8 = Hukin | first8 = J. | last9 = Sun | first9 = Y. | title = Immunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Jul | year = 2017 | doi = 10.1007/s00401-017-1752-4 | PMID = 28733933 }}</ref>
* Group B ependymomas:
**typically adults.
**midline.
**relatively favorable clinical outcomes.
**gene expression profiles similar to that of spinal cord ependymomas.
**increased Chromosomal 1q gains. <ref>{{Cite journal | last1 = Korshunov | first1 = A. | last2 = Witt | first2 = H. | last3 = Hielscher | first3 = T. | last4 = Benner | first4 = A. | last5 = Remke | first5 = M. | last6 = Ryzhova | first6 = M. | last7 = Milde | first7 = T. | last8 = Bender | first8 = S. | last9 = Wittmann | first9 = A. | title = Molecular staging of intracranial ependymoma in children and adults. | journal = J Clin Oncol | volume = 28 | issue = 19 | pages = 3182-90 | month = Jul | year = 2010 | doi = 10.1200/JCO.2009.27.3359 | PMID = 20516456 }}</ref>

Supratentorial ependymomas have also a distinct profile:
*70 % of these ependymomas are ZFTA-fusion positive and have recurrent gene fusions mostly involving RELA<ref>{{Cite journal | last1 = Parker | first1 = M. | last2 = Mohankumar | first2 = KM. | last3 = Punchihewa | first3 = C. | last4 = Weinlich | first4 = R. | last5 = Dalton | first5 = JD. | last6 = Li | first6 = Y. | last7 = Lee | first7 = R. | last8 = Tatevossian | first8 = RG. | last9 = Phoenix | first9 = TN. | title = C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. | journal = Nature | volume = 506 | issue = 7489 | pages = 451-5 | month = Feb | year = 2014 | doi = 10.1038/nature13109 | PMID = 24553141 }}</ref>
**EPHB2 amplifications and CDKN2A deletions in a subset of these tumors<ref>{{Cite journal | last1 = Philip-Hollingsworth | first1 = S. | last2 = Hollingsworth | first2 = RI. | last3 = Dazzo | first3 = FB. | title = Host-range related structural features of the acidic extracellular polysaccharides of Rhizobium trifolii and Rhizobium leguminosarum. | journal = J Biol Chem | volume = 264 | issue = 3 | pages = 1461-6 | month = Jan | year = 1989 | doi = | PMID = 2912966 }}</ref>
*6-8% are YAP1-fusion positive, mostly MAMLD1 as fusion partner.
Note: Molecular subgroups have no treatment implications (at the moment).

==See also==
*[[Subependymoma]].
*[[Myxopapillary ependymoma]].
*[[Neuropathology tumours]].

==References==
{{Reflist|1}}

[[Category:Diagnosis]]
[[Category:Neuropathology tumours]]

Ependymoma

2022-09-19T12:29:39Z

Jensflorian: /* General */ Update

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Ependymoma_H%26E.jpg
| Width =
| Caption = Ependymoma grade II WHO. [[H&E stain]]
| Synonyms =
| Micro = Perivascular pseudorosettes, ependymal rosettes
| Subtypes = Tanycytic, Clear cell, Papillary, Cellular
| LMDDx = [[Subependymoma]], [[Glioblastoma]], [[Pilocytic astrocytoma]], [[Oligodendroglioma]]
| Stains =
| IHC = GFAP +ve
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site =
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence =
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis = intermediate to poor (WHO Grades II & III)
| Other =
| ClinDDx =
| Tx =
}}

'''Ependymoma''' is a [[neuropathology tumour]].

==General==
*Called the forgotten glial tumour.
*Anatomic location and molecular data is essential for tumor diagnosis.

Epidemiology:<ref name=Ref_PBoD8_1334>{{Ref PBoD8|1334}}</ref>
*Usual site:
**Adults: usually spinal cord.
**Children: usually posterior fossa.
*May be associated with [[neurofibromatosis type 2]].

There are currently eight main ependymal tumors:<ref name=Ref_WHOCNS_74>{{Ref WHOCNS|74}}</ref>
#Supratentorial ependymoma, ZFTA-fusion positive
#Supratentorial ependymoma, YAP1-fusion positive
#Posterior fossa ependymoma group A
#Posterior fossa ependymoma group B
#Spinal ependymoma
#Spinal ependymoma, MYCN-amplified
#[[Myxopapillary ependymoma]]
#[[Subependymoma]]

Ependymoma, NOS (not otherwise specified): Molecular analysis still missing.
Ependymoma, NEC (not elsewhere classfied): Tumor cannot assigned to any of the defined entities.

Note: Molecularly defined ependymomas can be still graded as CNS grade 2 or 3 depending on histological features.

*Depreceated terminologies:
**Papillary ependymoma.
**Clear cell ependymoma.
**Tanycytic ependymoma.
**Cellular ependymoma.
**Ependymoma, RELA fusion-positive.<ref>{{Cite journal | last1 = Parker | first1 = M. | last2 = Mohankumar | first2 = KM. | last3 = Punchihewa | first3 = C. | last4 = Weinlich | first4 = R. | last5 = Dalton | first5 = JD. | last6 = Li | first6 = Y. | last7 = Lee | first7 = R. | last8 = Tatevossian | first8 = RG. | last9 = Phoenix | first9 = TN. | title = C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. | journal = Nature | volume = 506 | issue = 7489 | pages = 451-5 | month = Feb | year = 2014 | doi = 10.1038/nature13109 | PMID = 24553141 }}</ref><ref>{{Cite journal | last1 = Pietsch | first1 = T. | last2 = Wohlers | first2 = I. | last3 = Goschzik | first3 = T. | last4 = Dreschmann | first4 = V. | last5 = Denkhaus | first5 = D. | last6 = Dörner | first6 = E. | last7 = Rahmann | first7 = S. | last8 = Klein-Hitpass | first8 = L. | title = Supratentorial ependymomas of childhood carry C11orf95-RELA fusions leading to pathological activation of the NF-κB signaling pathway. | journal = Acta Neuropathol | volume = 127 | issue = 4 | pages = 609-11 | month = Apr | year = 2014 | doi = 10.1007/s00401-014-1264-4 | PMID = 24562983 }}</ref> This is now called Supratentorial ependymoma, ZFTA-fusion positive.
**Anaplastic ependymoma.

==Gross==
*Usually discrete and enhancing.
*Ventricular location, but also within the spinal cord.
*Dissemination possible.
*[[Myxopapillary ependymoma]] classically at [[filum terminale]].
*[[Subependymoma]] typically seen in IVth ventricle.
<gallery>
File:AFIP405711R-EPENDYMOMA.jpg | Radiology (AFIP)
File:AFIP405713G-EPENDYMOMA.jpg | Ependymoma in the fourth ventricle (AFIP)
File:Ependymoma in the fourth ventricle.jpg | Gross (AFIP)
</gallery>

==Microscopic==
==="Classic" ependymoma===
*Come in two CNS WHO grades: 2 and 3.
*Usu. sharply demarcated from surrounding brain parenchyma.
Features:
*Cells have a "tadpole-like" morphology.
**May also be described as ''ice cream cone-shaped''.<ref>[http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html]</ref>
*'''Rosettes''' = circular nuclear free zones/cells arranged in a pseudoglandular fashion; comes in two flavours in ependymoma:
**''Perivascular pseudorosettes'' = (tumour) cells arranged around a blood vessel; nuclei of cells distant from the blood vessel, i.e. rim of cytoplasm (from tumour cells) surround blood vessel (nucleus-free zone); more common than ependymal rosette... but less specific.
**''Ependymal rosette'' ([[AKA]] ''true ependymal rosette'') = rosette has an empty space at the centre - '''key feature'''.
*Nuclear features monotonous, i.e. "boring".<ref>MUN. 6 Oct 2009.</ref>
**There is little variation in size, shape and staining.
*Hyalinized vessels.
*Calcification.
*Rare cases with cartilagineous metaplasia.<ref>{{Cite journal | last1 = Wang | first1 = X. | last2 = Zhang | first2 = S. | last3 = Ye | first3 = Y. | last4 = Chen | first4 = Y. | last5 = Liu | first5 = X. | title = Ependymoma with cartilaginous metaplasia might have more aggressive behavior: a case report and literature review. | journal = Brain Tumor Pathol | volume = 29 | issue = 3 | pages = 172-6 | month = Jul | year = 2012 | doi = 10.1007/s10014-011-0079-4 | PMID = 22228122 }}</ref>
*Branching capillaries usu. only in supratentorial ependymomas.

DDx (supratentorial and posterior fossa ependymoma):
*[[Subependymoma]].
*[[Glioblastoma]] (GBM).
*Gliomas with BCOR internal tandem duplication.
*[[Astroblastoma]], MN1-altered.
**Invasive border = GBM; circumscribed border of lesion = ependymoma.
*[[Oligodendroglioma]] (Clear cell ependymoma))

DDx (spinal ependymoma):
*[[Pilocytic astrocytoma]] (Tanycytic ependymoma)
*Diffuse midline glioma, H3 K27-altered
*Small cell glioblastoma (MYCN-amplified spinal ependymoma)

====Images====
www:
*[http://www.flickr.com/photos/ckrishnan/3862487821/in/photostream Ependymoma (flickr.com)].
*[http://www.ajnr.org/cgi/content-nw/full/27/3/488/F10 Ependymoma - ependymal rosettes (ajnr.org)].
*[http://path.upmc.edu/cases/case95/micro.html Anaplastic ependymoma - case 1 (upmc.edu)].
*[http://path.upmc.edu/cases/case324.html Anaplastic ependymoma - case 2 (upmc.edu)].
<gallery>
File:AFIP405736M-EPENDYMOMA.jpg | Ependymoma smear. (AFIP)
File:AFIP405715M-EPENDYMOMA.jpg | Perivascular pseudorosettes in a ependymoma. (AFIP)
Image:Ependymoma_intermed_mag.jpg | Ependymoma - intermed. mag. (WC)
Image:Ependymoma_low_intermed_mag.jpg | Ependymoma - low mag. (WC)
File:Ependymoma_H%26E.jpg | Ependymoma - high mag. (WC/Sbrandner)
File:Ependymoma_true_ependymal_rosettes_and_pseudorosettes.jpg | True ependymal and pseudorosettes in a ependymoma. (WC/jensflorian)
File:Ependymal_linings_ependymoma_HE.jpg | Ependymal linings in a ependymoma. (WC/jensflorian)
File:Ependymoma_GFAP.jpg| GFAP IHC in a ependymoma. (WC/Sbrandner)
File:EMA_ependymoma_periluminal.jpg | Periluminal EMA positivity in a ependymoma. (WC/jensflorian)
File:Ependymoma_EMA.jpg | Dot-like EMA immunreactivity n a ependymoma. (WC/Marvin101)
File:Tanycytic ependymoma HE.jpg | Tanycytic morphology in ependymoma must not confused with [[pilocytic astrocytoma]]. (WC/jensflorian)
File:Tanicytic_ependymoma_x10.jpg | Tanycytic morphology in ependymoma - low mag. (WC/jensflorian)
File:Papillary_Ependymoma.jpg | Papillary morphology in ependymoma - low mag. (WC/jensflorian)
File:Papillary_ependymoma_HE_x40.jpg | Papillary morphology in ependymoma - intermed. mag. (WC/jensflorian)
File:Clear_cell_ependymoma_HE.jpg | Clear cell morphology in ependymoma may mimic [[oligodendroglioma]]. (WC/jensflorian)
File:HE_anaplastic_epedymomas_mitoses_pleomorphism.jpg | Brisk mitotic activity in a anaplastic ependymoma. (WC/jensflorian)
File:Cartilaginous metaplasia ependymoma.jpg|Metaplastic transformation in an anaplastic ependymoma. (WC/jensflorian)
File:Ependymoma_L1CAM_IHC.jpg | L1CAM immunohistochemistry indicates presence of ZFTA-fusion.
File:Ependymoma_NFkappaB_IHC.jpg | Nuclear NFkappaB IHC indicates presence of ZFTA-fusion.
</gallery>

===Grading===
Easy:
*Subependymoma = CNS WHO grade 1.
*Myxopapillary ependymoma = CNS WHO grade 2.

Not so easy:
All other ependymomas: WHO CNS Grade 2 vs. Grade 3 depends on:
*Cellular density.
*Mitoses (no clear cut-off).
*Necrosis (not prognostic).
*Microvascular proliferation.
*Poor interobserver reliability<ref>{{Cite journal | last1 = Ellison | first1 = DW. | last2 = Kocak | first2 = M. | last3 = Figarella-Branger | first3 = D. | last4 = Felice | first4 = G. | last5 = Catherine | first5 = G. | last6 = Pietsch | first6 = T. | last7 = Frappaz | first7 = D. | last8 = Massimino | first8 = M. | last9 = Grill | first9 = J. | title = Histopathological grading of pediatric ependymoma: reproducibility and clinical relevance in European trial cohorts. | journal = J Negat Results Biomed | volume = 10 | issue = | pages = 7 | month = May | year = 2011 | doi = 10.1186/1477-5751-10-7 | PMID = 21627842 }}</ref>

Notes:
*Many tumours fall between grade 2 and grade 3.
*Rare cases with sarcomatous or cartilaginous components.<ref>{{Cite journal | last1 = Vajtai | first1 = I. | last2 = Kuhlen | first2 = D. | last3 = Kappeler | first3 = A. | last4 = Mariani | first4 = L. | last5 = Zimmermann | first5 = A. | last6 = Paulus | first6 = W. | title = Rapid spontaneous malignant progression of supratentorial tanycytic ependymoma with sarcomatous features - "Ependymosarcoma". | journal = Pathol Res Pract | volume = 206 | issue = 7 | pages = 493-8 | month = Jul | year = 2010 | doi = 10.1016/j.prp.2009.07.013 | PMID = 19853384 }}</ref><ref>{{Cite journal | last1 = Boukas | first1 = A. | last2 = Joshi | first2 = A. | last3 = Jenkins | first3 = A. | last4 = Holliman | first4 = D. | title = Extensive cartilaginous metaplasia of recurrent posterior fossa ependymoma: case report and review of the literature. | journal = Pediatr Neurosurg | volume = 49 | issue = 2 | pages = 93-8 | month = | year = 2013 | doi = 10.1159/000356931 | PMID = 24401698 }}</ref>

==IHC==
*Reticulin-ve.
*GFAP+ve.
*MIB1 (usu low).
*[[IDH-1]]-ve.
*EMA (dots and rings).<ref>{{Cite journal | last1 = Hasselblatt | first1 = M. | last2 = Paulus | first2 = W. | title = Sensitivity and specificity of epithelial membrane antigen staining patterns in ependymomas. | journal = Acta Neuropathol | volume = 106 | issue = 4 | pages = 385-8 | month = Oct | year = 2003 | doi = 10.1007/s00401-003-0752-8 | PMID = 12898159 }}</ref>
**Widespread and strong EMA expression is indicative of YAP1-fused ependymoma.
*Olig2-ve.<ref>{{Cite journal | last1 = Švajdler | first1 = M. | last2 = Rychlý | first2 = B. | last3 = Mezencev | first3 = R. | last4 = Fröhlichová | first4 = L. | last5 = Bednárová | first5 = A. | last6 = Pataky | first6 = F. | last7 = Daum | first7 = O. | title = SOX10 and Olig2 as negative markers for the diagnosis of ependymomas: An immunohistochemical study of 98 glial tumors. | journal = Histol Histopathol | volume = 31 | issue = 1 | pages = 95-102 | month = Jan | year = 2016 | doi = 10.14670/HH-11-654 | PMID = 26287936 }}</ref>
*H3K27me3 nuclear loss in Posterior fossa group A ependymoma (nuclear loss is diagnostic).<ref>{{Cite journal | last1 = Panwalkar | first1 = P. | last2 = Clark | first2 = J. | last3 = Ramaswamy | first3 = V. | last4 = Hawes | first4 = D. | last5 = Yang | first5 = F. | last6 = Dunham | first6 = C. | last7 = Yip | first7 = S. | last8 = Hukin | first8 = J. | last9 = Sun | first9 = Y. | title = Immunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Jul | year = 2017 | doi = 10.1007/s00401-017-1752-4 | PMID = 28733933 }}</ref>
*L1CAM in supratentorial tumors (expression indicates ZFTA fusion).<ref>{{Cite journal | last1 = Parker | first1 = M. | last2 = Mohankumar | first2 = KM. | last3 = Punchihewa | first3 = C. | last4 = Weinlich | first4 = R. | last5 = Dalton | first5 = JD. | last6 = Li | first6 = Y. | last7 = Lee | first7 = R. | last8 = Tatevossian | first8 = RG. | last9 = Phoenix | first9 = TN. | title = C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. | journal = Nature | volume = 506 | issue = 7489 | pages = 451-5 | month = Feb | year = 2014 | doi = 10.1038/nature13109 | PMID = 24553141 }}</ref>
*p65 nuclear +ve in ZFTA-fused ependymoma.

==Molecular==
Two distinct molecular subgroups exist in the posterior fossa:<ref>{{Cite journal | last1 = Witt | first1 = H. | last2 = Mack | first2 = SC. | last3 = Ryzhova | first3 = M. | last4 = Bender | first4 = S. | last5 = Sill | first5 = M. | last6 = Isserlin | first6 = R. | last7 = Benner | first7 = A. | last8 = Hielscher | first8 = T. | last9 = Milde | first9 = T. | title = Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma. | journal = Cancer Cell | volume = 20 | issue = 2 | pages = 143-57 | month = Aug | year = 2011 | doi = 10.1016/j.ccr.2011.07.007 | PMID = 21840481 }}</ref>
* Group A ependymomas:
**typically found in children.
**laterally.
**relatively unfavorable clinical outcome.
**CpG island methylator phenotype.<ref>{{Cite journal | last1 = Mack | first1 = SC. | last2 = Witt | first2 = H. | last3 = Piro | first3 = RM. | last4 = Gu | first4 = L. | last5 = Zuyderduyn | first5 = S. | last6 = Stütz | first6 = AM. | last7 = Wang | first7 = X. | last8 = Gallo | first8 = M. | last9 = Garzia | first9 = L. | title = Epigenomic alterations define lethal CIMP-positive ependymomas of infancy. | journal = Nature | volume = 506 | issue = 7489 | pages = 445-50 | month = Feb | year = 2014 | doi = 10.1038/nature13108 | PMID = 24553142 }}</ref>
**Loss of H3K27me.<ref>{{Cite journal | last1 = Panwalkar | first1 = P. | last2 = Clark | first2 = J. | last3 = Ramaswamy | first3 = V. | last4 = Hawes | first4 = D. | last5 = Yang | first5 = F. | last6 = Dunham | first6 = C. | last7 = Yip | first7 = S. | last8 = Hukin | first8 = J. | last9 = Sun | first9 = Y. | title = Immunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Jul | year = 2017 | doi = 10.1007/s00401-017-1752-4 | PMID = 28733933 }}</ref>
* Group B ependymomas:
**typically adults.
**midline.
**relatively favorable clinical outcomes.
**gene expression profiles similar to that of spinal cord ependymomas.
**increased Chromosomal 1q gains. <ref>{{Cite journal | last1 = Korshunov | first1 = A. | last2 = Witt | first2 = H. | last3 = Hielscher | first3 = T. | last4 = Benner | first4 = A. | last5 = Remke | first5 = M. | last6 = Ryzhova | first6 = M. | last7 = Milde | first7 = T. | last8 = Bender | first8 = S. | last9 = Wittmann | first9 = A. | title = Molecular staging of intracranial ependymoma in children and adults. | journal = J Clin Oncol | volume = 28 | issue = 19 | pages = 3182-90 | month = Jul | year = 2010 | doi = 10.1200/JCO.2009.27.3359 | PMID = 20516456 }}</ref>

Supratentorial ependymomas have also a distinct profile:
*70 % of these ependymomas are ZFTA-fusion positive and have recurrent gene fusions mostly involving RELA<ref>{{Cite journal | last1 = Parker | first1 = M. | last2 = Mohankumar | first2 = KM. | last3 = Punchihewa | first3 = C. | last4 = Weinlich | first4 = R. | last5 = Dalton | first5 = JD. | last6 = Li | first6 = Y. | last7 = Lee | first7 = R. | last8 = Tatevossian | first8 = RG. | last9 = Phoenix | first9 = TN. | title = C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. | journal = Nature | volume = 506 | issue = 7489 | pages = 451-5 | month = Feb | year = 2014 | doi = 10.1038/nature13109 | PMID = 24553141 }}</ref>
**EPHB2 amplifications and CDKN2A deletions in a subset of these tumors<ref>{{Cite journal | last1 = Philip-Hollingsworth | first1 = S. | last2 = Hollingsworth | first2 = RI. | last3 = Dazzo | first3 = FB. | title = Host-range related structural features of the acidic extracellular polysaccharides of Rhizobium trifolii and Rhizobium leguminosarum. | journal = J Biol Chem | volume = 264 | issue = 3 | pages = 1461-6 | month = Jan | year = 1989 | doi = | PMID = 2912966 }}</ref>
*6-8% are YAP1-fusion positive, mostly MAMLD1 as fusion partner.
Note: Molecular subgroups have no treatment implications (at the moment).

==See also==
*[[Subependymoma]].
*[[Myxopapillary ependymoma]].
*[[Neuropathology tumours]].

==References==
{{Reflist|1}}

[[Category:Diagnosis]]
[[Category:Neuropathology tumours]]

Schwannoma

2022-06-27T09:55:16Z

Jensflorian: /* Molecular */ update

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Schwannoma - Antoni A and B - very high mag.jpg
| Width =
| Caption = Schwannoma showing Antoni A and Antoni B areas. [[HPS stain]].
| Micro = Antoni A areas (cellular, fibrillary, polar, elongated), Antoni B area (pauci-cellular, loose microcystic tissue), Verocay bodies (paucinuclear area surrounded by nuclei), hyaline thickened [[blood vessel]]s, thick capsule.
+/-peripheral lymphoid cuff (esp. GI tract)
| Subtypes = conventional schwannoma, cellular schwannoma, plexiform schwannoma, melanotic schwannoma
| LMDDx = [[meningioma]], [[leiomyoma]], [[GIST]], [[intranodal palisaded myofibroblastoma]], [[MPNST]], [[neurofibroma]], [[biphenotypic sinonasal sarcoma]]
| Stains =
| IHC = S-100 +ve, EMA -ve, CD34 +ve
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site = [[soft tissue lesions|soft tissue]] - [[peripheral nerve sheath tumours]]
| Assdx =
| Syndromes = [[neurofibromatosis type 2]], [[Carney complex]] (psammomatous melanotic schwannoma), schwannomatosis
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence = common
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis = good
| Other =
| ClinDDx = [[meningioma]] - esp. at [[cerebellopontine angle]]
}}
'''Schwannoma''' is a relatively common [[peripheral nerve sheath tumour]].

At the [[cerebellopontine angle|cerebellopontine (CP) angle]], they may be referred to as ''acoustic neuroma'' or ''vestibular schwannoma''.

==General==
*A common [[neuropathology]] [[CNS tumours|tumour]] that occasionally shows-up elsewhere.
*often encapsulated tumour of tissue surrounding a nerve.
**Axons adjacent to the tumour are normal... but may be compressed.
*May be a part of [[neurofibromatosis type 2]].
*Occurs at all ages.

==Macro==
*Usu. encapsulated.
*Cystic.
*Yellow patches on white surface.
**Variable lipidization.

==Microscopic==
Features:<ref name=pmid17893219>{{cite journal |author=Wippold FJ, Lubner M, Perrin RJ, Lämmle M, Perry A |title=Neuropathology for the neuroradiologist: Antoni A and Antoni B tissue patterns |journal=AJNR Am J Neuroradiol |volume=28 |issue=9 |pages=1633–8 |year=2007 |month=October |pmid=17893219 |doi=10.3174/ajnr.A0682 |url=http://www.ajnr.org/cgi/reprint/28/9/1633}}</ref>
*Antoni A:
**Cellular.
**'Fibrillary, polar, elongated'.
*Antoni B:
**Pauci-cellular.
**Loose microcystic tissue.
*Verocay bodies - paucinuclear area surrounded by clusters of nuclei - '''diagnostic feature'''.
*Hyaline thickened [[blood vessel]]s.
*Thick capsule.
*In the GI tract: classically have a ''peripheral lymphoid cuff''.<ref name=pmid15728600>{{cite journal |author=Levy AD, Quiles AM, Miettinen M, Sobin LH |title=Gastrointestinal schwannomas: CT features with clinicopathologic correlation |journal=AJR Am J Roentgenol |volume=184 |issue=3 |pages=797–802 |year=2005 |month=March |pmid=15728600 |doi= |url=http://www.ajronline.org/cgi/content/full/184/3/797}}</ref>
*+/-Hemosiderin deposition within tumour.
*Reticulin stain +ve (around individual cells).

Notes:
*Tumour does ''not'' smear well.<ref>MUN. 24 November 2010.</ref>
*Antoni A: may look somewhat like scattered matchsticks.
*Hybrid Schwannoma / [[Neurofibroma]] are overrepresented in hereditary conditions.<ref>{{Cite journal | last1 = Harder | first1 = A. | last2 = Wesemann | first2 = M. | last3 = Hagel | first3 = C. | last4 = Schittenhelm | first4 = J. | last5 = Fischer | first5 = S. | last6 = Tatagiba | first6 = M. | last7 = Nagel | first7 = C. | last8 = Jeibmann | first8 = A. | last9 = Bohring | first9 = A. | title = Hybrid neurofibroma/schwannoma is overrepresented among schwannomatosis and neurofibromatosis patients. | journal = Am J Surg Pathol | volume = 36 | issue = 5 | pages = 702-9 | month = May | year = 2012 | doi = 10.1097/PAS.0b013e31824d3155 | PMID = 22446939 }}</ref>

DDx:
*[[Meningioma]].
*[[Intranodal palisaded myofibroblastoma]] - if surrounded by a rim of lymphoid tissue, i.e. [[Lymph node pathology|intranodal]].
*[[Leiomyoma]].
*[[Gastrointestinal stromal tumour]].
*[[MPNST]] - schwannoma with ancient change has no significant mitotic activity.<ref name=pmid17244372>{{Cite journal | last1 = Chan | first1 = PT. | last2 = Tripathi | first2 = S. | last3 = Low | first3 = SE. | last4 = Robinson | first4 = LQ. | title = Case report--ancient schwannoma of the scrotum. | journal = BMC Urol | volume = 7 | issue = | pages = 1 | month = | year = 2007 | doi = 10.1186/1471-2490-7-1 | PMID = 17244372 }}</ref>
*[[Neurofibroma]].
*[[Biphenotypic sinonasal sarcoma]] - head and neck.

===Images===
<gallery>
Image:Schwannoma_-_Antoni_A_and_B_-_intermed_mag.jpg | Schwannoma - Antoni A & B - intermed. mag. (WC)
Image:Schwannoma_-_Antoni_A_and_B_-_very_high_mag.jpg | Schwannoma - Antoni A & B - very high mag. (WC)
File:Antoni a fibers schwannoma.jpg | Antoni-A pattern in cerebelloponine angle schwannoma. (WC/jensflorian)
File:Schwannoma 0023.jpg | Antoni-A pattern in cerebelloponine angle schwannoma.(WC/jensflorian)
Image:Nerve_root_schwannoma_-_intermed_mag.jpg | Nerve root schwannoma - intermed. mag. (WC)
File:Schwannoma, S-100 Immunostain (5203888371).jpg | S-100 immunostain in schwannoma. (WC/Ed Uthman)
</gallery>
www:
*[http://www.pathguy.com/~lulo/lulo0003.htm Antoni A (pathguy.com)].
*[http://www.ajnr.org/cgi/content/full/28/9/1633/F8 Antoni A & Antoni B side-by-side (ajnr.org)].
*[http://path.upmc.edu/cases/case639.html Cystic schwannoma - several images (upmc.edu)].
===Schwannoma subtypes===
There are four:<ref name=pmid12792904>{{cite journal |author=Kurtkaya-Yapicier O, Scheithauer B, Woodruff JM |title=The pathobiologic spectrum of Schwannomas |journal=Histol. Histopathol. |volume=18 |issue=3 |pages=925–34 |year=2003 |month=July |pmid=12792904 |doi= |url=}}</ref>
#Conventional schwannoma.
#Cellular schwannoma.
#Plexiform schwannoma.
#Melanotic schwannoma.

====Conventional schwannoma====
*Most common.

====Cellular schwannoma====
*May mimic [[MPNST]].
*Usu. <4 mitoses in 10 HPF (see [[HPFitis]]).
*Absence of Verocay bodies.
*Usu paravertebral location.

Images:
*[http://path.upmc.edu/cases/case518.html Cellular schwannoma (upmc.edu)].

====Plexiform schwannoma====
*May mimic [[MPNST]] if cellular - esp. in childhood.

Images:
<gallery>
Image:Plexiform_Schwannoma_2.jpg | Plexiform schwannoma - low mag. (WC)
Image:Plexiform_Schwannoma_1.jpg | Plexiform schwannoma - high mag. (WC)
</gallery>
====Melanotic schwannoma====
*May be confused with [[melanoma]].
*Psammomatous form (''psammomatous melanotic schwannoma'') associated with a heritable disorder ([[Carney complex]]).

Note:
*[[Carney complex]]:<ref name=pmid12792904/>
**Cutaneous lentigines.
**Myxomas (skin (subcutaneous), subcutanous, [[Atrial myxoma|heart]]).
**Endocrine neoplasms.

Images:
*[http://path.upmc.edu/cases/case387.html Psammomatous melanotic schwannoma - several images (upmc.edu)].
<gallery>
Image:Psammomatous_melanotic_schwannoma_-_high_mag.jpg | Psammomatous melanotic schwannoma - high mag. (WC)
</gallery>

==IHC==
Features:<ref name=pmid12692193>{{cite journal |author=Hirose T, Tani T, Shimada T, Ishizawa K, Shimada S, Sano T |title=Immunohistochemical demonstration of EMA/Glut1-positive perineurial cells and CD34-positive fibroblastic cells in peripheral nerve sheath tumors |journal=Mod. Pathol. |volume=16 |issue=4 |pages=293–8 |year=2003 |month=April |pmid=12692193 |doi=10.1097/01.MP.0000062654.83617.B7 |url=http://www.nature.com/modpathol/journal/v16/n4/full/3880761a.html }}</ref>
*S-100 +ve.
*Glut1 +ve.
*CD34 +ve.
*Cytokeratins ~70% +ve.<ref>{{Cite journal | last1 = Fanburg-Smith | first1 = JC. | last2 = Majidi | first2 = M. | last3 = Miettinen | first3 = M. | title = Keratin expression in schwannoma; a study of 115 retroperitoneal and 22 peripheral schwannomas. | journal = Mod Pathol | volume = 19 | issue = 1 | pages = 115-21 | month = Jan | year = 2006 | doi = 10.1038/modpathol.3800489 | PMID = 16357842 }}</ref>
*SOX10 +ve.<ref name=pmid18636017>{{cite journal |author=Nonaka D, Chiriboga L, Rubin BP |title=Sox10: a pan-schwannian and melanocytic marker |journal=Am. J. Surg. Pathol. |volume=32 |issue=9 |pages=1291–8 |year=2008 |month=September |pmid=18636017 |doi=10.1097/PAS.0b013e3181658c14 |url=}}</ref>
**-ve in [[synovial sarcoma]], [[rhabdomyosarcoma]], [[chondrosarcoma]].
*EMA -ve. (???)
**Usually +ve (~75% of the time) in meningiomas.<ref>{{Cite journal | last1 = Rushing | first1 = EJ. | last2 = Bouffard | first2 = JP. | last3 = McCall | first3 = S. | last4 = Olsen | first4 = C. | last5 = Mena | first5 = H. | last6 = Sandberg | first6 = GD. | last7 = Thompson | first7 = LD. | title = Primary extracranial meningiomas: an analysis of 146 cases. | journal = Head Neck Pathol | volume = 3 | issue = 2 | pages = 116-30 | month = Jun | year = 2009 | doi = 10.1007/s12105-009-0118-1 | PMID = 19644540 }}
</ref>

Others:
*Beta-catenin +ve<ref name=pmid11813884>{{Cite journal | last1 = Hasegawa | first1 = M. | last2 = Muramatsu | first2 = N. | last3 = Tohma | first3 = Y. | last4 = Fukaya | first4 = K. | last5 = Fujisawa | first5 = H. | last6 = Hayashi | first6 = Y. | last7 = Tachibana | first7 = O. | last8 = Kida | first8 = S. | last9 = Yamashita | first9 = J. | title = Expression of E-cadherin-catenin complex in human benign schwannomas. | journal = Histol Histopathol | volume = 17 | issue = 1 | pages = 39-44 | month = Jan | year = 2002 | doi = | PMID = 11813884 }}</ref> -- not nuclear.<ref name=pmid17711447>{{Cite journal | last1 = Carlson | first1 = JW. | last2 = Fletcher | first2 = CD. | title = Immunohistochemistry for beta-catenin in the differential diagnosis of spindle cell lesions: analysis of a series and review of the literature. | journal = Histopathology | volume = 51 | issue = 4 | pages = 509-14 | month = Oct | year = 2007 | doi = 10.1111/j.1365-2559.2007.02794.x | PMID = 17711447 }}</ref>

==Molecular==
Overview: <ref>{{Cite journal | last1 = Agnihotri | first1 = S. | last2 = Jalali | first2 = S. | last3 = Wilson | first3 = MR. | last4 = Danesh | first4 = A. | last5 = Li | first5 = M. | last6 = Klironomos | first6 = G. | last7 = Krieger | first7 = JR. | last8 = Mansouri | first8 = A. | last9 = Khan | first9 = O. | title = The genomic landscape of schwannoma. | journal = Nat Genet | volume = 48 | issue = 11 | pages = 1339-1348 | month = 11 | year = 2016 | doi = 10.1038/ng.3688 | PMID = 27723760 }}</ref>
* Most common: NF2 (in Vestibular Schwannoma up to84%).
* less common: ARID1A, ARID1B, DDR, TSC1, TSC2, CDC27 and USP8.
* SH3PXD2A-HTRA1 fusions (10%).

*INI1 mosaic pattern in familiar schwannomatosis.<ref>{{Cite journal | last1 = Caltabiano | first1 = R. | last2 = Magro | first2 = G. | last3 = Polizzi | first3 = A. | last4 = Praticò | first4 = AD. | last5 = Ortensi | first5 = A. | last6 = D'Orazi | first6 = V. | last7 = Panunzi | first7 = A. | last8 = Milone | first8 = P. | last9 = Maiolino | first9 = L. | title = A mosaic pattern of INI1/SMARCB1 protein expression distinguishes Schwannomatosis and NF2-associated peripheral schwannomas from solitary peripheral schwannomas and NF2-associated vestibular schwannomas. | journal = Childs Nerv Syst | volume = 33 | issue = 6 | pages = 933-940 | month = Jun | year = 2017 | doi = 10.1007/s00381-017-3340-2 | PMID = 28365909 }}</ref>
* LZTR1-associated vestibular schwannomas.<ref>{{Cite journal | last1 = Evans | first1 = DG. | last2 = Bowers | first2 = NL. | last3 = Tobi | first3 = S. | last4 = Hartley | first4 = C. | last5 = Wallace | first5 = AJ. | last6 = King | first6 = AT. | last7 = Lloyd | first7 = SKW. | last8 = Rutherford | first8 = SA. | last9 = Hammerbeck-Ward | first9 = C. | title = Schwannomatosis: a genetic and epidemiological study. | journal = J Neurol Neurosurg Psychiatry | volume = | issue = | pages = | month = Jun | year = 2018 | doi = 10.1136/jnnp-2018-318538 | PMID = 29909380 }}</ref>

Molecular subgroups:<ref>{{Cite journal | last1 = Agnihotri | first1 = S. | last2 = Jalali | first2 = S. | last3 = Wilson | first3 = MR. | last4 = Danesh | first4 = A. | last5 = Li | first5 = M. | last6 = Klironomos | first6 = G. | last7 = Krieger | first7 = JR. | last8 = Mansouri | first8 = A. | last9 = Khan | first9 = O. | title = The genomic landscape of schwannoma. | journal = Nat Genet | volume = 48 | issue = 11 | pages = 1339-1348 | month = 11 | year = 2016 | doi = 10.1038/ng.3688 | PMID = 27723760 }}</ref>
*Group 1: vestibular (has significant higher rate of 22q loss).
*Group 2: spinal.

==Sign out==
<pre>
Lesion, Right Ulnar Nerve, Excision:
- Schwannoma.
</pre>

===Block letters===
<pre>
LESION, LEFT ANTERIOR TIBIA, EXCISION:
- SCHWANNOMA.
- NEGATIVE FOR MALIGNANCY.
</pre>

===Micro===
The sections show a soft tissue spindle cell lesion, with cellular fibrillary areas (Antoni A) and pauci-cellular microcystic areas (Antoni B). There are also pauci-nuclear areas surrounded by clusters of nuclei (Verocay bodies). Thick hyaline blood vessels are present within the lesion. There is no apparent nuclear atypia. Mitotic activity is not readily apparent. No nerve is seen adjacent to the lesion. The lesion is partially encapsulated by fibrous tissue. Focally, ink is seen on the lesional cells.

==See also==
*[[Peripheral nerve sheath tumours]].

==References==
{{Reflist|2}}

[[Category:Peripheral nerve sheath tumours]]
[[Category:Diagnosis]]
[[Category:Neuropathology tumours]]

Astrocytoma, IDH-mutant

2022-04-14T09:10:49Z

Jensflorian: /* Molecular */ image text updated

'''Astrocytoma, IDH-mutant''' is a diffusely-growing, infiltrating astrocytoma of the adult occurring in the CNS white matter. IDH1 codon 132 or IDH2 codon 172 mutations is mandatory for diagnosis and are frequently associated with ATRX and TP53 mutations.

=General=
The current WHO classification recognizes three tumour grades:
* Astrocytoma, IDH mutant grade 2 (ICD-O: 9400/3)
* Astrocytoma, IDH mutant grade 3 (ICD-O: 9401/3)
* Astrocytoma, IDH mutant grade 4 (ICD-O: 9445/3)
* Diffuse astrocytoma,NOS (ICD-O 9400/3) - genetic testing still missing.

The existence of diffuse astrocytoma, IDH wildtype is challenged.<ref>{{Cite journal | last1 = Reuss | first1 = DE. | last2 = Kratz | first2 = A. | last3 = Sahm | first3 = F. | last4 = Capper | first4 = D. | last5 = Schrimpf | first5 = D. | last6 = Koelsche | first6 = C. | last7 = Hovestadt | first7 = V. | last8 = Bewerunge-Hudler | first8 = M. | last9 = Jones | first9 = DT. | title = Adult IDH wild type astrocytomas biologically and clinically resolve into other tumor entities. | journal = Acta Neuropathol | volume = 130 | issue = 3 | pages = 407-17 | month = Sep | year = 2015 | doi = 10.1007/s00401-015-1454-8 | PMID = 26087904 }}</ref> Most adult IDH wildtype cases show genetic alterations identical to glioblastoma.<ref>{{Cite journal | last1 = Hasselblatt | first1 = M. | last2 = Jaber | first2 = M. | last3 = Reuss | first3 = D. | last4 = Grauer | first4 = O. | last5 = Bibo | first5 = A. | last6 = Terwey | first6 = S. | last7 = Schick | first7 = U. | last8 = Ebel | first8 = H. | last9 = Niederstadt | first9 = T. | title = Diffuse Astrocytoma, IDH-Wildtype: A Dissolving Diagnosis. | journal = J Neuropathol Exp Neurol | volume = | issue = | pages = | month = Feb | year = 2018 | doi = 10.1093/jnen/nly012 | PMID = 29444314 }}</ref>

==Astrocytoma, IDH mutant grade 2==
* Most common CNS grade 2 WHO glioma in adults (peaks between 30-40 years).
* 10-15% of all [[astrocytoma]]s.
* Usually shows progression to WHO CNS grade 3 sooner or later. <ref>{{Cite journal | last1 = Louis | first1 = DN. | last2 = Perry | first2 = A. | last3 = Reifenberger | first3 = G. | last4 = von Deimling | first4 = A. | last5 = Figarella-Branger | first5 = D. | last6 = Cavenee | first6 = WK. | last7 = Ohgaki | first7 = H. | last8 = Wiestler | first8 = OD. | last9 = Kleihues | first9 = P. | title = The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. | journal = Acta Neuropathol | volume = 131 | issue = 6 | pages = 803-20 | month = Jun | year = 2016 | doi = 10.1007/s00401-016-1545-1 | PMID = 27157931 }}</ref>

==Astrocytoma, IDH mutant grade 3==
* Most common CNS grade 3 WHO glioma in adults (peaks between 40-50 years).
* Approx 5% of all [[glioma]]s.<ref>{{Cite journal | last1 = Ohgaki | first1 = H. | last2 = Kleihues | first2 = P. | title = Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. | journal = J Neuropathol Exp Neurol | volume = 64 | issue = 6 | pages = 479-89 | month = Jun | year = 2005 | doi = | PMID = 15977639 }}</ref>
* Usually shows progression to WHO CNS grade 4 sooner or later.
*Overall prognosis is rather poor (average survival 2-3 years).
*Grade 3 tumors share a similiar prognosis to grade 2 IDH-mutant tumors.<ref>{{Cite journal | last1 = Reuss | first1 = DE. | last2 = Mamatjan | first2 = Y. | last3 = Schrimpf | first3 = D. | last4 = Capper | first4 = D. | last5 = Hovestadt | first5 = V. | last6 = Kratz | first6 = A. | last7 = Sahm | first7 = F. | last8 = Koelsche | first8 = C. | last9 = Korshunov | first9 = A. | title = IDH mutant diffuse and anaplastic astrocytomas have similar age at presentation and little difference in survival: a grading problem for WHO. | journal = Acta Neuropathol | volume = 129 | issue = 6 | pages = 867-73 | month = Jun | year = 2015 | doi = 10.1007/s00401-015-1438-8 | PMID = 25962792 }}</ref>

==Astrocytoma, IDH mutant grade 4==
* Formely called glioblastoma, IDH-mutant or "secondary glioblastoma".
* CDKN2A deletion in grade 2 or grade 3 tumors results in upgrading to CNS WHO grade 4.

=Radiology/Clinic=
*Mass effect.
*Seizures.
*Neurologic decifit.
*CNS grade 2: Usually not contrast-enhanching, T2 bright.
*CNS grade 3 and 4: The majority are contrast-enhanching, T2 bright.

=Macroscopy=
*No clear demarcation from white matter.
*Softer consistency and opacity.
*May contain larger cysts
*Invaded structures may appear enlarged.
*CNS grade 2 and 3: No necrosis.

=Histology=
CNS grade 2 features: <ref name=AFIP2007>{{Ref AFIP2007|34}}</ref>
*Cell density higher than normal brain.
*Mild to moderate nuclear pleomorphism.
**Monotony of atypical nuclei and irregular distribution indicates neoplasm.
**"naked nuclei" without recognizeable processes.
**No prominent nucleolus.
*Cytoplasm highly variable (even within the same tumour).
**In normal CNS the cytoplasm blends within the neuropil.
*Mitoses absent or very rare.
*Microcystic spaces of the background (none to extensive).
*Lymphocytic cuffing (mostly in gemistocytic type)
*Abent to few rosenthal fibers.

CNS grade 3 features: <ref name=AFIP2007>{{Ref AFIP2007|34}}</ref>
*Increased cellularity (compared to CNS grade 2).
*Mitoses present (a single mitosis in a small specimen indicates a high-grade tumor).
**Specimens with low cellularity but plenty of mitoses are also considered grade 3.
*Distinct nuclear atypia and pleomorphism.
**May include multinucleated cells.
*Cytoplasm highly variable (even within the same tumour).
*Microcystic spaces of the background (none to extensive).
*No necrosis, no vascular proliferations.
**Except radiation necrosis after pretreatment.

CNS grade 4 features:
*Increased cellularity (compared to CNS grade 2).
*Mitoses frequently present.
*Distinct nuclear atypia and pleomorphism.
*Multinucleated cells.
*Microvascular proliferation.
*Necrosis (less common than in [[glioblastoma]]).

=IHC=
*[[GFAP]]+ve.
*[[MAP2]]+ve (especially in cell processes).
*OLIG2 +ve.
*Vimentin+ve (often perinuclear).
*S-100+ve.
*p53: Nuclear staining in 30% of the tumours (usually few cells).
*MIB-1: CNS grade 2: 0-5% (mean: 2%); CNS grade 3 usu. 5-10%.
*[[IDH-1]] (R132H)+ve in 60-70%.
**'Note:'' The mutation-specific antibody does not detect other less common IDH1/2 hotspot mutations.
*[[ATRX]] nuclear loss.

=Molecular=
*IDH1 R132- or IDH2 R172-hotspot mutations are mandatory.
*Absence of LOH 1p/19q (otherwise classify tumor as [[oligodendroglioma]], IDH-mutant and 1p/19q codeleted).
*Tp53 mutations in approx. 60% (80-90% in gemistocytic, 50% in fibrillary types).
*MGMT promotor methylated in approx. 50%.
*CDKN2A/B homozygous deletion results in CNS grade 4<ref>{{Cite journal | last1 = Shirahata | first1 = M. | last2 = Ono | first2 = T. | last3 = Stichel | first3 = D. | last4 = Schrimpf | first4 = D. | last5 = Reuss | first5 = DE. | last6 = Sahm | first6 = F. | last7 = Koelsche | first7 = C. | last8 = Wefers | first8 = A. | last9 = Reinhardt | first9 = A. | title = Novel, improved grading system(s) for IDH-mutant astrocytic gliomas. | journal = Acta Neuropathol | volume = 136 | issue = 1 | pages = 153-166 | month = Jul | year = 2018 | doi = 10.1007/s00401-018-1849-4 | PMID = 29687258 }}</ref><ref>{{Cite journal | last1 = Aoki | first1 = K. | last2 = Nakamura | first2 = H. | last3 = Suzuki | first3 = H. | last4 = Matsuo | first4 = K. | last5 = Kataoka | first5 = K. | last6 = Shimamura | first6 = T. | last7 = Motomura | first7 = K. | last8 = Ohka | first8 = F. | last9 = Shiina | first9 = S. | title = Prognostic relevance of genetic alterations in diffuse lower-grade gliomas. | journal = Neuro Oncol | volume = 20 | issue = 1 | pages = 66-77 | month = 01 | year = 2018 | doi = 10.1093/neuonc/nox132 | PMID = 29016839 }}</ref>
*Usu. no EGFR amplification, no combined whole chromosome 7 gain and whole chromosome 10 loss (+ 7/− 10).
*Absence of TERT promoter mutation (if present in IDH-mutant tumour, consider oligodendroglioma).<ref>{{Cite journal | last1 = Lee | first1 = Y. | last2 = Koh | first2 = J. | last3 = Kim | first3 = SI. | last4 = Won | first4 = JK. | last5 = Park | first5 = CK. | last6 = Choi | first6 = SH. | last7 = Park | first7 = SH. | title = The frequency and prognostic effect of TERT promoter mutation in diffuse gliomas. | journal = Acta Neuropathol Commun | volume = 5 | issue = 1 | pages = 62 | month = Aug | year = 2017 | doi = 10.1186/s40478-017-0465-1 | PMID = 28851427 }}</ref><ref>{{Cite journal | last1 = Koelsche | first1 = C. | last2 = Sahm | first2 = F. | last3 = Capper | first3 = D. | last4 = Reuss | first4 = D. | last5 = Sturm | first5 = D. | last6 = Jones | first6 = DT. | last7 = Kool | first7 = M. | last8 = Northcott | first8 = PA. | last9 = Wiestler | first9 = B. | title = Distribution of TERT promoter mutations in pediatric and adult tumors of the nervous system. | journal = Acta Neuropathol | volume = 126 | issue = 6 | pages = 907-15 | month = Dec | year = 2013 | doi = 10.1007/s00401-013-1195-5 | PMID = 24154961 }}</ref>

<gallery>
File:Diffuse_astrocytoma_HE_stain.jpg | Astrocytoma, grade 2 [[H&E]] (WC/jensflorian)
File:Image NP T2a 0002.JPG | Astrocytoma, grade 2 [[H&E]] (WC/jensflorian)
File:Astrocytoma whoII HE.jpg | Astrocytoma, fibrillary type (WC/jensflorian)
File:Neuropathology case II 02.jpg | Astrocytoma, protoplasmatic type (WC/jensflorian)
File:Gemistocytic astrocytoma.jpg | Astrocytoma, gemistocytic cells (WC/jensflorian)
File:Mitoses_astro_III.jpg | Marked mitotic activity in astrocytoma grade 3 (WC/jensflorian).
File:405551M-ANAPLASTIC_ASTROCYTOMA.jpg | Marked nuclear pleomorphism (AFIP).
File:GFAP astrocytoma.jpg| GFAP staining in astrocytoma (WC/jensflorian)
File:Neuropathology case II 04.jpg | ATRX loss in astrocytoma (WC/jensflorian)
File:IDH1 GBM 20x.jpg | IDH1 R132H immunreactivity in a Grade 4 astrocytoma (WC/Marvin101)
</gallery>

==DDx==
For CNS grade 2 tumours:
*Reactive astrocytosis.
*Demyelinisation.
*Grade 3 astrocytoma, IDH mutant - increased mitotic activity.
*[[Oligodendroglioma]], IDH-mutant and 1p/19q codeleted - esp. protoplasmatic forms. LOH 1p/19q testing required.
*[[SEGA]] - esp. gemistocytic forms.
*Diffuse glioma, MYB- or MYBL1-altered.
For CNS grade 3 tumours:
*Anaplastic [[Oligodendroglioma]], when LOH 1p/19q is present.
For CNS grade 4 tumours:
*[[Glioblastoma]] - vascular proliferations and / or necrosis.

==Outdated terminologies==
*Diffuse astrocytoma
*Gemistocytic astrocytoma
*Diffuse astrocytoma, IDH-wildtype
*Glioblastoma; IDH-mutant
*Fibrillary astrocytoma (ICD-O: 9420/3)
*Protoplasmatic astrocytoma (ICD-O:9410/3)

=See also=
*[[Astrocytoma]].
*[[Neuropathology_tumours#Infiltrative_astrocytomas]]

{{Reflist|2}}

[[Category:Diagnosis]]

Astrocytoma, IDH-mutant

2022-04-14T09:09:56Z

Jensflorian: /* Molecular */ moved from GBM

'''Astrocytoma, IDH-mutant''' is a diffusely-growing, infiltrating astrocytoma of the adult occurring in the CNS white matter. IDH1 codon 132 or IDH2 codon 172 mutations is mandatory for diagnosis and are frequently associated with ATRX and TP53 mutations.

=General=
The current WHO classification recognizes three tumour grades:
* Astrocytoma, IDH mutant grade 2 (ICD-O: 9400/3)
* Astrocytoma, IDH mutant grade 3 (ICD-O: 9401/3)
* Astrocytoma, IDH mutant grade 4 (ICD-O: 9445/3)
* Diffuse astrocytoma,NOS (ICD-O 9400/3) - genetic testing still missing.

The existence of diffuse astrocytoma, IDH wildtype is challenged.<ref>{{Cite journal | last1 = Reuss | first1 = DE. | last2 = Kratz | first2 = A. | last3 = Sahm | first3 = F. | last4 = Capper | first4 = D. | last5 = Schrimpf | first5 = D. | last6 = Koelsche | first6 = C. | last7 = Hovestadt | first7 = V. | last8 = Bewerunge-Hudler | first8 = M. | last9 = Jones | first9 = DT. | title = Adult IDH wild type astrocytomas biologically and clinically resolve into other tumor entities. | journal = Acta Neuropathol | volume = 130 | issue = 3 | pages = 407-17 | month = Sep | year = 2015 | doi = 10.1007/s00401-015-1454-8 | PMID = 26087904 }}</ref> Most adult IDH wildtype cases show genetic alterations identical to glioblastoma.<ref>{{Cite journal | last1 = Hasselblatt | first1 = M. | last2 = Jaber | first2 = M. | last3 = Reuss | first3 = D. | last4 = Grauer | first4 = O. | last5 = Bibo | first5 = A. | last6 = Terwey | first6 = S. | last7 = Schick | first7 = U. | last8 = Ebel | first8 = H. | last9 = Niederstadt | first9 = T. | title = Diffuse Astrocytoma, IDH-Wildtype: A Dissolving Diagnosis. | journal = J Neuropathol Exp Neurol | volume = | issue = | pages = | month = Feb | year = 2018 | doi = 10.1093/jnen/nly012 | PMID = 29444314 }}</ref>

==Astrocytoma, IDH mutant grade 2==
* Most common CNS grade 2 WHO glioma in adults (peaks between 30-40 years).
* 10-15% of all [[astrocytoma]]s.
* Usually shows progression to WHO CNS grade 3 sooner or later. <ref>{{Cite journal | last1 = Louis | first1 = DN. | last2 = Perry | first2 = A. | last3 = Reifenberger | first3 = G. | last4 = von Deimling | first4 = A. | last5 = Figarella-Branger | first5 = D. | last6 = Cavenee | first6 = WK. | last7 = Ohgaki | first7 = H. | last8 = Wiestler | first8 = OD. | last9 = Kleihues | first9 = P. | title = The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. | journal = Acta Neuropathol | volume = 131 | issue = 6 | pages = 803-20 | month = Jun | year = 2016 | doi = 10.1007/s00401-016-1545-1 | PMID = 27157931 }}</ref>

==Astrocytoma, IDH mutant grade 3==
* Most common CNS grade 3 WHO glioma in adults (peaks between 40-50 years).
* Approx 5% of all [[glioma]]s.<ref>{{Cite journal | last1 = Ohgaki | first1 = H. | last2 = Kleihues | first2 = P. | title = Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. | journal = J Neuropathol Exp Neurol | volume = 64 | issue = 6 | pages = 479-89 | month = Jun | year = 2005 | doi = | PMID = 15977639 }}</ref>
* Usually shows progression to WHO CNS grade 4 sooner or later.
*Overall prognosis is rather poor (average survival 2-3 years).
*Grade 3 tumors share a similiar prognosis to grade 2 IDH-mutant tumors.<ref>{{Cite journal | last1 = Reuss | first1 = DE. | last2 = Mamatjan | first2 = Y. | last3 = Schrimpf | first3 = D. | last4 = Capper | first4 = D. | last5 = Hovestadt | first5 = V. | last6 = Kratz | first6 = A. | last7 = Sahm | first7 = F. | last8 = Koelsche | first8 = C. | last9 = Korshunov | first9 = A. | title = IDH mutant diffuse and anaplastic astrocytomas have similar age at presentation and little difference in survival: a grading problem for WHO. | journal = Acta Neuropathol | volume = 129 | issue = 6 | pages = 867-73 | month = Jun | year = 2015 | doi = 10.1007/s00401-015-1438-8 | PMID = 25962792 }}</ref>

==Astrocytoma, IDH mutant grade 4==
* Formely called glioblastoma, IDH-mutant or "secondary glioblastoma".
* CDKN2A deletion in grade 2 or grade 3 tumors results in upgrading to CNS WHO grade 4.

=Radiology/Clinic=
*Mass effect.
*Seizures.
*Neurologic decifit.
*CNS grade 2: Usually not contrast-enhanching, T2 bright.
*CNS grade 3 and 4: The majority are contrast-enhanching, T2 bright.

=Macroscopy=
*No clear demarcation from white matter.
*Softer consistency and opacity.
*May contain larger cysts
*Invaded structures may appear enlarged.
*CNS grade 2 and 3: No necrosis.

=Histology=
CNS grade 2 features: <ref name=AFIP2007>{{Ref AFIP2007|34}}</ref>
*Cell density higher than normal brain.
*Mild to moderate nuclear pleomorphism.
**Monotony of atypical nuclei and irregular distribution indicates neoplasm.
**"naked nuclei" without recognizeable processes.
**No prominent nucleolus.
*Cytoplasm highly variable (even within the same tumour).
**In normal CNS the cytoplasm blends within the neuropil.
*Mitoses absent or very rare.
*Microcystic spaces of the background (none to extensive).
*Lymphocytic cuffing (mostly in gemistocytic type)
*Abent to few rosenthal fibers.

CNS grade 3 features: <ref name=AFIP2007>{{Ref AFIP2007|34}}</ref>
*Increased cellularity (compared to CNS grade 2).
*Mitoses present (a single mitosis in a small specimen indicates a high-grade tumor).
**Specimens with low cellularity but plenty of mitoses are also considered grade 3.
*Distinct nuclear atypia and pleomorphism.
**May include multinucleated cells.
*Cytoplasm highly variable (even within the same tumour).
*Microcystic spaces of the background (none to extensive).
*No necrosis, no vascular proliferations.
**Except radiation necrosis after pretreatment.

CNS grade 4 features:
*Increased cellularity (compared to CNS grade 2).
*Mitoses frequently present.
*Distinct nuclear atypia and pleomorphism.
*Multinucleated cells.
*Microvascular proliferation.
*Necrosis (less common than in [[glioblastoma]]).

=IHC=
*[[GFAP]]+ve.
*[[MAP2]]+ve (especially in cell processes).
*OLIG2 +ve.
*Vimentin+ve (often perinuclear).
*S-100+ve.
*p53: Nuclear staining in 30% of the tumours (usually few cells).
*MIB-1: CNS grade 2: 0-5% (mean: 2%); CNS grade 3 usu. 5-10%.
*[[IDH-1]] (R132H)+ve in 60-70%.
**'Note:'' The mutation-specific antibody does not detect other less common IDH1/2 hotspot mutations.
*[[ATRX]] nuclear loss.

=Molecular=
*IDH1 R132- or IDH2 R172-hotspot mutations are mandatory.
*Absence of LOH 1p/19q (otherwise classify tumor as [[oligodendroglioma]], IDH-mutant and 1p/19q codeleted).
*Tp53 mutations in approx. 60% (80-90% in gemistocytic, 50% in fibrillary types).
*MGMT promotor methylated in approx. 50%.
*CDKN2A/B homozygous deletion results in CNS grade 4<ref>{{Cite journal | last1 = Shirahata | first1 = M. | last2 = Ono | first2 = T. | last3 = Stichel | first3 = D. | last4 = Schrimpf | first4 = D. | last5 = Reuss | first5 = DE. | last6 = Sahm | first6 = F. | last7 = Koelsche | first7 = C. | last8 = Wefers | first8 = A. | last9 = Reinhardt | first9 = A. | title = Novel, improved grading system(s) for IDH-mutant astrocytic gliomas. | journal = Acta Neuropathol | volume = 136 | issue = 1 | pages = 153-166 | month = Jul | year = 2018 | doi = 10.1007/s00401-018-1849-4 | PMID = 29687258 }}</ref><ref>{{Cite journal | last1 = Aoki | first1 = K. | last2 = Nakamura | first2 = H. | last3 = Suzuki | first3 = H. | last4 = Matsuo | first4 = K. | last5 = Kataoka | first5 = K. | last6 = Shimamura | first6 = T. | last7 = Motomura | first7 = K. | last8 = Ohka | first8 = F. | last9 = Shiina | first9 = S. | title = Prognostic relevance of genetic alterations in diffuse lower-grade gliomas. | journal = Neuro Oncol | volume = 20 | issue = 1 | pages = 66-77 | month = 01 | year = 2018 | doi = 10.1093/neuonc/nox132 | PMID = 29016839 }}</ref>
*Usu. no EGFR amplification, no combined whole chromosome 7 gain and whole chromosome 10 loss (+ 7/− 10).
*Absence of TERT promoter mutation (if present in IDH-mutant tumour, consider oligodendroglioma).<ref>{{Cite journal | last1 = Lee | first1 = Y. | last2 = Koh | first2 = J. | last3 = Kim | first3 = SI. | last4 = Won | first4 = JK. | last5 = Park | first5 = CK. | last6 = Choi | first6 = SH. | last7 = Park | first7 = SH. | title = The frequency and prognostic effect of TERT promoter mutation in diffuse gliomas. | journal = Acta Neuropathol Commun | volume = 5 | issue = 1 | pages = 62 | month = Aug | year = 2017 | doi = 10.1186/s40478-017-0465-1 | PMID = 28851427 }}</ref><ref>{{Cite journal | last1 = Koelsche | first1 = C. | last2 = Sahm | first2 = F. | last3 = Capper | first3 = D. | last4 = Reuss | first4 = D. | last5 = Sturm | first5 = D. | last6 = Jones | first6 = DT. | last7 = Kool | first7 = M. | last8 = Northcott | first8 = PA. | last9 = Wiestler | first9 = B. | title = Distribution of TERT promoter mutations in pediatric and adult tumors of the nervous system. | journal = Acta Neuropathol | volume = 126 | issue = 6 | pages = 907-15 | month = Dec | year = 2013 | doi = 10.1007/s00401-013-1195-5 | PMID = 24154961 }}</ref>

<gallery>
File:Diffuse_astrocytoma_HE_stain.jpg | Astrocytoma, grade 2 [[H&E]] (WC/jensflorian)
File:Image NP T2a 0002.JPG | Astrocytoma, grade 2 [[H&E]] (WC/jensflorian)
File:Astrocytoma whoII HE.jpg | Astrocytoma, fibrillary type (WC/jensflorian)
File:Neuropathology case II 02.jpg | Astrocytoma, protoplasmatic type (WC/jensflorian)
File:Gemistocytic astrocytoma.jpg | Gemistocytic astrocytoma (WC/jensflorian)
File:Mitoses_astro_III.jpg | Marked mitotic activity in anaplastic astrocytoma (WC/jensflorian).
File:405551M-ANAPLASTIC_ASTROCYTOMA.jpg | Marked nuclear pleomorphism (AFIP).
File:GFAP astrocytoma.jpg| GFAP staining in astrocytoma (WC/jensflorian)
File:Neuropathology case II 04.jpg | ATRX loss in astrocytoma (WC/jensflorian)
File:IDH1 GBM 20x.jpg | IDH1 R132H immunreactivity in a Grade 4 astrocytoma (WC/Marvin101)
</gallery>

==DDx==
For CNS grade 2 tumours:
*Reactive astrocytosis.
*Demyelinisation.
*Grade 3 astrocytoma, IDH mutant - increased mitotic activity.
*[[Oligodendroglioma]], IDH-mutant and 1p/19q codeleted - esp. protoplasmatic forms. LOH 1p/19q testing required.
*[[SEGA]] - esp. gemistocytic forms.
*Diffuse glioma, MYB- or MYBL1-altered.
For CNS grade 3 tumours:
*Anaplastic [[Oligodendroglioma]], when LOH 1p/19q is present.
For CNS grade 4 tumours:
*[[Glioblastoma]] - vascular proliferations and / or necrosis.

==Outdated terminologies==
*Diffuse astrocytoma
*Gemistocytic astrocytoma
*Diffuse astrocytoma, IDH-wildtype
*Glioblastoma; IDH-mutant
*Fibrillary astrocytoma (ICD-O: 9420/3)
*Protoplasmatic astrocytoma (ICD-O:9410/3)

=See also=
*[[Astrocytoma]].
*[[Neuropathology_tumours#Infiltrative_astrocytomas]]

{{Reflist|2}}

[[Category:Diagnosis]]

Glioblastoma

2022-04-14T09:07:46Z

Jensflorian: /* IHC */ moved from neuropathology tumours

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Glioblastoma_-_high_mag.jpg
| Width =
| Caption = Glioblastoma. [[H&E stain]].
| Micro = astrocytic differentiation, nuclear atypia, [[necrosis]], microvascular proliferation, +/-pseudopalisading necrosis
| Subtypes = [[gliosarcoma]]
| LMDDx = [[anaplastic astrocytoma]]
| Stains =
| IHC = GFAP +ve, IDH-1 -ve/+ve
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site = brain, spinal cord
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence =
| Bloodwork =
| Rads = intra-axial
| Endoscopy =
| Prognosis = very poor
| Other =
| ClinDDx = [[Metastatic_brain_tumours|metastatic brain tumours]]
}}
'''Glioblastoma''' a very common malignant primary [[brain tumour]] in adults. It has a very poor prognosis.

It was previously known as ''glioblastoma multiforme'', abbreviated ''GBM''.
==General==
*Median survival is measured in months.<ref>{{Cite journal | last1 = Jubelirer | first1 = SJ. | title = A review of the treatment and survival rates of 138 patients with glioblastoma multiforme. | journal = W V Med J | volume = 92 | issue = 4 | pages = 186-90 | month = | year = | doi = | PMID = 8772403 }}</ref>
*Only about 5% can expect to survive more than three years.<ref name=pmid17785346>{{Cite journal | last1 = Krex | first1 = D. | last2 = Klink | first2 = B. | last3 = Hartmann | first3 = C. | last4 = von Deimling | first4 = A. | last5 = Pietsch | first5 = T. | last6 = Simon | first6 = M. | last7 = Sabel | first7 = M. | last8 = Steinbach | first8 = JP. | last9 = Heese | first9 = O. | title = Long-term survival with glioblastoma multiforme. | journal = Brain | volume = 130 | issue = Pt 10 | pages = 2596-606 | month = Oct | year = 2007 | doi = 10.1093/brain/awm204 | PMID = 17785346 }}</ref>
*Current classification recognizes three types:
** Glioblastoma, IDH-wildtype (aka primary GBM, ICD-O: 9440/3).
** Glioblastoma, IDH-mutant (aka secondary GBM, ICD-O: 9445/3).
** Glioblastoma, NOS (lack of molecular data).

==Macroscopy==
Features:
* Usu. in white matter.
** central necrotic core.
** ill-defined borders.
** yellowish to dark-brown changes.
** midline shift due to tumor mass.
* In the corpus callosum as bihemispheric "butterfly glioma"
<gallery>
File:Glioblastoma multiforme - MRT T1KM ax.jpg | Ring-enhancement in GBM (WC/Hellerhoff)
File:Glioblastoma macro.jpg | Left insular GBM macroscopy (WC/Sbrandner)
File:Glioblastoma multiforme.jpg | "Butterfly glioma" (WC/AFIP)
</gallery>

==Microscopic==
Features:
*Astrocytic tumour with:
**Nuclear atypia.
**Necrosis.
**Endothelial proliferation ([[AKA]] microvascular proliferation).
**+/-"Pseudopalisading necrosis" - tumour cells lined-up like a picket fence around necrotic areas.

Glioblastoma variants:
*Giant cell glioblastoma (ICD-O: 9441/3)
** Bizarre multinucleated giant cells.
** Reticulin may be abundant.
** Mean age 44 years, outcome somewhat better than conventional GBM.
** IDH-wildtype, but frequent p53 mutations.
*Epitheloid glioblastoma (ICD-O: 9440/3) <ref>te journal | last1 = Kleinschmidt-DeMasters | first1 = BK. | last2 = Aisner | first2 = DL. | last3 = Birks | first3 = DK. | last4 = Foreman | first4 = NK. | title = Epithelioid GBMs show a high percentage of BRAF V600E mutation. | journal = Am J Surg Pathol | volume = 37 | issue = 5 | pages = 685-98 | month = May | year = 2013 | doi = 10.1097/PAS.0b013e31827f9c5e | PMID = 23552385 }}</ref>
** Closely packed epithelioid to rhabdoid cells, often dicohesive.
** Xanthomaous changes less common than in PXA.
** Children and young adults, outcome particularly poor.
** Up to 50% BRAF V600E mutations.
*[[Gliosarcoma]] (ICD-O: 9442/3)

Morphological patterns in Glioblastoma:
* Lipidized (foamy)cells <ref>{{Cite journal | last1 = Kepes | first1 = JJ. | last2 = Rubinstein | first2 = LJ. | title = Malignant gliomas with heavily lipidized (foamy) tumor cells: a report of three cases with immunoperoxidase study. | journal = Cancer | volume = 47 | issue = 10 | pages = 2451-9 | month = May | year = 1981 | doi = | PMID = 7023643 }}</ref>
* Adipocyte-like maturation <ref>{{Cite journal | last1 = Rickert | first1 = CH. | last2 = Riemenschneider | first2 = MJ. | last3 = Schachenmayr | first3 = W. | last4 = Richter | first4 = HP. | last5 = Bockhorn | first5 = J. | last6 = Reifenberger | first6 = G. | last7 = Paulus | first7 = W. | title = Glioblastoma with adipocyte-like tumor cell differentiation--histological and molecular features of a rare differentiation pattern. | journal = Brain Pathol | volume = 19 | issue = 3 | pages = 431-8 | month = Jul | year = 2009 | doi = 10.1111/j.1750-3639.2008.00199.x | PMID = 18691268 }}</ref>
* Rhabdoid glioblastoma (focal loss of [[INI-1]]) <ref>{{Cite journal | last1 = Hiroyuki | first1 = M. | last2 = Ogino | first2 = J. | last3 = Takahashi | first3 = A. | last4 = Hasegawa | first4 = T. | last5 = Wakabayashi | first5 = T. | title = Rhabdoid glioblastoma: an aggressive variaty of astrocytic tumor. | journal = Nagoya J Med Sci | volume = 77 | issue = 1-2 | pages = 321-8 | month = Feb | year = 2015 | doi = | PMID = 25797998 }}</ref>
* Melanotic glioblastoma <ref>{{Cite journal | last1 = Jaiswal | first1 = S. | last2 = Agrawal | first2 = V. | last3 = Vij | first3 = M. | last4 = Sahu | first4 = RN. | last5 = Jaiswal | first5 = AK. | last6 = Behari | first6 = S. | title = Glioblastoma with melanotic differentiation. | journal = Clin Neuropathol | volume = 29 | issue = 5 | pages = 330-3 | month = | year = | doi = | PMID = 20860897 }}</ref>
* Glioblastoma with oligodendroglial component (no improved survival) <ref>{{Cite journal | last1 = Hegi | first1 = ME. | last2 = Janzer | first2 = RC. | last3 = Lambiv | first3 = WL. | last4 = Gorlia | first4 = T. | last5 = Kouwenhoven | first5 = MC. | last6 = Hartmann | first6 = C. | last7 = von Deimling | first7 = A. | last8 = Martinet | first8 = D. | last9 = Besuchet Schmutz | first9 = N. | title = Presence of an oligodendroglioma-like component in newly diagnosed glioblastoma identifies a pathogenetically heterogeneous subgroup and lacks prognostic value: central pathology review of the EORTC_26981/NCIC_CE.3 trial. | journal = Acta Neuropathol | volume = 123 | issue = 6 | pages = 841-52 | month = Jun | year = 2012 | doi = 10.1007/s00401-011-0938-4 | PMID = 22249618 }}</ref>
*Granular cell Glioblastoma <ref>{{Cite journal | last1 = Schittenhelm | first1 = J. | last2 = Psaras | first2 = T. | title = Glioblastoma with granular cell astrocytoma features: a case report and literature review. | journal = Clin Neuropathol | volume = 29 | issue = 5 | pages = 323-9 | month = | year = | doi = | PMID = 20860896 }}</ref>
*Glioblastoma with primitive neuronal component.<ref>{{Cite journal | last1 = Louis | first1 = DN. | last2 = Perry | first2 = A. | last3 = Reifenberger | first3 = G. | last4 = von Deimling | first4 = A. | last5 = Figarella-Branger | first5 = D. | last6 = Cavenee | first6 = WK. | last7 = Ohgaki | first7 = H. | last8 = Wiestler | first8 = OD. | last9 = Kleihues | first9 = P. | title = The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. | journal = Acta Neuropathol | volume = 131 | issue = 6 | pages = 803-20 | month = Jun | year = 2016 | doi = 10.1007/s00401-016-1545-1 | PMID = 27157931 }}</ref>
**formerly known as: PNET-like component.
**have a tendency to CSF dissemination.<ref>{{Cite journal | last1 = Perry | first1 = A. | last2 = Miller | first2 = CR. | last3 = Gujrati | first3 = M. | last4 = Scheithauer | first4 = BW. | last5 = Zambrano | first5 = SC. | last6 = Jost | first6 = SC. | last7 = Raghavan | first7 = R. | last8 = Qian | first8 = J. | last9 = Cochran | first9 = EJ. | title = Malignant gliomas with primitive neuroectodermal tumor-like components: a clinicopathologic and genetic study of 53 cases. | journal = Brain Pathol | volume = 19 | issue = 1 | pages = 81-90 | month = Jan | year = 2009 | doi = 10.1111/j.1750-3639.2008.00167.x | PMID = 18452568 }}</ref>
*Small cell glioblastoma.
*Ependymal-like growth patterns.
*Glioneuronal tumor with neuropil-like islands.<ref>{{Cite journal | last1 = Ishizawa | first1 = K. | last2 = Hirose | first2 = T. | last3 = Sugiyama | first3 = K. | last4 = Kageji | first4 = T. | last5 = Nobusawa | first5 = S. | last6 = Homma | first6 = T. | last7 = Komori | first7 = T. | last8 = Sasaki | first8 = A. | title = Pathologic diversity of glioneuronal tumor with neuropil-like islands: a histological and immunohistochemical study with a special reference to isocitrate dehydrogenase 1 (IDH1) in 5 cases. | journal = Clin Neuropathol | volume = 31 | issue = 2 | pages = 67-76 | month = | year = | doi = | PMID = 22385787 }}</ref>

===Images===

<gallery>
File:Gbm all in one.jpg | Core features of GBM: Necrosis, MVP and mitoses (WC/jensflorian)
File:Glioblastoma anaplastic cells HE.jpg | Anaplastic cells in GBM (WC/jensflorian)
File:Glioblastoma endothelial proliferations.jpg | Endothelial proliferations in GBM (WC/jensflorian)
File:Glioblastoma mitotic activity.jpg | Mitotic activity in GBM (WC/jensflorian)
File:GBM pseudopalisading necrosis.jpg | Pseudopalisading necrosis in GBM (WC/jensflorian)
File:Glioblastoma brain infiltration zone.jpg | Diffuse brain infiltration in GBM (WC/jensflorian)
File:Glioma vessels.jpg | MVP adjacent to tumor infiltration border in GBM (WC/jensflorian)
Image:Glioblastoma - low mag.jpg | GBM - low mag. (WC)
Image:Glioblastoma - intermed mag.jpg | GBM juxtaposed with near normal white matter - intermed. mag. (WC)
Image:Glioblastoma - high mag.jpg | GBM juxtaposed with near normal white matter - high mag. (WC)
Image:Glioblastoma - very high mag.jpg | GBM - very high mag. (WC)
Image:Glioblastoma with extreme nuclear enlargement - high mag.jpg | GBM - high mag. (WC)
Image:Glioblastoma_with_extreme_nuclear_enlargement_-_very_high_mag.jpg | Extreme nuclear enlargement in a GBM - very high mag. (WC)
File:Giant cell glioblastoma HE X200.jpg | Giant cell glioblastoma (WC/jensflorian)
File:Adenoid glioblastoma HE.jpg | Adenoid growth pattern in GBM (WC/jensflorian)
File:AFIP-00405573-Glioblastoma-Micro.jpg | Adenoid growth pattern in GBM (AFIP)
File:Epitheloid glioblastoma HE.jpg | Epitheloid glioblastoma (WC/jensflorian)
File:GBM PNET HE x10.jpg | GBM with PNET component (WC/jensflorian)
File:Glioblastoma PNET component.jpg | GBM with PNET component (WC/jensflorian)
File:Glioblastoma oligodendroglial features.jpg | GBM with oligodendroglial component (WC/jensflorian)
File:Glioblastoma pleomoprhism HE.jpg | Nuclear pleomorphism in with oligodendroglial component (WC/jensflorian)
File:Glioblastoma granular cell astrocytoma component.jpg | GBM with granular cell component (WC/jensflorian)
File:Glioblastoma ependymal features.jpg | Glioblastoma with ependymal-like growth pattern (WC/jensflorian)
File:GBM_with_Neuropil_island_HE.jpg | GBM with neuropil-like islands (WC/jensflorian)
File:AFIP00405522M-GLIOBLASTOMA ARISING IN ASTROCYTOMA.jpg | Spinal cord GBM (AFIP)
File:GBM mimicking melanoma.jpg | Glioblastoma mimicking a (amelanotic) melanoma (WC/jensflorian)
File:GBM layers.jpg | Resection borders in a recurrent GBM (WC/jensflorian)
File:Glioblastoma-radiation_changes_HE.jpg | Radiation changes in a recurrent GBM (WC/jensflorian)
File:GBM_nested_epithelial.jpg | Nested epitheloid appearance in a GBM specimen (WC/jensflorian)
Image:Glioblastoma_%281%29.jpg | Glioblastoma - pseudopalisading of tumour cells (WC)
Image:Glioblastoma_-_high_mag.jpg | Glioblastoma with fragment of near-normal white matter - high mag. (WC)
Image:Anaplastic_astrocytoma_-_very_high_mag_-_cropped.jpg | Anaplastic astrocytoma - very high mag. (WC)
</gallery>

www:
*[http://moon.ouhsc.edu/kfung/jty1/OPAQ/PathQuiz/PQ-Images/N0A002-1.gif Microvascular proliferation in a GBM (ouhsc.edu)].
*[http://cancerres.aacrjournals.org/content/64/3/920/F7.expansion.html Pseudopalisading necrosis in GBM (aacrjournals.org)].

==IHC==
*GFAP +ve (cytoplasm).
*[[MAP2]] +ve.
*[[IDH-1]] -ve (95%).
**+ve if developed from lower grade astrocytoma (secondary GBM) -> classify tumor as Glioblastoma, IDH-mutant.
*[[WT-1]] +ve (cytoplasm).
*p53 +ve (70%).
*Neurofilament -ve.
*Synaptophysin -ve (residual Cortex may be +ve).
*panCK -ve (except for GBM with epithelial component).
*[[ATRX]]: +ve (no loss, nuclei)
**-ve if developed from lower grade astrocytoma (secondary GBM).
*EMA: Dot-like expression less common than in [[ependymoma]]s.
*MIB-1 usu. 15-30%, but varies greatly.

<gallery>
File:Glioblastoma GFAP.jpg | GFAP immunostaining in GBM (WC/Marvin 101)
File:Wilms tumor protein wt1 immunohistocehmistry glioblastoma.JPG | WT1 immunostaining in GBM (WC/jensflorian)
File:Glioblastoma P53.jpg | GBM with strong p53 immunreactivity (WC/jensflorian)
File:Glioblastoma Ck7.jpg|CK7 staining in glioblastoma with epithelial component (WC/jensflorian)
File:GBM_with_Neuropil_island_MIB1.jpg|Reduced proliferation in neuropil-like islands (MIB1).
File:GBM_with_Neuropil_island_Syn.jpg |Synaptophysin immunoreactivity in neuropil-like islands (WC/jensflorian).
Image:Anaplastic_astrocytoma_-_gfap_-_very_high_mag.jpg | Anaplastic astrocytic tumor cells - GFAP - very high mag. (WC)
</gallery>

==Molecular==
*IDH1/2 sequencing in cases below 55 years is mandatory to separate between Glioblastoma, IDH-wildtype and Glioblastoma IDH-mutant.
** In cases above 55 years, negative IDH1 R132H immunohistochemistry may be sufficient.

* 70% of IDH-wildtype glioblastoma show chr.7 gain and chr.10 loss.<ref>{{Cite journal | last1 = Ceccarelli | first1 = M. | last2 = Barthel | first2 = FP. | last3 = Malta | first3 = TM. | last4 = Sabedot | first4 = TS. | last5 = Salama | first5 = SR. | last6 = Murray | first6 = BA. | last7 = Morozova | first7 = O. | last8 = Newton | first8 = Y. | last9 = Radenbaugh | first9 = A. | title = Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma. | journal = Cell | volume = 164 | issue = 3 | pages = 550-63 | month = Jan | year = 2016 | doi = 10.1016/j.cell.2015.12.028 | PMID = 26824661 }}</ref>

*Seen in inherited tumor syndromes:
**[[Lynch syndrome]]
**[[Neurofibromatosis 1]]
**[[Li-Fraumeni syndrome]]
**Turcot-Syndrome

*Most common alterations (TCGA<ref>{{Cite journal | last1 = Verhaak | first1 = RG. | last2 = Hoadley | first2 = KA. | last3 = Purdom | first3 = E. | last4 = Wang | first4 = V. | last5 = Qi | first5 = Y. | last6 = Wilkerson | first6 = MD. | last7 = Miller | first7 = CR. | last8 = Ding | first8 = L. | last9 = Golub | first9 = T. | title = Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. | journal = Cancer Cell | volume = 17 | issue = 1 | pages = 98-110 | month = Jan | year = 2010 | doi = 10.1016/j.ccr.2009.12.020 | PMID = 20129251 }}</ref>)
**Tp53 (42% of the tumors mutated)
**PTEN (33%).
**NF1 (21%).
**EGFR (18%).
**RB1 (11%).
**PI3K-pathway genes (7-10%).

*Pediatric glioblastoma
**are morphologically indistinct from adult GBM.
**show frequent H3F3A mutations and PDGFRA mutations (Note: H3F3A K27M mutations are classified as [[Astrocytoma#H3.3_K27M_mutated_glioma_of_the_midline|K27 mutated midline glioma]]).
**Consider Epithelioid GBM, when BRAF V600E mutated.

*Diagnostic/therapeutic relevant markers:
**[[MGMT]] promoter methylation status<ref>{{Cite journal | last1 = Quillien | first1 = V. | last2 = Lavenu | first2 = A. | last3 = Karayan-Tapon | first3 = L. | last4 = Carpentier | first4 = C. | last5 = Labussière | first5 = M. | last6 = Lesimple | first6 = T. | last7 = Chinot | first7 = O. | last8 = Wager | first8 = M. | last9 = Honnorat | first9 = J. | title = Comparative assessment of 5 methods (methylation-specific polymerase chain reaction, MethyLight, pyrosequencing, methylation-sensitive high-resolution melting, and immunohistochemistry) to analyze O6-methylguanine-DNA-methyltranferase in a series of 100 glioblastoma patients. | journal = Cancer | volume = 118 | issue = 17 | pages = 4201-11 | month = Sep | year = 2012 | doi = 10.1002/cncr.27392 | PMID = 22294349 }}</ref>
**Absence of LOH 1p/19q (otherwise classify tumor as [[oligodendroglioma]]).<ref>{{Cite journal | last1 = Masui | first1 = K. | last2 = Mischel | first2 = PS. | last3 = Reifenberger | first3 = G. | title = Molecular classification of gliomas. | journal = Handb Clin Neurol | volume = 134 | issue = | pages = 97-120 | month = | year = 2016 | doi = 10.1016/B978-0-12-802997-8.00006-2 | PMID = 26948350 }}</ref>

==See also==
*[[Astrocytoma]].
*[[Neuropathology tumours]].
*[[Neuropathology]].

==References==
{{Reflist|2}}

[[Category:Diagnosis]]
[[Category:Neuropathology]]
[[Category:Neuropathology tumours]]

Glioblastoma

2022-04-14T09:06:38Z

Jensflorian: /* Images */ moved from neuropathology tumours

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Glioblastoma_-_high_mag.jpg
| Width =
| Caption = Glioblastoma. [[H&E stain]].
| Micro = astrocytic differentiation, nuclear atypia, [[necrosis]], microvascular proliferation, +/-pseudopalisading necrosis
| Subtypes = [[gliosarcoma]]
| LMDDx = [[anaplastic astrocytoma]]
| Stains =
| IHC = GFAP +ve, IDH-1 -ve/+ve
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site = brain, spinal cord
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence =
| Bloodwork =
| Rads = intra-axial
| Endoscopy =
| Prognosis = very poor
| Other =
| ClinDDx = [[Metastatic_brain_tumours|metastatic brain tumours]]
}}
'''Glioblastoma''' a very common malignant primary [[brain tumour]] in adults. It has a very poor prognosis.

It was previously known as ''glioblastoma multiforme'', abbreviated ''GBM''.
==General==
*Median survival is measured in months.<ref>{{Cite journal | last1 = Jubelirer | first1 = SJ. | title = A review of the treatment and survival rates of 138 patients with glioblastoma multiforme. | journal = W V Med J | volume = 92 | issue = 4 | pages = 186-90 | month = | year = | doi = | PMID = 8772403 }}</ref>
*Only about 5% can expect to survive more than three years.<ref name=pmid17785346>{{Cite journal | last1 = Krex | first1 = D. | last2 = Klink | first2 = B. | last3 = Hartmann | first3 = C. | last4 = von Deimling | first4 = A. | last5 = Pietsch | first5 = T. | last6 = Simon | first6 = M. | last7 = Sabel | first7 = M. | last8 = Steinbach | first8 = JP. | last9 = Heese | first9 = O. | title = Long-term survival with glioblastoma multiforme. | journal = Brain | volume = 130 | issue = Pt 10 | pages = 2596-606 | month = Oct | year = 2007 | doi = 10.1093/brain/awm204 | PMID = 17785346 }}</ref>
*Current classification recognizes three types:
** Glioblastoma, IDH-wildtype (aka primary GBM, ICD-O: 9440/3).
** Glioblastoma, IDH-mutant (aka secondary GBM, ICD-O: 9445/3).
** Glioblastoma, NOS (lack of molecular data).

==Macroscopy==
Features:
* Usu. in white matter.
** central necrotic core.
** ill-defined borders.
** yellowish to dark-brown changes.
** midline shift due to tumor mass.
* In the corpus callosum as bihemispheric "butterfly glioma"
<gallery>
File:Glioblastoma multiforme - MRT T1KM ax.jpg | Ring-enhancement in GBM (WC/Hellerhoff)
File:Glioblastoma macro.jpg | Left insular GBM macroscopy (WC/Sbrandner)
File:Glioblastoma multiforme.jpg | "Butterfly glioma" (WC/AFIP)
</gallery>

==Microscopic==
Features:
*Astrocytic tumour with:
**Nuclear atypia.
**Necrosis.
**Endothelial proliferation ([[AKA]] microvascular proliferation).
**+/-"Pseudopalisading necrosis" - tumour cells lined-up like a picket fence around necrotic areas.

Glioblastoma variants:
*Giant cell glioblastoma (ICD-O: 9441/3)
** Bizarre multinucleated giant cells.
** Reticulin may be abundant.
** Mean age 44 years, outcome somewhat better than conventional GBM.
** IDH-wildtype, but frequent p53 mutations.
*Epitheloid glioblastoma (ICD-O: 9440/3) <ref>te journal | last1 = Kleinschmidt-DeMasters | first1 = BK. | last2 = Aisner | first2 = DL. | last3 = Birks | first3 = DK. | last4 = Foreman | first4 = NK. | title = Epithelioid GBMs show a high percentage of BRAF V600E mutation. | journal = Am J Surg Pathol | volume = 37 | issue = 5 | pages = 685-98 | month = May | year = 2013 | doi = 10.1097/PAS.0b013e31827f9c5e | PMID = 23552385 }}</ref>
** Closely packed epithelioid to rhabdoid cells, often dicohesive.
** Xanthomaous changes less common than in PXA.
** Children and young adults, outcome particularly poor.
** Up to 50% BRAF V600E mutations.
*[[Gliosarcoma]] (ICD-O: 9442/3)

Morphological patterns in Glioblastoma:
* Lipidized (foamy)cells <ref>{{Cite journal | last1 = Kepes | first1 = JJ. | last2 = Rubinstein | first2 = LJ. | title = Malignant gliomas with heavily lipidized (foamy) tumor cells: a report of three cases with immunoperoxidase study. | journal = Cancer | volume = 47 | issue = 10 | pages = 2451-9 | month = May | year = 1981 | doi = | PMID = 7023643 }}</ref>
* Adipocyte-like maturation <ref>{{Cite journal | last1 = Rickert | first1 = CH. | last2 = Riemenschneider | first2 = MJ. | last3 = Schachenmayr | first3 = W. | last4 = Richter | first4 = HP. | last5 = Bockhorn | first5 = J. | last6 = Reifenberger | first6 = G. | last7 = Paulus | first7 = W. | title = Glioblastoma with adipocyte-like tumor cell differentiation--histological and molecular features of a rare differentiation pattern. | journal = Brain Pathol | volume = 19 | issue = 3 | pages = 431-8 | month = Jul | year = 2009 | doi = 10.1111/j.1750-3639.2008.00199.x | PMID = 18691268 }}</ref>
* Rhabdoid glioblastoma (focal loss of [[INI-1]]) <ref>{{Cite journal | last1 = Hiroyuki | first1 = M. | last2 = Ogino | first2 = J. | last3 = Takahashi | first3 = A. | last4 = Hasegawa | first4 = T. | last5 = Wakabayashi | first5 = T. | title = Rhabdoid glioblastoma: an aggressive variaty of astrocytic tumor. | journal = Nagoya J Med Sci | volume = 77 | issue = 1-2 | pages = 321-8 | month = Feb | year = 2015 | doi = | PMID = 25797998 }}</ref>
* Melanotic glioblastoma <ref>{{Cite journal | last1 = Jaiswal | first1 = S. | last2 = Agrawal | first2 = V. | last3 = Vij | first3 = M. | last4 = Sahu | first4 = RN. | last5 = Jaiswal | first5 = AK. | last6 = Behari | first6 = S. | title = Glioblastoma with melanotic differentiation. | journal = Clin Neuropathol | volume = 29 | issue = 5 | pages = 330-3 | month = | year = | doi = | PMID = 20860897 }}</ref>
* Glioblastoma with oligodendroglial component (no improved survival) <ref>{{Cite journal | last1 = Hegi | first1 = ME. | last2 = Janzer | first2 = RC. | last3 = Lambiv | first3 = WL. | last4 = Gorlia | first4 = T. | last5 = Kouwenhoven | first5 = MC. | last6 = Hartmann | first6 = C. | last7 = von Deimling | first7 = A. | last8 = Martinet | first8 = D. | last9 = Besuchet Schmutz | first9 = N. | title = Presence of an oligodendroglioma-like component in newly diagnosed glioblastoma identifies a pathogenetically heterogeneous subgroup and lacks prognostic value: central pathology review of the EORTC_26981/NCIC_CE.3 trial. | journal = Acta Neuropathol | volume = 123 | issue = 6 | pages = 841-52 | month = Jun | year = 2012 | doi = 10.1007/s00401-011-0938-4 | PMID = 22249618 }}</ref>
*Granular cell Glioblastoma <ref>{{Cite journal | last1 = Schittenhelm | first1 = J. | last2 = Psaras | first2 = T. | title = Glioblastoma with granular cell astrocytoma features: a case report and literature review. | journal = Clin Neuropathol | volume = 29 | issue = 5 | pages = 323-9 | month = | year = | doi = | PMID = 20860896 }}</ref>
*Glioblastoma with primitive neuronal component.<ref>{{Cite journal | last1 = Louis | first1 = DN. | last2 = Perry | first2 = A. | last3 = Reifenberger | first3 = G. | last4 = von Deimling | first4 = A. | last5 = Figarella-Branger | first5 = D. | last6 = Cavenee | first6 = WK. | last7 = Ohgaki | first7 = H. | last8 = Wiestler | first8 = OD. | last9 = Kleihues | first9 = P. | title = The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. | journal = Acta Neuropathol | volume = 131 | issue = 6 | pages = 803-20 | month = Jun | year = 2016 | doi = 10.1007/s00401-016-1545-1 | PMID = 27157931 }}</ref>
**formerly known as: PNET-like component.
**have a tendency to CSF dissemination.<ref>{{Cite journal | last1 = Perry | first1 = A. | last2 = Miller | first2 = CR. | last3 = Gujrati | first3 = M. | last4 = Scheithauer | first4 = BW. | last5 = Zambrano | first5 = SC. | last6 = Jost | first6 = SC. | last7 = Raghavan | first7 = R. | last8 = Qian | first8 = J. | last9 = Cochran | first9 = EJ. | title = Malignant gliomas with primitive neuroectodermal tumor-like components: a clinicopathologic and genetic study of 53 cases. | journal = Brain Pathol | volume = 19 | issue = 1 | pages = 81-90 | month = Jan | year = 2009 | doi = 10.1111/j.1750-3639.2008.00167.x | PMID = 18452568 }}</ref>
*Small cell glioblastoma.
*Ependymal-like growth patterns.
*Glioneuronal tumor with neuropil-like islands.<ref>{{Cite journal | last1 = Ishizawa | first1 = K. | last2 = Hirose | first2 = T. | last3 = Sugiyama | first3 = K. | last4 = Kageji | first4 = T. | last5 = Nobusawa | first5 = S. | last6 = Homma | first6 = T. | last7 = Komori | first7 = T. | last8 = Sasaki | first8 = A. | title = Pathologic diversity of glioneuronal tumor with neuropil-like islands: a histological and immunohistochemical study with a special reference to isocitrate dehydrogenase 1 (IDH1) in 5 cases. | journal = Clin Neuropathol | volume = 31 | issue = 2 | pages = 67-76 | month = | year = | doi = | PMID = 22385787 }}</ref>

===Images===

<gallery>
File:Gbm all in one.jpg | Core features of GBM: Necrosis, MVP and mitoses (WC/jensflorian)
File:Glioblastoma anaplastic cells HE.jpg | Anaplastic cells in GBM (WC/jensflorian)
File:Glioblastoma endothelial proliferations.jpg | Endothelial proliferations in GBM (WC/jensflorian)
File:Glioblastoma mitotic activity.jpg | Mitotic activity in GBM (WC/jensflorian)
File:GBM pseudopalisading necrosis.jpg | Pseudopalisading necrosis in GBM (WC/jensflorian)
File:Glioblastoma brain infiltration zone.jpg | Diffuse brain infiltration in GBM (WC/jensflorian)
File:Glioma vessels.jpg | MVP adjacent to tumor infiltration border in GBM (WC/jensflorian)
Image:Glioblastoma - low mag.jpg | GBM - low mag. (WC)
Image:Glioblastoma - intermed mag.jpg | GBM juxtaposed with near normal white matter - intermed. mag. (WC)
Image:Glioblastoma - high mag.jpg | GBM juxtaposed with near normal white matter - high mag. (WC)
Image:Glioblastoma - very high mag.jpg | GBM - very high mag. (WC)
Image:Glioblastoma with extreme nuclear enlargement - high mag.jpg | GBM - high mag. (WC)
Image:Glioblastoma_with_extreme_nuclear_enlargement_-_very_high_mag.jpg | Extreme nuclear enlargement in a GBM - very high mag. (WC)
File:Giant cell glioblastoma HE X200.jpg | Giant cell glioblastoma (WC/jensflorian)
File:Adenoid glioblastoma HE.jpg | Adenoid growth pattern in GBM (WC/jensflorian)
File:AFIP-00405573-Glioblastoma-Micro.jpg | Adenoid growth pattern in GBM (AFIP)
File:Epitheloid glioblastoma HE.jpg | Epitheloid glioblastoma (WC/jensflorian)
File:GBM PNET HE x10.jpg | GBM with PNET component (WC/jensflorian)
File:Glioblastoma PNET component.jpg | GBM with PNET component (WC/jensflorian)
File:Glioblastoma oligodendroglial features.jpg | GBM with oligodendroglial component (WC/jensflorian)
File:Glioblastoma pleomoprhism HE.jpg | Nuclear pleomorphism in with oligodendroglial component (WC/jensflorian)
File:Glioblastoma granular cell astrocytoma component.jpg | GBM with granular cell component (WC/jensflorian)
File:Glioblastoma ependymal features.jpg | Glioblastoma with ependymal-like growth pattern (WC/jensflorian)
File:GBM_with_Neuropil_island_HE.jpg | GBM with neuropil-like islands (WC/jensflorian)
File:AFIP00405522M-GLIOBLASTOMA ARISING IN ASTROCYTOMA.jpg | Spinal cord GBM (AFIP)
File:GBM mimicking melanoma.jpg | Glioblastoma mimicking a (amelanotic) melanoma (WC/jensflorian)
File:GBM layers.jpg | Resection borders in a recurrent GBM (WC/jensflorian)
File:Glioblastoma-radiation_changes_HE.jpg | Radiation changes in a recurrent GBM (WC/jensflorian)
File:GBM_nested_epithelial.jpg | Nested epitheloid appearance in a GBM specimen (WC/jensflorian)
Image:Glioblastoma_%281%29.jpg | Glioblastoma - pseudopalisading of tumour cells (WC)
Image:Glioblastoma_-_high_mag.jpg | Glioblastoma with fragment of near-normal white matter - high mag. (WC)
Image:Anaplastic_astrocytoma_-_very_high_mag_-_cropped.jpg | Anaplastic astrocytoma - very high mag. (WC)
</gallery>

www:
*[http://moon.ouhsc.edu/kfung/jty1/OPAQ/PathQuiz/PQ-Images/N0A002-1.gif Microvascular proliferation in a GBM (ouhsc.edu)].
*[http://cancerres.aacrjournals.org/content/64/3/920/F7.expansion.html Pseudopalisading necrosis in GBM (aacrjournals.org)].

==IHC==
*GFAP +ve (cytoplasm).
*[[MAP2]] +ve.
*[[IDH-1]] -ve (95%).
**+ve if developed from lower grade astrocytoma (secondary GBM) -> classify tumor as Glioblastoma, IDH-mutant.
*[[WT-1]] +ve (cytoplasm).
*p53 +ve (70%).
*Neurofilament -ve.
*Synaptophysin -ve (residual Cortex may be +ve).
*panCK -ve (except for GBM with epithelial component).
*[[ATRX]]: +ve (no loss, nuclei)
**-ve if developed from lower grade astrocytoma (secondary GBM).
*EMA: Dot-like expression less common than in [[ependymoma]]s.
*MIB-1 usu. 15-30%, but varies greatly.

<gallery>
File:Glioblastoma GFAP.jpg | GFAP immunostaining in GBM (WC/Marvin 101)
File:Wilms tumor protein wt1 immunohistocehmistry glioblastoma.JPG | WT1 immunostaining in GBM (WC/jensflorian)
File:Glioblastoma P53.jpg | GBM with strong p53 immunreactivity (WC/jensflorian)
File:IDH1 GBM 20x.jpg | IDH1 R132H immunreactivity in a secondary GBM (WC/Marvin101)
File:Glioblastoma Ck7.jpg|CK7 staining in glioblastoma with epithelial component (WC/jensflorian)
File:GBM_with_Neuropil_island_MIB1.jpg|Reduced proliferation in neuropil-like islands (MIB1).
File:GBM_with_Neuropil_island_Syn.jpg |Synaptophysin immunoreactivity in neuropil-like islands (WC/jensflorian).
</gallery>

==Molecular==
*IDH1/2 sequencing in cases below 55 years is mandatory to separate between Glioblastoma, IDH-wildtype and Glioblastoma IDH-mutant.
** In cases above 55 years, negative IDH1 R132H immunohistochemistry may be sufficient.

* 70% of IDH-wildtype glioblastoma show chr.7 gain and chr.10 loss.<ref>{{Cite journal | last1 = Ceccarelli | first1 = M. | last2 = Barthel | first2 = FP. | last3 = Malta | first3 = TM. | last4 = Sabedot | first4 = TS. | last5 = Salama | first5 = SR. | last6 = Murray | first6 = BA. | last7 = Morozova | first7 = O. | last8 = Newton | first8 = Y. | last9 = Radenbaugh | first9 = A. | title = Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma. | journal = Cell | volume = 164 | issue = 3 | pages = 550-63 | month = Jan | year = 2016 | doi = 10.1016/j.cell.2015.12.028 | PMID = 26824661 }}</ref>

*Seen in inherited tumor syndromes:
**[[Lynch syndrome]]
**[[Neurofibromatosis 1]]
**[[Li-Fraumeni syndrome]]
**Turcot-Syndrome

*Most common alterations (TCGA<ref>{{Cite journal | last1 = Verhaak | first1 = RG. | last2 = Hoadley | first2 = KA. | last3 = Purdom | first3 = E. | last4 = Wang | first4 = V. | last5 = Qi | first5 = Y. | last6 = Wilkerson | first6 = MD. | last7 = Miller | first7 = CR. | last8 = Ding | first8 = L. | last9 = Golub | first9 = T. | title = Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. | journal = Cancer Cell | volume = 17 | issue = 1 | pages = 98-110 | month = Jan | year = 2010 | doi = 10.1016/j.ccr.2009.12.020 | PMID = 20129251 }}</ref>)
**Tp53 (42% of the tumors mutated)
**PTEN (33%).
**NF1 (21%).
**EGFR (18%).
**RB1 (11%).
**PI3K-pathway genes (7-10%).

*Pediatric glioblastoma
**are morphologically indistinct from adult GBM.
**show frequent H3F3A mutations and PDGFRA mutations (Note: H3F3A K27M mutations are classified as [[Astrocytoma#H3.3_K27M_mutated_glioma_of_the_midline|K27 mutated midline glioma]]).
**Consider Epithelioid GBM, when BRAF V600E mutated.

*Diagnostic/therapeutic relevant markers:
**[[MGMT]] promoter methylation status<ref>{{Cite journal | last1 = Quillien | first1 = V. | last2 = Lavenu | first2 = A. | last3 = Karayan-Tapon | first3 = L. | last4 = Carpentier | first4 = C. | last5 = Labussière | first5 = M. | last6 = Lesimple | first6 = T. | last7 = Chinot | first7 = O. | last8 = Wager | first8 = M. | last9 = Honnorat | first9 = J. | title = Comparative assessment of 5 methods (methylation-specific polymerase chain reaction, MethyLight, pyrosequencing, methylation-sensitive high-resolution melting, and immunohistochemistry) to analyze O6-methylguanine-DNA-methyltranferase in a series of 100 glioblastoma patients. | journal = Cancer | volume = 118 | issue = 17 | pages = 4201-11 | month = Sep | year = 2012 | doi = 10.1002/cncr.27392 | PMID = 22294349 }}</ref>
**Absence of LOH 1p/19q (otherwise classify tumor as [[oligodendroglioma]]).<ref>{{Cite journal | last1 = Masui | first1 = K. | last2 = Mischel | first2 = PS. | last3 = Reifenberger | first3 = G. | title = Molecular classification of gliomas. | journal = Handb Clin Neurol | volume = 134 | issue = | pages = 97-120 | month = | year = 2016 | doi = 10.1016/B978-0-12-802997-8.00006-2 | PMID = 26948350 }}</ref>

==See also==
*[[Astrocytoma]].
*[[Neuropathology tumours]].
*[[Neuropathology]].

==References==
{{Reflist|2}}

[[Category:Diagnosis]]
[[Category:Neuropathology]]
[[Category:Neuropathology tumours]]

Neuropathology tumours

2022-04-14T09:04:59Z

Jensflorian: Minor rearrangement

[[Image:Gemistocytic Astrocytoma 003.jpg|thumb|right|A brain stem [[astrocytoma]]. (WC)]]
The article covers '''tumours in neuropathology'''. Tumours are a large part of [[neuropathology]]. [[Cytopathology]] of CNS tumours is dealt with in the article ''[[CNS cytopathology]]''.

There are separate articles for ''[[peripheral nerve sheath tumours]]'' and ''[[pituitary gland|pituitary/peri-pituitary lesions]]''.

==Brain tumours - overview==
===Alphabetical===
For overview see [[:Category:Neuropathology_tumours|here]]

===By age group===
====Adult====
Four most common types of brain tumours:<ref>[http://neurosurgery.mgh.harvard.edu/abta/primer.htm http://neurosurgery.mgh.harvard.edu/abta/primer.htm]</ref>
# Metastatic brain tumours (barely edges out primary tumours)
#*[[Lung cancer|Lung]] (most common).
#*[[Invasive breast cancer|Breast]].
#*[[Melanoma]].
#*[[Renal cell carcinoma]] (RCC).
# [[Glioblastoma]], IDH-wildtype.
# [[Astrocytoma, IDH-mutant]].
# [[Meningioma]].

====Children====
# [[Pilocytic astrocytoma]].
# [[Medulloblastoma]].
# [[Ependymoma]].
# Pontine glioma, often [[Diffuse midline glioma, H3 K27-altered]].

===By location===
Certain tumours like to hang-out at certain places:<ref>URL: [http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/files/4ce563fb7e8e48fc9ed8b42e296a7747.gif http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/files/4ce563fb7e8e48fc9ed8b42e296a7747.gif] and [http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html]. Accessed on: 2 November 2010.</ref>
====Cerebrum====
*Cortical based - [[oligodendroglioma]].
*Grey-white junction - metastases.
*White matter - astrocytoma, [[glioblastoma]].
*Periventricular - CNS lymphoma.
*Cystic - [[ganglioglioma]], [[pilocytic astrocytoma]], [[pleomorphic xanthoastrocytoma]].
====Cerebellum====
*Midline/central - [[medulloblastoma]].
*Cystic lesion - pilocytic astrocytoma (younger individual), [[hemangioblastoma]] (older individual).
*Solid lesion (older individual) - [[metastasis]].
====Sella turcica====
* [[Pituitary adenoma]].
* [[Craniopharyngioma]].
less common:
* [[Pituicytoma]].
* [[Granular cell tumour]].
* [[Germinoma]].
* [[Chordoma]]
* Rathke cleft cyst.
* Hypophysitis.
* Xanthogranuloma.
====Spinal cord====
*[[Ependymoma]]
*[[Glioblastoma]]
*[[Meningioma]]
*Carcinoma metastasis
*[[Hemangioblastoma]]
====Filum terminale====
*[[Meningioma]].
*[[Myxopapillary ependymoma]].
*[[Neurofibroma]].
*[[Schwannoma]].
*[[Paraganglioma]].
====Meninges====
* [[Meningioma]].
* [[Solitary fibrous tumour]] / Hemangiopericytoma.
* [[Hemangioblastoma]].
less common:
* [[Melanoma]] / Melanocytoma.
* Lymphoproliferative diseases.
* [[Sarcoidosis]]
* [[Arachnoid cyst]].
* Disseminated oligodendroglial-like leptomeningeal tumour.
* Desmoplastic infantile astrocytoma / ganglioglioma.
* Meningioangiomatosis.
* Calcifying pseudoneoplasm.
====Skull====
* [[Fibrous dysplasia]].
* [[Paget disease]].
* [[Histiocytosis]].
* [[Hemangioma]].
* [[Aneurysmal bone cyst]].
* [[Plasma_cell_neoplasms#Multiple_myeloma|Multiple myeloma]].
====Skull base / Cerebellopontine angle====
* [[Schwannoma]].
* [[Meningioma]].
* [[Dermoid cyst]] / epidermoid cyst.
less common:
* [[Ependymoma]].
* [[Choroid plexus papilloma]].
* [[Glomus tumour]].
* [[Chordoma]].
* [[Chondrosarcoma]].
* [[Olfactory neuroblastoma]].
* [[Endolymphatic sac tumour]].

===Primary versus secondary===
*[[AKA]] (primary) brain tumour versus metastatic cancer.
====Primary====
[[Glioma|Glial tumours]]:
*Cytoplasmic processes - '''key feature'''.
**Best seen at highest magnification - usu. ~1 micrometer.
**Processes may branch.
*Ill-defined border/blend with the surrounding brain.

[[Meningioma]]:
*Lesion often dura-based.
*Mesenchymal tumor (often contains collagen).

[[Lymphoma]]:
*Primary CNS Lymphoma (PCNSL) is usu. a diffuse large B-cell lymphoma.
*Large (lymphoid) cells, ergo usu. not a difficult diagnosis.
**~2x size of resting lymphocyte, nucleoli.
*Lesion predominantly perivascular.

====Secondary====
*Carcinomas:
**Well-demarcated border between brain and lesion - '''key feature'''.
**No cytoplasmic processes.
**Usu. have nuclear atypia of malignancy.
**Nuclei often ~3-4x the size of a [[RBC]].
**+/-Glandular arrangement.
**+/-Nucleoli.
*Melanoma.
*Secondary Lymphoma.
*Sarcomas (rare).

===By growth pattern===
====Infiltrative astrocytomas====
*[[Astrocytoma, IDH-mutant]].
*[[Glioblastoma]], IDH-wildtype.

Notes:
**Glial: "blends into brain"/gradual transition to non-tumour brain.

====Non-infiltrative astrocytomas====
**[[Pilocytic astrocytoma]]
**[[Pleomorphic xanthoastrocytoma]]
**[[Subependymal giant cell astrocytoma]].

====Cystic tumours====
DDx:<ref>URL: [http://path.upmc.edu/cases/case320/dx.html http://path.upmc.edu/cases/case320/dx.html]. Accessed on: 14 January 2012.</ref>
*[[Pilocytic astrocytoma]].
*[[Pleomorphic xanthoastrocytoma]].
*[[Ganglioglioma]].
*[[Hemangioblastoma]].
*[[Craniopharyngioma]].<ref>URL: [http://www.pathologyoutlines.com/Cnstumor.html#cystsgeneral http://www.pathologyoutlines.com/Cnstumor.html#cystsgeneral]. Accessed on: 14 January 2012.</ref>

Notes:
**Non-glial: no radiating glial processes.
*Rosenthal fibres within the tumour... often seen in [[pilocytic astrocytoma]].
**Rosenthal fibres may be seen around a (very) slow growing tumour and represent a reactive process.
*Inflammatory cells and macrophages should prompt consideration of an alternate diagnosis (e.g. [[cerebral infarct]], [[multiple sclerosis]]) - esp. if this is a primary lesion.<ref>URL: [http://path.upmc.edu/cases/case79/dx.html http://path.upmc.edu/cases/case79/dx.html]. Accessed on: 2 January 2012.</ref>

====Grading====
Nuclear pleomorphism present:
*At least grade II (diffuse astrocytoma).

Mitotic figures present:
*At least grade III (anaplastic astrocytoma).

Microvascular proliferation ''or'' necrosis with pseudopalisading tumour cells:
*Grade IV (glioblastoma [[AKA]] glioblastoma multiforme).

Notes:
*Pseudopalisading tumour cells = high tumour cell density adjacent to regions of necrosis; palisade = a fence of poles forming a defensive barrier or fortification.
*WHO Grading is currently based on expected biologiocal behaviour without treatment.
**Grading does not reflect molecular divergent groups within a tumor class or response to therapy (Currently controversies in grading for IDH-mutant astrocytoma vs. IDH-wildtype astrocytoma).<ref>{{Cite journal | last1 = Louis | first1 = DN. | last2 = von Deimling | first2 = A. | title = Grading of diffuse astrocytic gliomas: Broders, Kernohan, Zülch, the WHO… and Shakespeare. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Aug | year = 2017 | doi = 10.1007/s00401-017-1765-z | PMID = 28801693 }}</ref>

===By IHC===
*GFAP - should stain cytoplasm of tumour cells and the perikaryon (nuclear membrane) of most [[Astrocytoma]]s.
*[[IDH-1]](R132H) (isocitrate dehydrogenase 1) in [[Astrocytoma, IDH-mutant]].<ref name=pmid19228619>{{cite journal |author=Yan H, Parsons DW, Jin G, ''et al.'' |title=IDH1 and IDH2 mutations in gliomas |journal=N. Engl. J. Med. |volume=360 |issue=8 |pages=765–73 |year=2009 |month=February |pmid=19228619 |pmc=2820383 |doi=10.1056/NEJMoa0808710 |url=}}</ref><ref name=pmid20975057>{{cite journal |author=Houillier C, Wang X, Kaloshi G, ''et al.'' |title=IDH1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas |journal=Neurology |volume=75 |issue=17 |pages=1560–6 |year=2010 |month=October |pmid=20975057 |doi=10.1212/WNL.0b013e3181f96282 |url=}}</ref>
*[[H3F3A|H3F3A K27M]] in [[Diffuse midline glioma, H3 K27-altered]].
*[[ATRX]] -ve in [[Astrocytoma, IDH-mutant]] or [[Diffuse hemispheric glioma, H3 G34-mutant]].
*[[CD20]] in PCNSL.
*Cytokeratins in Carcinoma brain metastases, Plexus choroid tumours, [[AT/RT]], [[Papillary tumour of the pineal region]], [[Craniopharyngioma]].
*[[EMA]] in [[Meningioma]] and carcinoma brain metastases.
*PrgR in [[Meningioma]] and carcinoma metastases.
*[[Synaptophysin]] in glioneuronal tumours and Pituitary adenoma and embryonal tumours.

===Common neuropathology tumours in a table===
{| class="wikitable"
|'''Type'''
|'''Key feature(s)'''
|'''Imaging'''
|'''History'''
|'''Notes'''
|'''IHC'''
|'''Images'''
|-
|Normal tissue
|cells regularly spaced, no nuc. atypia
|small lesion? / deep lesion?
|variable
|missed lesion?
|nil
|[[Image:Grey_matter_and_white_matter_-_very_high_mag.jpg |thumb|center|150px|Normal. (WC)]]
|-
|[[Reactive astrocytes]]
|astrocytes with well-demarcated eosinophilic cytoplasm, regular spacing, no nuc. atypia
|small lesion? / deep lesion?
|variable
|missed lesion / close to a lesion; non-specific pathologic process - need more tissue
|GFAP
|[[Image:Reactive_astrocytes_-_lfb_-_high_mag.jpg|thumb|center|150px|Reactive astrocytes. (WC)]]
|-
|[[Schwannoma]]
|cellular areas (Antoni A), paucicelluar areas (Antoni B), palisading of nuclei (Verocay bodies)
|extra-axial + intradural
|old or young
|need frozen section to Dx, DDx: [[meningioma]]
|S100, SOX10
|[[Image:Schwannoma_-_Antoni_A_and_B_-_very_high_mag.jpg|thumb|center|150px|Schwannoma. (WC)]]
|-
|[[Meningioma]]
|whorls, psammomatous calcs, nuclear inclusions
|extra-axial + intradural
|old or young
|may be diagnosed on smear, DDx: [[schwannoma]], choroid plexus
|EMA, PR, Ki-67
|[[Image:Meningioma_intermed_mag.jpg |thumb|center|150px|Meningioma. (WC)]]
|-
|[[Astrocytoma, IDH-mutant]] (CNS [[WHO]] grade 2 or grade 3)
|glial processes (esp. on smear), nuclear atypia (typical size var. ~3x, irreg. nuc. membrane, hyperchromasia), no Rosenthal fibres in the core of the lesion †, no microvascular proliferation, no necrosis
|often enhancing (suggests high grade), usu. supratentorial, usu. white matter
|usu. old, occ. young
|common
|IDH-1(R132H)+/-, GFAP+
| [[Image:Anaplastic_astrocytoma_-_very_high_mag_-_cropped.jpg | thumb| center| 150px|High-grade astrocytoma. (WC)]]
|-
|[[Glioblastoma]], IDH-wildtype (CNS [[WHO]] grade 4)
|glial processes (esp. on smear), nuclear atypia (typical size var. ~3x, irreg. nuc. membrane, hyperchromasia), no Rosenthal fibres in the core of the lesion †, microvascular proliferation or necrosis
|often enhancing (suggests high grade), usu. supratentorial, usu. white matter
|usu. old, occ. young
|very common, esp. glioblastoma
|IDH-1+/-, GFAP+
| [[Image:Glioblastoma (1).jpg | thumb| center| 150px|Glioblastoma. (WC)]]
|-
|[[Metastatic brain tumours|Metastasis]]
|sharp interface with brain, often glandular, +/-nucleoli, no glial processes
|often cerebellular, well-circumscribed
|usu. old
|often suspected to have metastatic disease
|[[TTF-1]], CK7, [[CK20]], BRST-2
|[[Image:Metastatic_adenocarcinoma_-_cerebellum_-_very_low_mag.jpg | thumb| center|150px |Metastasis. (WC)]]
|}
† Rosenthal fibres at the periphery of a lesion are a non-specific finding seen in chronic processes.

==Brain metastasis==
{{Main|Brain metastasis}}

===Molecular===
See also: [[Molecular_pathology_tests#Neuropathology|Molecular Neuropathology]]

==Gliomas==
{{Main|Glioma}}

Gliomas, glioneuronal tumours and neuronal tumours are often categorized together.

===Astrocytic tumours===
{{Main|Astrocytoma}}

* [[Astrocytoma]], IDH-mutant.
* [[Glioblastoma]], IDH-wildtype.
** [[Gliosarcoma]] (a glioblastoma subtype)

Features:<ref name=pmid>{{cite journal |author=Rong Y, Durden DL, Van Meir EG, Brat DJ |title='Pseudopalisading' necrosis in glioblastoma: a familiar morphologic feature that links vascular pathology, hypoxia, and angiogenesis |journal=J. Neuropathol. Exp. Neurol. |volume=65 |issue=6 |pages=529–39 |year=2006 |month=June |pmid=16783163 |doi= |url=}}</ref><ref>[http://dictionary.reference.com/browse/palisading http://dictionary.reference.com/browse/palisading]</ref>
*Glial processes - '''key feature'''.
**Thin stringy cytoplasmic processes - best seen at high power in less cellular areas.
*No Rosenthal fibres within the tumour itself.

Images:
*[http://moon.ouhsc.edu/kfung/jty1/opaq/PathQuiz/N0A002-PQ01-M.htm Endothelial proliferation in a GBM (ouhsc.edu)].
*[http://moon.ouhsc.edu/kfung/jty1/neurotest/Q05-Ans.htm Endothelial proliferation (ouhse.edu)].
*[http://path.upmc.edu/cases/case368.html Gemistocytic astrocytoma - several images (upmc.edu)].

Depreceated:
* Diffuse [[Astrocytoma]]
* [[Anaplastic astrocytoma]]
* [[Gliomatosis cerebri]]
* Spongioblastoma

===Oligodendroglial tumours===
* [[Oligodendroglioma]], IDH-mutant and 1p/19q codeleted.

Depreceated:
* Anaplastic oligodendroglioma
* [[Oligoastrocytoma]]
* Anaplastic oligoastrocytoma

===Pediatric-type diffuse high-grade glioma===
{{Main|Pediatric-type diffuse high-grade glioma}}
* [[Astrocytoma#Diffuse_midline_glioma.2C_H3_K27M_mutant|Diffuse midline glioma H3 K27-mutant]]

===Pediatric-type diffuse low-grade glioma===
{{Main|Pediatric-type diffuse low-grade glioma}}

===Circumscribed astrocytic gliomas===
* [[Pilocytic astrocytoma]] (PA)
** [[Pilomyxoid astrocytoma]] (PMA)
* [[Pleomorphic xanthoastrocytoma]] (PXA)
* [[Subependymal giant cell astrocytoma]] (SEGA)
* [[Neuropathology_tumours#Astroblastoma|Astroblastoma MN1-altered]].
* [[Neuropathology_tumours#Chordoid glioma of the third ventricl|Chordoid glioma]].

====Astroblastoma====
*No WHO grade yet.<ref>{{Ref WHOCNS|88}}</ref>
*Very rare superficial tumor of young age.<ref>{{Cite journal | last1 = Narayan | first1 = S. | last2 = Kapoor | first2 = A. | last3 = Singhal | first3 = MK. | last4 = Jakhar | first4 = SL. | last5 = Bagri | first5 = PK. | last6 = Rajput | first6 = PS. | last7 = Kumar | first7 = HS. | title = Astroblastoma of cerebrum: A rare case report and review of literature. | journal = J Cancer Res Ther | volume = 11 | issue = 3 | pages = 667 | month = | year = | doi = 10.4103/0973-1482.140800 | PMID = 26458709 }}</ref>
*Large, cystic. Pushing margin towards CNS.
*Vasocentric growth, plump cells with absence of fibrillary pattern.
*GFAP+ve, Synaptohysin-ve, Olig-2-ve, focally EMA/panCK+ve. MIB-1: 1-18 %.
*Molecular profile overlaps with classical [[CNS-PNET]].
**Gene fusions invoving meningioma gene (MN1)<ref>{{Cite journal | last1 = Sturm | first1 = D. | last2 = Orr | first2 = BA. | last3 = Toprak | first3 = UH. | last4 = Hovestadt | first4 = V. | last5 = Jones | first5 = DT. | last6 = Capper | first6 = D. | last7 = Sill | first7 = M. | last8 = Buchhalter | first8 = I. | last9 = Northcott | first9 = PA. | title = New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs. | journal = Cell | volume = 164 | issue = 5 | pages = 1060-72 | month = Feb | year = 2016 | doi = 10.1016/j.cell.2016.01.015 | PMID = 26919435 }}</ref>

<gallery>
File:Astroblastoma_HE_Specimen.jpg | HE. (WC/jensflorian)
File:Astroblastoma_HE_papillae.jpg | HE. (WC/jensflorian)
File:Astroblastoma.jpg | Astroblastoma (AFIP)
</gallery>

====Chordoid glioma of the third ventricle====
* WHO grade II.
* Slowly growing, non-invasive, in adults.
* Clusters of epithelioid cells in mucinous stroma.
* Lymphocytic infiltrates, adjacent Rosenthal fibers.
* Fibrosis may be present.
* Few mitoses.
* [[GFAP]]+ve, MIB-1 1-3%.
* [[TTF-1]]+ve.
* CD34+ve.
* [[IDH-1]]-ve, [[p53]]-ve.
* PRKCA D463H mutations.<ref>{{Cite journal | last1 = Goode | first1 = B. | last2 = Mondal | first2 = G. | last3 = Hyun | first3 = M. | last4 = Ruiz | first4 = DG. | last5 = Lin | first5 = YH. | last6 = Van Ziffle | first6 = J. | last7 = Joseph | first7 = NM. | last8 = Onodera | first8 = C. | last9 = Talevich | first9 = E. | title = A recurrent kinase domain mutation in PRKCA defines chordoid glioma of the third ventricle. | journal = Nat Commun | volume = 9 | issue = 1 | pages = 810 | month = 02 | year = 2018 | doi = 10.1038/s41467-018-02826-8 | PMID = 29476136 }}</ref>

<gallery>
File:NP op 20201028 009.jpg | Chordoid Glioma. (WC/jensflorian)
</gallery>

===Ependymal tumours===
* [[Subependymoma]]
* [[Myxopapillary Ependymoma]]
* [[Ependymoma]]
* Anaplastic ependymoma

==Choroid plexus tumours==
* [[Choroid plexus papilloma]]
* Atypical choroid plexus papilloma
* [[Choroid plexus carcinoma]]

==Other neuroepithelial tumours==
* [[Neuropathology_tumours#Cribiform_neuroepithelial_tumour|Cribifiorm neuroepithelial tumour]].

===Cribiform neuroepithelial tumour===
AKA: '''CRINET'''.
*Not listed in the current WHO classification.
*First description in 2009.<ref>{{Cite journal | last1 = Hasselblatt | first1 = M. | last2 = Oyen | first2 = F. | last3 = Gesk | first3 = S. | last4 = Kordes | first4 = U. | last5 = Wrede | first5 = B. | last6 = Bergmann | first6 = M. | last7 = Schmid | first7 = H. | last8 = Frühwald | first8 = MC. | last9 = Schneppenheim | first9 = R. | title = Cribriform neuroepithelial tumor (CRINET): a nonrhabdoid ventricular tumor with INI1 loss and relatively favorable prognosis. | journal = J Neuropathol Exp Neurol | volume = 68 | issue = 12 | pages = 1249-55 | month = Dec | year = 2009 | doi = 10.1097/NEN.0b013e3181c06a51 | PMID = 19915490 }}</ref>
*Around ventricles.<ref>{{Cite journal | last1 = Arnold | first1 = MA. | last2 = Stallings-Archer | first2 = K. | last3 = Marlin | first3 = E. | last4 = Grondin | first4 = R. | last5 = Olshefski | first5 = R. | last6 = Biegel | first6 = JA. | last7 = Pierson | first7 = CR. | title = Cribriform neuroepithelial tumor arising in the lateral ventricle. | journal = Pediatr Dev Pathol | volume = 16 | issue = 4 | pages = 301-7 | month = | year = | doi = 10.2350/12-12-1287-CR.1 | PMID = 23495723 }}</ref>
*Young children.<ref>{{Cite journal | last1 = Park | first1 = JY. | last2 = Kim | first2 = E. | last3 = Kim | first3 = DW. | last4 = Chang | first4 = HW. | last5 = Kim | first5 = SP. | title = Cribriform neuroepithelial tumor in the third ventricle: a case report and literature review. | journal = Neuropathology | volume = 32 | issue = 5 | pages = 570-6 | month = Oct | year = 2012 | doi = 10.1111/j.1440-1789.2011.01293.x | PMID = 22239490 }}</ref>
*Small undifferentiated cells arranged in cribriform strands and trabeculae of varying thickness.
*MAP2+ve, Synaptophysin+ve, CK+/-ve. MIB-1: 30%.
*INI-1 loss, but no rhabdoid features and good prognosis.
*Stable genomic profile.<ref>{{Cite journal | last1 = Gessi | first1 = M. | last2 = Japp | first2 = AS. | last3 = Dreschmann | first3 = V. | last4 = Zur Mühlen | first4 = A. | last5 = Goschzik | first5 = T. | last6 = Dörner | first6 = E. | last7 = Pietsch | first7 = T. | title = High-Resolution Genomic Analysis of Cribriform Neuroepithelial Tumors of the Central Nervous System. | journal = J Neuropathol Exp Neurol | volume = 74 | issue = 10 | pages = 970-4 | month = Oct | year = 2015 | doi = 10.1097/NEN.0000000000000239 | PMID = 26352987 }}</ref>

==Neuronal and mixed neuronal/glial tumours==
* [[Desmoplastic infantile astrocytoma]] / ganglioglioma (DIA/DIG)
* [[Dysembryoplastic neuroepithelial tumour]]
* [[Central Neurocytoma]] / Extraventricular [[neurocytoma]]
* Cerebellar liponeurocytoma
* [[Papillary glioneuronal tumour]] (PGNT)
* [[Rosette-forming glioneuronal tumour of the fourth ventricle]] (RGNT)
* Gangliocytoma / Ganglioglioma
* Dysplastic ganglioglioma of the cerebellum ([[Lhermitte-Duclos disease]])
* [[Paraganglioma]]

===Desmoplastic infantile astrocytoma / Desmoplastic infantile ganglioglioma===
* Abbreviated ''DIA'' or ''DIG''.
* ICD-O code: 9412/1
* Large, superficial, cystic tumor of the infancy.
* Biologic course corresponds to WHO grade I.
* Very rare, included in the WHO since 1993.
* Prominent desmoplastic stroma.
* Astrocytic cells within stroma.
**GFAP+.
**MIB-1 usu. 1%.
* Frequent BRAF V600E or V600D mutations.<ref>{{Cite journal | last1 = Wang | first1 = AC. | last2 = Jones | first2 = DTW. | last3 = Abecassis | first3 = IJ. | last4 = Cole | first4 = BL. | last5 = Leary | first5 = SES. | last6 = Lockwood | first6 = CM. | last7 = Chavez | first7 = L. | last8 = Capper | first8 = D. | last9 = Korshunov | first9 = A. | title = Desmoplastic Infantile Ganglioglioma/Astrocytoma (DIG/DIA) are Distinct Entities with Frequent BRAFV600 Mutations. | journal = Mol Cancer Res | volume = | issue = | pages = | month = Jul | year = 2018 | doi = 10.1158/1541-7786.MCR-17-0507 | PMID = 30006355 }}</ref>
*Single case with BRAF indel or BRAF fusion.
<gallery>
File:DIG-histology.jpg | Histopathology of DIG (HE stain)
File:DIG-histology2.jpg | Prominent ganglioid cells in DIG (HE stain)
</gallery>

===Cerebellar liponeurocytoma===
* Previously called ''lipomatous medulloblastoma'' (name changed in WHO 2000).
* Mean age: 50 years.
* As the name states: A tumour of the cerebellum.
** But cases outside cerebellum reported that would qualify.<ref>{{Cite journal | last1 = Gupta | first1 = K. | last2 = Salunke | first2 = P. | last3 = Kalra | first3 = I. | last4 = Vasishta | first4 = RK. | title = Central liponeurocytoma: case report and review of literature. | journal = Clin Neuropathol | volume = 30 | issue = 2 | pages = 80-5 | month = | year = | doi = | PMID = 21329617 }}</ref>
* WHO grade II <ref>{{Cite journal | last1 = Nishimoto | first1 = T. | last2 = Kaya | first2 = B. | title = Cerebellar liponeurocytoma. | journal = Arch Pathol Lab Med | volume = 136 | issue = 8 | pages = 965-9 | month = Aug | year = 2012 | doi = 10.5858/arpa.2011-0337-RS | PMID = 22849747 }}</ref> (upgraded from WHO grade I in 2007)<ref>{{Cite journal | last1 = Brat | first1 = DJ. | last2 = Parisi | first2 = JE. | last3 = Kleinschmidt-DeMasters | first3 = BK. | last4 = Yachnis | first4 = AT. | last5 = Montine | first5 = TJ. | last6 = Boyer | first6 = PJ. | last7 = Powell | first7 = SZ. | last8 = Prayson | first8 = RA. | last9 = McLendon | first9 = RE. | title = Surgical neuropathology update: a review of changes introduced by the WHO classification of tumours of the central nervous system, 4th edition. | journal = Arch Pathol Lab Med | volume = 132 | issue = 6 | pages = 993-1007 | month = Jun | year = 2008 | doi = 10.1043/1543-2165(2008)132[993:SNUARO]2.0.CO;2 | PMID = 18517285 }}</ref>
*ICD-O code: 9506/1

====Histo====
* Advanced neuronal and lipomatous differentiation.
* Neurocytes: round to oval nuclei with clear cytoplasm.
* Quite cellular.
* Mitoses almost absent.

====IHC====
* [[GFAP]] +/-ve (focal).
* [[MAP2]] +ve.
* Synaptophysin +ve.
* NeuN +ve.
* MIB-1: usu 1-3%.

====Molecular====
* Distinct methylation profile.
* Recurent losses on 2p and Chr. 14.<ref>{{Cite journal | last1 = Capper | first1 = D. | last2 = Stichel | first2 = D. | last3 = Sahm | first3 = F. | last4 = Jones | first4 = DTW. | last5 = Schrimpf | first5 = D. | last6 = Sill | first6 = M. | last7 = Schmid | first7 = S. | last8 = Hovestadt | first8 = V. | last9 = Reuss | first9 = DE. | title = Practical implementation of DNA methylation and copy-number-based CNS tumor diagnostics: the Heidelberg experience. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Jul | year = 2018 | doi = 10.1007/s00401-018-1879-y | PMID = 29967940 }}</ref>

<gallery>
File:Cerebellar liponeurocytoma.jpg | Liponeurocytoma, HE (WC/Marvin101).
File:Liponeurocytoma Synaptophysin.jpg | Liponeurocytoma, Synapto (WC/Marvin101).
File:Cerebellar Liponeurocytoma HE.jpg | Liponeurocytoma, HE (WC/jensflorian).
File:Cerebellar Liponeurocytoma Synaptophysin.jpg | Liponeurocytoma, Synapto (WC/jensflorian).
</gallery>

====DDx====
* [[Medulloblastoma]]
* [[Neurocytoma]]

===Gangliocytoma===
* Grade I WHO neuronal tumour.
** ICD-O code: 9492/0
* Groups of irregular large neurons.
* Non-neoplastic, reticulin-rich glial stroma.

===Ganglioglioma===
:'''Not''' to be confused with ''[[ganglioneuroma]]''.
====General====
*Gangliolioma: Grade I WHO mixed neuronal-glial tumour (ICD-O code: 9505/1).
*Anaplastic ganglioglioma: Grade III (ICD-O: 9505/3)
*Rare (approx. 0.5% of all CNS tumors).
*Usu. temporal lobe.
*Predominantly children (mean age: 9 years).
*Recognized as a cause of [[epilepsy]].<ref name=pmid12125968>{{Cite journal | last1 = Im | first1 = SH. | last2 = Chung | first2 = CK. | last3 = Cho | first3 = BK. | last4 = Lee | first4 = SK. | title = Supratentorial ganglioglioma and epilepsy: postoperative seizure outcome. | journal = J Neurooncol | volume = 57 | issue = 1 | pages = 59-66 | month = Mar | year = 2002 | doi = | PMID = 12125968 }}</ref>
*Favourable prognosis (survival rates up to 97%)
**Insufficient data für anaplastic ganglioglioma.

====Macroscopic====
*Circumscribed lesion.
*Usu. contrast enhancing.
*Solid, but intracortical cysts may be present.
*Little mass effect.

====Microscopic====
Features:
*Dysplastic neurons.
**Out of regular architecture / abnormal location.
**Cytomegaly
**Clustering
**Binucleated (very occassionally).
*Atypical glia.
*Eosinophilic granular bodies.
*Calcification.
*Prominent capillary network.
*Lymphocytic cuffing.
*May contain some reticulin.
*Glial component may resemble:
**Fibrillary astrocytoma.
**Oligodendroglioma.
**Pilocytic astrocytoma.

Anaplastic ganglioglioma:
*Brisk mitotic activity
*Necrosis

====IHC====
*Neurons:
**[[MAP2]] +ve
**Synaptophysin +ve
** Neurofilament +ve
*Glia:
**CD34+/-ve
*BRAF V600E +ve (approx. 25%, mainly ganglion cells).

====Molecular====
*BRAF V600E-mutated(approx. 25%).
*IDH1/2 wt.
*No 1p/19q codeletion.
*Usu. Chr. 7 gain.
*CDKN2A deletions in anaplastic ganglioglioma.

====DDx:====
*[[DNT]].
*[[Oligodendroglioma]].
*Trapped cortical neurons in diffuse astrocytoma.
*Papillary glioneuronal tumor.
*Dysembryoplastic neuroepithelial tumor.

====Images====
<gallery>
File:Ganglioglioma lymphocytic cuffing PAS.jpg | Lymphocytic cuffing in ganglioglioma (WC/jensflorian)
File:Ganglioglioma calcification.jpg | Calcification in ganglioglioma (WC/jensflorian)
File:Ganglioglioma Cd34 x200.jpg | CD34 immunostain in ganglioglioma (WC/jensflorian)
File:Anaplastic ganglioglioma HE.jpg | Pleomorphic ganglion cells in ganglioglioma (WC/jensflorian)
</gallery>
*[http://path.upmc.edu/cases/case142.html Ganglioglioma - case 1 (upmc.edu)].
*[http://path.upmc.edu/cases/case282.html Ganglioglioma - case 2 (upmc.edu)].

===Lhermitte-Duclos disease===
*Abbreviated ''LDD''.
*[[AKA]] ''dysplastic cerebellar gangliocytoma''.<ref name=pmid20060133>{{Cite journal | last1 = Yağci-Küpeli | first1 = B. | last2 = Oguz | first2 = KK. | last3 = Bilen | first3 = MA. | last4 = Yalçin | first4 = B. | last5 = Akalan | first5 = N. | last6 = Büyükpamukçu | first6 = M. | title = An unusual cause of posterior fossa mass: Lhermitte-Duclos disease. | journal = J Neurol Sci | volume = 290 | issue = 1-2 | pages = 138-41 | month = Mar | year = 2010 | doi = 10.1016/j.jns.2009.12.010 | PMID = 20060133 }}</ref>
*[[AKA]] ''dysplastic gangliocytoma of the cerebellum''.
{{Main|Lhermitte-Duclos disease}}
<gallery>
File:Dysplastic_gangliocytoma_lhermitte_duclos.jpg | Dysplastic gangliocytoma (low mag).
</gallery>

===Papillary glioneuronal tumour===
* Abbreviated ''PGNT''.
* A benign, supratentorial tumor of childhood.
** Biologic course corresponds to WHO grade I.
** Before WHO 2000, considered a [[Ganglioglioma]] variant.
*Prominent pseudopapillary architecture.
*Neurocytes to medium-sized ganglion cells.
*GFAP+ core, GFAP- layer
*Rosenthal fibers, Eosinophilic Granular bodies and lymphocytic cuffing may be present.
<gallery>
File:PGNT_HE_stain.jpg | PGNT (HE) (WC/jensflorian)
</gallery>

===Rosette-forming glioneuronal tumour of the fourth ventricle===
* Abbreviated ''RGNT''.
* Provisional ICD-O code: 9509/1
* A rare benign infratentorial tumour of the midline of children and adults.
* Biologic course corresponds to WHO grade I.
* Glial component corresponds to [[pilocytic astrocytoma]].
* Neurocytic rosettes.
* Eosinopil fibrillary cores / pseudorosettes.
* GFAP+ in fibrillary areas, Syn+ in rosettes.
* Neurocytic cells: MAP2+
* MIB-1 usu. below 3%.
<gallery>
File:Histology RGNT HE.jpg | RGNT, HE stain (WC/jensflorian).
File:RGNT HE 2.jpg | RGNT, higher magnification (WC/jensflorian).
</gallery>

===Polymorphous low-grade tumor of the young (PLNTY)===
* [[Pediatric-type diffuse low-grade glioma#Diffuse low-grade glioma, MAPK pathway-altered|Polymorphous low-grade tumor of the young (PLNTY)]]

==Pineal tumours==
{{Main|Pineal gland}}

* [[Pineocytoma]]
* [[Pineal parenchymal tumour of intermediate differentiation]]
* [[Pineoblastoma]]
* [[Papillary tumour of the pineal region]]

==Embryonal tumours==
* [[Atypical teratoid/rhabdoid tumour]] (AT/RT) or (AT-RT)
* [[Medulloblastoma]]
* [[Primitive neuroectodermal tumour]] (PNET)
* [[Embryonal tumour with abundant neuropil and true rosettes]] (ETANTR)

DDx:
* [[Ewing sarcoma]]
* [[Sarcoma with CIC-rearrangement]]

==Peripheral nerve sheath tumours==
{{Main|Peripheral nerve sheath tumours}}
A classification:<ref name=pmid17893219>{{cite journal |author=Wippold FJ, Lubner M, Perrin RJ, Lämmle M, Perry A |title=Neuropathology for the neuroradiologist: Antoni A and Antoni B tissue patterns |journal=AJNR Am J Neuroradiol |volume=28 |issue=9 |pages=1633–8 |year=2007 |month=October |pmid=17893219 |doi=10.3174/ajnr.A0682 |url=http://www.ajnr.org/cgi/reprint/28/9/1633}}</ref>
'''Benign:'''
*[[Schwannoma]].
*[[Neurofibroma]].
*[[Perineurioma]].
*Ganglioneuroma.
**[[Traumatic neuroma]].
'''Malignant:'''
*[[Malignant peripheral nerve sheath tumour]] (MPNST).

===Ganglioneuroma===
:'''Not''' to be confused with ''[[ganglioglioma]]''.
*[[AKA]] ganglioma.<ref>URL: [http://medical-dictionary.thefreedictionary.com/ganglioma http://medical-dictionary.thefreedictionary.com/ganglioma]. Accessed on: 8 November 2010.</ref>
{{Main|Ganglioneuroma}}

==Meningioma==
{{Main|Meningioma}}

==Chordoma==
{{Main|Chordoma}}

==Hemangioblastoma==
{{Main|Hemangioblastoma}}

==CNS lymphoma==
Classification:
*Primary CNS lymphoma.
*Non-primary CNS lymphoma - see ''[[lymphoma]]'' article.

===General - primary CNS===
*Classically periventicular distribution.
*Usually large B cell; can be considered a type of [[diffuse large B cell lymphoma]] (DLBCL).
**Prognosis of CNS (DLBCL) lymphomas worse than nodal (non-CNS) DLBCL.<ref name=pmid19925562>{{cite journal |author=Raoux D, Duband S, Forest F, ''et al.'' |title=Primary central nervous system lymphoma: Immunohistochemical profile and prognostic significance |journal=Neuropathology |volume=30 |issue=3 |pages=232–40 |year=2010 |month=June |pmid=19925562 |doi=10.1111/j.1440-1789.2009.01074.x |url=}}</ref>

===Microscopic===
Features:
*Large cell lymphoma.
**Size = 2x diameter normal lymphocyte.
**Nucleolus - common.
*Perivascular clustering.

====Images====
www:
*[http://frontalcortex.com/?page=image&topic=1&qid=1237 CNS lymphoma (frontalcortex.com)].
*[http://path.upmc.edu/cases/case403.html Primary CNS lymphoma - several images (upmc.edu)].
<gallery>
Image:Primary CNS lymphoma - low mag.jpg | CNS lymphoma - low mag. (WC)
Image:Primary CNS lymphoma - intermed mag.jpg | CNS lymphoma - intermed. mag. (WC)
Image:Primary CNS lymphoma - high mag.jpg | CNS lymphoma - high mag. (WC)
Image:Primary CNS lymphoma - very high mag.jpg | CNS lymphoma - very high mag. (WC)
</gallery>
<gallery>
Image: CNS lymphoma (1) B-cell type.jpg | CNS lymphoma. (WC/KGH)
Image: CNS lymphoma (2) B-cell type.jpg | CNS lymphoma. (WC/KGH)
</gallery>

===IHC===
Can be subclassified in ''GCB (germinal centre B-cell-like)'' and ''non-GCB'' by CD10, Bcl-6, MUM1/IRF-4, and Bcl-2.<ref name=pmid19925562/>

Common pattern:
*[[CD20]] +ve - key stain.
*CD3 -ve.
*Ki-67 ~40%.
*Bcl-6 +ve.
*Bcl-1 -ve.

==Ganglioneuroblastoma==
{{Main|Neuroblastoma}}
===General===
*Uncommon.
*Part of the ''neuroblastic tumours'' group which includes:<ref name=pmid10421272>{{cite journal |author=Shimada H, Ambros IM, Dehner LP, Hata J, Joshi VV, Roald B |title=Terminology and morphologic criteria of neuroblastic tumors: recommendations by the International Neuroblastoma Pathology Committee |journal=Cancer |volume=86 |issue=2 |pages=349–63 |year=1999 |month=July |pmid=10421272 |doi= |url=}}</ref>
**[[Ganglioneuroma]] (benign).
**Ganglioneuroblastoma (intermediate).
**[[Neuroblastoma]] (aggressive).

===Microscopic===
Features:
*Ganglion-like cells with a prominent nucleolus.
*Small undifferentiated cells with scant cytoplasm.
<gallery>
Image:Adrenal Ganglioneuroblastoma LP CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - Low power (SKB)
Image:Adrenal Ganglioneuroblastoma MP CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - Medium power (SKB)
Image:Adrenal Ganglioneuroblastoma HP CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - High power (SKB)
Image:Adrenal Ganglioneuroblastoma HP3 CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - High power (SKB)
Image:Adrenal Ganglioneuroblastoma HP2 CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - High power (SKB)
</gallery>
Images:
*[http://path.upmc.edu/cases/case530.html Ganglioneuroblastoma - several images (upmc.edu)].

===IHC===
*NSE +ve -- small cells.

==Lesions of the sella turcica==
{{Main|Pituitary gland}}
Lesions of the sella turcica, the pituitary gland environs, is a topic for it self. The differential diagnosis for lesions in this area includes:
*[[Pituitary adenoma]].
*[[Craniopharyngioma]].
*[[Rathke cleft cyst]].
*[[Germ cell tumour]].
*[[Meningioma]].
*[[Pilomyxoid astrocytoma]] - in children.

==See also==
*[[Neuropathology]].
*[[Muscle biopsy]].

==References==
{{reflist|2}}

==External links==
*[http://www.neuropathologyweb.org/ Neuropathology (neuropathologyweb.org)].
*[http://www.pathology.vcu.edu/WirSelfInst/tumor-1.html Neuropathology Mini-Course (pathology.vcu.edu)].
*[http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html Neuropathology Mini-Course (pathology.vcu.edu)].

[[Category:Neuropathology]]

Neuropathology tumours

2022-04-14T09:01:43Z

Jensflorian: /* Infiltrative astrocytomas */ typo

[[Image:Gemistocytic Astrocytoma 003.jpg|thumb|right|A brain stem [[astrocytoma]]. (WC)]]
The article covers '''tumours in neuropathology'''. Tumours are a large part of [[neuropathology]]. [[Cytopathology]] of CNS tumours is dealt with in the article ''[[CNS cytopathology]]''.

There are separate articles for ''[[peripheral nerve sheath tumours]]'' and ''[[pituitary gland|pituitary/peri-pituitary lesions]]''.

==Brain tumours - overview==
===Alphabetical===
For overview see [[:Category:Neuropathology_tumours|here]]

===By age group===
====Adult====
Four most common types of brain tumours:<ref>[http://neurosurgery.mgh.harvard.edu/abta/primer.htm http://neurosurgery.mgh.harvard.edu/abta/primer.htm]</ref>
# Metastatic brain tumours (barely edges out primary tumours)
#*[[Lung cancer|Lung]] (most common).
#*[[Invasive breast cancer|Breast]].
#*[[Melanoma]].
#*[[Renal cell carcinoma]] (RCC).
# [[Glioblastoma]], IDH-wildtype.
# [[Astrocytoma, IDH-mutant]].
# [[Meningioma]].

====Children====
# [[Pilocytic astrocytoma]].
# [[Medulloblastoma]].
# [[Ependymoma]].
# Pontine glioma, often [[Diffuse midline glioma, H3 K27-altered]].

===By location===
Certain tumours like to hang-out at certain places:<ref>URL: [http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/files/4ce563fb7e8e48fc9ed8b42e296a7747.gif http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/files/4ce563fb7e8e48fc9ed8b42e296a7747.gif] and [http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html]. Accessed on: 2 November 2010.</ref>
====Cerebrum====
*Cortical based - [[oligodendroglioma]].
*Grey-white junction - metastases.
*White matter - astrocytoma, [[glioblastoma]].
*Periventricular - CNS lymphoma.
*Cystic - [[ganglioglioma]], [[pilocytic astrocytoma]], [[pleomorphic xanthoastrocytoma]].
====Cerebellum====
*Midline/central - [[medulloblastoma]].
*Cystic lesion - pilocytic astrocytoma (younger individual), [[hemangioblastoma]] (older individual).
*Solid lesion (older individual) - [[metastasis]].
====Sella turcica====
* [[Pituitary adenoma]].
* [[Craniopharyngioma]].
less common:
* [[Pituicytoma]].
* [[Granular cell tumour]].
* [[Germinoma]].
* [[Chordoma]]
* Rathke cleft cyst.
* Hypophysitis.
* Xanthogranuloma.
====Spinal cord====
*[[Ependymoma]]
*[[Glioblastoma]]
*[[Meningioma]]
*Carcinoma metastasis
*[[Hemangioblastoma]]
====Filum terminale====
*[[Meningioma]].
*[[Myxopapillary ependymoma]].
*[[Neurofibroma]].
*[[Schwannoma]].
*[[Paraganglioma]].
====Meninges====
* [[Meningioma]].
* [[Solitary fibrous tumour]] / Hemangiopericytoma.
* [[Hemangioblastoma]].
less common:
* [[Melanoma]] / Melanocytoma.
* Lymphoproliferative diseases.
* [[Sarcoidosis]]
* [[Arachnoid cyst]].
* Disseminated oligodendroglial-like leptomeningeal tumour.
* Desmoplastic infantile astrocytoma / ganglioglioma.
* Meningioangiomatosis.
* Calcifying pseudoneoplasm.
====Skull====
* [[Fibrous dysplasia]].
* [[Paget disease]].
* [[Histiocytosis]].
* [[Hemangioma]].
* [[Aneurysmal bone cyst]].
* [[Plasma_cell_neoplasms#Multiple_myeloma|Multiple myeloma]].
====Skull base / Cerebellopontine angle====
* [[Schwannoma]].
* [[Meningioma]].
* [[Dermoid cyst]] / epidermoid cyst.
less common:
* [[Ependymoma]].
* [[Choroid plexus papilloma]].
* [[Glomus tumour]].
* [[Chordoma]].
* [[Chondrosarcoma]].
* [[Olfactory neuroblastoma]].
* [[Endolymphatic sac tumour]].

===Cystic tumours===
DDx:<ref>URL: [http://path.upmc.edu/cases/case320/dx.html http://path.upmc.edu/cases/case320/dx.html]. Accessed on: 14 January 2012.</ref>
*[[Pilocytic astrocytoma]].
*[[Pleomorphic xanthoastrocytoma]].
*[[Ganglioglioma]].
*[[Hemangioblastoma]].
*[[Craniopharyngioma]].<ref>URL: [http://www.pathologyoutlines.com/Cnstumor.html#cystsgeneral http://www.pathologyoutlines.com/Cnstumor.html#cystsgeneral]. Accessed on: 14 January 2012.</ref>

===Primary versus secondary===
*[[AKA]] (primary) brain tumour versus metastatic cancer.
====Primary====
[[Glioma|Glial tumours]]:
*Cytoplasmic processes - '''key feature'''.
**Best seen at highest magnification - usu. ~1 micrometer.
**Processes may branch.
*Ill-defined border/blend with the surrounding brain.

[[Meningioma]]:
*Lesion often dura-based.
*Mesenchymal tumor (often contains collagen).

[[Lymphoma]]:
*Primary CNS Lymphoma (PCNSL) is usu. a diffuse large B-cell lymphoma.
*Large (lymphoid) cells, ergo usu. not a difficult diagnosis.
**~2x size of resting lymphocyte, nucleoli.
*Lesion predominantly perivascular.

====Secondary====
*Carcinomas:
**Well-demarcated border between brain and lesion - '''key feature'''.
**No cytoplasmic processes.
**Usu. have nuclear atypia of malignancy.
**Nuclei often ~3-4x the size of a [[RBC]].
**+/-Glandular arrangement.
**+/-Nucleoli.
*Melanoma.
*Secondary Lymphoma.
*Sarcomas (rare).

===By growth pattern===
====Infiltrative astrocytomas====
*[[Astrocytoma, IDH-mutant]].
*[[Glioblastoma]], IDH-wildtype.

====Non-infiltrative astrocytomas====
**[[Pilocytic astrocytoma]]
**[[Pleomorphic xanthoastrocytoma]]
**[[Subependymal giant cell astrocytoma]].

Notes:
*Glial vs. non-glial tumours:
**Glial: "blends into brain"/gradual transition to non-tumour brain.
**Non-glial: no radiating glial processes.
*Rosenthal fibres within the tumour... often seen in [[pilocytic astrocytoma]].
**Rosenthal fibres may be seen around a (very) slow growing tumour and represent a reactive process.
*Inflammatory cells and macrophages should prompt consideration of an alternate diagnosis (e.g. [[cerebral infarct]], [[multiple sclerosis]]) - esp. if this is a primary lesion.<ref>URL: [http://path.upmc.edu/cases/case79/dx.html http://path.upmc.edu/cases/case79/dx.html]. Accessed on: 2 January 2012.</ref>

====Grading====
Nuclear pleomorphism present:
*At least grade II (diffuse astrocytoma).

Mitotic figures present:
*At least grade III (anaplastic astrocytoma).

Microvascular proliferation ''or'' necrosis with pseudopalisading tumour cells:
*Grade IV (glioblastoma [[AKA]] glioblastoma multiforme).

Notes:
*Pseudopalisading tumour cells = high tumour cell density adjacent to regions of necrosis; palisade = a fence of poles forming a defensive barrier or fortification.
*WHO Grading is currently based on expected biologiocal behaviour without treatment.
**Grading does not reflect molecular divergent groups within a tumor class or response to therapy (Currently controversies in grading for IDH-mutant astrocytoma vs. IDH-wildtype astrocytoma).<ref>{{Cite journal | last1 = Louis | first1 = DN. | last2 = von Deimling | first2 = A. | title = Grading of diffuse astrocytic gliomas: Broders, Kernohan, Zülch, the WHO… and Shakespeare. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Aug | year = 2017 | doi = 10.1007/s00401-017-1765-z | PMID = 28801693 }}</ref>

====Images====
Glioblastoma:
<gallery>
Image:Glioblastoma_%281%29.jpg | Glioblastoma - pseudopalisading of tumour cells (WC)
Image:Glioblastoma_-_high_mag.jpg | Glioblastoma with fragment of near-normal white matter - high mag. (WC)
</gallery>
Anaplastic astrocytoma:
<gallery>
Image:Anaplastic_astrocytoma_-_very_high_mag_-_cropped.jpg | Anaplastic astrocytoma - very high mag. (WC)
Image:Anaplastic_astrocytoma_-_gfap_-_very_high_mag.jpg | Anaplastic astrocytoma - GFAP - very high mag. (WC)
</gallery>

===By IHC===
*GFAP - should stain cytoplasm of tumour cells and the perikaryon (nuclear membrane) of most [[Astrocytoma]]s.
*[[IDH-1]](R132H) (isocitrate dehydrogenase 1) in [[Astrocytoma, IDH-mutant]].<ref name=pmid19228619>{{cite journal |author=Yan H, Parsons DW, Jin G, ''et al.'' |title=IDH1 and IDH2 mutations in gliomas |journal=N. Engl. J. Med. |volume=360 |issue=8 |pages=765–73 |year=2009 |month=February |pmid=19228619 |pmc=2820383 |doi=10.1056/NEJMoa0808710 |url=}}</ref><ref name=pmid20975057>{{cite journal |author=Houillier C, Wang X, Kaloshi G, ''et al.'' |title=IDH1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas |journal=Neurology |volume=75 |issue=17 |pages=1560–6 |year=2010 |month=October |pmid=20975057 |doi=10.1212/WNL.0b013e3181f96282 |url=}}</ref>
*[[H3F3A|H3F3A K27M]] in [[Diffuse midline glioma, H3 K27-altered]].
*[[ATRX]] -ve in [[Astrocytoma, IDH-mutant]] or [[Diffuse hemispheric glioma, H3 G34-mutant]].
*[[CD20]] in PCNSL.
*Cytokeratins in Carcinoma brain metastases, Plexus choroid tumours, [[AT/RT]], [[Papillary tumour of the pineal region]], [[Craniopharyngioma]].
*[[EMA]] in [[Meningioma]] and carcinoma brain metastases.
*PrgR in [[Meningioma]] and carcinoma metastases.
*[[Synaptophysin]] in glioneuronal tumours and Pituitary adenoma and embryonal tumours.

===Common neuropathology tumours in a table===
{| class="wikitable"
|'''Type'''
|'''Key feature(s)'''
|'''Imaging'''
|'''History'''
|'''Notes'''
|'''IHC'''
|'''Images'''
|-
|Normal tissue
|cells regularly spaced, no nuc. atypia
|small lesion? / deep lesion?
|variable
|missed lesion?
|nil
|[[Image:Grey_matter_and_white_matter_-_very_high_mag.jpg |thumb|center|150px|Normal. (WC)]]
|-
|[[Reactive astrocytes]]
|astrocytes with well-demarcated eosinophilic cytoplasm, regular spacing, no nuc. atypia
|small lesion? / deep lesion?
|variable
|missed lesion / close to a lesion; non-specific pathologic process - need more tissue
|GFAP
|[[Image:Reactive_astrocytes_-_lfb_-_high_mag.jpg|thumb|center|150px|Reactive astrocytes. (WC)]]
|-
|[[Schwannoma]]
|cellular areas (Antoni A), paucicelluar areas (Antoni B), palisading of nuclei (Verocay bodies)
|extra-axial + intradural
|old or young
|need frozen section to Dx, DDx: [[meningioma]]
|S100, SOX10
|[[Image:Schwannoma_-_Antoni_A_and_B_-_very_high_mag.jpg|thumb|center|150px|Schwannoma. (WC)]]
|-
|[[Meningioma]]
|whorls, psammomatous calcs, nuclear inclusions
|extra-axial + intradural
|old or young
|may be diagnosed on smear, DDx: [[schwannoma]], choroid plexus
|EMA, PR, Ki-67
|[[Image:Meningioma_intermed_mag.jpg |thumb|center|150px|Meningioma. (WC)]]
|-
|[[Astrocytoma, IDH-mutant]] (CNS [[WHO]] grade 2 or grade 3)
|glial processes (esp. on smear), nuclear atypia (typical size var. ~3x, irreg. nuc. membrane, hyperchromasia), no Rosenthal fibres in the core of the lesion †, no microvascular proliferation, no necrosis
|often enhancing (suggests high grade), usu. supratentorial, usu. white matter
|usu. old, occ. young
|common
|IDH-1(R132H)+/-, GFAP+
| [[Image:Anaplastic_astrocytoma_-_very_high_mag_-_cropped.jpg | thumb| center| 150px|High-grade astrocytoma. (WC)]]
|-
|[[Glioblastoma]], IDH-wildtype (CNS [[WHO]] grade 4)
|glial processes (esp. on smear), nuclear atypia (typical size var. ~3x, irreg. nuc. membrane, hyperchromasia), no Rosenthal fibres in the core of the lesion †, microvascular proliferation or necrosis
|often enhancing (suggests high grade), usu. supratentorial, usu. white matter
|usu. old, occ. young
|very common, esp. glioblastoma
|IDH-1+/-, GFAP+
| [[Image:Glioblastoma (1).jpg | thumb| center| 150px|Glioblastoma. (WC)]]
|-
|[[Metastatic brain tumours|Metastasis]]
|sharp interface with brain, often glandular, +/-nucleoli, no glial processes
|often cerebellular, well-circumscribed
|usu. old
|often suspected to have metastatic disease
|[[TTF-1]], CK7, [[CK20]], BRST-2
|[[Image:Metastatic_adenocarcinoma_-_cerebellum_-_very_low_mag.jpg | thumb| center|150px |Metastasis. (WC)]]
|}
† Rosenthal fibres at the periphery of a lesion are a non-specific finding seen in chronic processes.

==Brain metastasis==
{{Main|Brain metastasis}}

===Molecular===
See also: [[Molecular_pathology_tests#Neuropathology|Molecular Neuropathology]]

==Gliomas==
{{Main|Glioma}}

Gliomas, glioneuronal tumours and neuronal tumours are often categorized together.

===Astrocytic tumours===
{{Main|Astrocytoma}}

* [[Astrocytoma]], IDH-mutant.
* [[Glioblastoma]], IDH-wildtype.
** [[Gliosarcoma]] (a glioblastoma subtype)

Features:<ref name=pmid>{{cite journal |author=Rong Y, Durden DL, Van Meir EG, Brat DJ |title='Pseudopalisading' necrosis in glioblastoma: a familiar morphologic feature that links vascular pathology, hypoxia, and angiogenesis |journal=J. Neuropathol. Exp. Neurol. |volume=65 |issue=6 |pages=529–39 |year=2006 |month=June |pmid=16783163 |doi= |url=}}</ref><ref>[http://dictionary.reference.com/browse/palisading http://dictionary.reference.com/browse/palisading]</ref>
*Glial processes - '''key feature'''.
**Thin stringy cytoplasmic processes - best seen at high power in less cellular areas.
*No Rosenthal fibres within the tumour itself.

Images:
*[http://moon.ouhsc.edu/kfung/jty1/opaq/PathQuiz/N0A002-PQ01-M.htm Endothelial proliferation in a GBM (ouhsc.edu)].
*[http://moon.ouhsc.edu/kfung/jty1/neurotest/Q05-Ans.htm Endothelial proliferation (ouhse.edu)].
*[http://path.upmc.edu/cases/case368.html Gemistocytic astrocytoma - several images (upmc.edu)].

Depreceated:
* Diffuse [[Astrocytoma]]
* [[Anaplastic astrocytoma]]
* [[Gliomatosis cerebri]]
* Spongioblastoma

===Oligodendroglial tumours===
* [[Oligodendroglioma]], IDH-mutant and 1p/19q codeleted.

Depreceated:
* Anaplastic oligodendroglioma
* [[Oligoastrocytoma]]
* Anaplastic oligoastrocytoma

===Pediatric-type diffuse high-grade glioma===
{{Main|Pediatric-type diffuse high-grade glioma}}
* [[Astrocytoma#Diffuse_midline_glioma.2C_H3_K27M_mutant|Diffuse midline glioma H3 K27-mutant]]

===Pediatric-type diffuse low-grade glioma===
{{Main|Pediatric-type diffuse low-grade glioma}}

===Circumscribed astrocytic gliomas===
* [[Pilocytic astrocytoma]] (PA)
** [[Pilomyxoid astrocytoma]] (PMA)
* [[Pleomorphic xanthoastrocytoma]] (PXA)
* [[Subependymal giant cell astrocytoma]] (SEGA)
* [[Neuropathology_tumours#Astroblastoma|Astroblastoma MN1-altered]].
* [[Neuropathology_tumours#Chordoid glioma of the third ventricl|Chordoid glioma]].

====Astroblastoma====
*No WHO grade yet.<ref>{{Ref WHOCNS|88}}</ref>
*Very rare superficial tumor of young age.<ref>{{Cite journal | last1 = Narayan | first1 = S. | last2 = Kapoor | first2 = A. | last3 = Singhal | first3 = MK. | last4 = Jakhar | first4 = SL. | last5 = Bagri | first5 = PK. | last6 = Rajput | first6 = PS. | last7 = Kumar | first7 = HS. | title = Astroblastoma of cerebrum: A rare case report and review of literature. | journal = J Cancer Res Ther | volume = 11 | issue = 3 | pages = 667 | month = | year = | doi = 10.4103/0973-1482.140800 | PMID = 26458709 }}</ref>
*Large, cystic. Pushing margin towards CNS.
*Vasocentric growth, plump cells with absence of fibrillary pattern.
*GFAP+ve, Synaptohysin-ve, Olig-2-ve, focally EMA/panCK+ve. MIB-1: 1-18 %.
*Molecular profile overlaps with classical [[CNS-PNET]].
**Gene fusions invoving meningioma gene (MN1)<ref>{{Cite journal | last1 = Sturm | first1 = D. | last2 = Orr | first2 = BA. | last3 = Toprak | first3 = UH. | last4 = Hovestadt | first4 = V. | last5 = Jones | first5 = DT. | last6 = Capper | first6 = D. | last7 = Sill | first7 = M. | last8 = Buchhalter | first8 = I. | last9 = Northcott | first9 = PA. | title = New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs. | journal = Cell | volume = 164 | issue = 5 | pages = 1060-72 | month = Feb | year = 2016 | doi = 10.1016/j.cell.2016.01.015 | PMID = 26919435 }}</ref>

<gallery>
File:Astroblastoma_HE_Specimen.jpg | HE. (WC/jensflorian)
File:Astroblastoma_HE_papillae.jpg | HE. (WC/jensflorian)
File:Astroblastoma.jpg | Astroblastoma (AFIP)
</gallery>

====Chordoid glioma of the third ventricle====
* WHO grade II.
* Slowly growing, non-invasive, in adults.
* Clusters of epithelioid cells in mucinous stroma.
* Lymphocytic infiltrates, adjacent Rosenthal fibers.
* Fibrosis may be present.
* Few mitoses.
* [[GFAP]]+ve, MIB-1 1-3%.
* [[TTF-1]]+ve.
* CD34+ve.
* [[IDH-1]]-ve, [[p53]]-ve.
* PRKCA D463H mutations.<ref>{{Cite journal | last1 = Goode | first1 = B. | last2 = Mondal | first2 = G. | last3 = Hyun | first3 = M. | last4 = Ruiz | first4 = DG. | last5 = Lin | first5 = YH. | last6 = Van Ziffle | first6 = J. | last7 = Joseph | first7 = NM. | last8 = Onodera | first8 = C. | last9 = Talevich | first9 = E. | title = A recurrent kinase domain mutation in PRKCA defines chordoid glioma of the third ventricle. | journal = Nat Commun | volume = 9 | issue = 1 | pages = 810 | month = 02 | year = 2018 | doi = 10.1038/s41467-018-02826-8 | PMID = 29476136 }}</ref>

<gallery>
File:NP op 20201028 009.jpg | Chordoid Glioma. (WC/jensflorian)
</gallery>

===Ependymal tumours===
* [[Subependymoma]]
* [[Myxopapillary Ependymoma]]
* [[Ependymoma]]
* Anaplastic ependymoma

==Choroid plexus tumours==
* [[Choroid plexus papilloma]]
* Atypical choroid plexus papilloma
* [[Choroid plexus carcinoma]]

==Other neuroepithelial tumours==
* [[Neuropathology_tumours#Cribiform_neuroepithelial_tumour|Cribifiorm neuroepithelial tumour]].

===Cribiform neuroepithelial tumour===
AKA: '''CRINET'''.
*Not listed in the current WHO classification.
*First description in 2009.<ref>{{Cite journal | last1 = Hasselblatt | first1 = M. | last2 = Oyen | first2 = F. | last3 = Gesk | first3 = S. | last4 = Kordes | first4 = U. | last5 = Wrede | first5 = B. | last6 = Bergmann | first6 = M. | last7 = Schmid | first7 = H. | last8 = Frühwald | first8 = MC. | last9 = Schneppenheim | first9 = R. | title = Cribriform neuroepithelial tumor (CRINET): a nonrhabdoid ventricular tumor with INI1 loss and relatively favorable prognosis. | journal = J Neuropathol Exp Neurol | volume = 68 | issue = 12 | pages = 1249-55 | month = Dec | year = 2009 | doi = 10.1097/NEN.0b013e3181c06a51 | PMID = 19915490 }}</ref>
*Around ventricles.<ref>{{Cite journal | last1 = Arnold | first1 = MA. | last2 = Stallings-Archer | first2 = K. | last3 = Marlin | first3 = E. | last4 = Grondin | first4 = R. | last5 = Olshefski | first5 = R. | last6 = Biegel | first6 = JA. | last7 = Pierson | first7 = CR. | title = Cribriform neuroepithelial tumor arising in the lateral ventricle. | journal = Pediatr Dev Pathol | volume = 16 | issue = 4 | pages = 301-7 | month = | year = | doi = 10.2350/12-12-1287-CR.1 | PMID = 23495723 }}</ref>
*Young children.<ref>{{Cite journal | last1 = Park | first1 = JY. | last2 = Kim | first2 = E. | last3 = Kim | first3 = DW. | last4 = Chang | first4 = HW. | last5 = Kim | first5 = SP. | title = Cribriform neuroepithelial tumor in the third ventricle: a case report and literature review. | journal = Neuropathology | volume = 32 | issue = 5 | pages = 570-6 | month = Oct | year = 2012 | doi = 10.1111/j.1440-1789.2011.01293.x | PMID = 22239490 }}</ref>
*Small undifferentiated cells arranged in cribriform strands and trabeculae of varying thickness.
*MAP2+ve, Synaptophysin+ve, CK+/-ve. MIB-1: 30%.
*INI-1 loss, but no rhabdoid features and good prognosis.
*Stable genomic profile.<ref>{{Cite journal | last1 = Gessi | first1 = M. | last2 = Japp | first2 = AS. | last3 = Dreschmann | first3 = V. | last4 = Zur Mühlen | first4 = A. | last5 = Goschzik | first5 = T. | last6 = Dörner | first6 = E. | last7 = Pietsch | first7 = T. | title = High-Resolution Genomic Analysis of Cribriform Neuroepithelial Tumors of the Central Nervous System. | journal = J Neuropathol Exp Neurol | volume = 74 | issue = 10 | pages = 970-4 | month = Oct | year = 2015 | doi = 10.1097/NEN.0000000000000239 | PMID = 26352987 }}</ref>

==Neuronal and mixed neuronal/glial tumours==
* [[Desmoplastic infantile astrocytoma]] / ganglioglioma (DIA/DIG)
* [[Dysembryoplastic neuroepithelial tumour]]
* [[Central Neurocytoma]] / Extraventricular [[neurocytoma]]
* Cerebellar liponeurocytoma
* [[Papillary glioneuronal tumour]] (PGNT)
* [[Rosette-forming glioneuronal tumour of the fourth ventricle]] (RGNT)
* Gangliocytoma / Ganglioglioma
* Dysplastic ganglioglioma of the cerebellum ([[Lhermitte-Duclos disease]])
* [[Paraganglioma]]

===Desmoplastic infantile astrocytoma / Desmoplastic infantile ganglioglioma===
* Abbreviated ''DIA'' or ''DIG''.
* ICD-O code: 9412/1
* Large, superficial, cystic tumor of the infancy.
* Biologic course corresponds to WHO grade I.
* Very rare, included in the WHO since 1993.
* Prominent desmoplastic stroma.
* Astrocytic cells within stroma.
**GFAP+.
**MIB-1 usu. 1%.
* Frequent BRAF V600E or V600D mutations.<ref>{{Cite journal | last1 = Wang | first1 = AC. | last2 = Jones | first2 = DTW. | last3 = Abecassis | first3 = IJ. | last4 = Cole | first4 = BL. | last5 = Leary | first5 = SES. | last6 = Lockwood | first6 = CM. | last7 = Chavez | first7 = L. | last8 = Capper | first8 = D. | last9 = Korshunov | first9 = A. | title = Desmoplastic Infantile Ganglioglioma/Astrocytoma (DIG/DIA) are Distinct Entities with Frequent BRAFV600 Mutations. | journal = Mol Cancer Res | volume = | issue = | pages = | month = Jul | year = 2018 | doi = 10.1158/1541-7786.MCR-17-0507 | PMID = 30006355 }}</ref>
*Single case with BRAF indel or BRAF fusion.
<gallery>
File:DIG-histology.jpg | Histopathology of DIG (HE stain)
File:DIG-histology2.jpg | Prominent ganglioid cells in DIG (HE stain)
</gallery>

===Cerebellar liponeurocytoma===
* Previously called ''lipomatous medulloblastoma'' (name changed in WHO 2000).
* Mean age: 50 years.
* As the name states: A tumour of the cerebellum.
** But cases outside cerebellum reported that would qualify.<ref>{{Cite journal | last1 = Gupta | first1 = K. | last2 = Salunke | first2 = P. | last3 = Kalra | first3 = I. | last4 = Vasishta | first4 = RK. | title = Central liponeurocytoma: case report and review of literature. | journal = Clin Neuropathol | volume = 30 | issue = 2 | pages = 80-5 | month = | year = | doi = | PMID = 21329617 }}</ref>
* WHO grade II <ref>{{Cite journal | last1 = Nishimoto | first1 = T. | last2 = Kaya | first2 = B. | title = Cerebellar liponeurocytoma. | journal = Arch Pathol Lab Med | volume = 136 | issue = 8 | pages = 965-9 | month = Aug | year = 2012 | doi = 10.5858/arpa.2011-0337-RS | PMID = 22849747 }}</ref> (upgraded from WHO grade I in 2007)<ref>{{Cite journal | last1 = Brat | first1 = DJ. | last2 = Parisi | first2 = JE. | last3 = Kleinschmidt-DeMasters | first3 = BK. | last4 = Yachnis | first4 = AT. | last5 = Montine | first5 = TJ. | last6 = Boyer | first6 = PJ. | last7 = Powell | first7 = SZ. | last8 = Prayson | first8 = RA. | last9 = McLendon | first9 = RE. | title = Surgical neuropathology update: a review of changes introduced by the WHO classification of tumours of the central nervous system, 4th edition. | journal = Arch Pathol Lab Med | volume = 132 | issue = 6 | pages = 993-1007 | month = Jun | year = 2008 | doi = 10.1043/1543-2165(2008)132[993:SNUARO]2.0.CO;2 | PMID = 18517285 }}</ref>
*ICD-O code: 9506/1

====Histo====
* Advanced neuronal and lipomatous differentiation.
* Neurocytes: round to oval nuclei with clear cytoplasm.
* Quite cellular.
* Mitoses almost absent.

====IHC====
* [[GFAP]] +/-ve (focal).
* [[MAP2]] +ve.
* Synaptophysin +ve.
* NeuN +ve.
* MIB-1: usu 1-3%.

====Molecular====
* Distinct methylation profile.
* Recurent losses on 2p and Chr. 14.<ref>{{Cite journal | last1 = Capper | first1 = D. | last2 = Stichel | first2 = D. | last3 = Sahm | first3 = F. | last4 = Jones | first4 = DTW. | last5 = Schrimpf | first5 = D. | last6 = Sill | first6 = M. | last7 = Schmid | first7 = S. | last8 = Hovestadt | first8 = V. | last9 = Reuss | first9 = DE. | title = Practical implementation of DNA methylation and copy-number-based CNS tumor diagnostics: the Heidelberg experience. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Jul | year = 2018 | doi = 10.1007/s00401-018-1879-y | PMID = 29967940 }}</ref>

<gallery>
File:Cerebellar liponeurocytoma.jpg | Liponeurocytoma, HE (WC/Marvin101).
File:Liponeurocytoma Synaptophysin.jpg | Liponeurocytoma, Synapto (WC/Marvin101).
File:Cerebellar Liponeurocytoma HE.jpg | Liponeurocytoma, HE (WC/jensflorian).
File:Cerebellar Liponeurocytoma Synaptophysin.jpg | Liponeurocytoma, Synapto (WC/jensflorian).
</gallery>

====DDx====
* [[Medulloblastoma]]
* [[Neurocytoma]]

===Gangliocytoma===
* Grade I WHO neuronal tumour.
** ICD-O code: 9492/0
* Groups of irregular large neurons.
* Non-neoplastic, reticulin-rich glial stroma.

===Ganglioglioma===
:'''Not''' to be confused with ''[[ganglioneuroma]]''.
====General====
*Gangliolioma: Grade I WHO mixed neuronal-glial tumour (ICD-O code: 9505/1).
*Anaplastic ganglioglioma: Grade III (ICD-O: 9505/3)
*Rare (approx. 0.5% of all CNS tumors).
*Usu. temporal lobe.
*Predominantly children (mean age: 9 years).
*Recognized as a cause of [[epilepsy]].<ref name=pmid12125968>{{Cite journal | last1 = Im | first1 = SH. | last2 = Chung | first2 = CK. | last3 = Cho | first3 = BK. | last4 = Lee | first4 = SK. | title = Supratentorial ganglioglioma and epilepsy: postoperative seizure outcome. | journal = J Neurooncol | volume = 57 | issue = 1 | pages = 59-66 | month = Mar | year = 2002 | doi = | PMID = 12125968 }}</ref>
*Favourable prognosis (survival rates up to 97%)
**Insufficient data für anaplastic ganglioglioma.

====Macroscopic====
*Circumscribed lesion.
*Usu. contrast enhancing.
*Solid, but intracortical cysts may be present.
*Little mass effect.

====Microscopic====
Features:
*Dysplastic neurons.
**Out of regular architecture / abnormal location.
**Cytomegaly
**Clustering
**Binucleated (very occassionally).
*Atypical glia.
*Eosinophilic granular bodies.
*Calcification.
*Prominent capillary network.
*Lymphocytic cuffing.
*May contain some reticulin.
*Glial component may resemble:
**Fibrillary astrocytoma.
**Oligodendroglioma.
**Pilocytic astrocytoma.

Anaplastic ganglioglioma:
*Brisk mitotic activity
*Necrosis

====IHC====
*Neurons:
**[[MAP2]] +ve
**Synaptophysin +ve
** Neurofilament +ve
*Glia:
**CD34+/-ve
*BRAF V600E +ve (approx. 25%, mainly ganglion cells).

====Molecular====
*BRAF V600E-mutated(approx. 25%).
*IDH1/2 wt.
*No 1p/19q codeletion.
*Usu. Chr. 7 gain.
*CDKN2A deletions in anaplastic ganglioglioma.

====DDx:====
*[[DNT]].
*[[Oligodendroglioma]].
*Trapped cortical neurons in diffuse astrocytoma.
*Papillary glioneuronal tumor.
*Dysembryoplastic neuroepithelial tumor.

====Images====
<gallery>
File:Ganglioglioma lymphocytic cuffing PAS.jpg | Lymphocytic cuffing in ganglioglioma (WC/jensflorian)
File:Ganglioglioma calcification.jpg | Calcification in ganglioglioma (WC/jensflorian)
File:Ganglioglioma Cd34 x200.jpg | CD34 immunostain in ganglioglioma (WC/jensflorian)
File:Anaplastic ganglioglioma HE.jpg | Pleomorphic ganglion cells in ganglioglioma (WC/jensflorian)
</gallery>
*[http://path.upmc.edu/cases/case142.html Ganglioglioma - case 1 (upmc.edu)].
*[http://path.upmc.edu/cases/case282.html Ganglioglioma - case 2 (upmc.edu)].

===Lhermitte-Duclos disease===
*Abbreviated ''LDD''.
*[[AKA]] ''dysplastic cerebellar gangliocytoma''.<ref name=pmid20060133>{{Cite journal | last1 = Yağci-Küpeli | first1 = B. | last2 = Oguz | first2 = KK. | last3 = Bilen | first3 = MA. | last4 = Yalçin | first4 = B. | last5 = Akalan | first5 = N. | last6 = Büyükpamukçu | first6 = M. | title = An unusual cause of posterior fossa mass: Lhermitte-Duclos disease. | journal = J Neurol Sci | volume = 290 | issue = 1-2 | pages = 138-41 | month = Mar | year = 2010 | doi = 10.1016/j.jns.2009.12.010 | PMID = 20060133 }}</ref>
*[[AKA]] ''dysplastic gangliocytoma of the cerebellum''.
{{Main|Lhermitte-Duclos disease}}
<gallery>
File:Dysplastic_gangliocytoma_lhermitte_duclos.jpg | Dysplastic gangliocytoma (low mag).
</gallery>

===Papillary glioneuronal tumour===
* Abbreviated ''PGNT''.
* A benign, supratentorial tumor of childhood.
** Biologic course corresponds to WHO grade I.
** Before WHO 2000, considered a [[Ganglioglioma]] variant.
*Prominent pseudopapillary architecture.
*Neurocytes to medium-sized ganglion cells.
*GFAP+ core, GFAP- layer
*Rosenthal fibers, Eosinophilic Granular bodies and lymphocytic cuffing may be present.
<gallery>
File:PGNT_HE_stain.jpg | PGNT (HE) (WC/jensflorian)
</gallery>

===Rosette-forming glioneuronal tumour of the fourth ventricle===
* Abbreviated ''RGNT''.
* Provisional ICD-O code: 9509/1
* A rare benign infratentorial tumour of the midline of children and adults.
* Biologic course corresponds to WHO grade I.
* Glial component corresponds to [[pilocytic astrocytoma]].
* Neurocytic rosettes.
* Eosinopil fibrillary cores / pseudorosettes.
* GFAP+ in fibrillary areas, Syn+ in rosettes.
* Neurocytic cells: MAP2+
* MIB-1 usu. below 3%.
<gallery>
File:Histology RGNT HE.jpg | RGNT, HE stain (WC/jensflorian).
File:RGNT HE 2.jpg | RGNT, higher magnification (WC/jensflorian).
</gallery>

===Polymorphous low-grade tumor of the young (PLNTY)===
* [[Pediatric-type diffuse low-grade glioma#Diffuse low-grade glioma, MAPK pathway-altered|Polymorphous low-grade tumor of the young (PLNTY)]]

==Pineal tumours==
{{Main|Pineal gland}}

* [[Pineocytoma]]
* [[Pineal parenchymal tumour of intermediate differentiation]]
* [[Pineoblastoma]]
* [[Papillary tumour of the pineal region]]

==Embryonal tumours==
* [[Atypical teratoid/rhabdoid tumour]] (AT/RT) or (AT-RT)
* [[Medulloblastoma]]
* [[Primitive neuroectodermal tumour]] (PNET)
* [[Embryonal tumour with abundant neuropil and true rosettes]] (ETANTR)

DDx:
* [[Ewing sarcoma]]
* [[Sarcoma with CIC-rearrangement]]

==Peripheral nerve sheath tumours==
{{Main|Peripheral nerve sheath tumours}}
A classification:<ref name=pmid17893219>{{cite journal |author=Wippold FJ, Lubner M, Perrin RJ, Lämmle M, Perry A |title=Neuropathology for the neuroradiologist: Antoni A and Antoni B tissue patterns |journal=AJNR Am J Neuroradiol |volume=28 |issue=9 |pages=1633–8 |year=2007 |month=October |pmid=17893219 |doi=10.3174/ajnr.A0682 |url=http://www.ajnr.org/cgi/reprint/28/9/1633}}</ref>
'''Benign:'''
*[[Schwannoma]].
*[[Neurofibroma]].
*[[Perineurioma]].
*Ganglioneuroma.
**[[Traumatic neuroma]].
'''Malignant:'''
*[[Malignant peripheral nerve sheath tumour]] (MPNST).

===Ganglioneuroma===
:'''Not''' to be confused with ''[[ganglioglioma]]''.
*[[AKA]] ganglioma.<ref>URL: [http://medical-dictionary.thefreedictionary.com/ganglioma http://medical-dictionary.thefreedictionary.com/ganglioma]. Accessed on: 8 November 2010.</ref>
{{Main|Ganglioneuroma}}

==Meningioma==
{{Main|Meningioma}}

==Chordoma==
{{Main|Chordoma}}

==Hemangioblastoma==
{{Main|Hemangioblastoma}}

==CNS lymphoma==
Classification:
*Primary CNS lymphoma.
*Non-primary CNS lymphoma - see ''[[lymphoma]]'' article.

===General - primary CNS===
*Classically periventicular distribution.
*Usually large B cell; can be considered a type of [[diffuse large B cell lymphoma]] (DLBCL).
**Prognosis of CNS (DLBCL) lymphomas worse than nodal (non-CNS) DLBCL.<ref name=pmid19925562>{{cite journal |author=Raoux D, Duband S, Forest F, ''et al.'' |title=Primary central nervous system lymphoma: Immunohistochemical profile and prognostic significance |journal=Neuropathology |volume=30 |issue=3 |pages=232–40 |year=2010 |month=June |pmid=19925562 |doi=10.1111/j.1440-1789.2009.01074.x |url=}}</ref>

===Microscopic===
Features:
*Large cell lymphoma.
**Size = 2x diameter normal lymphocyte.
**Nucleolus - common.
*Perivascular clustering.

====Images====
www:
*[http://frontalcortex.com/?page=image&topic=1&qid=1237 CNS lymphoma (frontalcortex.com)].
*[http://path.upmc.edu/cases/case403.html Primary CNS lymphoma - several images (upmc.edu)].
<gallery>
Image:Primary CNS lymphoma - low mag.jpg | CNS lymphoma - low mag. (WC)
Image:Primary CNS lymphoma - intermed mag.jpg | CNS lymphoma - intermed. mag. (WC)
Image:Primary CNS lymphoma - high mag.jpg | CNS lymphoma - high mag. (WC)
Image:Primary CNS lymphoma - very high mag.jpg | CNS lymphoma - very high mag. (WC)
</gallery>
<gallery>
Image: CNS lymphoma (1) B-cell type.jpg | CNS lymphoma. (WC/KGH)
Image: CNS lymphoma (2) B-cell type.jpg | CNS lymphoma. (WC/KGH)
</gallery>

===IHC===
Can be subclassified in ''GCB (germinal centre B-cell-like)'' and ''non-GCB'' by CD10, Bcl-6, MUM1/IRF-4, and Bcl-2.<ref name=pmid19925562/>

Common pattern:
*[[CD20]] +ve - key stain.
*CD3 -ve.
*Ki-67 ~40%.
*Bcl-6 +ve.
*Bcl-1 -ve.

==Ganglioneuroblastoma==
{{Main|Neuroblastoma}}
===General===
*Uncommon.
*Part of the ''neuroblastic tumours'' group which includes:<ref name=pmid10421272>{{cite journal |author=Shimada H, Ambros IM, Dehner LP, Hata J, Joshi VV, Roald B |title=Terminology and morphologic criteria of neuroblastic tumors: recommendations by the International Neuroblastoma Pathology Committee |journal=Cancer |volume=86 |issue=2 |pages=349–63 |year=1999 |month=July |pmid=10421272 |doi= |url=}}</ref>
**[[Ganglioneuroma]] (benign).
**Ganglioneuroblastoma (intermediate).
**[[Neuroblastoma]] (aggressive).

===Microscopic===
Features:
*Ganglion-like cells with a prominent nucleolus.
*Small undifferentiated cells with scant cytoplasm.
<gallery>
Image:Adrenal Ganglioneuroblastoma LP CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - Low power (SKB)
Image:Adrenal Ganglioneuroblastoma MP CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - Medium power (SKB)
Image:Adrenal Ganglioneuroblastoma HP CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - High power (SKB)
Image:Adrenal Ganglioneuroblastoma HP3 CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - High power (SKB)
Image:Adrenal Ganglioneuroblastoma HP2 CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - High power (SKB)
</gallery>
Images:
*[http://path.upmc.edu/cases/case530.html Ganglioneuroblastoma - several images (upmc.edu)].

===IHC===
*NSE +ve -- small cells.

==Lesions of the sella turcica==
{{Main|Pituitary gland}}
Lesions of the sella turcica, the pituitary gland environs, is a topic for it self. The differential diagnosis for lesions in this area includes:
*[[Pituitary adenoma]].
*[[Craniopharyngioma]].
*[[Rathke cleft cyst]].
*[[Germ cell tumour]].
*[[Meningioma]].
*[[Pilomyxoid astrocytoma]] - in children.

==See also==
*[[Neuropathology]].
*[[Muscle biopsy]].

==References==
{{reflist|2}}

==External links==
*[http://www.neuropathologyweb.org/ Neuropathology (neuropathologyweb.org)].
*[http://www.pathology.vcu.edu/WirSelfInst/tumor-1.html Neuropathology Mini-Course (pathology.vcu.edu)].
*[http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html Neuropathology Mini-Course (pathology.vcu.edu)].

[[Category:Neuropathology]]

Neuropathology tumours

2022-04-13T12:07:12Z

Jensflorian: /* By IHC */ Update

[[Image:Gemistocytic Astrocytoma 003.jpg|thumb|right|A brain stem [[astrocytoma]]. (WC)]]
The article covers '''tumours in neuropathology'''. Tumours are a large part of [[neuropathology]]. [[Cytopathology]] of CNS tumours is dealt with in the article ''[[CNS cytopathology]]''.

There are separate articles for ''[[peripheral nerve sheath tumours]]'' and ''[[pituitary gland|pituitary/peri-pituitary lesions]]''.

==Brain tumours - overview==
===Alphabetical===
For overview see [[:Category:Neuropathology_tumours|here]]

===By age group===
====Adult====
Four most common types of brain tumours:<ref>[http://neurosurgery.mgh.harvard.edu/abta/primer.htm http://neurosurgery.mgh.harvard.edu/abta/primer.htm]</ref>
# Metastatic brain tumours (barely edges out primary tumours)
#*[[Lung cancer|Lung]] (most common).
#*[[Invasive breast cancer|Breast]].
#*[[Melanoma]].
#*[[Renal cell carcinoma]] (RCC).
# [[Glioblastoma]], IDH-wildtype.
# [[Astrocytoma, IDH-mutant]].
# [[Meningioma]].

====Children====
# [[Pilocytic astrocytoma]].
# [[Medulloblastoma]].
# [[Ependymoma]].
# Pontine glioma, often [[Diffuse midline glioma, H3 K27-altered]].

===By location===
Certain tumours like to hang-out at certain places:<ref>URL: [http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/files/4ce563fb7e8e48fc9ed8b42e296a7747.gif http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/files/4ce563fb7e8e48fc9ed8b42e296a7747.gif] and [http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html]. Accessed on: 2 November 2010.</ref>
====Cerebrum====
*Cortical based - [[oligodendroglioma]].
*Grey-white junction - metastases.
*White matter - astrocytoma, [[glioblastoma]].
*Periventricular - CNS lymphoma.
*Cystic - [[ganglioglioma]], [[pilocytic astrocytoma]], [[pleomorphic xanthoastrocytoma]].
====Cerebellum====
*Midline/central - [[medulloblastoma]].
*Cystic lesion - pilocytic astrocytoma (younger individual), [[hemangioblastoma]] (older individual).
*Solid lesion (older individual) - [[metastasis]].
====Sella turcica====
* [[Pituitary adenoma]].
* [[Craniopharyngioma]].
less common:
* [[Pituicytoma]].
* [[Granular cell tumour]].
* [[Germinoma]].
* [[Chordoma]]
* Rathke cleft cyst.
* Hypophysitis.
* Xanthogranuloma.
====Spinal cord====
*[[Ependymoma]]
*[[Glioblastoma]]
*[[Meningioma]]
*Carcinoma metastasis
*[[Hemangioblastoma]]
====Filum terminale====
*[[Meningioma]].
*[[Myxopapillary ependymoma]].
*[[Neurofibroma]].
*[[Schwannoma]].
*[[Paraganglioma]].
====Meninges====
* [[Meningioma]].
* [[Solitary fibrous tumour]] / Hemangiopericytoma.
* [[Hemangioblastoma]].
less common:
* [[Melanoma]] / Melanocytoma.
* Lymphoproliferative diseases.
* [[Sarcoidosis]]
* [[Arachnoid cyst]].
* Disseminated oligodendroglial-like leptomeningeal tumour.
* Desmoplastic infantile astrocytoma / ganglioglioma.
* Meningioangiomatosis.
* Calcifying pseudoneoplasm.
====Skull====
* [[Fibrous dysplasia]].
* [[Paget disease]].
* [[Histiocytosis]].
* [[Hemangioma]].
* [[Aneurysmal bone cyst]].
* [[Plasma_cell_neoplasms#Multiple_myeloma|Multiple myeloma]].
====Skull base / Cerebellopontine angle====
* [[Schwannoma]].
* [[Meningioma]].
* [[Dermoid cyst]] / epidermoid cyst.
less common:
* [[Ependymoma]].
* [[Choroid plexus papilloma]].
* [[Glomus tumour]].
* [[Chordoma]].
* [[Chondrosarcoma]].
* [[Olfactory neuroblastoma]].
* [[Endolymphatic sac tumour]].

===Cystic tumours===
DDx:<ref>URL: [http://path.upmc.edu/cases/case320/dx.html http://path.upmc.edu/cases/case320/dx.html]. Accessed on: 14 January 2012.</ref>
*[[Pilocytic astrocytoma]].
*[[Pleomorphic xanthoastrocytoma]].
*[[Ganglioglioma]].
*[[Hemangioblastoma]].
*[[Craniopharyngioma]].<ref>URL: [http://www.pathologyoutlines.com/Cnstumor.html#cystsgeneral http://www.pathologyoutlines.com/Cnstumor.html#cystsgeneral]. Accessed on: 14 January 2012.</ref>

===Primary versus secondary===
*[[AKA]] (primary) brain tumour versus metastatic cancer.
====Primary====
[[Glioma|Glial tumours]]:
*Cytoplasmic processes - '''key feature'''.
**Best seen at highest magnification - usu. ~1 micrometer.
**Processes may branch.
*Ill-defined border/blend with the surrounding brain.

[[Meningioma]]:
*Lesion often dura-based.
*Mesenchymal tumor (often contains collagen).

[[Lymphoma]]:
*Primary CNS Lymphoma (PCNSL) is usu. a diffuse large B-cell lymphoma.
*Large (lymphoid) cells, ergo usu. not a difficult diagnosis.
**~2x size of resting lymphocyte, nucleoli.
*Lesion predominantly perivascular.

====Secondary====
*Carcinomas:
**Well-demarcated border between brain and lesion - '''key feature'''.
**No cytoplasmic processes.
**Usu. have nuclear atypia of malignancy.
**Nuclei often ~3-4x the size of a [[RBC]].
**+/-Glandular arrangement.
**+/-Nucleoli.
*Melanoma.
*Secondary Lymphoma.
*Sarcomas (rare).

===By growth pattern===
====Infiltrative astrocytomas====
*[[Astrocytoma, IDH-mutant]].
*[[Glioblastoma]]IDH-wildtype.

====Non-infiltrative astrocytomas====
**[[Pilocytic astrocytoma]]
**[[Pleomorphic xanthoastrocytoma]]
**[[Subependymal giant cell astrocytoma]].

Notes:
*Glial vs. non-glial tumours:
**Glial: "blends into brain"/gradual transition to non-tumour brain.
**Non-glial: no radiating glial processes.
*Rosenthal fibres within the tumour... often seen in [[pilocytic astrocytoma]].
**Rosenthal fibres may be seen around a (very) slow growing tumour and represent a reactive process.
*Inflammatory cells and macrophages should prompt consideration of an alternate diagnosis (e.g. [[cerebral infarct]], [[multiple sclerosis]]) - esp. if this is a primary lesion.<ref>URL: [http://path.upmc.edu/cases/case79/dx.html http://path.upmc.edu/cases/case79/dx.html]. Accessed on: 2 January 2012.</ref>

====Grading====
Nuclear pleomorphism present:
*At least grade II (diffuse astrocytoma).

Mitotic figures present:
*At least grade III (anaplastic astrocytoma).

Microvascular proliferation ''or'' necrosis with pseudopalisading tumour cells:
*Grade IV (glioblastoma [[AKA]] glioblastoma multiforme).

Notes:
*Pseudopalisading tumour cells = high tumour cell density adjacent to regions of necrosis; palisade = a fence of poles forming a defensive barrier or fortification.
*WHO Grading is currently based on expected biologiocal behaviour without treatment.
**Grading does not reflect molecular divergent groups within a tumor class or response to therapy (Currently controversies in grading for IDH-mutant astrocytoma vs. IDH-wildtype astrocytoma).<ref>{{Cite journal | last1 = Louis | first1 = DN. | last2 = von Deimling | first2 = A. | title = Grading of diffuse astrocytic gliomas: Broders, Kernohan, Zülch, the WHO… and Shakespeare. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Aug | year = 2017 | doi = 10.1007/s00401-017-1765-z | PMID = 28801693 }}</ref>

====Images====
Glioblastoma:
<gallery>
Image:Glioblastoma_%281%29.jpg | Glioblastoma - pseudopalisading of tumour cells (WC)
Image:Glioblastoma_-_high_mag.jpg | Glioblastoma with fragment of near-normal white matter - high mag. (WC)
</gallery>
Anaplastic astrocytoma:
<gallery>
Image:Anaplastic_astrocytoma_-_very_high_mag_-_cropped.jpg | Anaplastic astrocytoma - very high mag. (WC)
Image:Anaplastic_astrocytoma_-_gfap_-_very_high_mag.jpg | Anaplastic astrocytoma - GFAP - very high mag. (WC)
</gallery>

===By IHC===
*GFAP - should stain cytoplasm of tumour cells and the perikaryon (nuclear membrane) of most [[Astrocytoma]]s.
*[[IDH-1]](R132H) (isocitrate dehydrogenase 1) in [[Astrocytoma, IDH-mutant]].<ref name=pmid19228619>{{cite journal |author=Yan H, Parsons DW, Jin G, ''et al.'' |title=IDH1 and IDH2 mutations in gliomas |journal=N. Engl. J. Med. |volume=360 |issue=8 |pages=765–73 |year=2009 |month=February |pmid=19228619 |pmc=2820383 |doi=10.1056/NEJMoa0808710 |url=}}</ref><ref name=pmid20975057>{{cite journal |author=Houillier C, Wang X, Kaloshi G, ''et al.'' |title=IDH1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas |journal=Neurology |volume=75 |issue=17 |pages=1560–6 |year=2010 |month=October |pmid=20975057 |doi=10.1212/WNL.0b013e3181f96282 |url=}}</ref>
*[[H3F3A|H3F3A K27M]] in [[Diffuse midline glioma, H3 K27-altered]].
*[[ATRX]] -ve in [[Astrocytoma, IDH-mutant]] or [[Diffuse hemispheric glioma, H3 G34-mutant]].
*[[CD20]] in PCNSL.
*Cytokeratins in Carcinoma brain metastases, Plexus choroid tumours, [[AT/RT]], [[Papillary tumour of the pineal region]], [[Craniopharyngioma]].
*[[EMA]] in [[Meningioma]] and carcinoma brain metastases.
*PrgR in [[Meningioma]] and carcinoma metastases.
*[[Synaptophysin]] in glioneuronal tumours and Pituitary adenoma and embryonal tumours.

===Common neuropathology tumours in a table===
{| class="wikitable"
|'''Type'''
|'''Key feature(s)'''
|'''Imaging'''
|'''History'''
|'''Notes'''
|'''IHC'''
|'''Images'''
|-
|Normal tissue
|cells regularly spaced, no nuc. atypia
|small lesion? / deep lesion?
|variable
|missed lesion?
|nil
|[[Image:Grey_matter_and_white_matter_-_very_high_mag.jpg |thumb|center|150px|Normal. (WC)]]
|-
|[[Reactive astrocytes]]
|astrocytes with well-demarcated eosinophilic cytoplasm, regular spacing, no nuc. atypia
|small lesion? / deep lesion?
|variable
|missed lesion / close to a lesion; non-specific pathologic process - need more tissue
|GFAP
|[[Image:Reactive_astrocytes_-_lfb_-_high_mag.jpg|thumb|center|150px|Reactive astrocytes. (WC)]]
|-
|[[Schwannoma]]
|cellular areas (Antoni A), paucicelluar areas (Antoni B), palisading of nuclei (Verocay bodies)
|extra-axial + intradural
|old or young
|need frozen section to Dx, DDx: [[meningioma]]
|S100, SOX10
|[[Image:Schwannoma_-_Antoni_A_and_B_-_very_high_mag.jpg|thumb|center|150px|Schwannoma. (WC)]]
|-
|[[Meningioma]]
|whorls, psammomatous calcs, nuclear inclusions
|extra-axial + intradural
|old or young
|may be diagnosed on smear, DDx: [[schwannoma]], choroid plexus
|EMA, PR, Ki-67
|[[Image:Meningioma_intermed_mag.jpg |thumb|center|150px|Meningioma. (WC)]]
|-
|[[Astrocytoma, IDH-mutant]] (CNS [[WHO]] grade 2 or grade 3)
|glial processes (esp. on smear), nuclear atypia (typical size var. ~3x, irreg. nuc. membrane, hyperchromasia), no Rosenthal fibres in the core of the lesion †, no microvascular proliferation, no necrosis
|often enhancing (suggests high grade), usu. supratentorial, usu. white matter
|usu. old, occ. young
|common
|IDH-1(R132H)+/-, GFAP+
| [[Image:Anaplastic_astrocytoma_-_very_high_mag_-_cropped.jpg | thumb| center| 150px|High-grade astrocytoma. (WC)]]
|-
|[[Glioblastoma]], IDH-wildtype (CNS [[WHO]] grade 4)
|glial processes (esp. on smear), nuclear atypia (typical size var. ~3x, irreg. nuc. membrane, hyperchromasia), no Rosenthal fibres in the core of the lesion †, microvascular proliferation or necrosis
|often enhancing (suggests high grade), usu. supratentorial, usu. white matter
|usu. old, occ. young
|very common, esp. glioblastoma
|IDH-1+/-, GFAP+
| [[Image:Glioblastoma (1).jpg | thumb| center| 150px|Glioblastoma. (WC)]]
|-
|[[Metastatic brain tumours|Metastasis]]
|sharp interface with brain, often glandular, +/-nucleoli, no glial processes
|often cerebellular, well-circumscribed
|usu. old
|often suspected to have metastatic disease
|[[TTF-1]], CK7, [[CK20]], BRST-2
|[[Image:Metastatic_adenocarcinoma_-_cerebellum_-_very_low_mag.jpg | thumb| center|150px |Metastasis. (WC)]]
|}
† Rosenthal fibres at the periphery of a lesion are a non-specific finding seen in chronic processes.

==Brain metastasis==
{{Main|Brain metastasis}}

===Molecular===
See also: [[Molecular_pathology_tests#Neuropathology|Molecular Neuropathology]]

==Gliomas==
{{Main|Glioma}}

Gliomas, glioneuronal tumours and neuronal tumours are often categorized together.

===Astrocytic tumours===
{{Main|Astrocytoma}}

* [[Astrocytoma]], IDH-mutant.
* [[Glioblastoma]], IDH-wildtype.
** [[Gliosarcoma]] (a glioblastoma subtype)

Features:<ref name=pmid>{{cite journal |author=Rong Y, Durden DL, Van Meir EG, Brat DJ |title='Pseudopalisading' necrosis in glioblastoma: a familiar morphologic feature that links vascular pathology, hypoxia, and angiogenesis |journal=J. Neuropathol. Exp. Neurol. |volume=65 |issue=6 |pages=529–39 |year=2006 |month=June |pmid=16783163 |doi= |url=}}</ref><ref>[http://dictionary.reference.com/browse/palisading http://dictionary.reference.com/browse/palisading]</ref>
*Glial processes - '''key feature'''.
**Thin stringy cytoplasmic processes - best seen at high power in less cellular areas.
*No Rosenthal fibres within the tumour itself.

Images:
*[http://moon.ouhsc.edu/kfung/jty1/opaq/PathQuiz/N0A002-PQ01-M.htm Endothelial proliferation in a GBM (ouhsc.edu)].
*[http://moon.ouhsc.edu/kfung/jty1/neurotest/Q05-Ans.htm Endothelial proliferation (ouhse.edu)].
*[http://path.upmc.edu/cases/case368.html Gemistocytic astrocytoma - several images (upmc.edu)].

Depreceated:
* Diffuse [[Astrocytoma]]
* [[Anaplastic astrocytoma]]
* [[Gliomatosis cerebri]]
* Spongioblastoma

===Oligodendroglial tumours===
* [[Oligodendroglioma]], IDH-mutant and 1p/19q codeleted.

Depreceated:
* Anaplastic oligodendroglioma
* [[Oligoastrocytoma]]
* Anaplastic oligoastrocytoma

===Pediatric-type diffuse high-grade glioma===
{{Main|Pediatric-type diffuse high-grade glioma}}
* [[Astrocytoma#Diffuse_midline_glioma.2C_H3_K27M_mutant|Diffuse midline glioma H3 K27-mutant]]

===Pediatric-type diffuse low-grade glioma===
{{Main|Pediatric-type diffuse low-grade glioma}}

===Circumscribed astrocytic gliomas===
* [[Pilocytic astrocytoma]] (PA)
** [[Pilomyxoid astrocytoma]] (PMA)
* [[Pleomorphic xanthoastrocytoma]] (PXA)
* [[Subependymal giant cell astrocytoma]] (SEGA)
* [[Neuropathology_tumours#Astroblastoma|Astroblastoma MN1-altered]].
* [[Neuropathology_tumours#Chordoid glioma of the third ventricl|Chordoid glioma]].

====Astroblastoma====
*No WHO grade yet.<ref>{{Ref WHOCNS|88}}</ref>
*Very rare superficial tumor of young age.<ref>{{Cite journal | last1 = Narayan | first1 = S. | last2 = Kapoor | first2 = A. | last3 = Singhal | first3 = MK. | last4 = Jakhar | first4 = SL. | last5 = Bagri | first5 = PK. | last6 = Rajput | first6 = PS. | last7 = Kumar | first7 = HS. | title = Astroblastoma of cerebrum: A rare case report and review of literature. | journal = J Cancer Res Ther | volume = 11 | issue = 3 | pages = 667 | month = | year = | doi = 10.4103/0973-1482.140800 | PMID = 26458709 }}</ref>
*Large, cystic. Pushing margin towards CNS.
*Vasocentric growth, plump cells with absence of fibrillary pattern.
*GFAP+ve, Synaptohysin-ve, Olig-2-ve, focally EMA/panCK+ve. MIB-1: 1-18 %.
*Molecular profile overlaps with classical [[CNS-PNET]].
**Gene fusions invoving meningioma gene (MN1)<ref>{{Cite journal | last1 = Sturm | first1 = D. | last2 = Orr | first2 = BA. | last3 = Toprak | first3 = UH. | last4 = Hovestadt | first4 = V. | last5 = Jones | first5 = DT. | last6 = Capper | first6 = D. | last7 = Sill | first7 = M. | last8 = Buchhalter | first8 = I. | last9 = Northcott | first9 = PA. | title = New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs. | journal = Cell | volume = 164 | issue = 5 | pages = 1060-72 | month = Feb | year = 2016 | doi = 10.1016/j.cell.2016.01.015 | PMID = 26919435 }}</ref>

<gallery>
File:Astroblastoma_HE_Specimen.jpg | HE. (WC/jensflorian)
File:Astroblastoma_HE_papillae.jpg | HE. (WC/jensflorian)
File:Astroblastoma.jpg | Astroblastoma (AFIP)
</gallery>

====Chordoid glioma of the third ventricle====
* WHO grade II.
* Slowly growing, non-invasive, in adults.
* Clusters of epithelioid cells in mucinous stroma.
* Lymphocytic infiltrates, adjacent Rosenthal fibers.
* Fibrosis may be present.
* Few mitoses.
* [[GFAP]]+ve, MIB-1 1-3%.
* [[TTF-1]]+ve.
* CD34+ve.
* [[IDH-1]]-ve, [[p53]]-ve.
* PRKCA D463H mutations.<ref>{{Cite journal | last1 = Goode | first1 = B. | last2 = Mondal | first2 = G. | last3 = Hyun | first3 = M. | last4 = Ruiz | first4 = DG. | last5 = Lin | first5 = YH. | last6 = Van Ziffle | first6 = J. | last7 = Joseph | first7 = NM. | last8 = Onodera | first8 = C. | last9 = Talevich | first9 = E. | title = A recurrent kinase domain mutation in PRKCA defines chordoid glioma of the third ventricle. | journal = Nat Commun | volume = 9 | issue = 1 | pages = 810 | month = 02 | year = 2018 | doi = 10.1038/s41467-018-02826-8 | PMID = 29476136 }}</ref>

<gallery>
File:NP op 20201028 009.jpg | Chordoid Glioma. (WC/jensflorian)
</gallery>

===Ependymal tumours===
* [[Subependymoma]]
* [[Myxopapillary Ependymoma]]
* [[Ependymoma]]
* Anaplastic ependymoma

==Choroid plexus tumours==
* [[Choroid plexus papilloma]]
* Atypical choroid plexus papilloma
* [[Choroid plexus carcinoma]]

==Other neuroepithelial tumours==
* [[Neuropathology_tumours#Cribiform_neuroepithelial_tumour|Cribifiorm neuroepithelial tumour]].

===Cribiform neuroepithelial tumour===
AKA: '''CRINET'''.
*Not listed in the current WHO classification.
*First description in 2009.<ref>{{Cite journal | last1 = Hasselblatt | first1 = M. | last2 = Oyen | first2 = F. | last3 = Gesk | first3 = S. | last4 = Kordes | first4 = U. | last5 = Wrede | first5 = B. | last6 = Bergmann | first6 = M. | last7 = Schmid | first7 = H. | last8 = Frühwald | first8 = MC. | last9 = Schneppenheim | first9 = R. | title = Cribriform neuroepithelial tumor (CRINET): a nonrhabdoid ventricular tumor with INI1 loss and relatively favorable prognosis. | journal = J Neuropathol Exp Neurol | volume = 68 | issue = 12 | pages = 1249-55 | month = Dec | year = 2009 | doi = 10.1097/NEN.0b013e3181c06a51 | PMID = 19915490 }}</ref>
*Around ventricles.<ref>{{Cite journal | last1 = Arnold | first1 = MA. | last2 = Stallings-Archer | first2 = K. | last3 = Marlin | first3 = E. | last4 = Grondin | first4 = R. | last5 = Olshefski | first5 = R. | last6 = Biegel | first6 = JA. | last7 = Pierson | first7 = CR. | title = Cribriform neuroepithelial tumor arising in the lateral ventricle. | journal = Pediatr Dev Pathol | volume = 16 | issue = 4 | pages = 301-7 | month = | year = | doi = 10.2350/12-12-1287-CR.1 | PMID = 23495723 }}</ref>
*Young children.<ref>{{Cite journal | last1 = Park | first1 = JY. | last2 = Kim | first2 = E. | last3 = Kim | first3 = DW. | last4 = Chang | first4 = HW. | last5 = Kim | first5 = SP. | title = Cribriform neuroepithelial tumor in the third ventricle: a case report and literature review. | journal = Neuropathology | volume = 32 | issue = 5 | pages = 570-6 | month = Oct | year = 2012 | doi = 10.1111/j.1440-1789.2011.01293.x | PMID = 22239490 }}</ref>
*Small undifferentiated cells arranged in cribriform strands and trabeculae of varying thickness.
*MAP2+ve, Synaptophysin+ve, CK+/-ve. MIB-1: 30%.
*INI-1 loss, but no rhabdoid features and good prognosis.
*Stable genomic profile.<ref>{{Cite journal | last1 = Gessi | first1 = M. | last2 = Japp | first2 = AS. | last3 = Dreschmann | first3 = V. | last4 = Zur Mühlen | first4 = A. | last5 = Goschzik | first5 = T. | last6 = Dörner | first6 = E. | last7 = Pietsch | first7 = T. | title = High-Resolution Genomic Analysis of Cribriform Neuroepithelial Tumors of the Central Nervous System. | journal = J Neuropathol Exp Neurol | volume = 74 | issue = 10 | pages = 970-4 | month = Oct | year = 2015 | doi = 10.1097/NEN.0000000000000239 | PMID = 26352987 }}</ref>

==Neuronal and mixed neuronal/glial tumours==
* [[Desmoplastic infantile astrocytoma]] / ganglioglioma (DIA/DIG)
* [[Dysembryoplastic neuroepithelial tumour]]
* [[Central Neurocytoma]] / Extraventricular [[neurocytoma]]
* Cerebellar liponeurocytoma
* [[Papillary glioneuronal tumour]] (PGNT)
* [[Rosette-forming glioneuronal tumour of the fourth ventricle]] (RGNT)
* Gangliocytoma / Ganglioglioma
* Dysplastic ganglioglioma of the cerebellum ([[Lhermitte-Duclos disease]])
* [[Paraganglioma]]

===Desmoplastic infantile astrocytoma / Desmoplastic infantile ganglioglioma===
* Abbreviated ''DIA'' or ''DIG''.
* ICD-O code: 9412/1
* Large, superficial, cystic tumor of the infancy.
* Biologic course corresponds to WHO grade I.
* Very rare, included in the WHO since 1993.
* Prominent desmoplastic stroma.
* Astrocytic cells within stroma.
**GFAP+.
**MIB-1 usu. 1%.
* Frequent BRAF V600E or V600D mutations.<ref>{{Cite journal | last1 = Wang | first1 = AC. | last2 = Jones | first2 = DTW. | last3 = Abecassis | first3 = IJ. | last4 = Cole | first4 = BL. | last5 = Leary | first5 = SES. | last6 = Lockwood | first6 = CM. | last7 = Chavez | first7 = L. | last8 = Capper | first8 = D. | last9 = Korshunov | first9 = A. | title = Desmoplastic Infantile Ganglioglioma/Astrocytoma (DIG/DIA) are Distinct Entities with Frequent BRAFV600 Mutations. | journal = Mol Cancer Res | volume = | issue = | pages = | month = Jul | year = 2018 | doi = 10.1158/1541-7786.MCR-17-0507 | PMID = 30006355 }}</ref>
*Single case with BRAF indel or BRAF fusion.
<gallery>
File:DIG-histology.jpg | Histopathology of DIG (HE stain)
File:DIG-histology2.jpg | Prominent ganglioid cells in DIG (HE stain)
</gallery>

===Cerebellar liponeurocytoma===
* Previously called ''lipomatous medulloblastoma'' (name changed in WHO 2000).
* Mean age: 50 years.
* As the name states: A tumour of the cerebellum.
** But cases outside cerebellum reported that would qualify.<ref>{{Cite journal | last1 = Gupta | first1 = K. | last2 = Salunke | first2 = P. | last3 = Kalra | first3 = I. | last4 = Vasishta | first4 = RK. | title = Central liponeurocytoma: case report and review of literature. | journal = Clin Neuropathol | volume = 30 | issue = 2 | pages = 80-5 | month = | year = | doi = | PMID = 21329617 }}</ref>
* WHO grade II <ref>{{Cite journal | last1 = Nishimoto | first1 = T. | last2 = Kaya | first2 = B. | title = Cerebellar liponeurocytoma. | journal = Arch Pathol Lab Med | volume = 136 | issue = 8 | pages = 965-9 | month = Aug | year = 2012 | doi = 10.5858/arpa.2011-0337-RS | PMID = 22849747 }}</ref> (upgraded from WHO grade I in 2007)<ref>{{Cite journal | last1 = Brat | first1 = DJ. | last2 = Parisi | first2 = JE. | last3 = Kleinschmidt-DeMasters | first3 = BK. | last4 = Yachnis | first4 = AT. | last5 = Montine | first5 = TJ. | last6 = Boyer | first6 = PJ. | last7 = Powell | first7 = SZ. | last8 = Prayson | first8 = RA. | last9 = McLendon | first9 = RE. | title = Surgical neuropathology update: a review of changes introduced by the WHO classification of tumours of the central nervous system, 4th edition. | journal = Arch Pathol Lab Med | volume = 132 | issue = 6 | pages = 993-1007 | month = Jun | year = 2008 | doi = 10.1043/1543-2165(2008)132[993:SNUARO]2.0.CO;2 | PMID = 18517285 }}</ref>
*ICD-O code: 9506/1

====Histo====
* Advanced neuronal and lipomatous differentiation.
* Neurocytes: round to oval nuclei with clear cytoplasm.
* Quite cellular.
* Mitoses almost absent.

====IHC====
* [[GFAP]] +/-ve (focal).
* [[MAP2]] +ve.
* Synaptophysin +ve.
* NeuN +ve.
* MIB-1: usu 1-3%.

====Molecular====
* Distinct methylation profile.
* Recurent losses on 2p and Chr. 14.<ref>{{Cite journal | last1 = Capper | first1 = D. | last2 = Stichel | first2 = D. | last3 = Sahm | first3 = F. | last4 = Jones | first4 = DTW. | last5 = Schrimpf | first5 = D. | last6 = Sill | first6 = M. | last7 = Schmid | first7 = S. | last8 = Hovestadt | first8 = V. | last9 = Reuss | first9 = DE. | title = Practical implementation of DNA methylation and copy-number-based CNS tumor diagnostics: the Heidelberg experience. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Jul | year = 2018 | doi = 10.1007/s00401-018-1879-y | PMID = 29967940 }}</ref>

<gallery>
File:Cerebellar liponeurocytoma.jpg | Liponeurocytoma, HE (WC/Marvin101).
File:Liponeurocytoma Synaptophysin.jpg | Liponeurocytoma, Synapto (WC/Marvin101).
File:Cerebellar Liponeurocytoma HE.jpg | Liponeurocytoma, HE (WC/jensflorian).
File:Cerebellar Liponeurocytoma Synaptophysin.jpg | Liponeurocytoma, Synapto (WC/jensflorian).
</gallery>

====DDx====
* [[Medulloblastoma]]
* [[Neurocytoma]]

===Gangliocytoma===
* Grade I WHO neuronal tumour.
** ICD-O code: 9492/0
* Groups of irregular large neurons.
* Non-neoplastic, reticulin-rich glial stroma.

===Ganglioglioma===
:'''Not''' to be confused with ''[[ganglioneuroma]]''.
====General====
*Gangliolioma: Grade I WHO mixed neuronal-glial tumour (ICD-O code: 9505/1).
*Anaplastic ganglioglioma: Grade III (ICD-O: 9505/3)
*Rare (approx. 0.5% of all CNS tumors).
*Usu. temporal lobe.
*Predominantly children (mean age: 9 years).
*Recognized as a cause of [[epilepsy]].<ref name=pmid12125968>{{Cite journal | last1 = Im | first1 = SH. | last2 = Chung | first2 = CK. | last3 = Cho | first3 = BK. | last4 = Lee | first4 = SK. | title = Supratentorial ganglioglioma and epilepsy: postoperative seizure outcome. | journal = J Neurooncol | volume = 57 | issue = 1 | pages = 59-66 | month = Mar | year = 2002 | doi = | PMID = 12125968 }}</ref>
*Favourable prognosis (survival rates up to 97%)
**Insufficient data für anaplastic ganglioglioma.

====Macroscopic====
*Circumscribed lesion.
*Usu. contrast enhancing.
*Solid, but intracortical cysts may be present.
*Little mass effect.

====Microscopic====
Features:
*Dysplastic neurons.
**Out of regular architecture / abnormal location.
**Cytomegaly
**Clustering
**Binucleated (very occassionally).
*Atypical glia.
*Eosinophilic granular bodies.
*Calcification.
*Prominent capillary network.
*Lymphocytic cuffing.
*May contain some reticulin.
*Glial component may resemble:
**Fibrillary astrocytoma.
**Oligodendroglioma.
**Pilocytic astrocytoma.

Anaplastic ganglioglioma:
*Brisk mitotic activity
*Necrosis

====IHC====
*Neurons:
**[[MAP2]] +ve
**Synaptophysin +ve
** Neurofilament +ve
*Glia:
**CD34+/-ve
*BRAF V600E +ve (approx. 25%, mainly ganglion cells).

====Molecular====
*BRAF V600E-mutated(approx. 25%).
*IDH1/2 wt.
*No 1p/19q codeletion.
*Usu. Chr. 7 gain.
*CDKN2A deletions in anaplastic ganglioglioma.

====DDx:====
*[[DNT]].
*[[Oligodendroglioma]].
*Trapped cortical neurons in diffuse astrocytoma.
*Papillary glioneuronal tumor.
*Dysembryoplastic neuroepithelial tumor.

====Images====
<gallery>
File:Ganglioglioma lymphocytic cuffing PAS.jpg | Lymphocytic cuffing in ganglioglioma (WC/jensflorian)
File:Ganglioglioma calcification.jpg | Calcification in ganglioglioma (WC/jensflorian)
File:Ganglioglioma Cd34 x200.jpg | CD34 immunostain in ganglioglioma (WC/jensflorian)
File:Anaplastic ganglioglioma HE.jpg | Pleomorphic ganglion cells in ganglioglioma (WC/jensflorian)
</gallery>
*[http://path.upmc.edu/cases/case142.html Ganglioglioma - case 1 (upmc.edu)].
*[http://path.upmc.edu/cases/case282.html Ganglioglioma - case 2 (upmc.edu)].

===Lhermitte-Duclos disease===
*Abbreviated ''LDD''.
*[[AKA]] ''dysplastic cerebellar gangliocytoma''.<ref name=pmid20060133>{{Cite journal | last1 = Yağci-Küpeli | first1 = B. | last2 = Oguz | first2 = KK. | last3 = Bilen | first3 = MA. | last4 = Yalçin | first4 = B. | last5 = Akalan | first5 = N. | last6 = Büyükpamukçu | first6 = M. | title = An unusual cause of posterior fossa mass: Lhermitte-Duclos disease. | journal = J Neurol Sci | volume = 290 | issue = 1-2 | pages = 138-41 | month = Mar | year = 2010 | doi = 10.1016/j.jns.2009.12.010 | PMID = 20060133 }}</ref>
*[[AKA]] ''dysplastic gangliocytoma of the cerebellum''.
{{Main|Lhermitte-Duclos disease}}
<gallery>
File:Dysplastic_gangliocytoma_lhermitte_duclos.jpg | Dysplastic gangliocytoma (low mag).
</gallery>

===Papillary glioneuronal tumour===
* Abbreviated ''PGNT''.
* A benign, supratentorial tumor of childhood.
** Biologic course corresponds to WHO grade I.
** Before WHO 2000, considered a [[Ganglioglioma]] variant.
*Prominent pseudopapillary architecture.
*Neurocytes to medium-sized ganglion cells.
*GFAP+ core, GFAP- layer
*Rosenthal fibers, Eosinophilic Granular bodies and lymphocytic cuffing may be present.
<gallery>
File:PGNT_HE_stain.jpg | PGNT (HE) (WC/jensflorian)
</gallery>

===Rosette-forming glioneuronal tumour of the fourth ventricle===
* Abbreviated ''RGNT''.
* Provisional ICD-O code: 9509/1
* A rare benign infratentorial tumour of the midline of children and adults.
* Biologic course corresponds to WHO grade I.
* Glial component corresponds to [[pilocytic astrocytoma]].
* Neurocytic rosettes.
* Eosinopil fibrillary cores / pseudorosettes.
* GFAP+ in fibrillary areas, Syn+ in rosettes.
* Neurocytic cells: MAP2+
* MIB-1 usu. below 3%.
<gallery>
File:Histology RGNT HE.jpg | RGNT, HE stain (WC/jensflorian).
File:RGNT HE 2.jpg | RGNT, higher magnification (WC/jensflorian).
</gallery>

===Polymorphous low-grade tumor of the young (PLNTY)===
* [[Pediatric-type diffuse low-grade glioma#Diffuse low-grade glioma, MAPK pathway-altered|Polymorphous low-grade tumor of the young (PLNTY)]]

==Pineal tumours==
{{Main|Pineal gland}}

* [[Pineocytoma]]
* [[Pineal parenchymal tumour of intermediate differentiation]]
* [[Pineoblastoma]]
* [[Papillary tumour of the pineal region]]

==Embryonal tumours==
* [[Atypical teratoid/rhabdoid tumour]] (AT/RT) or (AT-RT)
* [[Medulloblastoma]]
* [[Primitive neuroectodermal tumour]] (PNET)
* [[Embryonal tumour with abundant neuropil and true rosettes]] (ETANTR)

DDx:
* [[Ewing sarcoma]]
* [[Sarcoma with CIC-rearrangement]]

==Peripheral nerve sheath tumours==
{{Main|Peripheral nerve sheath tumours}}
A classification:<ref name=pmid17893219>{{cite journal |author=Wippold FJ, Lubner M, Perrin RJ, Lämmle M, Perry A |title=Neuropathology for the neuroradiologist: Antoni A and Antoni B tissue patterns |journal=AJNR Am J Neuroradiol |volume=28 |issue=9 |pages=1633–8 |year=2007 |month=October |pmid=17893219 |doi=10.3174/ajnr.A0682 |url=http://www.ajnr.org/cgi/reprint/28/9/1633}}</ref>
'''Benign:'''
*[[Schwannoma]].
*[[Neurofibroma]].
*[[Perineurioma]].
*Ganglioneuroma.
**[[Traumatic neuroma]].
'''Malignant:'''
*[[Malignant peripheral nerve sheath tumour]] (MPNST).

===Ganglioneuroma===
:'''Not''' to be confused with ''[[ganglioglioma]]''.
*[[AKA]] ganglioma.<ref>URL: [http://medical-dictionary.thefreedictionary.com/ganglioma http://medical-dictionary.thefreedictionary.com/ganglioma]. Accessed on: 8 November 2010.</ref>
{{Main|Ganglioneuroma}}

==Meningioma==
{{Main|Meningioma}}

==Chordoma==
{{Main|Chordoma}}

==Hemangioblastoma==
{{Main|Hemangioblastoma}}

==CNS lymphoma==
Classification:
*Primary CNS lymphoma.
*Non-primary CNS lymphoma - see ''[[lymphoma]]'' article.

===General - primary CNS===
*Classically periventicular distribution.
*Usually large B cell; can be considered a type of [[diffuse large B cell lymphoma]] (DLBCL).
**Prognosis of CNS (DLBCL) lymphomas worse than nodal (non-CNS) DLBCL.<ref name=pmid19925562>{{cite journal |author=Raoux D, Duband S, Forest F, ''et al.'' |title=Primary central nervous system lymphoma: Immunohistochemical profile and prognostic significance |journal=Neuropathology |volume=30 |issue=3 |pages=232–40 |year=2010 |month=June |pmid=19925562 |doi=10.1111/j.1440-1789.2009.01074.x |url=}}</ref>

===Microscopic===
Features:
*Large cell lymphoma.
**Size = 2x diameter normal lymphocyte.
**Nucleolus - common.
*Perivascular clustering.

====Images====
www:
*[http://frontalcortex.com/?page=image&topic=1&qid=1237 CNS lymphoma (frontalcortex.com)].
*[http://path.upmc.edu/cases/case403.html Primary CNS lymphoma - several images (upmc.edu)].
<gallery>
Image:Primary CNS lymphoma - low mag.jpg | CNS lymphoma - low mag. (WC)
Image:Primary CNS lymphoma - intermed mag.jpg | CNS lymphoma - intermed. mag. (WC)
Image:Primary CNS lymphoma - high mag.jpg | CNS lymphoma - high mag. (WC)
Image:Primary CNS lymphoma - very high mag.jpg | CNS lymphoma - very high mag. (WC)
</gallery>
<gallery>
Image: CNS lymphoma (1) B-cell type.jpg | CNS lymphoma. (WC/KGH)
Image: CNS lymphoma (2) B-cell type.jpg | CNS lymphoma. (WC/KGH)
</gallery>

===IHC===
Can be subclassified in ''GCB (germinal centre B-cell-like)'' and ''non-GCB'' by CD10, Bcl-6, MUM1/IRF-4, and Bcl-2.<ref name=pmid19925562/>

Common pattern:
*[[CD20]] +ve - key stain.
*CD3 -ve.
*Ki-67 ~40%.
*Bcl-6 +ve.
*Bcl-1 -ve.

==Ganglioneuroblastoma==
{{Main|Neuroblastoma}}
===General===
*Uncommon.
*Part of the ''neuroblastic tumours'' group which includes:<ref name=pmid10421272>{{cite journal |author=Shimada H, Ambros IM, Dehner LP, Hata J, Joshi VV, Roald B |title=Terminology and morphologic criteria of neuroblastic tumors: recommendations by the International Neuroblastoma Pathology Committee |journal=Cancer |volume=86 |issue=2 |pages=349–63 |year=1999 |month=July |pmid=10421272 |doi= |url=}}</ref>
**[[Ganglioneuroma]] (benign).
**Ganglioneuroblastoma (intermediate).
**[[Neuroblastoma]] (aggressive).

===Microscopic===
Features:
*Ganglion-like cells with a prominent nucleolus.
*Small undifferentiated cells with scant cytoplasm.
<gallery>
Image:Adrenal Ganglioneuroblastoma LP CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - Low power (SKB)
Image:Adrenal Ganglioneuroblastoma MP CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - Medium power (SKB)
Image:Adrenal Ganglioneuroblastoma HP CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - High power (SKB)
Image:Adrenal Ganglioneuroblastoma HP3 CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - High power (SKB)
Image:Adrenal Ganglioneuroblastoma HP2 CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - High power (SKB)
</gallery>
Images:
*[http://path.upmc.edu/cases/case530.html Ganglioneuroblastoma - several images (upmc.edu)].

===IHC===
*NSE +ve -- small cells.

==Lesions of the sella turcica==
{{Main|Pituitary gland}}
Lesions of the sella turcica, the pituitary gland environs, is a topic for it self. The differential diagnosis for lesions in this area includes:
*[[Pituitary adenoma]].
*[[Craniopharyngioma]].
*[[Rathke cleft cyst]].
*[[Germ cell tumour]].
*[[Meningioma]].
*[[Pilomyxoid astrocytoma]] - in children.

==See also==
*[[Neuropathology]].
*[[Muscle biopsy]].

==References==
{{reflist|2}}

==External links==
*[http://www.neuropathologyweb.org/ Neuropathology (neuropathologyweb.org)].
*[http://www.pathology.vcu.edu/WirSelfInst/tumor-1.html Neuropathology Mini-Course (pathology.vcu.edu)].
*[http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html Neuropathology Mini-Course (pathology.vcu.edu)].

[[Category:Neuropathology]]

Neuropathology tumours

2022-04-13T12:04:34Z

Jensflorian: /* IHC */ Update

[[Image:Gemistocytic Astrocytoma 003.jpg|thumb|right|A brain stem [[astrocytoma]]. (WC)]]
The article covers '''tumours in neuropathology'''. Tumours are a large part of [[neuropathology]]. [[Cytopathology]] of CNS tumours is dealt with in the article ''[[CNS cytopathology]]''.

There are separate articles for ''[[peripheral nerve sheath tumours]]'' and ''[[pituitary gland|pituitary/peri-pituitary lesions]]''.

==Brain tumours - overview==
===Alphabetical===
For overview see [[:Category:Neuropathology_tumours|here]]

===By age group===
====Adult====
Four most common types of brain tumours:<ref>[http://neurosurgery.mgh.harvard.edu/abta/primer.htm http://neurosurgery.mgh.harvard.edu/abta/primer.htm]</ref>
# Metastatic brain tumours (barely edges out primary tumours)
#*[[Lung cancer|Lung]] (most common).
#*[[Invasive breast cancer|Breast]].
#*[[Melanoma]].
#*[[Renal cell carcinoma]] (RCC).
# [[Glioblastoma]], IDH-wildtype.
# [[Astrocytoma, IDH-mutant]].
# [[Meningioma]].

====Children====
# [[Pilocytic astrocytoma]].
# [[Medulloblastoma]].
# [[Ependymoma]].
# Pontine glioma, often [[Diffuse midline glioma, H3 K27-altered]].

===By location===
Certain tumours like to hang-out at certain places:<ref>URL: [http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/files/4ce563fb7e8e48fc9ed8b42e296a7747.gif http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/files/4ce563fb7e8e48fc9ed8b42e296a7747.gif] and [http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html]. Accessed on: 2 November 2010.</ref>
====Cerebrum====
*Cortical based - [[oligodendroglioma]].
*Grey-white junction - metastases.
*White matter - astrocytoma, [[glioblastoma]].
*Periventricular - CNS lymphoma.
*Cystic - [[ganglioglioma]], [[pilocytic astrocytoma]], [[pleomorphic xanthoastrocytoma]].
====Cerebellum====
*Midline/central - [[medulloblastoma]].
*Cystic lesion - pilocytic astrocytoma (younger individual), [[hemangioblastoma]] (older individual).
*Solid lesion (older individual) - [[metastasis]].
====Sella turcica====
* [[Pituitary adenoma]].
* [[Craniopharyngioma]].
less common:
* [[Pituicytoma]].
* [[Granular cell tumour]].
* [[Germinoma]].
* [[Chordoma]]
* Rathke cleft cyst.
* Hypophysitis.
* Xanthogranuloma.
====Spinal cord====
*[[Ependymoma]]
*[[Glioblastoma]]
*[[Meningioma]]
*Carcinoma metastasis
*[[Hemangioblastoma]]
====Filum terminale====
*[[Meningioma]].
*[[Myxopapillary ependymoma]].
*[[Neurofibroma]].
*[[Schwannoma]].
*[[Paraganglioma]].
====Meninges====
* [[Meningioma]].
* [[Solitary fibrous tumour]] / Hemangiopericytoma.
* [[Hemangioblastoma]].
less common:
* [[Melanoma]] / Melanocytoma.
* Lymphoproliferative diseases.
* [[Sarcoidosis]]
* [[Arachnoid cyst]].
* Disseminated oligodendroglial-like leptomeningeal tumour.
* Desmoplastic infantile astrocytoma / ganglioglioma.
* Meningioangiomatosis.
* Calcifying pseudoneoplasm.
====Skull====
* [[Fibrous dysplasia]].
* [[Paget disease]].
* [[Histiocytosis]].
* [[Hemangioma]].
* [[Aneurysmal bone cyst]].
* [[Plasma_cell_neoplasms#Multiple_myeloma|Multiple myeloma]].
====Skull base / Cerebellopontine angle====
* [[Schwannoma]].
* [[Meningioma]].
* [[Dermoid cyst]] / epidermoid cyst.
less common:
* [[Ependymoma]].
* [[Choroid plexus papilloma]].
* [[Glomus tumour]].
* [[Chordoma]].
* [[Chondrosarcoma]].
* [[Olfactory neuroblastoma]].
* [[Endolymphatic sac tumour]].

===Cystic tumours===
DDx:<ref>URL: [http://path.upmc.edu/cases/case320/dx.html http://path.upmc.edu/cases/case320/dx.html]. Accessed on: 14 January 2012.</ref>
*[[Pilocytic astrocytoma]].
*[[Pleomorphic xanthoastrocytoma]].
*[[Ganglioglioma]].
*[[Hemangioblastoma]].
*[[Craniopharyngioma]].<ref>URL: [http://www.pathologyoutlines.com/Cnstumor.html#cystsgeneral http://www.pathologyoutlines.com/Cnstumor.html#cystsgeneral]. Accessed on: 14 January 2012.</ref>

===Primary versus secondary===
*[[AKA]] (primary) brain tumour versus metastatic cancer.
====Primary====
[[Glioma|Glial tumours]]:
*Cytoplasmic processes - '''key feature'''.
**Best seen at highest magnification - usu. ~1 micrometer.
**Processes may branch.
*Ill-defined border/blend with the surrounding brain.

[[Meningioma]]:
*Lesion often dura-based.
*Mesenchymal tumor (often contains collagen).

[[Lymphoma]]:
*Primary CNS Lymphoma (PCNSL) is usu. a diffuse large B-cell lymphoma.
*Large (lymphoid) cells, ergo usu. not a difficult diagnosis.
**~2x size of resting lymphocyte, nucleoli.
*Lesion predominantly perivascular.

====Secondary====
*Carcinomas:
**Well-demarcated border between brain and lesion - '''key feature'''.
**No cytoplasmic processes.
**Usu. have nuclear atypia of malignancy.
**Nuclei often ~3-4x the size of a [[RBC]].
**+/-Glandular arrangement.
**+/-Nucleoli.
*Melanoma.
*Secondary Lymphoma.
*Sarcomas (rare).

===By growth pattern===
====Infiltrative astrocytomas====
*[[Astrocytoma, IDH-mutant]].
*[[Glioblastoma]]IDH-wildtype.

====Non-infiltrative astrocytomas====
**[[Pilocytic astrocytoma]]
**[[Pleomorphic xanthoastrocytoma]]
**[[Subependymal giant cell astrocytoma]].

Notes:
*Glial vs. non-glial tumours:
**Glial: "blends into brain"/gradual transition to non-tumour brain.
**Non-glial: no radiating glial processes.
*Rosenthal fibres within the tumour... often seen in [[pilocytic astrocytoma]].
**Rosenthal fibres may be seen around a (very) slow growing tumour and represent a reactive process.
*Inflammatory cells and macrophages should prompt consideration of an alternate diagnosis (e.g. [[cerebral infarct]], [[multiple sclerosis]]) - esp. if this is a primary lesion.<ref>URL: [http://path.upmc.edu/cases/case79/dx.html http://path.upmc.edu/cases/case79/dx.html]. Accessed on: 2 January 2012.</ref>

====Grading====
Nuclear pleomorphism present:
*At least grade II (diffuse astrocytoma).

Mitotic figures present:
*At least grade III (anaplastic astrocytoma).

Microvascular proliferation ''or'' necrosis with pseudopalisading tumour cells:
*Grade IV (glioblastoma [[AKA]] glioblastoma multiforme).

Notes:
*Pseudopalisading tumour cells = high tumour cell density adjacent to regions of necrosis; palisade = a fence of poles forming a defensive barrier or fortification.
*WHO Grading is currently based on expected biologiocal behaviour without treatment.
**Grading does not reflect molecular divergent groups within a tumor class or response to therapy (Currently controversies in grading for IDH-mutant astrocytoma vs. IDH-wildtype astrocytoma).<ref>{{Cite journal | last1 = Louis | first1 = DN. | last2 = von Deimling | first2 = A. | title = Grading of diffuse astrocytic gliomas: Broders, Kernohan, Zülch, the WHO… and Shakespeare. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Aug | year = 2017 | doi = 10.1007/s00401-017-1765-z | PMID = 28801693 }}</ref>

====Images====
Glioblastoma:
<gallery>
Image:Glioblastoma_%281%29.jpg | Glioblastoma - pseudopalisading of tumour cells (WC)
Image:Glioblastoma_-_high_mag.jpg | Glioblastoma with fragment of near-normal white matter - high mag. (WC)
</gallery>
Anaplastic astrocytoma:
<gallery>
Image:Anaplastic_astrocytoma_-_very_high_mag_-_cropped.jpg | Anaplastic astrocytoma - very high mag. (WC)
Image:Anaplastic_astrocytoma_-_gfap_-_very_high_mag.jpg | Anaplastic astrocytoma - GFAP - very high mag. (WC)
</gallery>

===By IHC===
*GFAP - should stain cytoplasm of tumour cells and the perikaryon (nuclear membrane) of most [[Astrocytoma]]s.
*[[IDH-1]](R132H) (isocitrate dehydrogenase 1) in [[Astrocytoma, IDH-mutant]].<ref name=pmid19228619>{{cite journal |author=Yan H, Parsons DW, Jin G, ''et al.'' |title=IDH1 and IDH2 mutations in gliomas |journal=N. Engl. J. Med. |volume=360 |issue=8 |pages=765–73 |year=2009 |month=February |pmid=19228619 |pmc=2820383 |doi=10.1056/NEJMoa0808710 |url=}}</ref><ref name=pmid20975057>{{cite journal |author=Houillier C, Wang X, Kaloshi G, ''et al.'' |title=IDH1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas |journal=Neurology |volume=75 |issue=17 |pages=1560–6 |year=2010 |month=October |pmid=20975057 |doi=10.1212/WNL.0b013e3181f96282 |url=}}</ref>
*[[H3F3A|H3F3A K27M]] in [[Diffuse midline glioma, H3 K27-altered]].
*[[ATRX]] -ve in [[Astrocytoma, IDH-mutant]] or [[Diffuse hemispheric glioma, H3 G34-mutant]].
*[[CD20]] in PCNSL.
*Cytokeratins in Carcinoma brain metastases, Plexus choroid tumours, [[AT/RT]], [[Papillary tumour of the pineal region]], [[Craniopharyngioma]].

===Common neuropathology tumours in a table===
{| class="wikitable"
|'''Type'''
|'''Key feature(s)'''
|'''Imaging'''
|'''History'''
|'''Notes'''
|'''IHC'''
|'''Images'''
|-
|Normal tissue
|cells regularly spaced, no nuc. atypia
|small lesion? / deep lesion?
|variable
|missed lesion?
|nil
|[[Image:Grey_matter_and_white_matter_-_very_high_mag.jpg |thumb|center|150px|Normal. (WC)]]
|-
|[[Reactive astrocytes]]
|astrocytes with well-demarcated eosinophilic cytoplasm, regular spacing, no nuc. atypia
|small lesion? / deep lesion?
|variable
|missed lesion / close to a lesion; non-specific pathologic process - need more tissue
|GFAP
|[[Image:Reactive_astrocytes_-_lfb_-_high_mag.jpg|thumb|center|150px|Reactive astrocytes. (WC)]]
|-
|[[Schwannoma]]
|cellular areas (Antoni A), paucicelluar areas (Antoni B), palisading of nuclei (Verocay bodies)
|extra-axial + intradural
|old or young
|need frozen section to Dx, DDx: [[meningioma]]
|S100, SOX10
|[[Image:Schwannoma_-_Antoni_A_and_B_-_very_high_mag.jpg|thumb|center|150px|Schwannoma. (WC)]]
|-
|[[Meningioma]]
|whorls, psammomatous calcs, nuclear inclusions
|extra-axial + intradural
|old or young
|may be diagnosed on smear, DDx: [[schwannoma]], choroid plexus
|EMA, PR, Ki-67
|[[Image:Meningioma_intermed_mag.jpg |thumb|center|150px|Meningioma. (WC)]]
|-
|[[Astrocytoma, IDH-mutant]] (CNS [[WHO]] grade 2 or grade 3)
|glial processes (esp. on smear), nuclear atypia (typical size var. ~3x, irreg. nuc. membrane, hyperchromasia), no Rosenthal fibres in the core of the lesion †, no microvascular proliferation, no necrosis
|often enhancing (suggests high grade), usu. supratentorial, usu. white matter
|usu. old, occ. young
|common
|IDH-1(R132H)+/-, GFAP+
| [[Image:Anaplastic_astrocytoma_-_very_high_mag_-_cropped.jpg | thumb| center| 150px|High-grade astrocytoma. (WC)]]
|-
|[[Glioblastoma]], IDH-wildtype (CNS [[WHO]] grade 4)
|glial processes (esp. on smear), nuclear atypia (typical size var. ~3x, irreg. nuc. membrane, hyperchromasia), no Rosenthal fibres in the core of the lesion †, microvascular proliferation or necrosis
|often enhancing (suggests high grade), usu. supratentorial, usu. white matter
|usu. old, occ. young
|very common, esp. glioblastoma
|IDH-1+/-, GFAP+
| [[Image:Glioblastoma (1).jpg | thumb| center| 150px|Glioblastoma. (WC)]]
|-
|[[Metastatic brain tumours|Metastasis]]
|sharp interface with brain, often glandular, +/-nucleoli, no glial processes
|often cerebellular, well-circumscribed
|usu. old
|often suspected to have metastatic disease
|[[TTF-1]], CK7, [[CK20]], BRST-2
|[[Image:Metastatic_adenocarcinoma_-_cerebellum_-_very_low_mag.jpg | thumb| center|150px |Metastasis. (WC)]]
|}
† Rosenthal fibres at the periphery of a lesion are a non-specific finding seen in chronic processes.

==Brain metastasis==
{{Main|Brain metastasis}}

===Molecular===
See also: [[Molecular_pathology_tests#Neuropathology|Molecular Neuropathology]]

==Gliomas==
{{Main|Glioma}}

Gliomas, glioneuronal tumours and neuronal tumours are often categorized together.

===Astrocytic tumours===
{{Main|Astrocytoma}}

* [[Astrocytoma]], IDH-mutant.
* [[Glioblastoma]], IDH-wildtype.
** [[Gliosarcoma]] (a glioblastoma subtype)

Features:<ref name=pmid>{{cite journal |author=Rong Y, Durden DL, Van Meir EG, Brat DJ |title='Pseudopalisading' necrosis in glioblastoma: a familiar morphologic feature that links vascular pathology, hypoxia, and angiogenesis |journal=J. Neuropathol. Exp. Neurol. |volume=65 |issue=6 |pages=529–39 |year=2006 |month=June |pmid=16783163 |doi= |url=}}</ref><ref>[http://dictionary.reference.com/browse/palisading http://dictionary.reference.com/browse/palisading]</ref>
*Glial processes - '''key feature'''.
**Thin stringy cytoplasmic processes - best seen at high power in less cellular areas.
*No Rosenthal fibres within the tumour itself.

Images:
*[http://moon.ouhsc.edu/kfung/jty1/opaq/PathQuiz/N0A002-PQ01-M.htm Endothelial proliferation in a GBM (ouhsc.edu)].
*[http://moon.ouhsc.edu/kfung/jty1/neurotest/Q05-Ans.htm Endothelial proliferation (ouhse.edu)].
*[http://path.upmc.edu/cases/case368.html Gemistocytic astrocytoma - several images (upmc.edu)].

Depreceated:
* Diffuse [[Astrocytoma]]
* [[Anaplastic astrocytoma]]
* [[Gliomatosis cerebri]]
* Spongioblastoma

===Oligodendroglial tumours===
* [[Oligodendroglioma]], IDH-mutant and 1p/19q codeleted.

Depreceated:
* Anaplastic oligodendroglioma
* [[Oligoastrocytoma]]
* Anaplastic oligoastrocytoma

===Pediatric-type diffuse high-grade glioma===
{{Main|Pediatric-type diffuse high-grade glioma}}
* [[Astrocytoma#Diffuse_midline_glioma.2C_H3_K27M_mutant|Diffuse midline glioma H3 K27-mutant]]

===Pediatric-type diffuse low-grade glioma===
{{Main|Pediatric-type diffuse low-grade glioma}}

===Circumscribed astrocytic gliomas===
* [[Pilocytic astrocytoma]] (PA)
** [[Pilomyxoid astrocytoma]] (PMA)
* [[Pleomorphic xanthoastrocytoma]] (PXA)
* [[Subependymal giant cell astrocytoma]] (SEGA)
* [[Neuropathology_tumours#Astroblastoma|Astroblastoma MN1-altered]].
* [[Neuropathology_tumours#Chordoid glioma of the third ventricl|Chordoid glioma]].

====Astroblastoma====
*No WHO grade yet.<ref>{{Ref WHOCNS|88}}</ref>
*Very rare superficial tumor of young age.<ref>{{Cite journal | last1 = Narayan | first1 = S. | last2 = Kapoor | first2 = A. | last3 = Singhal | first3 = MK. | last4 = Jakhar | first4 = SL. | last5 = Bagri | first5 = PK. | last6 = Rajput | first6 = PS. | last7 = Kumar | first7 = HS. | title = Astroblastoma of cerebrum: A rare case report and review of literature. | journal = J Cancer Res Ther | volume = 11 | issue = 3 | pages = 667 | month = | year = | doi = 10.4103/0973-1482.140800 | PMID = 26458709 }}</ref>
*Large, cystic. Pushing margin towards CNS.
*Vasocentric growth, plump cells with absence of fibrillary pattern.
*GFAP+ve, Synaptohysin-ve, Olig-2-ve, focally EMA/panCK+ve. MIB-1: 1-18 %.
*Molecular profile overlaps with classical [[CNS-PNET]].
**Gene fusions invoving meningioma gene (MN1)<ref>{{Cite journal | last1 = Sturm | first1 = D. | last2 = Orr | first2 = BA. | last3 = Toprak | first3 = UH. | last4 = Hovestadt | first4 = V. | last5 = Jones | first5 = DT. | last6 = Capper | first6 = D. | last7 = Sill | first7 = M. | last8 = Buchhalter | first8 = I. | last9 = Northcott | first9 = PA. | title = New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs. | journal = Cell | volume = 164 | issue = 5 | pages = 1060-72 | month = Feb | year = 2016 | doi = 10.1016/j.cell.2016.01.015 | PMID = 26919435 }}</ref>

<gallery>
File:Astroblastoma_HE_Specimen.jpg | HE. (WC/jensflorian)
File:Astroblastoma_HE_papillae.jpg | HE. (WC/jensflorian)
File:Astroblastoma.jpg | Astroblastoma (AFIP)
</gallery>

====Chordoid glioma of the third ventricle====
* WHO grade II.
* Slowly growing, non-invasive, in adults.
* Clusters of epithelioid cells in mucinous stroma.
* Lymphocytic infiltrates, adjacent Rosenthal fibers.
* Fibrosis may be present.
* Few mitoses.
* [[GFAP]]+ve, MIB-1 1-3%.
* [[TTF-1]]+ve.
* CD34+ve.
* [[IDH-1]]-ve, [[p53]]-ve.
* PRKCA D463H mutations.<ref>{{Cite journal | last1 = Goode | first1 = B. | last2 = Mondal | first2 = G. | last3 = Hyun | first3 = M. | last4 = Ruiz | first4 = DG. | last5 = Lin | first5 = YH. | last6 = Van Ziffle | first6 = J. | last7 = Joseph | first7 = NM. | last8 = Onodera | first8 = C. | last9 = Talevich | first9 = E. | title = A recurrent kinase domain mutation in PRKCA defines chordoid glioma of the third ventricle. | journal = Nat Commun | volume = 9 | issue = 1 | pages = 810 | month = 02 | year = 2018 | doi = 10.1038/s41467-018-02826-8 | PMID = 29476136 }}</ref>

<gallery>
File:NP op 20201028 009.jpg | Chordoid Glioma. (WC/jensflorian)
</gallery>

===Ependymal tumours===
* [[Subependymoma]]
* [[Myxopapillary Ependymoma]]
* [[Ependymoma]]
* Anaplastic ependymoma

==Choroid plexus tumours==
* [[Choroid plexus papilloma]]
* Atypical choroid plexus papilloma
* [[Choroid plexus carcinoma]]

==Other neuroepithelial tumours==
* [[Neuropathology_tumours#Cribiform_neuroepithelial_tumour|Cribifiorm neuroepithelial tumour]].

===Cribiform neuroepithelial tumour===
AKA: '''CRINET'''.
*Not listed in the current WHO classification.
*First description in 2009.<ref>{{Cite journal | last1 = Hasselblatt | first1 = M. | last2 = Oyen | first2 = F. | last3 = Gesk | first3 = S. | last4 = Kordes | first4 = U. | last5 = Wrede | first5 = B. | last6 = Bergmann | first6 = M. | last7 = Schmid | first7 = H. | last8 = Frühwald | first8 = MC. | last9 = Schneppenheim | first9 = R. | title = Cribriform neuroepithelial tumor (CRINET): a nonrhabdoid ventricular tumor with INI1 loss and relatively favorable prognosis. | journal = J Neuropathol Exp Neurol | volume = 68 | issue = 12 | pages = 1249-55 | month = Dec | year = 2009 | doi = 10.1097/NEN.0b013e3181c06a51 | PMID = 19915490 }}</ref>
*Around ventricles.<ref>{{Cite journal | last1 = Arnold | first1 = MA. | last2 = Stallings-Archer | first2 = K. | last3 = Marlin | first3 = E. | last4 = Grondin | first4 = R. | last5 = Olshefski | first5 = R. | last6 = Biegel | first6 = JA. | last7 = Pierson | first7 = CR. | title = Cribriform neuroepithelial tumor arising in the lateral ventricle. | journal = Pediatr Dev Pathol | volume = 16 | issue = 4 | pages = 301-7 | month = | year = | doi = 10.2350/12-12-1287-CR.1 | PMID = 23495723 }}</ref>
*Young children.<ref>{{Cite journal | last1 = Park | first1 = JY. | last2 = Kim | first2 = E. | last3 = Kim | first3 = DW. | last4 = Chang | first4 = HW. | last5 = Kim | first5 = SP. | title = Cribriform neuroepithelial tumor in the third ventricle: a case report and literature review. | journal = Neuropathology | volume = 32 | issue = 5 | pages = 570-6 | month = Oct | year = 2012 | doi = 10.1111/j.1440-1789.2011.01293.x | PMID = 22239490 }}</ref>
*Small undifferentiated cells arranged in cribriform strands and trabeculae of varying thickness.
*MAP2+ve, Synaptophysin+ve, CK+/-ve. MIB-1: 30%.
*INI-1 loss, but no rhabdoid features and good prognosis.
*Stable genomic profile.<ref>{{Cite journal | last1 = Gessi | first1 = M. | last2 = Japp | first2 = AS. | last3 = Dreschmann | first3 = V. | last4 = Zur Mühlen | first4 = A. | last5 = Goschzik | first5 = T. | last6 = Dörner | first6 = E. | last7 = Pietsch | first7 = T. | title = High-Resolution Genomic Analysis of Cribriform Neuroepithelial Tumors of the Central Nervous System. | journal = J Neuropathol Exp Neurol | volume = 74 | issue = 10 | pages = 970-4 | month = Oct | year = 2015 | doi = 10.1097/NEN.0000000000000239 | PMID = 26352987 }}</ref>

==Neuronal and mixed neuronal/glial tumours==
* [[Desmoplastic infantile astrocytoma]] / ganglioglioma (DIA/DIG)
* [[Dysembryoplastic neuroepithelial tumour]]
* [[Central Neurocytoma]] / Extraventricular [[neurocytoma]]
* Cerebellar liponeurocytoma
* [[Papillary glioneuronal tumour]] (PGNT)
* [[Rosette-forming glioneuronal tumour of the fourth ventricle]] (RGNT)
* Gangliocytoma / Ganglioglioma
* Dysplastic ganglioglioma of the cerebellum ([[Lhermitte-Duclos disease]])
* [[Paraganglioma]]

===Desmoplastic infantile astrocytoma / Desmoplastic infantile ganglioglioma===
* Abbreviated ''DIA'' or ''DIG''.
* ICD-O code: 9412/1
* Large, superficial, cystic tumor of the infancy.
* Biologic course corresponds to WHO grade I.
* Very rare, included in the WHO since 1993.
* Prominent desmoplastic stroma.
* Astrocytic cells within stroma.
**GFAP+.
**MIB-1 usu. 1%.
* Frequent BRAF V600E or V600D mutations.<ref>{{Cite journal | last1 = Wang | first1 = AC. | last2 = Jones | first2 = DTW. | last3 = Abecassis | first3 = IJ. | last4 = Cole | first4 = BL. | last5 = Leary | first5 = SES. | last6 = Lockwood | first6 = CM. | last7 = Chavez | first7 = L. | last8 = Capper | first8 = D. | last9 = Korshunov | first9 = A. | title = Desmoplastic Infantile Ganglioglioma/Astrocytoma (DIG/DIA) are Distinct Entities with Frequent BRAFV600 Mutations. | journal = Mol Cancer Res | volume = | issue = | pages = | month = Jul | year = 2018 | doi = 10.1158/1541-7786.MCR-17-0507 | PMID = 30006355 }}</ref>
*Single case with BRAF indel or BRAF fusion.
<gallery>
File:DIG-histology.jpg | Histopathology of DIG (HE stain)
File:DIG-histology2.jpg | Prominent ganglioid cells in DIG (HE stain)
</gallery>

===Cerebellar liponeurocytoma===
* Previously called ''lipomatous medulloblastoma'' (name changed in WHO 2000).
* Mean age: 50 years.
* As the name states: A tumour of the cerebellum.
** But cases outside cerebellum reported that would qualify.<ref>{{Cite journal | last1 = Gupta | first1 = K. | last2 = Salunke | first2 = P. | last3 = Kalra | first3 = I. | last4 = Vasishta | first4 = RK. | title = Central liponeurocytoma: case report and review of literature. | journal = Clin Neuropathol | volume = 30 | issue = 2 | pages = 80-5 | month = | year = | doi = | PMID = 21329617 }}</ref>
* WHO grade II <ref>{{Cite journal | last1 = Nishimoto | first1 = T. | last2 = Kaya | first2 = B. | title = Cerebellar liponeurocytoma. | journal = Arch Pathol Lab Med | volume = 136 | issue = 8 | pages = 965-9 | month = Aug | year = 2012 | doi = 10.5858/arpa.2011-0337-RS | PMID = 22849747 }}</ref> (upgraded from WHO grade I in 2007)<ref>{{Cite journal | last1 = Brat | first1 = DJ. | last2 = Parisi | first2 = JE. | last3 = Kleinschmidt-DeMasters | first3 = BK. | last4 = Yachnis | first4 = AT. | last5 = Montine | first5 = TJ. | last6 = Boyer | first6 = PJ. | last7 = Powell | first7 = SZ. | last8 = Prayson | first8 = RA. | last9 = McLendon | first9 = RE. | title = Surgical neuropathology update: a review of changes introduced by the WHO classification of tumours of the central nervous system, 4th edition. | journal = Arch Pathol Lab Med | volume = 132 | issue = 6 | pages = 993-1007 | month = Jun | year = 2008 | doi = 10.1043/1543-2165(2008)132[993:SNUARO]2.0.CO;2 | PMID = 18517285 }}</ref>
*ICD-O code: 9506/1

====Histo====
* Advanced neuronal and lipomatous differentiation.
* Neurocytes: round to oval nuclei with clear cytoplasm.
* Quite cellular.
* Mitoses almost absent.

====IHC====
* [[GFAP]] +/-ve (focal).
* [[MAP2]] +ve.
* Synaptophysin +ve.
* NeuN +ve.
* MIB-1: usu 1-3%.

====Molecular====
* Distinct methylation profile.
* Recurent losses on 2p and Chr. 14.<ref>{{Cite journal | last1 = Capper | first1 = D. | last2 = Stichel | first2 = D. | last3 = Sahm | first3 = F. | last4 = Jones | first4 = DTW. | last5 = Schrimpf | first5 = D. | last6 = Sill | first6 = M. | last7 = Schmid | first7 = S. | last8 = Hovestadt | first8 = V. | last9 = Reuss | first9 = DE. | title = Practical implementation of DNA methylation and copy-number-based CNS tumor diagnostics: the Heidelberg experience. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Jul | year = 2018 | doi = 10.1007/s00401-018-1879-y | PMID = 29967940 }}</ref>

<gallery>
File:Cerebellar liponeurocytoma.jpg | Liponeurocytoma, HE (WC/Marvin101).
File:Liponeurocytoma Synaptophysin.jpg | Liponeurocytoma, Synapto (WC/Marvin101).
File:Cerebellar Liponeurocytoma HE.jpg | Liponeurocytoma, HE (WC/jensflorian).
File:Cerebellar Liponeurocytoma Synaptophysin.jpg | Liponeurocytoma, Synapto (WC/jensflorian).
</gallery>

====DDx====
* [[Medulloblastoma]]
* [[Neurocytoma]]

===Gangliocytoma===
* Grade I WHO neuronal tumour.
** ICD-O code: 9492/0
* Groups of irregular large neurons.
* Non-neoplastic, reticulin-rich glial stroma.

===Ganglioglioma===
:'''Not''' to be confused with ''[[ganglioneuroma]]''.
====General====
*Gangliolioma: Grade I WHO mixed neuronal-glial tumour (ICD-O code: 9505/1).
*Anaplastic ganglioglioma: Grade III (ICD-O: 9505/3)
*Rare (approx. 0.5% of all CNS tumors).
*Usu. temporal lobe.
*Predominantly children (mean age: 9 years).
*Recognized as a cause of [[epilepsy]].<ref name=pmid12125968>{{Cite journal | last1 = Im | first1 = SH. | last2 = Chung | first2 = CK. | last3 = Cho | first3 = BK. | last4 = Lee | first4 = SK. | title = Supratentorial ganglioglioma and epilepsy: postoperative seizure outcome. | journal = J Neurooncol | volume = 57 | issue = 1 | pages = 59-66 | month = Mar | year = 2002 | doi = | PMID = 12125968 }}</ref>
*Favourable prognosis (survival rates up to 97%)
**Insufficient data für anaplastic ganglioglioma.

====Macroscopic====
*Circumscribed lesion.
*Usu. contrast enhancing.
*Solid, but intracortical cysts may be present.
*Little mass effect.

====Microscopic====
Features:
*Dysplastic neurons.
**Out of regular architecture / abnormal location.
**Cytomegaly
**Clustering
**Binucleated (very occassionally).
*Atypical glia.
*Eosinophilic granular bodies.
*Calcification.
*Prominent capillary network.
*Lymphocytic cuffing.
*May contain some reticulin.
*Glial component may resemble:
**Fibrillary astrocytoma.
**Oligodendroglioma.
**Pilocytic astrocytoma.

Anaplastic ganglioglioma:
*Brisk mitotic activity
*Necrosis

====IHC====
*Neurons:
**[[MAP2]] +ve
**Synaptophysin +ve
** Neurofilament +ve
*Glia:
**CD34+/-ve
*BRAF V600E +ve (approx. 25%, mainly ganglion cells).

====Molecular====
*BRAF V600E-mutated(approx. 25%).
*IDH1/2 wt.
*No 1p/19q codeletion.
*Usu. Chr. 7 gain.
*CDKN2A deletions in anaplastic ganglioglioma.

====DDx:====
*[[DNT]].
*[[Oligodendroglioma]].
*Trapped cortical neurons in diffuse astrocytoma.
*Papillary glioneuronal tumor.
*Dysembryoplastic neuroepithelial tumor.

====Images====
<gallery>
File:Ganglioglioma lymphocytic cuffing PAS.jpg | Lymphocytic cuffing in ganglioglioma (WC/jensflorian)
File:Ganglioglioma calcification.jpg | Calcification in ganglioglioma (WC/jensflorian)
File:Ganglioglioma Cd34 x200.jpg | CD34 immunostain in ganglioglioma (WC/jensflorian)
File:Anaplastic ganglioglioma HE.jpg | Pleomorphic ganglion cells in ganglioglioma (WC/jensflorian)
</gallery>
*[http://path.upmc.edu/cases/case142.html Ganglioglioma - case 1 (upmc.edu)].
*[http://path.upmc.edu/cases/case282.html Ganglioglioma - case 2 (upmc.edu)].

===Lhermitte-Duclos disease===
*Abbreviated ''LDD''.
*[[AKA]] ''dysplastic cerebellar gangliocytoma''.<ref name=pmid20060133>{{Cite journal | last1 = Yağci-Küpeli | first1 = B. | last2 = Oguz | first2 = KK. | last3 = Bilen | first3 = MA. | last4 = Yalçin | first4 = B. | last5 = Akalan | first5 = N. | last6 = Büyükpamukçu | first6 = M. | title = An unusual cause of posterior fossa mass: Lhermitte-Duclos disease. | journal = J Neurol Sci | volume = 290 | issue = 1-2 | pages = 138-41 | month = Mar | year = 2010 | doi = 10.1016/j.jns.2009.12.010 | PMID = 20060133 }}</ref>
*[[AKA]] ''dysplastic gangliocytoma of the cerebellum''.
{{Main|Lhermitte-Duclos disease}}
<gallery>
File:Dysplastic_gangliocytoma_lhermitte_duclos.jpg | Dysplastic gangliocytoma (low mag).
</gallery>

===Papillary glioneuronal tumour===
* Abbreviated ''PGNT''.
* A benign, supratentorial tumor of childhood.
** Biologic course corresponds to WHO grade I.
** Before WHO 2000, considered a [[Ganglioglioma]] variant.
*Prominent pseudopapillary architecture.
*Neurocytes to medium-sized ganglion cells.
*GFAP+ core, GFAP- layer
*Rosenthal fibers, Eosinophilic Granular bodies and lymphocytic cuffing may be present.
<gallery>
File:PGNT_HE_stain.jpg | PGNT (HE) (WC/jensflorian)
</gallery>

===Rosette-forming glioneuronal tumour of the fourth ventricle===
* Abbreviated ''RGNT''.
* Provisional ICD-O code: 9509/1
* A rare benign infratentorial tumour of the midline of children and adults.
* Biologic course corresponds to WHO grade I.
* Glial component corresponds to [[pilocytic astrocytoma]].
* Neurocytic rosettes.
* Eosinopil fibrillary cores / pseudorosettes.
* GFAP+ in fibrillary areas, Syn+ in rosettes.
* Neurocytic cells: MAP2+
* MIB-1 usu. below 3%.
<gallery>
File:Histology RGNT HE.jpg | RGNT, HE stain (WC/jensflorian).
File:RGNT HE 2.jpg | RGNT, higher magnification (WC/jensflorian).
</gallery>

===Polymorphous low-grade tumor of the young (PLNTY)===
* [[Pediatric-type diffuse low-grade glioma#Diffuse low-grade glioma, MAPK pathway-altered|Polymorphous low-grade tumor of the young (PLNTY)]]

==Pineal tumours==
{{Main|Pineal gland}}

* [[Pineocytoma]]
* [[Pineal parenchymal tumour of intermediate differentiation]]
* [[Pineoblastoma]]
* [[Papillary tumour of the pineal region]]

==Embryonal tumours==
* [[Atypical teratoid/rhabdoid tumour]] (AT/RT) or (AT-RT)
* [[Medulloblastoma]]
* [[Primitive neuroectodermal tumour]] (PNET)
* [[Embryonal tumour with abundant neuropil and true rosettes]] (ETANTR)

DDx:
* [[Ewing sarcoma]]
* [[Sarcoma with CIC-rearrangement]]

==Peripheral nerve sheath tumours==
{{Main|Peripheral nerve sheath tumours}}
A classification:<ref name=pmid17893219>{{cite journal |author=Wippold FJ, Lubner M, Perrin RJ, Lämmle M, Perry A |title=Neuropathology for the neuroradiologist: Antoni A and Antoni B tissue patterns |journal=AJNR Am J Neuroradiol |volume=28 |issue=9 |pages=1633–8 |year=2007 |month=October |pmid=17893219 |doi=10.3174/ajnr.A0682 |url=http://www.ajnr.org/cgi/reprint/28/9/1633}}</ref>
'''Benign:'''
*[[Schwannoma]].
*[[Neurofibroma]].
*[[Perineurioma]].
*Ganglioneuroma.
**[[Traumatic neuroma]].
'''Malignant:'''
*[[Malignant peripheral nerve sheath tumour]] (MPNST).

===Ganglioneuroma===
:'''Not''' to be confused with ''[[ganglioglioma]]''.
*[[AKA]] ganglioma.<ref>URL: [http://medical-dictionary.thefreedictionary.com/ganglioma http://medical-dictionary.thefreedictionary.com/ganglioma]. Accessed on: 8 November 2010.</ref>
{{Main|Ganglioneuroma}}

==Meningioma==
{{Main|Meningioma}}

==Chordoma==
{{Main|Chordoma}}

==Hemangioblastoma==
{{Main|Hemangioblastoma}}

==CNS lymphoma==
Classification:
*Primary CNS lymphoma.
*Non-primary CNS lymphoma - see ''[[lymphoma]]'' article.

===General - primary CNS===
*Classically periventicular distribution.
*Usually large B cell; can be considered a type of [[diffuse large B cell lymphoma]] (DLBCL).
**Prognosis of CNS (DLBCL) lymphomas worse than nodal (non-CNS) DLBCL.<ref name=pmid19925562>{{cite journal |author=Raoux D, Duband S, Forest F, ''et al.'' |title=Primary central nervous system lymphoma: Immunohistochemical profile and prognostic significance |journal=Neuropathology |volume=30 |issue=3 |pages=232–40 |year=2010 |month=June |pmid=19925562 |doi=10.1111/j.1440-1789.2009.01074.x |url=}}</ref>

===Microscopic===
Features:
*Large cell lymphoma.
**Size = 2x diameter normal lymphocyte.
**Nucleolus - common.
*Perivascular clustering.

====Images====
www:
*[http://frontalcortex.com/?page=image&topic=1&qid=1237 CNS lymphoma (frontalcortex.com)].
*[http://path.upmc.edu/cases/case403.html Primary CNS lymphoma - several images (upmc.edu)].
<gallery>
Image:Primary CNS lymphoma - low mag.jpg | CNS lymphoma - low mag. (WC)
Image:Primary CNS lymphoma - intermed mag.jpg | CNS lymphoma - intermed. mag. (WC)
Image:Primary CNS lymphoma - high mag.jpg | CNS lymphoma - high mag. (WC)
Image:Primary CNS lymphoma - very high mag.jpg | CNS lymphoma - very high mag. (WC)
</gallery>
<gallery>
Image: CNS lymphoma (1) B-cell type.jpg | CNS lymphoma. (WC/KGH)
Image: CNS lymphoma (2) B-cell type.jpg | CNS lymphoma. (WC/KGH)
</gallery>

===IHC===
Can be subclassified in ''GCB (germinal centre B-cell-like)'' and ''non-GCB'' by CD10, Bcl-6, MUM1/IRF-4, and Bcl-2.<ref name=pmid19925562/>

Common pattern:
*[[CD20]] +ve - key stain.
*CD3 -ve.
*Ki-67 ~40%.
*Bcl-6 +ve.
*Bcl-1 -ve.

==Ganglioneuroblastoma==
{{Main|Neuroblastoma}}
===General===
*Uncommon.
*Part of the ''neuroblastic tumours'' group which includes:<ref name=pmid10421272>{{cite journal |author=Shimada H, Ambros IM, Dehner LP, Hata J, Joshi VV, Roald B |title=Terminology and morphologic criteria of neuroblastic tumors: recommendations by the International Neuroblastoma Pathology Committee |journal=Cancer |volume=86 |issue=2 |pages=349–63 |year=1999 |month=July |pmid=10421272 |doi= |url=}}</ref>
**[[Ganglioneuroma]] (benign).
**Ganglioneuroblastoma (intermediate).
**[[Neuroblastoma]] (aggressive).

===Microscopic===
Features:
*Ganglion-like cells with a prominent nucleolus.
*Small undifferentiated cells with scant cytoplasm.
<gallery>
Image:Adrenal Ganglioneuroblastoma LP CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - Low power (SKB)
Image:Adrenal Ganglioneuroblastoma MP CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - Medium power (SKB)
Image:Adrenal Ganglioneuroblastoma HP CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - High power (SKB)
Image:Adrenal Ganglioneuroblastoma HP3 CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - High power (SKB)
Image:Adrenal Ganglioneuroblastoma HP2 CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - High power (SKB)
</gallery>
Images:
*[http://path.upmc.edu/cases/case530.html Ganglioneuroblastoma - several images (upmc.edu)].

===IHC===
*NSE +ve -- small cells.

==Lesions of the sella turcica==
{{Main|Pituitary gland}}
Lesions of the sella turcica, the pituitary gland environs, is a topic for it self. The differential diagnosis for lesions in this area includes:
*[[Pituitary adenoma]].
*[[Craniopharyngioma]].
*[[Rathke cleft cyst]].
*[[Germ cell tumour]].
*[[Meningioma]].
*[[Pilomyxoid astrocytoma]] - in children.

==See also==
*[[Neuropathology]].
*[[Muscle biopsy]].

==References==
{{reflist|2}}

==External links==
*[http://www.neuropathologyweb.org/ Neuropathology (neuropathologyweb.org)].
*[http://www.pathology.vcu.edu/WirSelfInst/tumor-1.html Neuropathology Mini-Course (pathology.vcu.edu)].
*[http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html Neuropathology Mini-Course (pathology.vcu.edu)].

[[Category:Neuropathology]]

Neuropathology tumours

2022-04-13T11:58:58Z

Jensflorian: Cleaning up

[[Image:Gemistocytic Astrocytoma 003.jpg|thumb|right|A brain stem [[astrocytoma]]. (WC)]]
The article covers '''tumours in neuropathology'''. Tumours are a large part of [[neuropathology]]. [[Cytopathology]] of CNS tumours is dealt with in the article ''[[CNS cytopathology]]''.

There are separate articles for ''[[peripheral nerve sheath tumours]]'' and ''[[pituitary gland|pituitary/peri-pituitary lesions]]''.

==Brain tumours - overview==
===Alphabetical===
For overview see [[:Category:Neuropathology_tumours|here]]

===By age group===
====Adult====
Four most common types of brain tumours:<ref>[http://neurosurgery.mgh.harvard.edu/abta/primer.htm http://neurosurgery.mgh.harvard.edu/abta/primer.htm]</ref>
# Metastatic brain tumours (barely edges out primary tumours)
#*[[Lung cancer|Lung]] (most common).
#*[[Invasive breast cancer|Breast]].
#*[[Melanoma]].
#*[[Renal cell carcinoma]] (RCC).
# [[Glioblastoma]], IDH-wildtype.
# [[Astrocytoma, IDH-mutant]].
# [[Meningioma]].

====Children====
# [[Pilocytic astrocytoma]].
# [[Medulloblastoma]].
# [[Ependymoma]].
# Pontine glioma, often [[Diffuse midline glioma, H3 K27-altered]].

===By location===
Certain tumours like to hang-out at certain places:<ref>URL: [http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/files/4ce563fb7e8e48fc9ed8b42e296a7747.gif http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/files/4ce563fb7e8e48fc9ed8b42e296a7747.gif] and [http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html]. Accessed on: 2 November 2010.</ref>
====Cerebrum====
*Cortical based - [[oligodendroglioma]].
*Grey-white junction - metastases.
*White matter - astrocytoma, [[glioblastoma]].
*Periventricular - CNS lymphoma.
*Cystic - [[ganglioglioma]], [[pilocytic astrocytoma]], [[pleomorphic xanthoastrocytoma]].
====Cerebellum====
*Midline/central - [[medulloblastoma]].
*Cystic lesion - pilocytic astrocytoma (younger individual), [[hemangioblastoma]] (older individual).
*Solid lesion (older individual) - [[metastasis]].
====Sella turcica====
* [[Pituitary adenoma]].
* [[Craniopharyngioma]].
less common:
* [[Pituicytoma]].
* [[Granular cell tumour]].
* [[Germinoma]].
* [[Chordoma]]
* Rathke cleft cyst.
* Hypophysitis.
* Xanthogranuloma.
====Spinal cord====
*[[Ependymoma]]
*[[Glioblastoma]]
*[[Meningioma]]
*Carcinoma metastasis
*[[Hemangioblastoma]]
====Filum terminale====
*[[Meningioma]].
*[[Myxopapillary ependymoma]].
*[[Neurofibroma]].
*[[Schwannoma]].
*[[Paraganglioma]].
====Meninges====
* [[Meningioma]].
* [[Solitary fibrous tumour]] / Hemangiopericytoma.
* [[Hemangioblastoma]].
less common:
* [[Melanoma]] / Melanocytoma.
* Lymphoproliferative diseases.
* [[Sarcoidosis]]
* [[Arachnoid cyst]].
* Disseminated oligodendroglial-like leptomeningeal tumour.
* Desmoplastic infantile astrocytoma / ganglioglioma.
* Meningioangiomatosis.
* Calcifying pseudoneoplasm.
====Skull====
* [[Fibrous dysplasia]].
* [[Paget disease]].
* [[Histiocytosis]].
* [[Hemangioma]].
* [[Aneurysmal bone cyst]].
* [[Plasma_cell_neoplasms#Multiple_myeloma|Multiple myeloma]].
====Skull base / Cerebellopontine angle====
* [[Schwannoma]].
* [[Meningioma]].
* [[Dermoid cyst]] / epidermoid cyst.
less common:
* [[Ependymoma]].
* [[Choroid plexus papilloma]].
* [[Glomus tumour]].
* [[Chordoma]].
* [[Chondrosarcoma]].
* [[Olfactory neuroblastoma]].
* [[Endolymphatic sac tumour]].

===Cystic tumours===
DDx:<ref>URL: [http://path.upmc.edu/cases/case320/dx.html http://path.upmc.edu/cases/case320/dx.html]. Accessed on: 14 January 2012.</ref>
*[[Pilocytic astrocytoma]].
*[[Pleomorphic xanthoastrocytoma]].
*[[Ganglioglioma]].
*[[Hemangioblastoma]].
*[[Craniopharyngioma]].<ref>URL: [http://www.pathologyoutlines.com/Cnstumor.html#cystsgeneral http://www.pathologyoutlines.com/Cnstumor.html#cystsgeneral]. Accessed on: 14 January 2012.</ref>

===Primary versus secondary===
*[[AKA]] (primary) brain tumour versus metastatic cancer.
====Primary====
[[Glioma|Glial tumours]]:
*Cytoplasmic processes - '''key feature'''.
**Best seen at highest magnification - usu. ~1 micrometer.
**Processes may branch.
*Ill-defined border/blend with the surrounding brain.

[[Meningioma]]:
*Lesion often dura-based.
*Mesenchymal tumor (often contains collagen).

[[Lymphoma]]:
*Primary CNS Lymphoma (PCNSL) is usu. a diffuse large B-cell lymphoma.
*Large (lymphoid) cells, ergo usu. not a difficult diagnosis.
**~2x size of resting lymphocyte, nucleoli.
*Lesion predominantly perivascular.

====Secondary====
*Carcinomas:
**Well-demarcated border between brain and lesion - '''key feature'''.
**No cytoplasmic processes.
**Usu. have nuclear atypia of malignancy.
**Nuclei often ~3-4x the size of a [[RBC]].
**+/-Glandular arrangement.
**+/-Nucleoli.
*Melanoma.
*Secondary Lymphoma.
*Sarcomas (rare).

===By growth pattern===
====Infiltrative astrocytomas====
*[[Astrocytoma, IDH-mutant]].
*[[Glioblastoma]]IDH-wildtype.

====Non-infiltrative astrocytomas====
**[[Pilocytic astrocytoma]]
**[[Pleomorphic xanthoastrocytoma]]
**[[Subependymal giant cell astrocytoma]].

Notes:
*Glial vs. non-glial tumours:
**Glial: "blends into brain"/gradual transition to non-tumour brain.
**Non-glial: no radiating glial processes.
*Rosenthal fibres within the tumour... often seen in [[pilocytic astrocytoma]].
**Rosenthal fibres may be seen around a (very) slow growing tumour and represent a reactive process.
*Inflammatory cells and macrophages should prompt consideration of an alternate diagnosis (e.g. [[cerebral infarct]], [[multiple sclerosis]]) - esp. if this is a primary lesion.<ref>URL: [http://path.upmc.edu/cases/case79/dx.html http://path.upmc.edu/cases/case79/dx.html]. Accessed on: 2 January 2012.</ref>

====Grading====
Nuclear pleomorphism present:
*At least grade II (diffuse astrocytoma).

Mitotic figures present:
*At least grade III (anaplastic astrocytoma).

Microvascular proliferation ''or'' necrosis with pseudopalisading tumour cells:
*Grade IV (glioblastoma [[AKA]] glioblastoma multiforme).

Notes:
*Pseudopalisading tumour cells = high tumour cell density adjacent to regions of necrosis; palisade = a fence of poles forming a defensive barrier or fortification.
*WHO Grading is currently based on expected biologiocal behaviour without treatment.
**Grading does not reflect molecular divergent groups within a tumor class or response to therapy (Currently controversies in grading for IDH-mutant astrocytoma vs. IDH-wildtype astrocytoma).<ref>{{Cite journal | last1 = Louis | first1 = DN. | last2 = von Deimling | first2 = A. | title = Grading of diffuse astrocytic gliomas: Broders, Kernohan, Zülch, the WHO… and Shakespeare. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Aug | year = 2017 | doi = 10.1007/s00401-017-1765-z | PMID = 28801693 }}</ref>

====Images====
Glioblastoma:
<gallery>
Image:Glioblastoma_%281%29.jpg | Glioblastoma - pseudopalisading of tumour cells (WC)
Image:Glioblastoma_-_high_mag.jpg | Glioblastoma with fragment of near-normal white matter - high mag. (WC)
</gallery>
Anaplastic astrocytoma:
<gallery>
Image:Anaplastic_astrocytoma_-_very_high_mag_-_cropped.jpg | Anaplastic astrocytoma - very high mag. (WC)
Image:Anaplastic_astrocytoma_-_gfap_-_very_high_mag.jpg | Anaplastic astrocytoma - GFAP - very high mag. (WC)
</gallery>

===IHC===
*GFAP - should stain cytoplasm of tumour cells and the perikaryon (nuclear membrane).
*Ki-67 - usu. high >20% of cells.
*p53 - often +ve.
*[[IDH-1]] (isocitrate dehydrogenase 1).
**+ve in tumours that arose from low-grade gliomas.<ref name=pmid19228619>{{cite journal |author=Yan H, Parsons DW, Jin G, ''et al.'' |title=IDH1 and IDH2 mutations in gliomas |journal=N. Engl. J. Med. |volume=360 |issue=8 |pages=765–73 |year=2009 |month=February |pmid=19228619 |pmc=2820383 |doi=10.1056/NEJMoa0808710 |url=}}</ref>
*[[H3F3A|H3F3A K27M]] -ve
**+ve cases to be classified as [[Astrocytoma#H3.3_K27M_mutated_glioma_of_the_midline|K27 mutated midline glioma]].
*[[ATRX]] -ve in tumors with low-grade precursor(most of them also IDH1/2 mutant).

Notes:
*IDH1 and IDH2 mutations - better survival.<ref name=pmid20975057>{{cite journal |author=Houillier C, Wang X, Kaloshi G, ''et al.'' |title=IDH1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas |journal=Neurology |volume=75 |issue=17 |pages=1560–6 |year=2010 |month=October |pmid=20975057 |doi=10.1212/WNL.0b013e3181f96282 |url=}}</ref>

===Common neuropathology tumours in a table===
{| class="wikitable"
|'''Type'''
|'''Key feature(s)'''
|'''Imaging'''
|'''History'''
|'''Notes'''
|'''IHC'''
|'''Images'''
|-
|Normal tissue
|cells regularly spaced, no nuc. atypia
|small lesion? / deep lesion?
|variable
|missed lesion?
|nil
|[[Image:Grey_matter_and_white_matter_-_very_high_mag.jpg |thumb|center|150px|Normal. (WC)]]
|-
|[[Reactive astrocytes]]
|astrocytes with well-demarcated eosinophilic cytoplasm, regular spacing, no nuc. atypia
|small lesion? / deep lesion?
|variable
|missed lesion / close to a lesion; non-specific pathologic process - need more tissue
|GFAP
|[[Image:Reactive_astrocytes_-_lfb_-_high_mag.jpg|thumb|center|150px|Reactive astrocytes. (WC)]]
|-
|[[Schwannoma]]
|cellular areas (Antoni A), paucicelluar areas (Antoni B), palisading of nuclei (Verocay bodies)
|extra-axial + intradural
|old or young
|need frozen section to Dx, DDx: [[meningioma]]
|S100, SOX10
|[[Image:Schwannoma_-_Antoni_A_and_B_-_very_high_mag.jpg|thumb|center|150px|Schwannoma. (WC)]]
|-
|[[Meningioma]]
|whorls, psammomatous calcs, nuclear inclusions
|extra-axial + intradural
|old or young
|may be diagnosed on smear, DDx: [[schwannoma]], choroid plexus
|EMA, PR, Ki-67
|[[Image:Meningioma_intermed_mag.jpg |thumb|center|150px|Meningioma. (WC)]]
|-
|[[Astrocytoma, IDH-mutant]] (CNS [[WHO]] grade 2 or grade 3)
|glial processes (esp. on smear), nuclear atypia (typical size var. ~3x, irreg. nuc. membrane, hyperchromasia), no Rosenthal fibres in the core of the lesion †, no microvascular proliferation, no necrosis
|often enhancing (suggests high grade), usu. supratentorial, usu. white matter
|usu. old, occ. young
|common
|IDH-1(R132H)+/-, GFAP+
| [[Image:Anaplastic_astrocytoma_-_very_high_mag_-_cropped.jpg | thumb| center| 150px|High-grade astrocytoma. (WC)]]
|-
|[[Glioblastoma]], IDH-wildtype (CNS [[WHO]] grade 4)
|glial processes (esp. on smear), nuclear atypia (typical size var. ~3x, irreg. nuc. membrane, hyperchromasia), no Rosenthal fibres in the core of the lesion †, microvascular proliferation or necrosis
|often enhancing (suggests high grade), usu. supratentorial, usu. white matter
|usu. old, occ. young
|very common, esp. glioblastoma
|IDH-1+/-, GFAP+
| [[Image:Glioblastoma (1).jpg | thumb| center| 150px|Glioblastoma. (WC)]]
|-
|[[Metastatic brain tumours|Metastasis]]
|sharp interface with brain, often glandular, +/-nucleoli, no glial processes
|often cerebellular, well-circumscribed
|usu. old
|often suspected to have metastatic disease
|[[TTF-1]], CK7, [[CK20]], BRST-2
|[[Image:Metastatic_adenocarcinoma_-_cerebellum_-_very_low_mag.jpg | thumb| center|150px |Metastasis. (WC)]]
|}
† Rosenthal fibres at the periphery of a lesion are a non-specific finding seen in chronic processes.

==Brain metastasis==
{{Main|Brain metastasis}}

===Molecular===
See also: [[Molecular_pathology_tests#Neuropathology|Molecular Neuropathology]]

==Gliomas==
{{Main|Glioma}}

Gliomas, glioneuronal tumours and neuronal tumours are often categorized together.

===Astrocytic tumours===
{{Main|Astrocytoma}}

* [[Astrocytoma]], IDH-mutant.
* [[Glioblastoma]], IDH-wildtype.
** [[Gliosarcoma]] (a glioblastoma subtype)

Features:<ref name=pmid>{{cite journal |author=Rong Y, Durden DL, Van Meir EG, Brat DJ |title='Pseudopalisading' necrosis in glioblastoma: a familiar morphologic feature that links vascular pathology, hypoxia, and angiogenesis |journal=J. Neuropathol. Exp. Neurol. |volume=65 |issue=6 |pages=529–39 |year=2006 |month=June |pmid=16783163 |doi= |url=}}</ref><ref>[http://dictionary.reference.com/browse/palisading http://dictionary.reference.com/browse/palisading]</ref>
*Glial processes - '''key feature'''.
**Thin stringy cytoplasmic processes - best seen at high power in less cellular areas.
*No Rosenthal fibres within the tumour itself.

Images:
*[http://moon.ouhsc.edu/kfung/jty1/opaq/PathQuiz/N0A002-PQ01-M.htm Endothelial proliferation in a GBM (ouhsc.edu)].
*[http://moon.ouhsc.edu/kfung/jty1/neurotest/Q05-Ans.htm Endothelial proliferation (ouhse.edu)].
*[http://path.upmc.edu/cases/case368.html Gemistocytic astrocytoma - several images (upmc.edu)].

Depreceated:
* Diffuse [[Astrocytoma]]
* [[Anaplastic astrocytoma]]
* [[Gliomatosis cerebri]]
* Spongioblastoma

===Oligodendroglial tumours===
* [[Oligodendroglioma]], IDH-mutant and 1p/19q codeleted.

Depreceated:
* Anaplastic oligodendroglioma
* [[Oligoastrocytoma]]
* Anaplastic oligoastrocytoma

===Pediatric-type diffuse high-grade glioma===
{{Main|Pediatric-type diffuse high-grade glioma}}
* [[Astrocytoma#Diffuse_midline_glioma.2C_H3_K27M_mutant|Diffuse midline glioma H3 K27-mutant]]

===Pediatric-type diffuse low-grade glioma===
{{Main|Pediatric-type diffuse low-grade glioma}}

===Circumscribed astrocytic gliomas===
* [[Pilocytic astrocytoma]] (PA)
** [[Pilomyxoid astrocytoma]] (PMA)
* [[Pleomorphic xanthoastrocytoma]] (PXA)
* [[Subependymal giant cell astrocytoma]] (SEGA)
* [[Neuropathology_tumours#Astroblastoma|Astroblastoma MN1-altered]].
* [[Neuropathology_tumours#Chordoid glioma of the third ventricl|Chordoid glioma]].

====Astroblastoma====
*No WHO grade yet.<ref>{{Ref WHOCNS|88}}</ref>
*Very rare superficial tumor of young age.<ref>{{Cite journal | last1 = Narayan | first1 = S. | last2 = Kapoor | first2 = A. | last3 = Singhal | first3 = MK. | last4 = Jakhar | first4 = SL. | last5 = Bagri | first5 = PK. | last6 = Rajput | first6 = PS. | last7 = Kumar | first7 = HS. | title = Astroblastoma of cerebrum: A rare case report and review of literature. | journal = J Cancer Res Ther | volume = 11 | issue = 3 | pages = 667 | month = | year = | doi = 10.4103/0973-1482.140800 | PMID = 26458709 }}</ref>
*Large, cystic. Pushing margin towards CNS.
*Vasocentric growth, plump cells with absence of fibrillary pattern.
*GFAP+ve, Synaptohysin-ve, Olig-2-ve, focally EMA/panCK+ve. MIB-1: 1-18 %.
*Molecular profile overlaps with classical [[CNS-PNET]].
**Gene fusions invoving meningioma gene (MN1)<ref>{{Cite journal | last1 = Sturm | first1 = D. | last2 = Orr | first2 = BA. | last3 = Toprak | first3 = UH. | last4 = Hovestadt | first4 = V. | last5 = Jones | first5 = DT. | last6 = Capper | first6 = D. | last7 = Sill | first7 = M. | last8 = Buchhalter | first8 = I. | last9 = Northcott | first9 = PA. | title = New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs. | journal = Cell | volume = 164 | issue = 5 | pages = 1060-72 | month = Feb | year = 2016 | doi = 10.1016/j.cell.2016.01.015 | PMID = 26919435 }}</ref>

<gallery>
File:Astroblastoma_HE_Specimen.jpg | HE. (WC/jensflorian)
File:Astroblastoma_HE_papillae.jpg | HE. (WC/jensflorian)
File:Astroblastoma.jpg | Astroblastoma (AFIP)
</gallery>

====Chordoid glioma of the third ventricle====
* WHO grade II.
* Slowly growing, non-invasive, in adults.
* Clusters of epithelioid cells in mucinous stroma.
* Lymphocytic infiltrates, adjacent Rosenthal fibers.
* Fibrosis may be present.
* Few mitoses.
* [[GFAP]]+ve, MIB-1 1-3%.
* [[TTF-1]]+ve.
* CD34+ve.
* [[IDH-1]]-ve, [[p53]]-ve.
* PRKCA D463H mutations.<ref>{{Cite journal | last1 = Goode | first1 = B. | last2 = Mondal | first2 = G. | last3 = Hyun | first3 = M. | last4 = Ruiz | first4 = DG. | last5 = Lin | first5 = YH. | last6 = Van Ziffle | first6 = J. | last7 = Joseph | first7 = NM. | last8 = Onodera | first8 = C. | last9 = Talevich | first9 = E. | title = A recurrent kinase domain mutation in PRKCA defines chordoid glioma of the third ventricle. | journal = Nat Commun | volume = 9 | issue = 1 | pages = 810 | month = 02 | year = 2018 | doi = 10.1038/s41467-018-02826-8 | PMID = 29476136 }}</ref>

<gallery>
File:NP op 20201028 009.jpg | Chordoid Glioma. (WC/jensflorian)
</gallery>

===Ependymal tumours===
* [[Subependymoma]]
* [[Myxopapillary Ependymoma]]
* [[Ependymoma]]
* Anaplastic ependymoma

==Choroid plexus tumours==
* [[Choroid plexus papilloma]]
* Atypical choroid plexus papilloma
* [[Choroid plexus carcinoma]]

==Other neuroepithelial tumours==
* [[Neuropathology_tumours#Cribiform_neuroepithelial_tumour|Cribifiorm neuroepithelial tumour]].

===Cribiform neuroepithelial tumour===
AKA: '''CRINET'''.
*Not listed in the current WHO classification.
*First description in 2009.<ref>{{Cite journal | last1 = Hasselblatt | first1 = M. | last2 = Oyen | first2 = F. | last3 = Gesk | first3 = S. | last4 = Kordes | first4 = U. | last5 = Wrede | first5 = B. | last6 = Bergmann | first6 = M. | last7 = Schmid | first7 = H. | last8 = Frühwald | first8 = MC. | last9 = Schneppenheim | first9 = R. | title = Cribriform neuroepithelial tumor (CRINET): a nonrhabdoid ventricular tumor with INI1 loss and relatively favorable prognosis. | journal = J Neuropathol Exp Neurol | volume = 68 | issue = 12 | pages = 1249-55 | month = Dec | year = 2009 | doi = 10.1097/NEN.0b013e3181c06a51 | PMID = 19915490 }}</ref>
*Around ventricles.<ref>{{Cite journal | last1 = Arnold | first1 = MA. | last2 = Stallings-Archer | first2 = K. | last3 = Marlin | first3 = E. | last4 = Grondin | first4 = R. | last5 = Olshefski | first5 = R. | last6 = Biegel | first6 = JA. | last7 = Pierson | first7 = CR. | title = Cribriform neuroepithelial tumor arising in the lateral ventricle. | journal = Pediatr Dev Pathol | volume = 16 | issue = 4 | pages = 301-7 | month = | year = | doi = 10.2350/12-12-1287-CR.1 | PMID = 23495723 }}</ref>
*Young children.<ref>{{Cite journal | last1 = Park | first1 = JY. | last2 = Kim | first2 = E. | last3 = Kim | first3 = DW. | last4 = Chang | first4 = HW. | last5 = Kim | first5 = SP. | title = Cribriform neuroepithelial tumor in the third ventricle: a case report and literature review. | journal = Neuropathology | volume = 32 | issue = 5 | pages = 570-6 | month = Oct | year = 2012 | doi = 10.1111/j.1440-1789.2011.01293.x | PMID = 22239490 }}</ref>
*Small undifferentiated cells arranged in cribriform strands and trabeculae of varying thickness.
*MAP2+ve, Synaptophysin+ve, CK+/-ve. MIB-1: 30%.
*INI-1 loss, but no rhabdoid features and good prognosis.
*Stable genomic profile.<ref>{{Cite journal | last1 = Gessi | first1 = M. | last2 = Japp | first2 = AS. | last3 = Dreschmann | first3 = V. | last4 = Zur Mühlen | first4 = A. | last5 = Goschzik | first5 = T. | last6 = Dörner | first6 = E. | last7 = Pietsch | first7 = T. | title = High-Resolution Genomic Analysis of Cribriform Neuroepithelial Tumors of the Central Nervous System. | journal = J Neuropathol Exp Neurol | volume = 74 | issue = 10 | pages = 970-4 | month = Oct | year = 2015 | doi = 10.1097/NEN.0000000000000239 | PMID = 26352987 }}</ref>

==Neuronal and mixed neuronal/glial tumours==
* [[Desmoplastic infantile astrocytoma]] / ganglioglioma (DIA/DIG)
* [[Dysembryoplastic neuroepithelial tumour]]
* [[Central Neurocytoma]] / Extraventricular [[neurocytoma]]
* Cerebellar liponeurocytoma
* [[Papillary glioneuronal tumour]] (PGNT)
* [[Rosette-forming glioneuronal tumour of the fourth ventricle]] (RGNT)
* Gangliocytoma / Ganglioglioma
* Dysplastic ganglioglioma of the cerebellum ([[Lhermitte-Duclos disease]])
* [[Paraganglioma]]

===Desmoplastic infantile astrocytoma / Desmoplastic infantile ganglioglioma===
* Abbreviated ''DIA'' or ''DIG''.
* ICD-O code: 9412/1
* Large, superficial, cystic tumor of the infancy.
* Biologic course corresponds to WHO grade I.
* Very rare, included in the WHO since 1993.
* Prominent desmoplastic stroma.
* Astrocytic cells within stroma.
**GFAP+.
**MIB-1 usu. 1%.
* Frequent BRAF V600E or V600D mutations.<ref>{{Cite journal | last1 = Wang | first1 = AC. | last2 = Jones | first2 = DTW. | last3 = Abecassis | first3 = IJ. | last4 = Cole | first4 = BL. | last5 = Leary | first5 = SES. | last6 = Lockwood | first6 = CM. | last7 = Chavez | first7 = L. | last8 = Capper | first8 = D. | last9 = Korshunov | first9 = A. | title = Desmoplastic Infantile Ganglioglioma/Astrocytoma (DIG/DIA) are Distinct Entities with Frequent BRAFV600 Mutations. | journal = Mol Cancer Res | volume = | issue = | pages = | month = Jul | year = 2018 | doi = 10.1158/1541-7786.MCR-17-0507 | PMID = 30006355 }}</ref>
*Single case with BRAF indel or BRAF fusion.
<gallery>
File:DIG-histology.jpg | Histopathology of DIG (HE stain)
File:DIG-histology2.jpg | Prominent ganglioid cells in DIG (HE stain)
</gallery>

===Cerebellar liponeurocytoma===
* Previously called ''lipomatous medulloblastoma'' (name changed in WHO 2000).
* Mean age: 50 years.
* As the name states: A tumour of the cerebellum.
** But cases outside cerebellum reported that would qualify.<ref>{{Cite journal | last1 = Gupta | first1 = K. | last2 = Salunke | first2 = P. | last3 = Kalra | first3 = I. | last4 = Vasishta | first4 = RK. | title = Central liponeurocytoma: case report and review of literature. | journal = Clin Neuropathol | volume = 30 | issue = 2 | pages = 80-5 | month = | year = | doi = | PMID = 21329617 }}</ref>
* WHO grade II <ref>{{Cite journal | last1 = Nishimoto | first1 = T. | last2 = Kaya | first2 = B. | title = Cerebellar liponeurocytoma. | journal = Arch Pathol Lab Med | volume = 136 | issue = 8 | pages = 965-9 | month = Aug | year = 2012 | doi = 10.5858/arpa.2011-0337-RS | PMID = 22849747 }}</ref> (upgraded from WHO grade I in 2007)<ref>{{Cite journal | last1 = Brat | first1 = DJ. | last2 = Parisi | first2 = JE. | last3 = Kleinschmidt-DeMasters | first3 = BK. | last4 = Yachnis | first4 = AT. | last5 = Montine | first5 = TJ. | last6 = Boyer | first6 = PJ. | last7 = Powell | first7 = SZ. | last8 = Prayson | first8 = RA. | last9 = McLendon | first9 = RE. | title = Surgical neuropathology update: a review of changes introduced by the WHO classification of tumours of the central nervous system, 4th edition. | journal = Arch Pathol Lab Med | volume = 132 | issue = 6 | pages = 993-1007 | month = Jun | year = 2008 | doi = 10.1043/1543-2165(2008)132[993:SNUARO]2.0.CO;2 | PMID = 18517285 }}</ref>
*ICD-O code: 9506/1

====Histo====
* Advanced neuronal and lipomatous differentiation.
* Neurocytes: round to oval nuclei with clear cytoplasm.
* Quite cellular.
* Mitoses almost absent.

====IHC====
* [[GFAP]] +/-ve (focal).
* [[MAP2]] +ve.
* Synaptophysin +ve.
* NeuN +ve.
* MIB-1: usu 1-3%.

====Molecular====
* Distinct methylation profile.
* Recurent losses on 2p and Chr. 14.<ref>{{Cite journal | last1 = Capper | first1 = D. | last2 = Stichel | first2 = D. | last3 = Sahm | first3 = F. | last4 = Jones | first4 = DTW. | last5 = Schrimpf | first5 = D. | last6 = Sill | first6 = M. | last7 = Schmid | first7 = S. | last8 = Hovestadt | first8 = V. | last9 = Reuss | first9 = DE. | title = Practical implementation of DNA methylation and copy-number-based CNS tumor diagnostics: the Heidelberg experience. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Jul | year = 2018 | doi = 10.1007/s00401-018-1879-y | PMID = 29967940 }}</ref>

<gallery>
File:Cerebellar liponeurocytoma.jpg | Liponeurocytoma, HE (WC/Marvin101).
File:Liponeurocytoma Synaptophysin.jpg | Liponeurocytoma, Synapto (WC/Marvin101).
File:Cerebellar Liponeurocytoma HE.jpg | Liponeurocytoma, HE (WC/jensflorian).
File:Cerebellar Liponeurocytoma Synaptophysin.jpg | Liponeurocytoma, Synapto (WC/jensflorian).
</gallery>

====DDx====
* [[Medulloblastoma]]
* [[Neurocytoma]]

===Gangliocytoma===
* Grade I WHO neuronal tumour.
** ICD-O code: 9492/0
* Groups of irregular large neurons.
* Non-neoplastic, reticulin-rich glial stroma.

===Ganglioglioma===
:'''Not''' to be confused with ''[[ganglioneuroma]]''.
====General====
*Gangliolioma: Grade I WHO mixed neuronal-glial tumour (ICD-O code: 9505/1).
*Anaplastic ganglioglioma: Grade III (ICD-O: 9505/3)
*Rare (approx. 0.5% of all CNS tumors).
*Usu. temporal lobe.
*Predominantly children (mean age: 9 years).
*Recognized as a cause of [[epilepsy]].<ref name=pmid12125968>{{Cite journal | last1 = Im | first1 = SH. | last2 = Chung | first2 = CK. | last3 = Cho | first3 = BK. | last4 = Lee | first4 = SK. | title = Supratentorial ganglioglioma and epilepsy: postoperative seizure outcome. | journal = J Neurooncol | volume = 57 | issue = 1 | pages = 59-66 | month = Mar | year = 2002 | doi = | PMID = 12125968 }}</ref>
*Favourable prognosis (survival rates up to 97%)
**Insufficient data für anaplastic ganglioglioma.

====Macroscopic====
*Circumscribed lesion.
*Usu. contrast enhancing.
*Solid, but intracortical cysts may be present.
*Little mass effect.

====Microscopic====
Features:
*Dysplastic neurons.
**Out of regular architecture / abnormal location.
**Cytomegaly
**Clustering
**Binucleated (very occassionally).
*Atypical glia.
*Eosinophilic granular bodies.
*Calcification.
*Prominent capillary network.
*Lymphocytic cuffing.
*May contain some reticulin.
*Glial component may resemble:
**Fibrillary astrocytoma.
**Oligodendroglioma.
**Pilocytic astrocytoma.

Anaplastic ganglioglioma:
*Brisk mitotic activity
*Necrosis

====IHC====
*Neurons:
**[[MAP2]] +ve
**Synaptophysin +ve
** Neurofilament +ve
*Glia:
**CD34+/-ve
*BRAF V600E +ve (approx. 25%, mainly ganglion cells).

====Molecular====
*BRAF V600E-mutated(approx. 25%).
*IDH1/2 wt.
*No 1p/19q codeletion.
*Usu. Chr. 7 gain.
*CDKN2A deletions in anaplastic ganglioglioma.

====DDx:====
*[[DNT]].
*[[Oligodendroglioma]].
*Trapped cortical neurons in diffuse astrocytoma.
*Papillary glioneuronal tumor.
*Dysembryoplastic neuroepithelial tumor.

====Images====
<gallery>
File:Ganglioglioma lymphocytic cuffing PAS.jpg | Lymphocytic cuffing in ganglioglioma (WC/jensflorian)
File:Ganglioglioma calcification.jpg | Calcification in ganglioglioma (WC/jensflorian)
File:Ganglioglioma Cd34 x200.jpg | CD34 immunostain in ganglioglioma (WC/jensflorian)
File:Anaplastic ganglioglioma HE.jpg | Pleomorphic ganglion cells in ganglioglioma (WC/jensflorian)
</gallery>
*[http://path.upmc.edu/cases/case142.html Ganglioglioma - case 1 (upmc.edu)].
*[http://path.upmc.edu/cases/case282.html Ganglioglioma - case 2 (upmc.edu)].

===Lhermitte-Duclos disease===
*Abbreviated ''LDD''.
*[[AKA]] ''dysplastic cerebellar gangliocytoma''.<ref name=pmid20060133>{{Cite journal | last1 = Yağci-Küpeli | first1 = B. | last2 = Oguz | first2 = KK. | last3 = Bilen | first3 = MA. | last4 = Yalçin | first4 = B. | last5 = Akalan | first5 = N. | last6 = Büyükpamukçu | first6 = M. | title = An unusual cause of posterior fossa mass: Lhermitte-Duclos disease. | journal = J Neurol Sci | volume = 290 | issue = 1-2 | pages = 138-41 | month = Mar | year = 2010 | doi = 10.1016/j.jns.2009.12.010 | PMID = 20060133 }}</ref>
*[[AKA]] ''dysplastic gangliocytoma of the cerebellum''.
{{Main|Lhermitte-Duclos disease}}
<gallery>
File:Dysplastic_gangliocytoma_lhermitte_duclos.jpg | Dysplastic gangliocytoma (low mag).
</gallery>

===Papillary glioneuronal tumour===
* Abbreviated ''PGNT''.
* A benign, supratentorial tumor of childhood.
** Biologic course corresponds to WHO grade I.
** Before WHO 2000, considered a [[Ganglioglioma]] variant.
*Prominent pseudopapillary architecture.
*Neurocytes to medium-sized ganglion cells.
*GFAP+ core, GFAP- layer
*Rosenthal fibers, Eosinophilic Granular bodies and lymphocytic cuffing may be present.
<gallery>
File:PGNT_HE_stain.jpg | PGNT (HE) (WC/jensflorian)
</gallery>

===Rosette-forming glioneuronal tumour of the fourth ventricle===
* Abbreviated ''RGNT''.
* Provisional ICD-O code: 9509/1
* A rare benign infratentorial tumour of the midline of children and adults.
* Biologic course corresponds to WHO grade I.
* Glial component corresponds to [[pilocytic astrocytoma]].
* Neurocytic rosettes.
* Eosinopil fibrillary cores / pseudorosettes.
* GFAP+ in fibrillary areas, Syn+ in rosettes.
* Neurocytic cells: MAP2+
* MIB-1 usu. below 3%.
<gallery>
File:Histology RGNT HE.jpg | RGNT, HE stain (WC/jensflorian).
File:RGNT HE 2.jpg | RGNT, higher magnification (WC/jensflorian).
</gallery>

===Polymorphous low-grade tumor of the young (PLNTY)===
* [[Pediatric-type diffuse low-grade glioma#Diffuse low-grade glioma, MAPK pathway-altered|Polymorphous low-grade tumor of the young (PLNTY)]]

==Pineal tumours==
{{Main|Pineal gland}}

* [[Pineocytoma]]
* [[Pineal parenchymal tumour of intermediate differentiation]]
* [[Pineoblastoma]]
* [[Papillary tumour of the pineal region]]

==Embryonal tumours==
* [[Atypical teratoid/rhabdoid tumour]] (AT/RT) or (AT-RT)
* [[Medulloblastoma]]
* [[Primitive neuroectodermal tumour]] (PNET)
* [[Embryonal tumour with abundant neuropil and true rosettes]] (ETANTR)

DDx:
* [[Ewing sarcoma]]
* [[Sarcoma with CIC-rearrangement]]

==Peripheral nerve sheath tumours==
{{Main|Peripheral nerve sheath tumours}}
A classification:<ref name=pmid17893219>{{cite journal |author=Wippold FJ, Lubner M, Perrin RJ, Lämmle M, Perry A |title=Neuropathology for the neuroradiologist: Antoni A and Antoni B tissue patterns |journal=AJNR Am J Neuroradiol |volume=28 |issue=9 |pages=1633–8 |year=2007 |month=October |pmid=17893219 |doi=10.3174/ajnr.A0682 |url=http://www.ajnr.org/cgi/reprint/28/9/1633}}</ref>
'''Benign:'''
*[[Schwannoma]].
*[[Neurofibroma]].
*[[Perineurioma]].
*Ganglioneuroma.
**[[Traumatic neuroma]].
'''Malignant:'''
*[[Malignant peripheral nerve sheath tumour]] (MPNST).

===Ganglioneuroma===
:'''Not''' to be confused with ''[[ganglioglioma]]''.
*[[AKA]] ganglioma.<ref>URL: [http://medical-dictionary.thefreedictionary.com/ganglioma http://medical-dictionary.thefreedictionary.com/ganglioma]. Accessed on: 8 November 2010.</ref>
{{Main|Ganglioneuroma}}

==Meningioma==
{{Main|Meningioma}}

==Chordoma==
{{Main|Chordoma}}

==Hemangioblastoma==
{{Main|Hemangioblastoma}}

==CNS lymphoma==
Classification:
*Primary CNS lymphoma.
*Non-primary CNS lymphoma - see ''[[lymphoma]]'' article.

===General - primary CNS===
*Classically periventicular distribution.
*Usually large B cell; can be considered a type of [[diffuse large B cell lymphoma]] (DLBCL).
**Prognosis of CNS (DLBCL) lymphomas worse than nodal (non-CNS) DLBCL.<ref name=pmid19925562>{{cite journal |author=Raoux D, Duband S, Forest F, ''et al.'' |title=Primary central nervous system lymphoma: Immunohistochemical profile and prognostic significance |journal=Neuropathology |volume=30 |issue=3 |pages=232–40 |year=2010 |month=June |pmid=19925562 |doi=10.1111/j.1440-1789.2009.01074.x |url=}}</ref>

===Microscopic===
Features:
*Large cell lymphoma.
**Size = 2x diameter normal lymphocyte.
**Nucleolus - common.
*Perivascular clustering.

====Images====
www:
*[http://frontalcortex.com/?page=image&topic=1&qid=1237 CNS lymphoma (frontalcortex.com)].
*[http://path.upmc.edu/cases/case403.html Primary CNS lymphoma - several images (upmc.edu)].
<gallery>
Image:Primary CNS lymphoma - low mag.jpg | CNS lymphoma - low mag. (WC)
Image:Primary CNS lymphoma - intermed mag.jpg | CNS lymphoma - intermed. mag. (WC)
Image:Primary CNS lymphoma - high mag.jpg | CNS lymphoma - high mag. (WC)
Image:Primary CNS lymphoma - very high mag.jpg | CNS lymphoma - very high mag. (WC)
</gallery>
<gallery>
Image: CNS lymphoma (1) B-cell type.jpg | CNS lymphoma. (WC/KGH)
Image: CNS lymphoma (2) B-cell type.jpg | CNS lymphoma. (WC/KGH)
</gallery>

===IHC===
Can be subclassified in ''GCB (germinal centre B-cell-like)'' and ''non-GCB'' by CD10, Bcl-6, MUM1/IRF-4, and Bcl-2.<ref name=pmid19925562/>

Common pattern:
*[[CD20]] +ve - key stain.
*CD3 -ve.
*Ki-67 ~40%.
*Bcl-6 +ve.
*Bcl-1 -ve.

==Ganglioneuroblastoma==
{{Main|Neuroblastoma}}
===General===
*Uncommon.
*Part of the ''neuroblastic tumours'' group which includes:<ref name=pmid10421272>{{cite journal |author=Shimada H, Ambros IM, Dehner LP, Hata J, Joshi VV, Roald B |title=Terminology and morphologic criteria of neuroblastic tumors: recommendations by the International Neuroblastoma Pathology Committee |journal=Cancer |volume=86 |issue=2 |pages=349–63 |year=1999 |month=July |pmid=10421272 |doi= |url=}}</ref>
**[[Ganglioneuroma]] (benign).
**Ganglioneuroblastoma (intermediate).
**[[Neuroblastoma]] (aggressive).

===Microscopic===
Features:
*Ganglion-like cells with a prominent nucleolus.
*Small undifferentiated cells with scant cytoplasm.
<gallery>
Image:Adrenal Ganglioneuroblastoma LP CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - Low power (SKB)
Image:Adrenal Ganglioneuroblastoma MP CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - Medium power (SKB)
Image:Adrenal Ganglioneuroblastoma HP CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - High power (SKB)
Image:Adrenal Ganglioneuroblastoma HP3 CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - High power (SKB)
Image:Adrenal Ganglioneuroblastoma HP2 CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - High power (SKB)
</gallery>
Images:
*[http://path.upmc.edu/cases/case530.html Ganglioneuroblastoma - several images (upmc.edu)].

===IHC===
*NSE +ve -- small cells.

==Lesions of the sella turcica==
{{Main|Pituitary gland}}
Lesions of the sella turcica, the pituitary gland environs, is a topic for it self. The differential diagnosis for lesions in this area includes:
*[[Pituitary adenoma]].
*[[Craniopharyngioma]].
*[[Rathke cleft cyst]].
*[[Germ cell tumour]].
*[[Meningioma]].
*[[Pilomyxoid astrocytoma]] - in children.

==See also==
*[[Neuropathology]].
*[[Muscle biopsy]].

==References==
{{reflist|2}}

==External links==
*[http://www.neuropathologyweb.org/ Neuropathology (neuropathologyweb.org)].
*[http://www.pathology.vcu.edu/WirSelfInst/tumor-1.html Neuropathology Mini-Course (pathology.vcu.edu)].
*[http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html Neuropathology Mini-Course (pathology.vcu.edu)].

[[Category:Neuropathology]]

Neuropathology tumours

2022-04-13T11:54:00Z

Jensflorian: /* Common neuropathology tumours in a table */ IHC update

[[Image:Gemistocytic Astrocytoma 003.jpg|thumb|right|A brain stem [[astrocytoma]]. (WC)]]
The article covers '''tumours in neuropathology'''. Tumours are a large part of [[neuropathology]]. [[Cytopathology]] of CNS tumours is dealt with in the article ''[[CNS cytopathology]]''.

There are separate articles for ''[[peripheral nerve sheath tumours]]'' and ''[[pituitary gland|pituitary/peri-pituitary lesions]]''.

==Brain tumours - overview==
===Alphabetical===
For overview see [[:Category:Neuropathology_tumours|here]]

===By age group===
====Adult====
Four most common types of brain tumours:<ref>[http://neurosurgery.mgh.harvard.edu/abta/primer.htm http://neurosurgery.mgh.harvard.edu/abta/primer.htm]</ref>
# Metastatic brain tumours (barely edges out primary tumours)
#*[[Lung cancer|Lung]] (most common).
#*[[Invasive breast cancer|Breast]].
#*[[Melanoma]].
#*[[Renal cell carcinoma]] (RCC).
# [[Glioblastoma]], IDH-wildtype.
# [[Astrocytoma, IDH-mutant]].
# [[Meningioma]].

====Children====
# [[Pilocytic astrocytoma]].
# [[Medulloblastoma]].
# [[Ependymoma]].
# Pontine glioma, often [[Diffuse midline glioma, H3 K27-altered]].

===By location===
Certain tumours like to hang-out at certain places:<ref>URL: [http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/files/4ce563fb7e8e48fc9ed8b42e296a7747.gif http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/files/4ce563fb7e8e48fc9ed8b42e296a7747.gif] and [http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html]. Accessed on: 2 November 2010.</ref>
====Cerebrum====
*Cortical based - [[oligodendroglioma]].
*Grey-white junction - metastases.
*White matter - astrocytoma, [[glioblastoma]].
*Periventricular - CNS lymphoma.
*Cystic - [[ganglioglioma]], [[pilocytic astrocytoma]], [[pleomorphic xanthoastrocytoma]].
====Cerebellum====
*Midline/central - [[medulloblastoma]].
*Cystic lesion - pilocytic astrocytoma (younger individual), [[hemangioblastoma]] (older individual).
*Solid lesion (older individual) - [[metastasis]].
====Sella turcica====
* [[Pituitary adenoma]].
* [[Craniopharyngioma]].
less common:
* [[Pituicytoma]].
* [[Granular cell tumour]].
* [[Germinoma]].
* [[Chordoma]]
* Rathke cleft cyst.
* Hypophysitis.
* Xanthogranuloma.
====Spinal cord====
*[[Ependymoma]]
*[[Glioblastoma]]
*[[Meningioma]]
*Carcinoma metastasis
*[[Hemangioblastoma]]
====Filum terminale====
*[[Meningioma]].
*[[Myxopapillary ependymoma]].
*[[Neurofibroma]].
*[[Schwannoma]].
*[[Paraganglioma]].
====Meninges====
* [[Meningioma]].
* [[Solitary fibrous tumour]] / Hemangiopericytoma.
* [[Hemangioblastoma]].
less common:
* [[Melanoma]] / Melanocytoma.
* Lymphoproliferative diseases.
* [[Sarcoidosis]]
* [[Arachnoid cyst]].
* Disseminated oligodendroglial-like leptomeningeal tumour.
* Desmoplastic infantile astrocytoma / ganglioglioma.
* Meningioangiomatosis.
* Calcifying pseudoneoplasm.
====Skull====
* [[Fibrous dysplasia]].
* [[Paget disease]].
* [[Histiocytosis]].
* [[Hemangioma]].
* [[Aneurysmal bone cyst]].
* [[Plasma_cell_neoplasms#Multiple_myeloma|Multiple myeloma]].
====Skull base / Cerebellopontine angle====
* [[Schwannoma]].
* [[Meningioma]].
* [[Dermoid cyst]] / epidermoid cyst.
less common:
* [[Ependymoma]].
* [[Choroid plexus papilloma]].
* [[Glomus tumour]].
* [[Chordoma]].
* [[Chondrosarcoma]].
* [[Olfactory neuroblastoma]].
* [[Endolymphatic sac tumour]].

===Cystic tumours===
DDx:<ref>URL: [http://path.upmc.edu/cases/case320/dx.html http://path.upmc.edu/cases/case320/dx.html]. Accessed on: 14 January 2012.</ref>
*[[Pilocytic astrocytoma]].
*[[Pleomorphic xanthoastrocytoma]].
*[[Ganglioglioma]].
*[[Hemangioblastoma]].
*[[Craniopharyngioma]].<ref>URL: [http://www.pathologyoutlines.com/Cnstumor.html#cystsgeneral http://www.pathologyoutlines.com/Cnstumor.html#cystsgeneral]. Accessed on: 14 January 2012.</ref>

===Primary versus secondary===
*[[AKA]] (primary) brain tumour versus metastatic cancer.
====Primary====
[[Glioma|Glial tumours]]:
*Cytoplasmic processes - '''key feature'''.
**Best seen at highest magnification - usu. ~1 micrometer.
**Processes may branch.
*Ill-defined border/blend with the surrounding brain.

[[Meningioma]]:
*Lesion often dura-based.
*Mesenchymal tumor (often contains collagen).

[[Lymphoma]]:
*Primary CNS Lymphoma (PCNSL) is usu. a diffuse large B-cell lymphoma.
*Large (lymphoid) cells, ergo usu. not a difficult diagnosis.
**~2x size of resting lymphocyte, nucleoli.
*Lesion predominantly perivascular.

====Secondary====
*Carcinomas:
**Well-demarcated border between brain and lesion - '''key feature'''.
**No cytoplasmic processes.
**Usu. have nuclear atypia of malignancy.
**Nuclei often ~3-4x the size of a [[RBC]].
**+/-Glandular arrangement.
**+/-Nucleoli.
*Melanoma.
*Secondary Lymphoma.
*Sarcomas (rare).

===Common neuropathology tumours in a table===
{| class="wikitable"
|'''Type'''
|'''Key feature(s)'''
|'''Imaging'''
|'''History'''
|'''Notes'''
|'''IHC'''
|'''Images'''
|-
|Normal tissue
|cells regularly spaced, no nuc. atypia
|small lesion? / deep lesion?
|variable
|missed lesion?
|nil
|[[Image:Grey_matter_and_white_matter_-_very_high_mag.jpg |thumb|center|150px|Normal. (WC)]]
|-
|[[Reactive astrocytes]]
|astrocytes with well-demarcated eosinophilic cytoplasm, regular spacing, no nuc. atypia
|small lesion? / deep lesion?
|variable
|missed lesion / close to a lesion; non-specific pathologic process - need more tissue
|GFAP
|[[Image:Reactive_astrocytes_-_lfb_-_high_mag.jpg|thumb|center|150px|Reactive astrocytes. (WC)]]
|-
|[[Schwannoma]]
|cellular areas (Antoni A), paucicelluar areas (Antoni B), palisading of nuclei (Verocay bodies)
|extra-axial + intradural
|old or young
|need frozen section to Dx, DDx: [[meningioma]]
|S100, SOX10
|[[Image:Schwannoma_-_Antoni_A_and_B_-_very_high_mag.jpg|thumb|center|150px|Schwannoma. (WC)]]
|-
|[[Meningioma]]
|whorls, psammomatous calcs, nuclear inclusions
|extra-axial + intradural
|old or young
|may be diagnosed on smear, DDx: [[schwannoma]], choroid plexus
|EMA, PR, Ki-67
|[[Image:Meningioma_intermed_mag.jpg |thumb|center|150px|Meningioma. (WC)]]
|-
|[[Astrocytoma, IDH-mutant]] (CNS [[WHO]] grade 2 or grade 3)
|glial processes (esp. on smear), nuclear atypia (typical size var. ~3x, irreg. nuc. membrane, hyperchromasia), no Rosenthal fibres in the core of the lesion †, no microvascular proliferation, no necrosis
|often enhancing (suggests high grade), usu. supratentorial, usu. white matter
|usu. old, occ. young
|common
|IDH-1(R132H)+/-, GFAP+
| [[Image:Anaplastic_astrocytoma_-_very_high_mag_-_cropped.jpg | thumb| center| 150px|High-grade astrocytoma. (WC)]]
|-
|[[Glioblastoma]], IDH-wildtype (CNS [[WHO]] grade 4)
|glial processes (esp. on smear), nuclear atypia (typical size var. ~3x, irreg. nuc. membrane, hyperchromasia), no Rosenthal fibres in the core of the lesion †, microvascular proliferation or necrosis
|often enhancing (suggests high grade), usu. supratentorial, usu. white matter
|usu. old, occ. young
|very common, esp. glioblastoma
|IDH-1+/-, GFAP+
| [[Image:Glioblastoma (1).jpg | thumb| center| 150px|Glioblastoma. (WC)]]
|-
|[[Metastatic brain tumours|Metastasis]]
|sharp interface with brain, often glandular, +/-nucleoli, no glial processes
|often cerebellular, well-circumscribed
|usu. old
|often suspected to have metastatic disease
|[[TTF-1]], CK7, [[CK20]], BRST-2
|[[Image:Metastatic_adenocarcinoma_-_cerebellum_-_very_low_mag.jpg | thumb| center|150px |Metastasis. (WC)]]
|}
† Rosenthal fibres at the periphery of a lesion are a non-specific finding seen in chronic processes.

==Brain metastasis==
{{Main|Brain metastasis}}

==Infiltrative astrocytomas==
{{Main|Astrocytoma}}

===Overview===
*Low-grade (diffuse) astrocytomas (WHO Grade II).
*Anaplastic astrocytomas (WHO Grade III).
*[[Glioblastoma]](WHO Grade IV).
**[[Gliosarcoma]] (WHO Grade IV).
*[[Gliomatosis cerebri]] (Grade III/IV).

Notes:
*Non-infiltrative astrocytomas:
**[[Pilocytic astrocytoma]] (WHO Grade I).
***[[Pilomyxoid astrocytoma]] (WHO Grade II).
**[[Pleomorphic xanthoastrocytoma]] (WHO grade II).
**[[Subependymal giant cell astrocytoma]] (WHO grade I).

===Microscopic===
Features:<ref name=pmid>{{cite journal |author=Rong Y, Durden DL, Van Meir EG, Brat DJ |title='Pseudopalisading' necrosis in glioblastoma: a familiar morphologic feature that links vascular pathology, hypoxia, and angiogenesis |journal=J. Neuropathol. Exp. Neurol. |volume=65 |issue=6 |pages=529–39 |year=2006 |month=June |pmid=16783163 |doi= |url=}}</ref><ref>[http://dictionary.reference.com/browse/palisading http://dictionary.reference.com/browse/palisading]</ref>
*Glial processes - '''key feature'''.
**Thin stringy cytoplasmic processes - best seen at high power in less cellular areas.
*No Rosenthal fibres within the tumour itself.

Images:
*[http://moon.ouhsc.edu/kfung/jty1/opaq/PathQuiz/N0A002-PQ01-M.htm Endothelial proliferation in a GBM (ouhsc.edu)].
*[http://moon.ouhsc.edu/kfung/jty1/neurotest/Q05-Ans.htm Endothelial proliferation (ouhse.edu)].
*[http://path.upmc.edu/cases/case368.html Gemistocytic astrocytoma - several images (upmc.edu)].

Notes:
*Glial vs. non-glial tumours:
**Glial: "blends into brain"/gradual transition to non-tumour brain.
**Non-glial: no glial processes.
*Rosenthal fibres within the tumour... make it into a [[pilocytic astrocytoma]].
**Rosenthal fibres may be seen around a (very) slow growing tumour and represent a reactive process.
*Inflammatory cells and macrophages should prompt consideration of an alternate diagnosis (e.g. [[cerebral infarct]], [[multiple sclerosis]]) - esp. if this is a primary lesion.<ref>URL: [http://path.upmc.edu/cases/case79/dx.html http://path.upmc.edu/cases/case79/dx.html]. Accessed on: 2 January 2012.</ref>

====Grading====
Nuclear pleomorphism present:
*At least grade II (diffuse astrocytoma).

Mitotic figures present:
*At least grade III (anaplastic astrocytoma).

Microvascular proliferation ''or'' necrosis with pseudopalisading tumour cells:
*Grade IV (glioblastoma [[AKA]] glioblastoma multiforme).

Notes:
*Pseudopalisading tumour cells = high tumour cell density adjacent to regions of necrosis; palisade = a fence of poles forming a defensive barrier or fortification.
*WHO Grading is currently based on expected biologiocal behaviour without treatment.
**Grading does not reflect molecular divergent groups within a tumor class or response to therapy (Currently controversies in grading for IDH-mutant astrocytoma vs. IDH-wildtype astrocytoma).<ref>{{Cite journal | last1 = Louis | first1 = DN. | last2 = von Deimling | first2 = A. | title = Grading of diffuse astrocytic gliomas: Broders, Kernohan, Zülch, the WHO… and Shakespeare. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Aug | year = 2017 | doi = 10.1007/s00401-017-1765-z | PMID = 28801693 }}</ref>

====Images====
Glioblastoma:
<gallery>
Image:Glioblastoma_%281%29.jpg | Glioblastoma - pseudopalisading of tumour cells (WC)
Image:Glioblastoma_-_high_mag.jpg | Glioblastoma with fragment of near-normal white matter - high mag. (WC)
</gallery>
Anaplastic astrocytoma:
<gallery>
Image:Anaplastic_astrocytoma_-_very_high_mag_-_cropped.jpg | Anaplastic astrocytoma - very high mag. (WC)
Image:Anaplastic_astrocytoma_-_gfap_-_very_high_mag.jpg | Anaplastic astrocytoma - GFAP - very high mag. (WC)
</gallery>

===IHC===
*GFAP - should stain cytoplasm of tumour cells and the perikaryon (nuclear membrane).
*Ki-67 - usu. high >20% of cells.
*p53 - often +ve.
*[[IDH-1]] (isocitrate dehydrogenase 1).
**+ve in tumours that arose from low-grade gliomas.<ref name=pmid19228619>{{cite journal |author=Yan H, Parsons DW, Jin G, ''et al.'' |title=IDH1 and IDH2 mutations in gliomas |journal=N. Engl. J. Med. |volume=360 |issue=8 |pages=765–73 |year=2009 |month=February |pmid=19228619 |pmc=2820383 |doi=10.1056/NEJMoa0808710 |url=}}</ref>
*[[H3F3A|H3F3A K27M]] -ve
**+ve cases to be classified as [[Astrocytoma#H3.3_K27M_mutated_glioma_of_the_midline|K27 mutated midline glioma]].
*[[ATRX]] -ve in tumors with low-grade precursor(most of them also IDH1/2 mutant).

Notes:
*IDH1 and IDH2 mutations - better survival.<ref name=pmid20975057>{{cite journal |author=Houillier C, Wang X, Kaloshi G, ''et al.'' |title=IDH1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas |journal=Neurology |volume=75 |issue=17 |pages=1560–6 |year=2010 |month=October |pmid=20975057 |doi=10.1212/WNL.0b013e3181f96282 |url=}}</ref>

===Molecular===
See also: [[Molecular_pathology_tests#Neuropathology|Molecular Neuropathology]]

==Gliomas==
{{Main|Glioma}}

Gliomas, glioneuronal tumours and neuronal tumours are often categorized together.

===Astrocytic tumours===
{{Main|Astrocytoma}}

* [[Astrocytoma]], IDH-mutant.
* [[Glioblastoma]], IDH-wildtype.
** [[Gliosarcoma]] (a glioblastoma subtype)

Depreceated:
* Diffuse [[Astrocytoma]]
* [[Anaplastic astrocytoma]]
* [[Gliomatosis cerebri]]
* Spongioblastoma

===Oligodendroglial tumours===
* [[Oligodendroglioma]], IDH-mutant and 1p/19q codeleted.

Depreceated:
* Anaplastic oligodendroglioma
* [[Oligoastrocytoma]]
* Anaplastic oligoastrocytoma

===Pediatric-type diffuse high-grade glioma===
{{Main|Pediatric-type diffuse high-grade glioma}}
* [[Astrocytoma#Diffuse_midline_glioma.2C_H3_K27M_mutant|Diffuse midline glioma H3 K27-mutant]]

===Pediatric-type diffuse low-grade glioma===
{{Main|Pediatric-type diffuse low-grade glioma}}

===Circumscribed astrocytic gliomas===
* [[Pilocytic astrocytoma]] (PA)
** [[Pilomyxoid astrocytoma]] (PMA)
* [[Pleomorphic xanthoastrocytoma]] (PXA)
* [[Subependymal giant cell astrocytoma]] (SEGA)
* [[Neuropathology_tumours#Astroblastoma|Astroblastoma MN1-altered]].
* [[Neuropathology_tumours#Chordoid glioma of the third ventricl|Chordoid glioma]].

====Astroblastoma====
*No WHO grade yet.<ref>{{Ref WHOCNS|88}}</ref>
*Very rare superficial tumor of young age.<ref>{{Cite journal | last1 = Narayan | first1 = S. | last2 = Kapoor | first2 = A. | last3 = Singhal | first3 = MK. | last4 = Jakhar | first4 = SL. | last5 = Bagri | first5 = PK. | last6 = Rajput | first6 = PS. | last7 = Kumar | first7 = HS. | title = Astroblastoma of cerebrum: A rare case report and review of literature. | journal = J Cancer Res Ther | volume = 11 | issue = 3 | pages = 667 | month = | year = | doi = 10.4103/0973-1482.140800 | PMID = 26458709 }}</ref>
*Large, cystic. Pushing margin towards CNS.
*Vasocentric growth, plump cells with absence of fibrillary pattern.
*GFAP+ve, Synaptohysin-ve, Olig-2-ve, focally EMA/panCK+ve. MIB-1: 1-18 %.
*Molecular profile overlaps with classical [[CNS-PNET]].
**Gene fusions invoving meningioma gene (MN1)<ref>{{Cite journal | last1 = Sturm | first1 = D. | last2 = Orr | first2 = BA. | last3 = Toprak | first3 = UH. | last4 = Hovestadt | first4 = V. | last5 = Jones | first5 = DT. | last6 = Capper | first6 = D. | last7 = Sill | first7 = M. | last8 = Buchhalter | first8 = I. | last9 = Northcott | first9 = PA. | title = New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs. | journal = Cell | volume = 164 | issue = 5 | pages = 1060-72 | month = Feb | year = 2016 | doi = 10.1016/j.cell.2016.01.015 | PMID = 26919435 }}</ref>

<gallery>
File:Astroblastoma_HE_Specimen.jpg | HE. (WC/jensflorian)
File:Astroblastoma_HE_papillae.jpg | HE. (WC/jensflorian)
File:Astroblastoma.jpg | Astroblastoma (AFIP)
</gallery>

====Chordoid glioma of the third ventricle====
* WHO grade II.
* Slowly growing, non-invasive, in adults.
* Clusters of epithelioid cells in mucinous stroma.
* Lymphocytic infiltrates, adjacent Rosenthal fibers.
* Fibrosis may be present.
* Few mitoses.
* [[GFAP]]+ve, MIB-1 1-3%.
* [[TTF-1]]+ve.
* CD34+ve.
* [[IDH-1]]-ve, [[p53]]-ve.
* PRKCA D463H mutations.<ref>{{Cite journal | last1 = Goode | first1 = B. | last2 = Mondal | first2 = G. | last3 = Hyun | first3 = M. | last4 = Ruiz | first4 = DG. | last5 = Lin | first5 = YH. | last6 = Van Ziffle | first6 = J. | last7 = Joseph | first7 = NM. | last8 = Onodera | first8 = C. | last9 = Talevich | first9 = E. | title = A recurrent kinase domain mutation in PRKCA defines chordoid glioma of the third ventricle. | journal = Nat Commun | volume = 9 | issue = 1 | pages = 810 | month = 02 | year = 2018 | doi = 10.1038/s41467-018-02826-8 | PMID = 29476136 }}</ref>

<gallery>
File:NP op 20201028 009.jpg | Chordoid Glioma. (WC/jensflorian)
</gallery>

===Ependymal tumours===
* [[Subependymoma]]
* [[Myxopapillary Ependymoma]]
* [[Ependymoma]]
* Anaplastic ependymoma

==Choroid plexus tumours==
* [[Choroid plexus papilloma]]
* Atypical choroid plexus papilloma
* [[Choroid plexus carcinoma]]

==Other neuroepithelial tumours==
* [[Neuropathology_tumours#Cribiform_neuroepithelial_tumour|Cribifiorm neuroepithelial tumour]].

===Cribiform neuroepithelial tumour===
AKA: '''CRINET'''.
*Not listed in the current WHO classification.
*First description in 2009.<ref>{{Cite journal | last1 = Hasselblatt | first1 = M. | last2 = Oyen | first2 = F. | last3 = Gesk | first3 = S. | last4 = Kordes | first4 = U. | last5 = Wrede | first5 = B. | last6 = Bergmann | first6 = M. | last7 = Schmid | first7 = H. | last8 = Frühwald | first8 = MC. | last9 = Schneppenheim | first9 = R. | title = Cribriform neuroepithelial tumor (CRINET): a nonrhabdoid ventricular tumor with INI1 loss and relatively favorable prognosis. | journal = J Neuropathol Exp Neurol | volume = 68 | issue = 12 | pages = 1249-55 | month = Dec | year = 2009 | doi = 10.1097/NEN.0b013e3181c06a51 | PMID = 19915490 }}</ref>
*Around ventricles.<ref>{{Cite journal | last1 = Arnold | first1 = MA. | last2 = Stallings-Archer | first2 = K. | last3 = Marlin | first3 = E. | last4 = Grondin | first4 = R. | last5 = Olshefski | first5 = R. | last6 = Biegel | first6 = JA. | last7 = Pierson | first7 = CR. | title = Cribriform neuroepithelial tumor arising in the lateral ventricle. | journal = Pediatr Dev Pathol | volume = 16 | issue = 4 | pages = 301-7 | month = | year = | doi = 10.2350/12-12-1287-CR.1 | PMID = 23495723 }}</ref>
*Young children.<ref>{{Cite journal | last1 = Park | first1 = JY. | last2 = Kim | first2 = E. | last3 = Kim | first3 = DW. | last4 = Chang | first4 = HW. | last5 = Kim | first5 = SP. | title = Cribriform neuroepithelial tumor in the third ventricle: a case report and literature review. | journal = Neuropathology | volume = 32 | issue = 5 | pages = 570-6 | month = Oct | year = 2012 | doi = 10.1111/j.1440-1789.2011.01293.x | PMID = 22239490 }}</ref>
*Small undifferentiated cells arranged in cribriform strands and trabeculae of varying thickness.
*MAP2+ve, Synaptophysin+ve, CK+/-ve. MIB-1: 30%.
*INI-1 loss, but no rhabdoid features and good prognosis.
*Stable genomic profile.<ref>{{Cite journal | last1 = Gessi | first1 = M. | last2 = Japp | first2 = AS. | last3 = Dreschmann | first3 = V. | last4 = Zur Mühlen | first4 = A. | last5 = Goschzik | first5 = T. | last6 = Dörner | first6 = E. | last7 = Pietsch | first7 = T. | title = High-Resolution Genomic Analysis of Cribriform Neuroepithelial Tumors of the Central Nervous System. | journal = J Neuropathol Exp Neurol | volume = 74 | issue = 10 | pages = 970-4 | month = Oct | year = 2015 | doi = 10.1097/NEN.0000000000000239 | PMID = 26352987 }}</ref>

==Neuronal and mixed neuronal/glial tumours==
* [[Desmoplastic infantile astrocytoma]] / ganglioglioma (DIA/DIG)
* [[Dysembryoplastic neuroepithelial tumour]]
* [[Central Neurocytoma]] / Extraventricular [[neurocytoma]]
* Cerebellar liponeurocytoma
* [[Papillary glioneuronal tumour]] (PGNT)
* [[Rosette-forming glioneuronal tumour of the fourth ventricle]] (RGNT)
* Gangliocytoma / Ganglioglioma
* Dysplastic ganglioglioma of the cerebellum ([[Lhermitte-Duclos disease]])
* [[Paraganglioma]]

===Desmoplastic infantile astrocytoma / Desmoplastic infantile ganglioglioma===
* Abbreviated ''DIA'' or ''DIG''.
* ICD-O code: 9412/1
* Large, superficial, cystic tumor of the infancy.
* Biologic course corresponds to WHO grade I.
* Very rare, included in the WHO since 1993.
* Prominent desmoplastic stroma.
* Astrocytic cells within stroma.
**GFAP+.
**MIB-1 usu. 1%.
* Frequent BRAF V600E or V600D mutations.<ref>{{Cite journal | last1 = Wang | first1 = AC. | last2 = Jones | first2 = DTW. | last3 = Abecassis | first3 = IJ. | last4 = Cole | first4 = BL. | last5 = Leary | first5 = SES. | last6 = Lockwood | first6 = CM. | last7 = Chavez | first7 = L. | last8 = Capper | first8 = D. | last9 = Korshunov | first9 = A. | title = Desmoplastic Infantile Ganglioglioma/Astrocytoma (DIG/DIA) are Distinct Entities with Frequent BRAFV600 Mutations. | journal = Mol Cancer Res | volume = | issue = | pages = | month = Jul | year = 2018 | doi = 10.1158/1541-7786.MCR-17-0507 | PMID = 30006355 }}</ref>
*Single case with BRAF indel or BRAF fusion.
<gallery>
File:DIG-histology.jpg | Histopathology of DIG (HE stain)
File:DIG-histology2.jpg | Prominent ganglioid cells in DIG (HE stain)
</gallery>

===Cerebellar liponeurocytoma===
* Previously called ''lipomatous medulloblastoma'' (name changed in WHO 2000).
* Mean age: 50 years.
* As the name states: A tumour of the cerebellum.
** But cases outside cerebellum reported that would qualify.<ref>{{Cite journal | last1 = Gupta | first1 = K. | last2 = Salunke | first2 = P. | last3 = Kalra | first3 = I. | last4 = Vasishta | first4 = RK. | title = Central liponeurocytoma: case report and review of literature. | journal = Clin Neuropathol | volume = 30 | issue = 2 | pages = 80-5 | month = | year = | doi = | PMID = 21329617 }}</ref>
* WHO grade II <ref>{{Cite journal | last1 = Nishimoto | first1 = T. | last2 = Kaya | first2 = B. | title = Cerebellar liponeurocytoma. | journal = Arch Pathol Lab Med | volume = 136 | issue = 8 | pages = 965-9 | month = Aug | year = 2012 | doi = 10.5858/arpa.2011-0337-RS | PMID = 22849747 }}</ref> (upgraded from WHO grade I in 2007)<ref>{{Cite journal | last1 = Brat | first1 = DJ. | last2 = Parisi | first2 = JE. | last3 = Kleinschmidt-DeMasters | first3 = BK. | last4 = Yachnis | first4 = AT. | last5 = Montine | first5 = TJ. | last6 = Boyer | first6 = PJ. | last7 = Powell | first7 = SZ. | last8 = Prayson | first8 = RA. | last9 = McLendon | first9 = RE. | title = Surgical neuropathology update: a review of changes introduced by the WHO classification of tumours of the central nervous system, 4th edition. | journal = Arch Pathol Lab Med | volume = 132 | issue = 6 | pages = 993-1007 | month = Jun | year = 2008 | doi = 10.1043/1543-2165(2008)132[993:SNUARO]2.0.CO;2 | PMID = 18517285 }}</ref>
*ICD-O code: 9506/1

====Histo====
* Advanced neuronal and lipomatous differentiation.
* Neurocytes: round to oval nuclei with clear cytoplasm.
* Quite cellular.
* Mitoses almost absent.

====IHC====
* [[GFAP]] +/-ve (focal).
* [[MAP2]] +ve.
* Synaptophysin +ve.
* NeuN +ve.
* MIB-1: usu 1-3%.

====Molecular====
* Distinct methylation profile.
* Recurent losses on 2p and Chr. 14.<ref>{{Cite journal | last1 = Capper | first1 = D. | last2 = Stichel | first2 = D. | last3 = Sahm | first3 = F. | last4 = Jones | first4 = DTW. | last5 = Schrimpf | first5 = D. | last6 = Sill | first6 = M. | last7 = Schmid | first7 = S. | last8 = Hovestadt | first8 = V. | last9 = Reuss | first9 = DE. | title = Practical implementation of DNA methylation and copy-number-based CNS tumor diagnostics: the Heidelberg experience. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Jul | year = 2018 | doi = 10.1007/s00401-018-1879-y | PMID = 29967940 }}</ref>

<gallery>
File:Cerebellar liponeurocytoma.jpg | Liponeurocytoma, HE (WC/Marvin101).
File:Liponeurocytoma Synaptophysin.jpg | Liponeurocytoma, Synapto (WC/Marvin101).
File:Cerebellar Liponeurocytoma HE.jpg | Liponeurocytoma, HE (WC/jensflorian).
File:Cerebellar Liponeurocytoma Synaptophysin.jpg | Liponeurocytoma, Synapto (WC/jensflorian).
</gallery>

====DDx====
* [[Medulloblastoma]]
* [[Neurocytoma]]

===Gangliocytoma===
* Grade I WHO neuronal tumour.
** ICD-O code: 9492/0
* Groups of irregular large neurons.
* Non-neoplastic, reticulin-rich glial stroma.

===Ganglioglioma===
:'''Not''' to be confused with ''[[ganglioneuroma]]''.
====General====
*Gangliolioma: Grade I WHO mixed neuronal-glial tumour (ICD-O code: 9505/1).
*Anaplastic ganglioglioma: Grade III (ICD-O: 9505/3)
*Rare (approx. 0.5% of all CNS tumors).
*Usu. temporal lobe.
*Predominantly children (mean age: 9 years).
*Recognized as a cause of [[epilepsy]].<ref name=pmid12125968>{{Cite journal | last1 = Im | first1 = SH. | last2 = Chung | first2 = CK. | last3 = Cho | first3 = BK. | last4 = Lee | first4 = SK. | title = Supratentorial ganglioglioma and epilepsy: postoperative seizure outcome. | journal = J Neurooncol | volume = 57 | issue = 1 | pages = 59-66 | month = Mar | year = 2002 | doi = | PMID = 12125968 }}</ref>
*Favourable prognosis (survival rates up to 97%)
**Insufficient data für anaplastic ganglioglioma.

====Macroscopic====
*Circumscribed lesion.
*Usu. contrast enhancing.
*Solid, but intracortical cysts may be present.
*Little mass effect.

====Microscopic====
Features:
*Dysplastic neurons.
**Out of regular architecture / abnormal location.
**Cytomegaly
**Clustering
**Binucleated (very occassionally).
*Atypical glia.
*Eosinophilic granular bodies.
*Calcification.
*Prominent capillary network.
*Lymphocytic cuffing.
*May contain some reticulin.
*Glial component may resemble:
**Fibrillary astrocytoma.
**Oligodendroglioma.
**Pilocytic astrocytoma.

Anaplastic ganglioglioma:
*Brisk mitotic activity
*Necrosis

====IHC====
*Neurons:
**[[MAP2]] +ve
**Synaptophysin +ve
** Neurofilament +ve
*Glia:
**CD34+/-ve
*BRAF V600E +ve (approx. 25%, mainly ganglion cells).

====Molecular====
*BRAF V600E-mutated(approx. 25%).
*IDH1/2 wt.
*No 1p/19q codeletion.
*Usu. Chr. 7 gain.
*CDKN2A deletions in anaplastic ganglioglioma.

====DDx:====
*[[DNT]].
*[[Oligodendroglioma]].
*Trapped cortical neurons in diffuse astrocytoma.
*Papillary glioneuronal tumor.
*Dysembryoplastic neuroepithelial tumor.

====Images====
<gallery>
File:Ganglioglioma lymphocytic cuffing PAS.jpg | Lymphocytic cuffing in ganglioglioma (WC/jensflorian)
File:Ganglioglioma calcification.jpg | Calcification in ganglioglioma (WC/jensflorian)
File:Ganglioglioma Cd34 x200.jpg | CD34 immunostain in ganglioglioma (WC/jensflorian)
File:Anaplastic ganglioglioma HE.jpg | Pleomorphic ganglion cells in ganglioglioma (WC/jensflorian)
</gallery>
*[http://path.upmc.edu/cases/case142.html Ganglioglioma - case 1 (upmc.edu)].
*[http://path.upmc.edu/cases/case282.html Ganglioglioma - case 2 (upmc.edu)].

===Lhermitte-Duclos disease===
*Abbreviated ''LDD''.
*[[AKA]] ''dysplastic cerebellar gangliocytoma''.<ref name=pmid20060133>{{Cite journal | last1 = Yağci-Küpeli | first1 = B. | last2 = Oguz | first2 = KK. | last3 = Bilen | first3 = MA. | last4 = Yalçin | first4 = B. | last5 = Akalan | first5 = N. | last6 = Büyükpamukçu | first6 = M. | title = An unusual cause of posterior fossa mass: Lhermitte-Duclos disease. | journal = J Neurol Sci | volume = 290 | issue = 1-2 | pages = 138-41 | month = Mar | year = 2010 | doi = 10.1016/j.jns.2009.12.010 | PMID = 20060133 }}</ref>
*[[AKA]] ''dysplastic gangliocytoma of the cerebellum''.
{{Main|Lhermitte-Duclos disease}}
<gallery>
File:Dysplastic_gangliocytoma_lhermitte_duclos.jpg | Dysplastic gangliocytoma (low mag).
</gallery>

===Papillary glioneuronal tumour===
* Abbreviated ''PGNT''.
* A benign, supratentorial tumor of childhood.
** Biologic course corresponds to WHO grade I.
** Before WHO 2000, considered a [[Ganglioglioma]] variant.
*Prominent pseudopapillary architecture.
*Neurocytes to medium-sized ganglion cells.
*GFAP+ core, GFAP- layer
*Rosenthal fibers, Eosinophilic Granular bodies and lymphocytic cuffing may be present.
<gallery>
File:PGNT_HE_stain.jpg | PGNT (HE) (WC/jensflorian)
</gallery>

===Rosette-forming glioneuronal tumour of the fourth ventricle===
* Abbreviated ''RGNT''.
* Provisional ICD-O code: 9509/1
* A rare benign infratentorial tumour of the midline of children and adults.
* Biologic course corresponds to WHO grade I.
* Glial component corresponds to [[pilocytic astrocytoma]].
* Neurocytic rosettes.
* Eosinopil fibrillary cores / pseudorosettes.
* GFAP+ in fibrillary areas, Syn+ in rosettes.
* Neurocytic cells: MAP2+
* MIB-1 usu. below 3%.
<gallery>
File:Histology RGNT HE.jpg | RGNT, HE stain (WC/jensflorian).
File:RGNT HE 2.jpg | RGNT, higher magnification (WC/jensflorian).
</gallery>

===Polymorphous low-grade tumor of the young (PLNTY)===
* [[Pediatric-type diffuse low-grade glioma#Diffuse low-grade glioma, MAPK pathway-altered|Polymorphous low-grade tumor of the young (PLNTY)]]

==Pineal tumours==
{{Main|Pineal gland}}

* [[Pineocytoma]]
* [[Pineal parenchymal tumour of intermediate differentiation]]
* [[Pineoblastoma]]
* [[Papillary tumour of the pineal region]]

==Embryonal tumours==
* [[Atypical teratoid/rhabdoid tumour]] (AT/RT) or (AT-RT)
* [[Medulloblastoma]]
* [[Primitive neuroectodermal tumour]] (PNET)
* [[Embryonal tumour with abundant neuropil and true rosettes]] (ETANTR)

DDx:
* [[Ewing sarcoma]]
* [[Sarcoma with CIC-rearrangement]]

==Peripheral nerve sheath tumours==
{{Main|Peripheral nerve sheath tumours}}
A classification:<ref name=pmid17893219>{{cite journal |author=Wippold FJ, Lubner M, Perrin RJ, Lämmle M, Perry A |title=Neuropathology for the neuroradiologist: Antoni A and Antoni B tissue patterns |journal=AJNR Am J Neuroradiol |volume=28 |issue=9 |pages=1633–8 |year=2007 |month=October |pmid=17893219 |doi=10.3174/ajnr.A0682 |url=http://www.ajnr.org/cgi/reprint/28/9/1633}}</ref>
'''Benign:'''
*[[Schwannoma]].
*[[Neurofibroma]].
*[[Perineurioma]].
*Ganglioneuroma.
**[[Traumatic neuroma]].
'''Malignant:'''
*[[Malignant peripheral nerve sheath tumour]] (MPNST).

===Ganglioneuroma===
:'''Not''' to be confused with ''[[ganglioglioma]]''.
*[[AKA]] ganglioma.<ref>URL: [http://medical-dictionary.thefreedictionary.com/ganglioma http://medical-dictionary.thefreedictionary.com/ganglioma]. Accessed on: 8 November 2010.</ref>
{{Main|Ganglioneuroma}}

==Meningioma==
{{Main|Meningioma}}

==Chordoma==
{{Main|Chordoma}}

==Hemangioblastoma==
{{Main|Hemangioblastoma}}

==CNS lymphoma==
Classification:
*Primary CNS lymphoma.
*Non-primary CNS lymphoma - see ''[[lymphoma]]'' article.

===General - primary CNS===
*Classically periventicular distribution.
*Usually large B cell; can be considered a type of [[diffuse large B cell lymphoma]] (DLBCL).
**Prognosis of CNS (DLBCL) lymphomas worse than nodal (non-CNS) DLBCL.<ref name=pmid19925562>{{cite journal |author=Raoux D, Duband S, Forest F, ''et al.'' |title=Primary central nervous system lymphoma: Immunohistochemical profile and prognostic significance |journal=Neuropathology |volume=30 |issue=3 |pages=232–40 |year=2010 |month=June |pmid=19925562 |doi=10.1111/j.1440-1789.2009.01074.x |url=}}</ref>

===Microscopic===
Features:
*Large cell lymphoma.
**Size = 2x diameter normal lymphocyte.
**Nucleolus - common.
*Perivascular clustering.

====Images====
www:
*[http://frontalcortex.com/?page=image&topic=1&qid=1237 CNS lymphoma (frontalcortex.com)].
*[http://path.upmc.edu/cases/case403.html Primary CNS lymphoma - several images (upmc.edu)].
<gallery>
Image:Primary CNS lymphoma - low mag.jpg | CNS lymphoma - low mag. (WC)
Image:Primary CNS lymphoma - intermed mag.jpg | CNS lymphoma - intermed. mag. (WC)
Image:Primary CNS lymphoma - high mag.jpg | CNS lymphoma - high mag. (WC)
Image:Primary CNS lymphoma - very high mag.jpg | CNS lymphoma - very high mag. (WC)
</gallery>
<gallery>
Image: CNS lymphoma (1) B-cell type.jpg | CNS lymphoma. (WC/KGH)
Image: CNS lymphoma (2) B-cell type.jpg | CNS lymphoma. (WC/KGH)
</gallery>

===IHC===
Can be subclassified in ''GCB (germinal centre B-cell-like)'' and ''non-GCB'' by CD10, Bcl-6, MUM1/IRF-4, and Bcl-2.<ref name=pmid19925562/>

Common pattern:
*[[CD20]] +ve - key stain.
*CD3 -ve.
*Ki-67 ~40%.
*Bcl-6 +ve.
*Bcl-1 -ve.

==Ganglioneuroblastoma==
{{Main|Neuroblastoma}}
===General===
*Uncommon.
*Part of the ''neuroblastic tumours'' group which includes:<ref name=pmid10421272>{{cite journal |author=Shimada H, Ambros IM, Dehner LP, Hata J, Joshi VV, Roald B |title=Terminology and morphologic criteria of neuroblastic tumors: recommendations by the International Neuroblastoma Pathology Committee |journal=Cancer |volume=86 |issue=2 |pages=349–63 |year=1999 |month=July |pmid=10421272 |doi= |url=}}</ref>
**[[Ganglioneuroma]] (benign).
**Ganglioneuroblastoma (intermediate).
**[[Neuroblastoma]] (aggressive).

===Microscopic===
Features:
*Ganglion-like cells with a prominent nucleolus.
*Small undifferentiated cells with scant cytoplasm.
<gallery>
Image:Adrenal Ganglioneuroblastoma LP CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - Low power (SKB)
Image:Adrenal Ganglioneuroblastoma MP CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - Medium power (SKB)
Image:Adrenal Ganglioneuroblastoma HP CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - High power (SKB)
Image:Adrenal Ganglioneuroblastoma HP3 CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - High power (SKB)
Image:Adrenal Ganglioneuroblastoma HP2 CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - High power (SKB)
</gallery>
Images:
*[http://path.upmc.edu/cases/case530.html Ganglioneuroblastoma - several images (upmc.edu)].

===IHC===
*NSE +ve -- small cells.

==Lesions of the sella turcica==
{{Main|Pituitary gland}}
Lesions of the sella turcica, the pituitary gland environs, is a topic for it self. The differential diagnosis for lesions in this area includes:
*[[Pituitary adenoma]].
*[[Craniopharyngioma]].
*[[Rathke cleft cyst]].
*[[Germ cell tumour]].
*[[Meningioma]].
*[[Pilomyxoid astrocytoma]] - in children.

==See also==
*[[Neuropathology]].
*[[Muscle biopsy]].

==References==
{{reflist|2}}

==External links==
*[http://www.neuropathologyweb.org/ Neuropathology (neuropathologyweb.org)].
*[http://www.pathology.vcu.edu/WirSelfInst/tumor-1.html Neuropathology Mini-Course (pathology.vcu.edu)].
*[http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html Neuropathology Mini-Course (pathology.vcu.edu)].

[[Category:Neuropathology]]

Neuropathology tumours

2022-04-13T11:53:30Z

Jensflorian: /* Primary versus secondary */ Update

[[Image:Gemistocytic Astrocytoma 003.jpg|thumb|right|A brain stem [[astrocytoma]]. (WC)]]
The article covers '''tumours in neuropathology'''. Tumours are a large part of [[neuropathology]]. [[Cytopathology]] of CNS tumours is dealt with in the article ''[[CNS cytopathology]]''.

There are separate articles for ''[[peripheral nerve sheath tumours]]'' and ''[[pituitary gland|pituitary/peri-pituitary lesions]]''.

==Brain tumours - overview==
===Alphabetical===
For overview see [[:Category:Neuropathology_tumours|here]]

===By age group===
====Adult====
Four most common types of brain tumours:<ref>[http://neurosurgery.mgh.harvard.edu/abta/primer.htm http://neurosurgery.mgh.harvard.edu/abta/primer.htm]</ref>
# Metastatic brain tumours (barely edges out primary tumours)
#*[[Lung cancer|Lung]] (most common).
#*[[Invasive breast cancer|Breast]].
#*[[Melanoma]].
#*[[Renal cell carcinoma]] (RCC).
# [[Glioblastoma]], IDH-wildtype.
# [[Astrocytoma, IDH-mutant]].
# [[Meningioma]].

====Children====
# [[Pilocytic astrocytoma]].
# [[Medulloblastoma]].
# [[Ependymoma]].
# Pontine glioma, often [[Diffuse midline glioma, H3 K27-altered]].

===By location===
Certain tumours like to hang-out at certain places:<ref>URL: [http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/files/4ce563fb7e8e48fc9ed8b42e296a7747.gif http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/files/4ce563fb7e8e48fc9ed8b42e296a7747.gif] and [http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html]. Accessed on: 2 November 2010.</ref>
====Cerebrum====
*Cortical based - [[oligodendroglioma]].
*Grey-white junction - metastases.
*White matter - astrocytoma, [[glioblastoma]].
*Periventricular - CNS lymphoma.
*Cystic - [[ganglioglioma]], [[pilocytic astrocytoma]], [[pleomorphic xanthoastrocytoma]].
====Cerebellum====
*Midline/central - [[medulloblastoma]].
*Cystic lesion - pilocytic astrocytoma (younger individual), [[hemangioblastoma]] (older individual).
*Solid lesion (older individual) - [[metastasis]].
====Sella turcica====
* [[Pituitary adenoma]].
* [[Craniopharyngioma]].
less common:
* [[Pituicytoma]].
* [[Granular cell tumour]].
* [[Germinoma]].
* [[Chordoma]]
* Rathke cleft cyst.
* Hypophysitis.
* Xanthogranuloma.
====Spinal cord====
*[[Ependymoma]]
*[[Glioblastoma]]
*[[Meningioma]]
*Carcinoma metastasis
*[[Hemangioblastoma]]
====Filum terminale====
*[[Meningioma]].
*[[Myxopapillary ependymoma]].
*[[Neurofibroma]].
*[[Schwannoma]].
*[[Paraganglioma]].
====Meninges====
* [[Meningioma]].
* [[Solitary fibrous tumour]] / Hemangiopericytoma.
* [[Hemangioblastoma]].
less common:
* [[Melanoma]] / Melanocytoma.
* Lymphoproliferative diseases.
* [[Sarcoidosis]]
* [[Arachnoid cyst]].
* Disseminated oligodendroglial-like leptomeningeal tumour.
* Desmoplastic infantile astrocytoma / ganglioglioma.
* Meningioangiomatosis.
* Calcifying pseudoneoplasm.
====Skull====
* [[Fibrous dysplasia]].
* [[Paget disease]].
* [[Histiocytosis]].
* [[Hemangioma]].
* [[Aneurysmal bone cyst]].
* [[Plasma_cell_neoplasms#Multiple_myeloma|Multiple myeloma]].
====Skull base / Cerebellopontine angle====
* [[Schwannoma]].
* [[Meningioma]].
* [[Dermoid cyst]] / epidermoid cyst.
less common:
* [[Ependymoma]].
* [[Choroid plexus papilloma]].
* [[Glomus tumour]].
* [[Chordoma]].
* [[Chondrosarcoma]].
* [[Olfactory neuroblastoma]].
* [[Endolymphatic sac tumour]].

===Cystic tumours===
DDx:<ref>URL: [http://path.upmc.edu/cases/case320/dx.html http://path.upmc.edu/cases/case320/dx.html]. Accessed on: 14 January 2012.</ref>
*[[Pilocytic astrocytoma]].
*[[Pleomorphic xanthoastrocytoma]].
*[[Ganglioglioma]].
*[[Hemangioblastoma]].
*[[Craniopharyngioma]].<ref>URL: [http://www.pathologyoutlines.com/Cnstumor.html#cystsgeneral http://www.pathologyoutlines.com/Cnstumor.html#cystsgeneral]. Accessed on: 14 January 2012.</ref>

===Primary versus secondary===
*[[AKA]] (primary) brain tumour versus metastatic cancer.
====Primary====
[[Glioma|Glial tumours]]:
*Cytoplasmic processes - '''key feature'''.
**Best seen at highest magnification - usu. ~1 micrometer.
**Processes may branch.
*Ill-defined border/blend with the surrounding brain.

[[Meningioma]]:
*Lesion often dura-based.
*Mesenchymal tumor (often contains collagen).

[[Lymphoma]]:
*Primary CNS Lymphoma (PCNSL) is usu. a diffuse large B-cell lymphoma.
*Large (lymphoid) cells, ergo usu. not a difficult diagnosis.
**~2x size of resting lymphocyte, nucleoli.
*Lesion predominantly perivascular.

====Secondary====
*Carcinomas:
**Well-demarcated border between brain and lesion - '''key feature'''.
**No cytoplasmic processes.
**Usu. have nuclear atypia of malignancy.
**Nuclei often ~3-4x the size of a [[RBC]].
**+/-Glandular arrangement.
**+/-Nucleoli.
*Melanoma.
*Secondary Lymphoma.
*Sarcomas (rare).

===Common neuropathology tumours in a table===
{| class="wikitable"
|'''Type'''
|'''Key feature(s)'''
|'''Imaging'''
|'''History'''
|'''Notes'''
|'''IHC'''
|'''Images'''
|-
|Normal tissue
|cells regularly spaced, no nuc. atypia
|small lesion? / deep lesion?
|variable
|missed lesion?
|nil
|[[Image:Grey_matter_and_white_matter_-_very_high_mag.jpg |thumb|center|150px|Normal. (WC)]]
|-
|[[Reactive astrocytes]]
|astrocytes with well-demarcated eosinophilic cytoplasm, regular spacing, no nuc. atypia
|small lesion? / deep lesion?
|variable
|missed lesion / close to a lesion; non-specific pathologic process - need more tissue
|nil
|[[Image:Reactive_astrocytes_-_lfb_-_high_mag.jpg|thumb|center|150px|Reactive astrocytes. (WC)]]
|-
|[[Schwannoma]]
|cellular areas (Antoni A), paucicelluar areas (Antoni B), palisading of nuclei (Verocay bodies)
|extra-axial + intradural
|old or young
|need frozen section to Dx, DDx: [[meningioma]]
|S100
|[[Image:Schwannoma_-_Antoni_A_and_B_-_very_high_mag.jpg|thumb|center|150px|Schwannoma. (WC)]]
|-
|[[Meningioma]]
|whorls, psammomatous calcs, nuclear inclusions
|extra-axial + intradural
|old or young
|may be diagnosed on smear, DDx: [[schwannoma]], choroid plexus
|EMA, PR, Ki-67
|[[Image:Meningioma_intermed_mag.jpg |thumb|center|150px|Meningioma. (WC)]]
|-
|[[Astrocytoma, IDH-mutant]] (CNS [[WHO]] grade 2 or grade 3)
|glial processes (esp. on smear), nuclear atypia (typical size var. ~3x, irreg. nuc. membrane, hyperchromasia), no Rosenthal fibres in the core of the lesion †, no microvascular proliferation, no necrosis
|often enhancing (suggests high grade), usu. supratentorial, usu. white matter
|usu. old, occ. young
|common
|IDH-1(R132H)+/-, GFAP+
| [[Image:Anaplastic_astrocytoma_-_very_high_mag_-_cropped.jpg | thumb| center| 150px|High-grade astrocytoma. (WC)]]
|-
|[[Glioblastoma]], IDH-wildtype (CNS [[WHO]] grade 4)
|glial processes (esp. on smear), nuclear atypia (typical size var. ~3x, irreg. nuc. membrane, hyperchromasia), no Rosenthal fibres in the core of the lesion †, microvascular proliferation or necrosis
|often enhancing (suggests high grade), usu. supratentorial, usu. white matter
|usu. old, occ. young
|very common, esp. glioblastoma
|IDH-1+/-, GFAP+
| [[Image:Glioblastoma (1).jpg | thumb| center| 150px|Glioblastoma. (WC)]]
|-
|[[Metastatic brain tumours|Metastasis]]
|sharp interface with brain, often glandular, +/-nucleoli, no glial processes
|often cerebellular, well-circumscribed
|usu. old
|often suspected to have metastatic disease
|[[TTF-1]], CK7, [[CK20]], BRST-2
|[[Image:Metastatic_adenocarcinoma_-_cerebellum_-_very_low_mag.jpg | thumb| center|150px |Metastasis. (WC)]]
|}
† Rosenthal fibres at the periphery of a lesion are a non-specific finding seen in chronic processes.

==Brain metastasis==
{{Main|Brain metastasis}}

==Infiltrative astrocytomas==
{{Main|Astrocytoma}}

===Overview===
*Low-grade (diffuse) astrocytomas (WHO Grade II).
*Anaplastic astrocytomas (WHO Grade III).
*[[Glioblastoma]](WHO Grade IV).
**[[Gliosarcoma]] (WHO Grade IV).
*[[Gliomatosis cerebri]] (Grade III/IV).

Notes:
*Non-infiltrative astrocytomas:
**[[Pilocytic astrocytoma]] (WHO Grade I).
***[[Pilomyxoid astrocytoma]] (WHO Grade II).
**[[Pleomorphic xanthoastrocytoma]] (WHO grade II).
**[[Subependymal giant cell astrocytoma]] (WHO grade I).

===Microscopic===
Features:<ref name=pmid>{{cite journal |author=Rong Y, Durden DL, Van Meir EG, Brat DJ |title='Pseudopalisading' necrosis in glioblastoma: a familiar morphologic feature that links vascular pathology, hypoxia, and angiogenesis |journal=J. Neuropathol. Exp. Neurol. |volume=65 |issue=6 |pages=529–39 |year=2006 |month=June |pmid=16783163 |doi= |url=}}</ref><ref>[http://dictionary.reference.com/browse/palisading http://dictionary.reference.com/browse/palisading]</ref>
*Glial processes - '''key feature'''.
**Thin stringy cytoplasmic processes - best seen at high power in less cellular areas.
*No Rosenthal fibres within the tumour itself.

Images:
*[http://moon.ouhsc.edu/kfung/jty1/opaq/PathQuiz/N0A002-PQ01-M.htm Endothelial proliferation in a GBM (ouhsc.edu)].
*[http://moon.ouhsc.edu/kfung/jty1/neurotest/Q05-Ans.htm Endothelial proliferation (ouhse.edu)].
*[http://path.upmc.edu/cases/case368.html Gemistocytic astrocytoma - several images (upmc.edu)].

Notes:
*Glial vs. non-glial tumours:
**Glial: "blends into brain"/gradual transition to non-tumour brain.
**Non-glial: no glial processes.
*Rosenthal fibres within the tumour... make it into a [[pilocytic astrocytoma]].
**Rosenthal fibres may be seen around a (very) slow growing tumour and represent a reactive process.
*Inflammatory cells and macrophages should prompt consideration of an alternate diagnosis (e.g. [[cerebral infarct]], [[multiple sclerosis]]) - esp. if this is a primary lesion.<ref>URL: [http://path.upmc.edu/cases/case79/dx.html http://path.upmc.edu/cases/case79/dx.html]. Accessed on: 2 January 2012.</ref>

====Grading====
Nuclear pleomorphism present:
*At least grade II (diffuse astrocytoma).

Mitotic figures present:
*At least grade III (anaplastic astrocytoma).

Microvascular proliferation ''or'' necrosis with pseudopalisading tumour cells:
*Grade IV (glioblastoma [[AKA]] glioblastoma multiforme).

Notes:
*Pseudopalisading tumour cells = high tumour cell density adjacent to regions of necrosis; palisade = a fence of poles forming a defensive barrier or fortification.
*WHO Grading is currently based on expected biologiocal behaviour without treatment.
**Grading does not reflect molecular divergent groups within a tumor class or response to therapy (Currently controversies in grading for IDH-mutant astrocytoma vs. IDH-wildtype astrocytoma).<ref>{{Cite journal | last1 = Louis | first1 = DN. | last2 = von Deimling | first2 = A. | title = Grading of diffuse astrocytic gliomas: Broders, Kernohan, Zülch, the WHO… and Shakespeare. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Aug | year = 2017 | doi = 10.1007/s00401-017-1765-z | PMID = 28801693 }}</ref>

====Images====
Glioblastoma:
<gallery>
Image:Glioblastoma_%281%29.jpg | Glioblastoma - pseudopalisading of tumour cells (WC)
Image:Glioblastoma_-_high_mag.jpg | Glioblastoma with fragment of near-normal white matter - high mag. (WC)
</gallery>
Anaplastic astrocytoma:
<gallery>
Image:Anaplastic_astrocytoma_-_very_high_mag_-_cropped.jpg | Anaplastic astrocytoma - very high mag. (WC)
Image:Anaplastic_astrocytoma_-_gfap_-_very_high_mag.jpg | Anaplastic astrocytoma - GFAP - very high mag. (WC)
</gallery>

===IHC===
*GFAP - should stain cytoplasm of tumour cells and the perikaryon (nuclear membrane).
*Ki-67 - usu. high >20% of cells.
*p53 - often +ve.
*[[IDH-1]] (isocitrate dehydrogenase 1).
**+ve in tumours that arose from low-grade gliomas.<ref name=pmid19228619>{{cite journal |author=Yan H, Parsons DW, Jin G, ''et al.'' |title=IDH1 and IDH2 mutations in gliomas |journal=N. Engl. J. Med. |volume=360 |issue=8 |pages=765–73 |year=2009 |month=February |pmid=19228619 |pmc=2820383 |doi=10.1056/NEJMoa0808710 |url=}}</ref>
*[[H3F3A|H3F3A K27M]] -ve
**+ve cases to be classified as [[Astrocytoma#H3.3_K27M_mutated_glioma_of_the_midline|K27 mutated midline glioma]].
*[[ATRX]] -ve in tumors with low-grade precursor(most of them also IDH1/2 mutant).

Notes:
*IDH1 and IDH2 mutations - better survival.<ref name=pmid20975057>{{cite journal |author=Houillier C, Wang X, Kaloshi G, ''et al.'' |title=IDH1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas |journal=Neurology |volume=75 |issue=17 |pages=1560–6 |year=2010 |month=October |pmid=20975057 |doi=10.1212/WNL.0b013e3181f96282 |url=}}</ref>

===Molecular===
See also: [[Molecular_pathology_tests#Neuropathology|Molecular Neuropathology]]

==Gliomas==
{{Main|Glioma}}

Gliomas, glioneuronal tumours and neuronal tumours are often categorized together.

===Astrocytic tumours===
{{Main|Astrocytoma}}

* [[Astrocytoma]], IDH-mutant.
* [[Glioblastoma]], IDH-wildtype.
** [[Gliosarcoma]] (a glioblastoma subtype)

Depreceated:
* Diffuse [[Astrocytoma]]
* [[Anaplastic astrocytoma]]
* [[Gliomatosis cerebri]]
* Spongioblastoma

===Oligodendroglial tumours===
* [[Oligodendroglioma]], IDH-mutant and 1p/19q codeleted.

Depreceated:
* Anaplastic oligodendroglioma
* [[Oligoastrocytoma]]
* Anaplastic oligoastrocytoma

===Pediatric-type diffuse high-grade glioma===
{{Main|Pediatric-type diffuse high-grade glioma}}
* [[Astrocytoma#Diffuse_midline_glioma.2C_H3_K27M_mutant|Diffuse midline glioma H3 K27-mutant]]

===Pediatric-type diffuse low-grade glioma===
{{Main|Pediatric-type diffuse low-grade glioma}}

===Circumscribed astrocytic gliomas===
* [[Pilocytic astrocytoma]] (PA)
** [[Pilomyxoid astrocytoma]] (PMA)
* [[Pleomorphic xanthoastrocytoma]] (PXA)
* [[Subependymal giant cell astrocytoma]] (SEGA)
* [[Neuropathology_tumours#Astroblastoma|Astroblastoma MN1-altered]].
* [[Neuropathology_tumours#Chordoid glioma of the third ventricl|Chordoid glioma]].

====Astroblastoma====
*No WHO grade yet.<ref>{{Ref WHOCNS|88}}</ref>
*Very rare superficial tumor of young age.<ref>{{Cite journal | last1 = Narayan | first1 = S. | last2 = Kapoor | first2 = A. | last3 = Singhal | first3 = MK. | last4 = Jakhar | first4 = SL. | last5 = Bagri | first5 = PK. | last6 = Rajput | first6 = PS. | last7 = Kumar | first7 = HS. | title = Astroblastoma of cerebrum: A rare case report and review of literature. | journal = J Cancer Res Ther | volume = 11 | issue = 3 | pages = 667 | month = | year = | doi = 10.4103/0973-1482.140800 | PMID = 26458709 }}</ref>
*Large, cystic. Pushing margin towards CNS.
*Vasocentric growth, plump cells with absence of fibrillary pattern.
*GFAP+ve, Synaptohysin-ve, Olig-2-ve, focally EMA/panCK+ve. MIB-1: 1-18 %.
*Molecular profile overlaps with classical [[CNS-PNET]].
**Gene fusions invoving meningioma gene (MN1)<ref>{{Cite journal | last1 = Sturm | first1 = D. | last2 = Orr | first2 = BA. | last3 = Toprak | first3 = UH. | last4 = Hovestadt | first4 = V. | last5 = Jones | first5 = DT. | last6 = Capper | first6 = D. | last7 = Sill | first7 = M. | last8 = Buchhalter | first8 = I. | last9 = Northcott | first9 = PA. | title = New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs. | journal = Cell | volume = 164 | issue = 5 | pages = 1060-72 | month = Feb | year = 2016 | doi = 10.1016/j.cell.2016.01.015 | PMID = 26919435 }}</ref>

<gallery>
File:Astroblastoma_HE_Specimen.jpg | HE. (WC/jensflorian)
File:Astroblastoma_HE_papillae.jpg | HE. (WC/jensflorian)
File:Astroblastoma.jpg | Astroblastoma (AFIP)
</gallery>

====Chordoid glioma of the third ventricle====
* WHO grade II.
* Slowly growing, non-invasive, in adults.
* Clusters of epithelioid cells in mucinous stroma.
* Lymphocytic infiltrates, adjacent Rosenthal fibers.
* Fibrosis may be present.
* Few mitoses.
* [[GFAP]]+ve, MIB-1 1-3%.
* [[TTF-1]]+ve.
* CD34+ve.
* [[IDH-1]]-ve, [[p53]]-ve.
* PRKCA D463H mutations.<ref>{{Cite journal | last1 = Goode | first1 = B. | last2 = Mondal | first2 = G. | last3 = Hyun | first3 = M. | last4 = Ruiz | first4 = DG. | last5 = Lin | first5 = YH. | last6 = Van Ziffle | first6 = J. | last7 = Joseph | first7 = NM. | last8 = Onodera | first8 = C. | last9 = Talevich | first9 = E. | title = A recurrent kinase domain mutation in PRKCA defines chordoid glioma of the third ventricle. | journal = Nat Commun | volume = 9 | issue = 1 | pages = 810 | month = 02 | year = 2018 | doi = 10.1038/s41467-018-02826-8 | PMID = 29476136 }}</ref>

<gallery>
File:NP op 20201028 009.jpg | Chordoid Glioma. (WC/jensflorian)
</gallery>

===Ependymal tumours===
* [[Subependymoma]]
* [[Myxopapillary Ependymoma]]
* [[Ependymoma]]
* Anaplastic ependymoma

==Choroid plexus tumours==
* [[Choroid plexus papilloma]]
* Atypical choroid plexus papilloma
* [[Choroid plexus carcinoma]]

==Other neuroepithelial tumours==
* [[Neuropathology_tumours#Cribiform_neuroepithelial_tumour|Cribifiorm neuroepithelial tumour]].

===Cribiform neuroepithelial tumour===
AKA: '''CRINET'''.
*Not listed in the current WHO classification.
*First description in 2009.<ref>{{Cite journal | last1 = Hasselblatt | first1 = M. | last2 = Oyen | first2 = F. | last3 = Gesk | first3 = S. | last4 = Kordes | first4 = U. | last5 = Wrede | first5 = B. | last6 = Bergmann | first6 = M. | last7 = Schmid | first7 = H. | last8 = Frühwald | first8 = MC. | last9 = Schneppenheim | first9 = R. | title = Cribriform neuroepithelial tumor (CRINET): a nonrhabdoid ventricular tumor with INI1 loss and relatively favorable prognosis. | journal = J Neuropathol Exp Neurol | volume = 68 | issue = 12 | pages = 1249-55 | month = Dec | year = 2009 | doi = 10.1097/NEN.0b013e3181c06a51 | PMID = 19915490 }}</ref>
*Around ventricles.<ref>{{Cite journal | last1 = Arnold | first1 = MA. | last2 = Stallings-Archer | first2 = K. | last3 = Marlin | first3 = E. | last4 = Grondin | first4 = R. | last5 = Olshefski | first5 = R. | last6 = Biegel | first6 = JA. | last7 = Pierson | first7 = CR. | title = Cribriform neuroepithelial tumor arising in the lateral ventricle. | journal = Pediatr Dev Pathol | volume = 16 | issue = 4 | pages = 301-7 | month = | year = | doi = 10.2350/12-12-1287-CR.1 | PMID = 23495723 }}</ref>
*Young children.<ref>{{Cite journal | last1 = Park | first1 = JY. | last2 = Kim | first2 = E. | last3 = Kim | first3 = DW. | last4 = Chang | first4 = HW. | last5 = Kim | first5 = SP. | title = Cribriform neuroepithelial tumor in the third ventricle: a case report and literature review. | journal = Neuropathology | volume = 32 | issue = 5 | pages = 570-6 | month = Oct | year = 2012 | doi = 10.1111/j.1440-1789.2011.01293.x | PMID = 22239490 }}</ref>
*Small undifferentiated cells arranged in cribriform strands and trabeculae of varying thickness.
*MAP2+ve, Synaptophysin+ve, CK+/-ve. MIB-1: 30%.
*INI-1 loss, but no rhabdoid features and good prognosis.
*Stable genomic profile.<ref>{{Cite journal | last1 = Gessi | first1 = M. | last2 = Japp | first2 = AS. | last3 = Dreschmann | first3 = V. | last4 = Zur Mühlen | first4 = A. | last5 = Goschzik | first5 = T. | last6 = Dörner | first6 = E. | last7 = Pietsch | first7 = T. | title = High-Resolution Genomic Analysis of Cribriform Neuroepithelial Tumors of the Central Nervous System. | journal = J Neuropathol Exp Neurol | volume = 74 | issue = 10 | pages = 970-4 | month = Oct | year = 2015 | doi = 10.1097/NEN.0000000000000239 | PMID = 26352987 }}</ref>

==Neuronal and mixed neuronal/glial tumours==
* [[Desmoplastic infantile astrocytoma]] / ganglioglioma (DIA/DIG)
* [[Dysembryoplastic neuroepithelial tumour]]
* [[Central Neurocytoma]] / Extraventricular [[neurocytoma]]
* Cerebellar liponeurocytoma
* [[Papillary glioneuronal tumour]] (PGNT)
* [[Rosette-forming glioneuronal tumour of the fourth ventricle]] (RGNT)
* Gangliocytoma / Ganglioglioma
* Dysplastic ganglioglioma of the cerebellum ([[Lhermitte-Duclos disease]])
* [[Paraganglioma]]

===Desmoplastic infantile astrocytoma / Desmoplastic infantile ganglioglioma===
* Abbreviated ''DIA'' or ''DIG''.
* ICD-O code: 9412/1
* Large, superficial, cystic tumor of the infancy.
* Biologic course corresponds to WHO grade I.
* Very rare, included in the WHO since 1993.
* Prominent desmoplastic stroma.
* Astrocytic cells within stroma.
**GFAP+.
**MIB-1 usu. 1%.
* Frequent BRAF V600E or V600D mutations.<ref>{{Cite journal | last1 = Wang | first1 = AC. | last2 = Jones | first2 = DTW. | last3 = Abecassis | first3 = IJ. | last4 = Cole | first4 = BL. | last5 = Leary | first5 = SES. | last6 = Lockwood | first6 = CM. | last7 = Chavez | first7 = L. | last8 = Capper | first8 = D. | last9 = Korshunov | first9 = A. | title = Desmoplastic Infantile Ganglioglioma/Astrocytoma (DIG/DIA) are Distinct Entities with Frequent BRAFV600 Mutations. | journal = Mol Cancer Res | volume = | issue = | pages = | month = Jul | year = 2018 | doi = 10.1158/1541-7786.MCR-17-0507 | PMID = 30006355 }}</ref>
*Single case with BRAF indel or BRAF fusion.
<gallery>
File:DIG-histology.jpg | Histopathology of DIG (HE stain)
File:DIG-histology2.jpg | Prominent ganglioid cells in DIG (HE stain)
</gallery>

===Cerebellar liponeurocytoma===
* Previously called ''lipomatous medulloblastoma'' (name changed in WHO 2000).
* Mean age: 50 years.
* As the name states: A tumour of the cerebellum.
** But cases outside cerebellum reported that would qualify.<ref>{{Cite journal | last1 = Gupta | first1 = K. | last2 = Salunke | first2 = P. | last3 = Kalra | first3 = I. | last4 = Vasishta | first4 = RK. | title = Central liponeurocytoma: case report and review of literature. | journal = Clin Neuropathol | volume = 30 | issue = 2 | pages = 80-5 | month = | year = | doi = | PMID = 21329617 }}</ref>
* WHO grade II <ref>{{Cite journal | last1 = Nishimoto | first1 = T. | last2 = Kaya | first2 = B. | title = Cerebellar liponeurocytoma. | journal = Arch Pathol Lab Med | volume = 136 | issue = 8 | pages = 965-9 | month = Aug | year = 2012 | doi = 10.5858/arpa.2011-0337-RS | PMID = 22849747 }}</ref> (upgraded from WHO grade I in 2007)<ref>{{Cite journal | last1 = Brat | first1 = DJ. | last2 = Parisi | first2 = JE. | last3 = Kleinschmidt-DeMasters | first3 = BK. | last4 = Yachnis | first4 = AT. | last5 = Montine | first5 = TJ. | last6 = Boyer | first6 = PJ. | last7 = Powell | first7 = SZ. | last8 = Prayson | first8 = RA. | last9 = McLendon | first9 = RE. | title = Surgical neuropathology update: a review of changes introduced by the WHO classification of tumours of the central nervous system, 4th edition. | journal = Arch Pathol Lab Med | volume = 132 | issue = 6 | pages = 993-1007 | month = Jun | year = 2008 | doi = 10.1043/1543-2165(2008)132[993:SNUARO]2.0.CO;2 | PMID = 18517285 }}</ref>
*ICD-O code: 9506/1

====Histo====
* Advanced neuronal and lipomatous differentiation.
* Neurocytes: round to oval nuclei with clear cytoplasm.
* Quite cellular.
* Mitoses almost absent.

====IHC====
* [[GFAP]] +/-ve (focal).
* [[MAP2]] +ve.
* Synaptophysin +ve.
* NeuN +ve.
* MIB-1: usu 1-3%.

====Molecular====
* Distinct methylation profile.
* Recurent losses on 2p and Chr. 14.<ref>{{Cite journal | last1 = Capper | first1 = D. | last2 = Stichel | first2 = D. | last3 = Sahm | first3 = F. | last4 = Jones | first4 = DTW. | last5 = Schrimpf | first5 = D. | last6 = Sill | first6 = M. | last7 = Schmid | first7 = S. | last8 = Hovestadt | first8 = V. | last9 = Reuss | first9 = DE. | title = Practical implementation of DNA methylation and copy-number-based CNS tumor diagnostics: the Heidelberg experience. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Jul | year = 2018 | doi = 10.1007/s00401-018-1879-y | PMID = 29967940 }}</ref>

<gallery>
File:Cerebellar liponeurocytoma.jpg | Liponeurocytoma, HE (WC/Marvin101).
File:Liponeurocytoma Synaptophysin.jpg | Liponeurocytoma, Synapto (WC/Marvin101).
File:Cerebellar Liponeurocytoma HE.jpg | Liponeurocytoma, HE (WC/jensflorian).
File:Cerebellar Liponeurocytoma Synaptophysin.jpg | Liponeurocytoma, Synapto (WC/jensflorian).
</gallery>

====DDx====
* [[Medulloblastoma]]
* [[Neurocytoma]]

===Gangliocytoma===
* Grade I WHO neuronal tumour.
** ICD-O code: 9492/0
* Groups of irregular large neurons.
* Non-neoplastic, reticulin-rich glial stroma.

===Ganglioglioma===
:'''Not''' to be confused with ''[[ganglioneuroma]]''.
====General====
*Gangliolioma: Grade I WHO mixed neuronal-glial tumour (ICD-O code: 9505/1).
*Anaplastic ganglioglioma: Grade III (ICD-O: 9505/3)
*Rare (approx. 0.5% of all CNS tumors).
*Usu. temporal lobe.
*Predominantly children (mean age: 9 years).
*Recognized as a cause of [[epilepsy]].<ref name=pmid12125968>{{Cite journal | last1 = Im | first1 = SH. | last2 = Chung | first2 = CK. | last3 = Cho | first3 = BK. | last4 = Lee | first4 = SK. | title = Supratentorial ganglioglioma and epilepsy: postoperative seizure outcome. | journal = J Neurooncol | volume = 57 | issue = 1 | pages = 59-66 | month = Mar | year = 2002 | doi = | PMID = 12125968 }}</ref>
*Favourable prognosis (survival rates up to 97%)
**Insufficient data für anaplastic ganglioglioma.

====Macroscopic====
*Circumscribed lesion.
*Usu. contrast enhancing.
*Solid, but intracortical cysts may be present.
*Little mass effect.

====Microscopic====
Features:
*Dysplastic neurons.
**Out of regular architecture / abnormal location.
**Cytomegaly
**Clustering
**Binucleated (very occassionally).
*Atypical glia.
*Eosinophilic granular bodies.
*Calcification.
*Prominent capillary network.
*Lymphocytic cuffing.
*May contain some reticulin.
*Glial component may resemble:
**Fibrillary astrocytoma.
**Oligodendroglioma.
**Pilocytic astrocytoma.

Anaplastic ganglioglioma:
*Brisk mitotic activity
*Necrosis

====IHC====
*Neurons:
**[[MAP2]] +ve
**Synaptophysin +ve
** Neurofilament +ve
*Glia:
**CD34+/-ve
*BRAF V600E +ve (approx. 25%, mainly ganglion cells).

====Molecular====
*BRAF V600E-mutated(approx. 25%).
*IDH1/2 wt.
*No 1p/19q codeletion.
*Usu. Chr. 7 gain.
*CDKN2A deletions in anaplastic ganglioglioma.

====DDx:====
*[[DNT]].
*[[Oligodendroglioma]].
*Trapped cortical neurons in diffuse astrocytoma.
*Papillary glioneuronal tumor.
*Dysembryoplastic neuroepithelial tumor.

====Images====
<gallery>
File:Ganglioglioma lymphocytic cuffing PAS.jpg | Lymphocytic cuffing in ganglioglioma (WC/jensflorian)
File:Ganglioglioma calcification.jpg | Calcification in ganglioglioma (WC/jensflorian)
File:Ganglioglioma Cd34 x200.jpg | CD34 immunostain in ganglioglioma (WC/jensflorian)
File:Anaplastic ganglioglioma HE.jpg | Pleomorphic ganglion cells in ganglioglioma (WC/jensflorian)
</gallery>
*[http://path.upmc.edu/cases/case142.html Ganglioglioma - case 1 (upmc.edu)].
*[http://path.upmc.edu/cases/case282.html Ganglioglioma - case 2 (upmc.edu)].

===Lhermitte-Duclos disease===
*Abbreviated ''LDD''.
*[[AKA]] ''dysplastic cerebellar gangliocytoma''.<ref name=pmid20060133>{{Cite journal | last1 = Yağci-Küpeli | first1 = B. | last2 = Oguz | first2 = KK. | last3 = Bilen | first3 = MA. | last4 = Yalçin | first4 = B. | last5 = Akalan | first5 = N. | last6 = Büyükpamukçu | first6 = M. | title = An unusual cause of posterior fossa mass: Lhermitte-Duclos disease. | journal = J Neurol Sci | volume = 290 | issue = 1-2 | pages = 138-41 | month = Mar | year = 2010 | doi = 10.1016/j.jns.2009.12.010 | PMID = 20060133 }}</ref>
*[[AKA]] ''dysplastic gangliocytoma of the cerebellum''.
{{Main|Lhermitte-Duclos disease}}
<gallery>
File:Dysplastic_gangliocytoma_lhermitte_duclos.jpg | Dysplastic gangliocytoma (low mag).
</gallery>

===Papillary glioneuronal tumour===
* Abbreviated ''PGNT''.
* A benign, supratentorial tumor of childhood.
** Biologic course corresponds to WHO grade I.
** Before WHO 2000, considered a [[Ganglioglioma]] variant.
*Prominent pseudopapillary architecture.
*Neurocytes to medium-sized ganglion cells.
*GFAP+ core, GFAP- layer
*Rosenthal fibers, Eosinophilic Granular bodies and lymphocytic cuffing may be present.
<gallery>
File:PGNT_HE_stain.jpg | PGNT (HE) (WC/jensflorian)
</gallery>

===Rosette-forming glioneuronal tumour of the fourth ventricle===
* Abbreviated ''RGNT''.
* Provisional ICD-O code: 9509/1
* A rare benign infratentorial tumour of the midline of children and adults.
* Biologic course corresponds to WHO grade I.
* Glial component corresponds to [[pilocytic astrocytoma]].
* Neurocytic rosettes.
* Eosinopil fibrillary cores / pseudorosettes.
* GFAP+ in fibrillary areas, Syn+ in rosettes.
* Neurocytic cells: MAP2+
* MIB-1 usu. below 3%.
<gallery>
File:Histology RGNT HE.jpg | RGNT, HE stain (WC/jensflorian).
File:RGNT HE 2.jpg | RGNT, higher magnification (WC/jensflorian).
</gallery>

===Polymorphous low-grade tumor of the young (PLNTY)===
* [[Pediatric-type diffuse low-grade glioma#Diffuse low-grade glioma, MAPK pathway-altered|Polymorphous low-grade tumor of the young (PLNTY)]]

==Pineal tumours==
{{Main|Pineal gland}}

* [[Pineocytoma]]
* [[Pineal parenchymal tumour of intermediate differentiation]]
* [[Pineoblastoma]]
* [[Papillary tumour of the pineal region]]

==Embryonal tumours==
* [[Atypical teratoid/rhabdoid tumour]] (AT/RT) or (AT-RT)
* [[Medulloblastoma]]
* [[Primitive neuroectodermal tumour]] (PNET)
* [[Embryonal tumour with abundant neuropil and true rosettes]] (ETANTR)

DDx:
* [[Ewing sarcoma]]
* [[Sarcoma with CIC-rearrangement]]

==Peripheral nerve sheath tumours==
{{Main|Peripheral nerve sheath tumours}}
A classification:<ref name=pmid17893219>{{cite journal |author=Wippold FJ, Lubner M, Perrin RJ, Lämmle M, Perry A |title=Neuropathology for the neuroradiologist: Antoni A and Antoni B tissue patterns |journal=AJNR Am J Neuroradiol |volume=28 |issue=9 |pages=1633–8 |year=2007 |month=October |pmid=17893219 |doi=10.3174/ajnr.A0682 |url=http://www.ajnr.org/cgi/reprint/28/9/1633}}</ref>
'''Benign:'''
*[[Schwannoma]].
*[[Neurofibroma]].
*[[Perineurioma]].
*Ganglioneuroma.
**[[Traumatic neuroma]].
'''Malignant:'''
*[[Malignant peripheral nerve sheath tumour]] (MPNST).

===Ganglioneuroma===
:'''Not''' to be confused with ''[[ganglioglioma]]''.
*[[AKA]] ganglioma.<ref>URL: [http://medical-dictionary.thefreedictionary.com/ganglioma http://medical-dictionary.thefreedictionary.com/ganglioma]. Accessed on: 8 November 2010.</ref>
{{Main|Ganglioneuroma}}

==Meningioma==
{{Main|Meningioma}}

==Chordoma==
{{Main|Chordoma}}

==Hemangioblastoma==
{{Main|Hemangioblastoma}}

==CNS lymphoma==
Classification:
*Primary CNS lymphoma.
*Non-primary CNS lymphoma - see ''[[lymphoma]]'' article.

===General - primary CNS===
*Classically periventicular distribution.
*Usually large B cell; can be considered a type of [[diffuse large B cell lymphoma]] (DLBCL).
**Prognosis of CNS (DLBCL) lymphomas worse than nodal (non-CNS) DLBCL.<ref name=pmid19925562>{{cite journal |author=Raoux D, Duband S, Forest F, ''et al.'' |title=Primary central nervous system lymphoma: Immunohistochemical profile and prognostic significance |journal=Neuropathology |volume=30 |issue=3 |pages=232–40 |year=2010 |month=June |pmid=19925562 |doi=10.1111/j.1440-1789.2009.01074.x |url=}}</ref>

===Microscopic===
Features:
*Large cell lymphoma.
**Size = 2x diameter normal lymphocyte.
**Nucleolus - common.
*Perivascular clustering.

====Images====
www:
*[http://frontalcortex.com/?page=image&topic=1&qid=1237 CNS lymphoma (frontalcortex.com)].
*[http://path.upmc.edu/cases/case403.html Primary CNS lymphoma - several images (upmc.edu)].
<gallery>
Image:Primary CNS lymphoma - low mag.jpg | CNS lymphoma - low mag. (WC)
Image:Primary CNS lymphoma - intermed mag.jpg | CNS lymphoma - intermed. mag. (WC)
Image:Primary CNS lymphoma - high mag.jpg | CNS lymphoma - high mag. (WC)
Image:Primary CNS lymphoma - very high mag.jpg | CNS lymphoma - very high mag. (WC)
</gallery>
<gallery>
Image: CNS lymphoma (1) B-cell type.jpg | CNS lymphoma. (WC/KGH)
Image: CNS lymphoma (2) B-cell type.jpg | CNS lymphoma. (WC/KGH)
</gallery>

===IHC===
Can be subclassified in ''GCB (germinal centre B-cell-like)'' and ''non-GCB'' by CD10, Bcl-6, MUM1/IRF-4, and Bcl-2.<ref name=pmid19925562/>

Common pattern:
*[[CD20]] +ve - key stain.
*CD3 -ve.
*Ki-67 ~40%.
*Bcl-6 +ve.
*Bcl-1 -ve.

==Ganglioneuroblastoma==
{{Main|Neuroblastoma}}
===General===
*Uncommon.
*Part of the ''neuroblastic tumours'' group which includes:<ref name=pmid10421272>{{cite journal |author=Shimada H, Ambros IM, Dehner LP, Hata J, Joshi VV, Roald B |title=Terminology and morphologic criteria of neuroblastic tumors: recommendations by the International Neuroblastoma Pathology Committee |journal=Cancer |volume=86 |issue=2 |pages=349–63 |year=1999 |month=July |pmid=10421272 |doi= |url=}}</ref>
**[[Ganglioneuroma]] (benign).
**Ganglioneuroblastoma (intermediate).
**[[Neuroblastoma]] (aggressive).

===Microscopic===
Features:
*Ganglion-like cells with a prominent nucleolus.
*Small undifferentiated cells with scant cytoplasm.
<gallery>
Image:Adrenal Ganglioneuroblastoma LP CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - Low power (SKB)
Image:Adrenal Ganglioneuroblastoma MP CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - Medium power (SKB)
Image:Adrenal Ganglioneuroblastoma HP CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - High power (SKB)
Image:Adrenal Ganglioneuroblastoma HP3 CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - High power (SKB)
Image:Adrenal Ganglioneuroblastoma HP2 CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - High power (SKB)
</gallery>
Images:
*[http://path.upmc.edu/cases/case530.html Ganglioneuroblastoma - several images (upmc.edu)].

===IHC===
*NSE +ve -- small cells.

==Lesions of the sella turcica==
{{Main|Pituitary gland}}
Lesions of the sella turcica, the pituitary gland environs, is a topic for it self. The differential diagnosis for lesions in this area includes:
*[[Pituitary adenoma]].
*[[Craniopharyngioma]].
*[[Rathke cleft cyst]].
*[[Germ cell tumour]].
*[[Meningioma]].
*[[Pilomyxoid astrocytoma]] - in children.

==See also==
*[[Neuropathology]].
*[[Muscle biopsy]].

==References==
{{reflist|2}}

==External links==
*[http://www.neuropathologyweb.org/ Neuropathology (neuropathologyweb.org)].
*[http://www.pathology.vcu.edu/WirSelfInst/tumor-1.html Neuropathology Mini-Course (pathology.vcu.edu)].
*[http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html Neuropathology Mini-Course (pathology.vcu.edu)].

[[Category:Neuropathology]]

Neuropathology tumours

2022-04-13T11:51:06Z

Jensflorian: /* By age group */ Update

[[Image:Gemistocytic Astrocytoma 003.jpg|thumb|right|A brain stem [[astrocytoma]]. (WC)]]
The article covers '''tumours in neuropathology'''. Tumours are a large part of [[neuropathology]]. [[Cytopathology]] of CNS tumours is dealt with in the article ''[[CNS cytopathology]]''.

There are separate articles for ''[[peripheral nerve sheath tumours]]'' and ''[[pituitary gland|pituitary/peri-pituitary lesions]]''.

==Brain tumours - overview==
===Alphabetical===
For overview see [[:Category:Neuropathology_tumours|here]]

===By age group===
====Adult====
Four most common types of brain tumours:<ref>[http://neurosurgery.mgh.harvard.edu/abta/primer.htm http://neurosurgery.mgh.harvard.edu/abta/primer.htm]</ref>
# Metastatic brain tumours (barely edges out primary tumours)
#*[[Lung cancer|Lung]] (most common).
#*[[Invasive breast cancer|Breast]].
#*[[Melanoma]].
#*[[Renal cell carcinoma]] (RCC).
# [[Glioblastoma]], IDH-wildtype.
# [[Astrocytoma, IDH-mutant]].
# [[Meningioma]].

====Children====
# [[Pilocytic astrocytoma]].
# [[Medulloblastoma]].
# [[Ependymoma]].
# Pontine glioma, often [[Diffuse midline glioma, H3 K27-altered]].

===By location===
Certain tumours like to hang-out at certain places:<ref>URL: [http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/files/4ce563fb7e8e48fc9ed8b42e296a7747.gif http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/files/4ce563fb7e8e48fc9ed8b42e296a7747.gif] and [http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html]. Accessed on: 2 November 2010.</ref>
====Cerebrum====
*Cortical based - [[oligodendroglioma]].
*Grey-white junction - metastases.
*White matter - astrocytoma, [[glioblastoma]].
*Periventricular - CNS lymphoma.
*Cystic - [[ganglioglioma]], [[pilocytic astrocytoma]], [[pleomorphic xanthoastrocytoma]].
====Cerebellum====
*Midline/central - [[medulloblastoma]].
*Cystic lesion - pilocytic astrocytoma (younger individual), [[hemangioblastoma]] (older individual).
*Solid lesion (older individual) - [[metastasis]].
====Sella turcica====
* [[Pituitary adenoma]].
* [[Craniopharyngioma]].
less common:
* [[Pituicytoma]].
* [[Granular cell tumour]].
* [[Germinoma]].
* [[Chordoma]]
* Rathke cleft cyst.
* Hypophysitis.
* Xanthogranuloma.
====Spinal cord====
*[[Ependymoma]]
*[[Glioblastoma]]
*[[Meningioma]]
*Carcinoma metastasis
*[[Hemangioblastoma]]
====Filum terminale====
*[[Meningioma]].
*[[Myxopapillary ependymoma]].
*[[Neurofibroma]].
*[[Schwannoma]].
*[[Paraganglioma]].
====Meninges====
* [[Meningioma]].
* [[Solitary fibrous tumour]] / Hemangiopericytoma.
* [[Hemangioblastoma]].
less common:
* [[Melanoma]] / Melanocytoma.
* Lymphoproliferative diseases.
* [[Sarcoidosis]]
* [[Arachnoid cyst]].
* Disseminated oligodendroglial-like leptomeningeal tumour.
* Desmoplastic infantile astrocytoma / ganglioglioma.
* Meningioangiomatosis.
* Calcifying pseudoneoplasm.
====Skull====
* [[Fibrous dysplasia]].
* [[Paget disease]].
* [[Histiocytosis]].
* [[Hemangioma]].
* [[Aneurysmal bone cyst]].
* [[Plasma_cell_neoplasms#Multiple_myeloma|Multiple myeloma]].
====Skull base / Cerebellopontine angle====
* [[Schwannoma]].
* [[Meningioma]].
* [[Dermoid cyst]] / epidermoid cyst.
less common:
* [[Ependymoma]].
* [[Choroid plexus papilloma]].
* [[Glomus tumour]].
* [[Chordoma]].
* [[Chondrosarcoma]].
* [[Olfactory neuroblastoma]].
* [[Endolymphatic sac tumour]].

===Cystic tumours===
DDx:<ref>URL: [http://path.upmc.edu/cases/case320/dx.html http://path.upmc.edu/cases/case320/dx.html]. Accessed on: 14 January 2012.</ref>
*[[Pilocytic astrocytoma]].
*[[Pleomorphic xanthoastrocytoma]].
*[[Ganglioglioma]].
*[[Hemangioblastoma]].
*[[Craniopharyngioma]].<ref>URL: [http://www.pathologyoutlines.com/Cnstumor.html#cystsgeneral http://www.pathologyoutlines.com/Cnstumor.html#cystsgeneral]. Accessed on: 14 January 2012.</ref>

===Primary versus secondary===
*[[AKA]] (primary) brain tumour versus metastatic cancer.
====Primary====
[[Glioma|Glial tumours]]:
*Cytoplasmic processes - '''key feature'''.
**Best seen at highest magnification - usu. ~1 micrometer.
**Processes may branch.
*Ill-defined border/blend with the surrounding brain.

[[Meningioma]]:
*Lesion often dura-based.
*Mesenchymal tumor (often contains collagen).

[[Lymphoma]]:
*Large (lymphoid) cells, ergo usu. not a difficult diagnosis.
**~2x size of resting lymphocyte, nucleoli.
*Lesion predominantly perivascular.

====Secondary====
Carcinomas:
*Well-demarcated border between brain and lesion - '''key feature'''.
*No cytoplasmic processes.
*Usu. have nuclear atypia of malignancy.
**Nuclei often ~3-4x the size of a [[RBC]].
*+/-Glandular arrangement.
*+/-Nucleoli.

===Common neuropathology tumours in a table===
{| class="wikitable"
|'''Type'''
|'''Key feature(s)'''
|'''Imaging'''
|'''History'''
|'''Notes'''
|'''IHC'''
|'''Images'''
|-
|Normal tissue
|cells regularly spaced, no nuc. atypia
|small lesion? / deep lesion?
|variable
|missed lesion?
|nil
|[[Image:Grey_matter_and_white_matter_-_very_high_mag.jpg |thumb|center|150px|Normal. (WC)]]
|-
|[[Reactive astrocytes]]
|astrocytes with well-demarcated eosinophilic cytoplasm, regular spacing, no nuc. atypia
|small lesion? / deep lesion?
|variable
|missed lesion / close to a lesion; non-specific pathologic process - need more tissue
|nil
|[[Image:Reactive_astrocytes_-_lfb_-_high_mag.jpg|thumb|center|150px|Reactive astrocytes. (WC)]]
|-
|[[Schwannoma]]
|cellular areas (Antoni A), paucicelluar areas (Antoni B), palisading of nuclei (Verocay bodies)
|extra-axial + intradural
|old or young
|need frozen section to Dx, DDx: [[meningioma]]
|S100
|[[Image:Schwannoma_-_Antoni_A_and_B_-_very_high_mag.jpg|thumb|center|150px|Schwannoma. (WC)]]
|-
|[[Meningioma]]
|whorls, psammomatous calcs, nuclear inclusions
|extra-axial + intradural
|old or young
|may be diagnosed on smear, DDx: [[schwannoma]], choroid plexus
|EMA, PR, Ki-67
|[[Image:Meningioma_intermed_mag.jpg |thumb|center|150px|Meningioma. (WC)]]
|-
|[[Astrocytoma, IDH-mutant]] (CNS [[WHO]] grade 2 or grade 3)
|glial processes (esp. on smear), nuclear atypia (typical size var. ~3x, irreg. nuc. membrane, hyperchromasia), no Rosenthal fibres in the core of the lesion †, no microvascular proliferation, no necrosis
|often enhancing (suggests high grade), usu. supratentorial, usu. white matter
|usu. old, occ. young
|common
|IDH-1(R132H)+/-, GFAP+
| [[Image:Anaplastic_astrocytoma_-_very_high_mag_-_cropped.jpg | thumb| center| 150px|High-grade astrocytoma. (WC)]]
|-
|[[Glioblastoma]], IDH-wildtype (CNS [[WHO]] grade 4)
|glial processes (esp. on smear), nuclear atypia (typical size var. ~3x, irreg. nuc. membrane, hyperchromasia), no Rosenthal fibres in the core of the lesion †, microvascular proliferation or necrosis
|often enhancing (suggests high grade), usu. supratentorial, usu. white matter
|usu. old, occ. young
|very common, esp. glioblastoma
|IDH-1+/-, GFAP+
| [[Image:Glioblastoma (1).jpg | thumb| center| 150px|Glioblastoma. (WC)]]
|-
|[[Metastatic brain tumours|Metastasis]]
|sharp interface with brain, often glandular, +/-nucleoli, no glial processes
|often cerebellular, well-circumscribed
|usu. old
|often suspected to have metastatic disease
|[[TTF-1]], CK7, [[CK20]], BRST-2
|[[Image:Metastatic_adenocarcinoma_-_cerebellum_-_very_low_mag.jpg | thumb| center|150px |Metastasis. (WC)]]
|}
† Rosenthal fibres at the periphery of a lesion are a non-specific finding seen in chronic processes.

==Brain metastasis==
{{Main|Brain metastasis}}

==Infiltrative astrocytomas==
{{Main|Astrocytoma}}

===Overview===
*Low-grade (diffuse) astrocytomas (WHO Grade II).
*Anaplastic astrocytomas (WHO Grade III).
*[[Glioblastoma]](WHO Grade IV).
**[[Gliosarcoma]] (WHO Grade IV).
*[[Gliomatosis cerebri]] (Grade III/IV).

Notes:
*Non-infiltrative astrocytomas:
**[[Pilocytic astrocytoma]] (WHO Grade I).
***[[Pilomyxoid astrocytoma]] (WHO Grade II).
**[[Pleomorphic xanthoastrocytoma]] (WHO grade II).
**[[Subependymal giant cell astrocytoma]] (WHO grade I).

===Microscopic===
Features:<ref name=pmid>{{cite journal |author=Rong Y, Durden DL, Van Meir EG, Brat DJ |title='Pseudopalisading' necrosis in glioblastoma: a familiar morphologic feature that links vascular pathology, hypoxia, and angiogenesis |journal=J. Neuropathol. Exp. Neurol. |volume=65 |issue=6 |pages=529–39 |year=2006 |month=June |pmid=16783163 |doi= |url=}}</ref><ref>[http://dictionary.reference.com/browse/palisading http://dictionary.reference.com/browse/palisading]</ref>
*Glial processes - '''key feature'''.
**Thin stringy cytoplasmic processes - best seen at high power in less cellular areas.
*No Rosenthal fibres within the tumour itself.

Images:
*[http://moon.ouhsc.edu/kfung/jty1/opaq/PathQuiz/N0A002-PQ01-M.htm Endothelial proliferation in a GBM (ouhsc.edu)].
*[http://moon.ouhsc.edu/kfung/jty1/neurotest/Q05-Ans.htm Endothelial proliferation (ouhse.edu)].
*[http://path.upmc.edu/cases/case368.html Gemistocytic astrocytoma - several images (upmc.edu)].

Notes:
*Glial vs. non-glial tumours:
**Glial: "blends into brain"/gradual transition to non-tumour brain.
**Non-glial: no glial processes.
*Rosenthal fibres within the tumour... make it into a [[pilocytic astrocytoma]].
**Rosenthal fibres may be seen around a (very) slow growing tumour and represent a reactive process.
*Inflammatory cells and macrophages should prompt consideration of an alternate diagnosis (e.g. [[cerebral infarct]], [[multiple sclerosis]]) - esp. if this is a primary lesion.<ref>URL: [http://path.upmc.edu/cases/case79/dx.html http://path.upmc.edu/cases/case79/dx.html]. Accessed on: 2 January 2012.</ref>

====Grading====
Nuclear pleomorphism present:
*At least grade II (diffuse astrocytoma).

Mitotic figures present:
*At least grade III (anaplastic astrocytoma).

Microvascular proliferation ''or'' necrosis with pseudopalisading tumour cells:
*Grade IV (glioblastoma [[AKA]] glioblastoma multiforme).

Notes:
*Pseudopalisading tumour cells = high tumour cell density adjacent to regions of necrosis; palisade = a fence of poles forming a defensive barrier or fortification.
*WHO Grading is currently based on expected biologiocal behaviour without treatment.
**Grading does not reflect molecular divergent groups within a tumor class or response to therapy (Currently controversies in grading for IDH-mutant astrocytoma vs. IDH-wildtype astrocytoma).<ref>{{Cite journal | last1 = Louis | first1 = DN. | last2 = von Deimling | first2 = A. | title = Grading of diffuse astrocytic gliomas: Broders, Kernohan, Zülch, the WHO… and Shakespeare. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Aug | year = 2017 | doi = 10.1007/s00401-017-1765-z | PMID = 28801693 }}</ref>

====Images====
Glioblastoma:
<gallery>
Image:Glioblastoma_%281%29.jpg | Glioblastoma - pseudopalisading of tumour cells (WC)
Image:Glioblastoma_-_high_mag.jpg | Glioblastoma with fragment of near-normal white matter - high mag. (WC)
</gallery>
Anaplastic astrocytoma:
<gallery>
Image:Anaplastic_astrocytoma_-_very_high_mag_-_cropped.jpg | Anaplastic astrocytoma - very high mag. (WC)
Image:Anaplastic_astrocytoma_-_gfap_-_very_high_mag.jpg | Anaplastic astrocytoma - GFAP - very high mag. (WC)
</gallery>

===IHC===
*GFAP - should stain cytoplasm of tumour cells and the perikaryon (nuclear membrane).
*Ki-67 - usu. high >20% of cells.
*p53 - often +ve.
*[[IDH-1]] (isocitrate dehydrogenase 1).
**+ve in tumours that arose from low-grade gliomas.<ref name=pmid19228619>{{cite journal |author=Yan H, Parsons DW, Jin G, ''et al.'' |title=IDH1 and IDH2 mutations in gliomas |journal=N. Engl. J. Med. |volume=360 |issue=8 |pages=765–73 |year=2009 |month=February |pmid=19228619 |pmc=2820383 |doi=10.1056/NEJMoa0808710 |url=}}</ref>
*[[H3F3A|H3F3A K27M]] -ve
**+ve cases to be classified as [[Astrocytoma#H3.3_K27M_mutated_glioma_of_the_midline|K27 mutated midline glioma]].
*[[ATRX]] -ve in tumors with low-grade precursor(most of them also IDH1/2 mutant).

Notes:
*IDH1 and IDH2 mutations - better survival.<ref name=pmid20975057>{{cite journal |author=Houillier C, Wang X, Kaloshi G, ''et al.'' |title=IDH1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas |journal=Neurology |volume=75 |issue=17 |pages=1560–6 |year=2010 |month=October |pmid=20975057 |doi=10.1212/WNL.0b013e3181f96282 |url=}}</ref>

===Molecular===
See also: [[Molecular_pathology_tests#Neuropathology|Molecular Neuropathology]]

==Gliomas==
{{Main|Glioma}}

Gliomas, glioneuronal tumours and neuronal tumours are often categorized together.

===Astrocytic tumours===
{{Main|Astrocytoma}}

* [[Astrocytoma]], IDH-mutant.
* [[Glioblastoma]], IDH-wildtype.
** [[Gliosarcoma]] (a glioblastoma subtype)

Depreceated:
* Diffuse [[Astrocytoma]]
* [[Anaplastic astrocytoma]]
* [[Gliomatosis cerebri]]
* Spongioblastoma

===Oligodendroglial tumours===
* [[Oligodendroglioma]], IDH-mutant and 1p/19q codeleted.

Depreceated:
* Anaplastic oligodendroglioma
* [[Oligoastrocytoma]]
* Anaplastic oligoastrocytoma

===Pediatric-type diffuse high-grade glioma===
{{Main|Pediatric-type diffuse high-grade glioma}}
* [[Astrocytoma#Diffuse_midline_glioma.2C_H3_K27M_mutant|Diffuse midline glioma H3 K27-mutant]]

===Pediatric-type diffuse low-grade glioma===
{{Main|Pediatric-type diffuse low-grade glioma}}

===Circumscribed astrocytic gliomas===
* [[Pilocytic astrocytoma]] (PA)
** [[Pilomyxoid astrocytoma]] (PMA)
* [[Pleomorphic xanthoastrocytoma]] (PXA)
* [[Subependymal giant cell astrocytoma]] (SEGA)
* [[Neuropathology_tumours#Astroblastoma|Astroblastoma MN1-altered]].
* [[Neuropathology_tumours#Chordoid glioma of the third ventricl|Chordoid glioma]].

====Astroblastoma====
*No WHO grade yet.<ref>{{Ref WHOCNS|88}}</ref>
*Very rare superficial tumor of young age.<ref>{{Cite journal | last1 = Narayan | first1 = S. | last2 = Kapoor | first2 = A. | last3 = Singhal | first3 = MK. | last4 = Jakhar | first4 = SL. | last5 = Bagri | first5 = PK. | last6 = Rajput | first6 = PS. | last7 = Kumar | first7 = HS. | title = Astroblastoma of cerebrum: A rare case report and review of literature. | journal = J Cancer Res Ther | volume = 11 | issue = 3 | pages = 667 | month = | year = | doi = 10.4103/0973-1482.140800 | PMID = 26458709 }}</ref>
*Large, cystic. Pushing margin towards CNS.
*Vasocentric growth, plump cells with absence of fibrillary pattern.
*GFAP+ve, Synaptohysin-ve, Olig-2-ve, focally EMA/panCK+ve. MIB-1: 1-18 %.
*Molecular profile overlaps with classical [[CNS-PNET]].
**Gene fusions invoving meningioma gene (MN1)<ref>{{Cite journal | last1 = Sturm | first1 = D. | last2 = Orr | first2 = BA. | last3 = Toprak | first3 = UH. | last4 = Hovestadt | first4 = V. | last5 = Jones | first5 = DT. | last6 = Capper | first6 = D. | last7 = Sill | first7 = M. | last8 = Buchhalter | first8 = I. | last9 = Northcott | first9 = PA. | title = New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs. | journal = Cell | volume = 164 | issue = 5 | pages = 1060-72 | month = Feb | year = 2016 | doi = 10.1016/j.cell.2016.01.015 | PMID = 26919435 }}</ref>

<gallery>
File:Astroblastoma_HE_Specimen.jpg | HE. (WC/jensflorian)
File:Astroblastoma_HE_papillae.jpg | HE. (WC/jensflorian)
File:Astroblastoma.jpg | Astroblastoma (AFIP)
</gallery>

====Chordoid glioma of the third ventricle====
* WHO grade II.
* Slowly growing, non-invasive, in adults.
* Clusters of epithelioid cells in mucinous stroma.
* Lymphocytic infiltrates, adjacent Rosenthal fibers.
* Fibrosis may be present.
* Few mitoses.
* [[GFAP]]+ve, MIB-1 1-3%.
* [[TTF-1]]+ve.
* CD34+ve.
* [[IDH-1]]-ve, [[p53]]-ve.
* PRKCA D463H mutations.<ref>{{Cite journal | last1 = Goode | first1 = B. | last2 = Mondal | first2 = G. | last3 = Hyun | first3 = M. | last4 = Ruiz | first4 = DG. | last5 = Lin | first5 = YH. | last6 = Van Ziffle | first6 = J. | last7 = Joseph | first7 = NM. | last8 = Onodera | first8 = C. | last9 = Talevich | first9 = E. | title = A recurrent kinase domain mutation in PRKCA defines chordoid glioma of the third ventricle. | journal = Nat Commun | volume = 9 | issue = 1 | pages = 810 | month = 02 | year = 2018 | doi = 10.1038/s41467-018-02826-8 | PMID = 29476136 }}</ref>

<gallery>
File:NP op 20201028 009.jpg | Chordoid Glioma. (WC/jensflorian)
</gallery>

===Ependymal tumours===
* [[Subependymoma]]
* [[Myxopapillary Ependymoma]]
* [[Ependymoma]]
* Anaplastic ependymoma

==Choroid plexus tumours==
* [[Choroid plexus papilloma]]
* Atypical choroid plexus papilloma
* [[Choroid plexus carcinoma]]

==Other neuroepithelial tumours==
* [[Neuropathology_tumours#Cribiform_neuroepithelial_tumour|Cribifiorm neuroepithelial tumour]].

===Cribiform neuroepithelial tumour===
AKA: '''CRINET'''.
*Not listed in the current WHO classification.
*First description in 2009.<ref>{{Cite journal | last1 = Hasselblatt | first1 = M. | last2 = Oyen | first2 = F. | last3 = Gesk | first3 = S. | last4 = Kordes | first4 = U. | last5 = Wrede | first5 = B. | last6 = Bergmann | first6 = M. | last7 = Schmid | first7 = H. | last8 = Frühwald | first8 = MC. | last9 = Schneppenheim | first9 = R. | title = Cribriform neuroepithelial tumor (CRINET): a nonrhabdoid ventricular tumor with INI1 loss and relatively favorable prognosis. | journal = J Neuropathol Exp Neurol | volume = 68 | issue = 12 | pages = 1249-55 | month = Dec | year = 2009 | doi = 10.1097/NEN.0b013e3181c06a51 | PMID = 19915490 }}</ref>
*Around ventricles.<ref>{{Cite journal | last1 = Arnold | first1 = MA. | last2 = Stallings-Archer | first2 = K. | last3 = Marlin | first3 = E. | last4 = Grondin | first4 = R. | last5 = Olshefski | first5 = R. | last6 = Biegel | first6 = JA. | last7 = Pierson | first7 = CR. | title = Cribriform neuroepithelial tumor arising in the lateral ventricle. | journal = Pediatr Dev Pathol | volume = 16 | issue = 4 | pages = 301-7 | month = | year = | doi = 10.2350/12-12-1287-CR.1 | PMID = 23495723 }}</ref>
*Young children.<ref>{{Cite journal | last1 = Park | first1 = JY. | last2 = Kim | first2 = E. | last3 = Kim | first3 = DW. | last4 = Chang | first4 = HW. | last5 = Kim | first5 = SP. | title = Cribriform neuroepithelial tumor in the third ventricle: a case report and literature review. | journal = Neuropathology | volume = 32 | issue = 5 | pages = 570-6 | month = Oct | year = 2012 | doi = 10.1111/j.1440-1789.2011.01293.x | PMID = 22239490 }}</ref>
*Small undifferentiated cells arranged in cribriform strands and trabeculae of varying thickness.
*MAP2+ve, Synaptophysin+ve, CK+/-ve. MIB-1: 30%.
*INI-1 loss, but no rhabdoid features and good prognosis.
*Stable genomic profile.<ref>{{Cite journal | last1 = Gessi | first1 = M. | last2 = Japp | first2 = AS. | last3 = Dreschmann | first3 = V. | last4 = Zur Mühlen | first4 = A. | last5 = Goschzik | first5 = T. | last6 = Dörner | first6 = E. | last7 = Pietsch | first7 = T. | title = High-Resolution Genomic Analysis of Cribriform Neuroepithelial Tumors of the Central Nervous System. | journal = J Neuropathol Exp Neurol | volume = 74 | issue = 10 | pages = 970-4 | month = Oct | year = 2015 | doi = 10.1097/NEN.0000000000000239 | PMID = 26352987 }}</ref>

==Neuronal and mixed neuronal/glial tumours==
* [[Desmoplastic infantile astrocytoma]] / ganglioglioma (DIA/DIG)
* [[Dysembryoplastic neuroepithelial tumour]]
* [[Central Neurocytoma]] / Extraventricular [[neurocytoma]]
* Cerebellar liponeurocytoma
* [[Papillary glioneuronal tumour]] (PGNT)
* [[Rosette-forming glioneuronal tumour of the fourth ventricle]] (RGNT)
* Gangliocytoma / Ganglioglioma
* Dysplastic ganglioglioma of the cerebellum ([[Lhermitte-Duclos disease]])
* [[Paraganglioma]]

===Desmoplastic infantile astrocytoma / Desmoplastic infantile ganglioglioma===
* Abbreviated ''DIA'' or ''DIG''.
* ICD-O code: 9412/1
* Large, superficial, cystic tumor of the infancy.
* Biologic course corresponds to WHO grade I.
* Very rare, included in the WHO since 1993.
* Prominent desmoplastic stroma.
* Astrocytic cells within stroma.
**GFAP+.
**MIB-1 usu. 1%.
* Frequent BRAF V600E or V600D mutations.<ref>{{Cite journal | last1 = Wang | first1 = AC. | last2 = Jones | first2 = DTW. | last3 = Abecassis | first3 = IJ. | last4 = Cole | first4 = BL. | last5 = Leary | first5 = SES. | last6 = Lockwood | first6 = CM. | last7 = Chavez | first7 = L. | last8 = Capper | first8 = D. | last9 = Korshunov | first9 = A. | title = Desmoplastic Infantile Ganglioglioma/Astrocytoma (DIG/DIA) are Distinct Entities with Frequent BRAFV600 Mutations. | journal = Mol Cancer Res | volume = | issue = | pages = | month = Jul | year = 2018 | doi = 10.1158/1541-7786.MCR-17-0507 | PMID = 30006355 }}</ref>
*Single case with BRAF indel or BRAF fusion.
<gallery>
File:DIG-histology.jpg | Histopathology of DIG (HE stain)
File:DIG-histology2.jpg | Prominent ganglioid cells in DIG (HE stain)
</gallery>

===Cerebellar liponeurocytoma===
* Previously called ''lipomatous medulloblastoma'' (name changed in WHO 2000).
* Mean age: 50 years.
* As the name states: A tumour of the cerebellum.
** But cases outside cerebellum reported that would qualify.<ref>{{Cite journal | last1 = Gupta | first1 = K. | last2 = Salunke | first2 = P. | last3 = Kalra | first3 = I. | last4 = Vasishta | first4 = RK. | title = Central liponeurocytoma: case report and review of literature. | journal = Clin Neuropathol | volume = 30 | issue = 2 | pages = 80-5 | month = | year = | doi = | PMID = 21329617 }}</ref>
* WHO grade II <ref>{{Cite journal | last1 = Nishimoto | first1 = T. | last2 = Kaya | first2 = B. | title = Cerebellar liponeurocytoma. | journal = Arch Pathol Lab Med | volume = 136 | issue = 8 | pages = 965-9 | month = Aug | year = 2012 | doi = 10.5858/arpa.2011-0337-RS | PMID = 22849747 }}</ref> (upgraded from WHO grade I in 2007)<ref>{{Cite journal | last1 = Brat | first1 = DJ. | last2 = Parisi | first2 = JE. | last3 = Kleinschmidt-DeMasters | first3 = BK. | last4 = Yachnis | first4 = AT. | last5 = Montine | first5 = TJ. | last6 = Boyer | first6 = PJ. | last7 = Powell | first7 = SZ. | last8 = Prayson | first8 = RA. | last9 = McLendon | first9 = RE. | title = Surgical neuropathology update: a review of changes introduced by the WHO classification of tumours of the central nervous system, 4th edition. | journal = Arch Pathol Lab Med | volume = 132 | issue = 6 | pages = 993-1007 | month = Jun | year = 2008 | doi = 10.1043/1543-2165(2008)132[993:SNUARO]2.0.CO;2 | PMID = 18517285 }}</ref>
*ICD-O code: 9506/1

====Histo====
* Advanced neuronal and lipomatous differentiation.
* Neurocytes: round to oval nuclei with clear cytoplasm.
* Quite cellular.
* Mitoses almost absent.

====IHC====
* [[GFAP]] +/-ve (focal).
* [[MAP2]] +ve.
* Synaptophysin +ve.
* NeuN +ve.
* MIB-1: usu 1-3%.

====Molecular====
* Distinct methylation profile.
* Recurent losses on 2p and Chr. 14.<ref>{{Cite journal | last1 = Capper | first1 = D. | last2 = Stichel | first2 = D. | last3 = Sahm | first3 = F. | last4 = Jones | first4 = DTW. | last5 = Schrimpf | first5 = D. | last6 = Sill | first6 = M. | last7 = Schmid | first7 = S. | last8 = Hovestadt | first8 = V. | last9 = Reuss | first9 = DE. | title = Practical implementation of DNA methylation and copy-number-based CNS tumor diagnostics: the Heidelberg experience. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Jul | year = 2018 | doi = 10.1007/s00401-018-1879-y | PMID = 29967940 }}</ref>

<gallery>
File:Cerebellar liponeurocytoma.jpg | Liponeurocytoma, HE (WC/Marvin101).
File:Liponeurocytoma Synaptophysin.jpg | Liponeurocytoma, Synapto (WC/Marvin101).
File:Cerebellar Liponeurocytoma HE.jpg | Liponeurocytoma, HE (WC/jensflorian).
File:Cerebellar Liponeurocytoma Synaptophysin.jpg | Liponeurocytoma, Synapto (WC/jensflorian).
</gallery>

====DDx====
* [[Medulloblastoma]]
* [[Neurocytoma]]

===Gangliocytoma===
* Grade I WHO neuronal tumour.
** ICD-O code: 9492/0
* Groups of irregular large neurons.
* Non-neoplastic, reticulin-rich glial stroma.

===Ganglioglioma===
:'''Not''' to be confused with ''[[ganglioneuroma]]''.
====General====
*Gangliolioma: Grade I WHO mixed neuronal-glial tumour (ICD-O code: 9505/1).
*Anaplastic ganglioglioma: Grade III (ICD-O: 9505/3)
*Rare (approx. 0.5% of all CNS tumors).
*Usu. temporal lobe.
*Predominantly children (mean age: 9 years).
*Recognized as a cause of [[epilepsy]].<ref name=pmid12125968>{{Cite journal | last1 = Im | first1 = SH. | last2 = Chung | first2 = CK. | last3 = Cho | first3 = BK. | last4 = Lee | first4 = SK. | title = Supratentorial ganglioglioma and epilepsy: postoperative seizure outcome. | journal = J Neurooncol | volume = 57 | issue = 1 | pages = 59-66 | month = Mar | year = 2002 | doi = | PMID = 12125968 }}</ref>
*Favourable prognosis (survival rates up to 97%)
**Insufficient data für anaplastic ganglioglioma.

====Macroscopic====
*Circumscribed lesion.
*Usu. contrast enhancing.
*Solid, but intracortical cysts may be present.
*Little mass effect.

====Microscopic====
Features:
*Dysplastic neurons.
**Out of regular architecture / abnormal location.
**Cytomegaly
**Clustering
**Binucleated (very occassionally).
*Atypical glia.
*Eosinophilic granular bodies.
*Calcification.
*Prominent capillary network.
*Lymphocytic cuffing.
*May contain some reticulin.
*Glial component may resemble:
**Fibrillary astrocytoma.
**Oligodendroglioma.
**Pilocytic astrocytoma.

Anaplastic ganglioglioma:
*Brisk mitotic activity
*Necrosis

====IHC====
*Neurons:
**[[MAP2]] +ve
**Synaptophysin +ve
** Neurofilament +ve
*Glia:
**CD34+/-ve
*BRAF V600E +ve (approx. 25%, mainly ganglion cells).

====Molecular====
*BRAF V600E-mutated(approx. 25%).
*IDH1/2 wt.
*No 1p/19q codeletion.
*Usu. Chr. 7 gain.
*CDKN2A deletions in anaplastic ganglioglioma.

====DDx:====
*[[DNT]].
*[[Oligodendroglioma]].
*Trapped cortical neurons in diffuse astrocytoma.
*Papillary glioneuronal tumor.
*Dysembryoplastic neuroepithelial tumor.

====Images====
<gallery>
File:Ganglioglioma lymphocytic cuffing PAS.jpg | Lymphocytic cuffing in ganglioglioma (WC/jensflorian)
File:Ganglioglioma calcification.jpg | Calcification in ganglioglioma (WC/jensflorian)
File:Ganglioglioma Cd34 x200.jpg | CD34 immunostain in ganglioglioma (WC/jensflorian)
File:Anaplastic ganglioglioma HE.jpg | Pleomorphic ganglion cells in ganglioglioma (WC/jensflorian)
</gallery>
*[http://path.upmc.edu/cases/case142.html Ganglioglioma - case 1 (upmc.edu)].
*[http://path.upmc.edu/cases/case282.html Ganglioglioma - case 2 (upmc.edu)].

===Lhermitte-Duclos disease===
*Abbreviated ''LDD''.
*[[AKA]] ''dysplastic cerebellar gangliocytoma''.<ref name=pmid20060133>{{Cite journal | last1 = Yağci-Küpeli | first1 = B. | last2 = Oguz | first2 = KK. | last3 = Bilen | first3 = MA. | last4 = Yalçin | first4 = B. | last5 = Akalan | first5 = N. | last6 = Büyükpamukçu | first6 = M. | title = An unusual cause of posterior fossa mass: Lhermitte-Duclos disease. | journal = J Neurol Sci | volume = 290 | issue = 1-2 | pages = 138-41 | month = Mar | year = 2010 | doi = 10.1016/j.jns.2009.12.010 | PMID = 20060133 }}</ref>
*[[AKA]] ''dysplastic gangliocytoma of the cerebellum''.
{{Main|Lhermitte-Duclos disease}}
<gallery>
File:Dysplastic_gangliocytoma_lhermitte_duclos.jpg | Dysplastic gangliocytoma (low mag).
</gallery>

===Papillary glioneuronal tumour===
* Abbreviated ''PGNT''.
* A benign, supratentorial tumor of childhood.
** Biologic course corresponds to WHO grade I.
** Before WHO 2000, considered a [[Ganglioglioma]] variant.
*Prominent pseudopapillary architecture.
*Neurocytes to medium-sized ganglion cells.
*GFAP+ core, GFAP- layer
*Rosenthal fibers, Eosinophilic Granular bodies and lymphocytic cuffing may be present.
<gallery>
File:PGNT_HE_stain.jpg | PGNT (HE) (WC/jensflorian)
</gallery>

===Rosette-forming glioneuronal tumour of the fourth ventricle===
* Abbreviated ''RGNT''.
* Provisional ICD-O code: 9509/1
* A rare benign infratentorial tumour of the midline of children and adults.
* Biologic course corresponds to WHO grade I.
* Glial component corresponds to [[pilocytic astrocytoma]].
* Neurocytic rosettes.
* Eosinopil fibrillary cores / pseudorosettes.
* GFAP+ in fibrillary areas, Syn+ in rosettes.
* Neurocytic cells: MAP2+
* MIB-1 usu. below 3%.
<gallery>
File:Histology RGNT HE.jpg | RGNT, HE stain (WC/jensflorian).
File:RGNT HE 2.jpg | RGNT, higher magnification (WC/jensflorian).
</gallery>

===Polymorphous low-grade tumor of the young (PLNTY)===
* [[Pediatric-type diffuse low-grade glioma#Diffuse low-grade glioma, MAPK pathway-altered|Polymorphous low-grade tumor of the young (PLNTY)]]

==Pineal tumours==
{{Main|Pineal gland}}

* [[Pineocytoma]]
* [[Pineal parenchymal tumour of intermediate differentiation]]
* [[Pineoblastoma]]
* [[Papillary tumour of the pineal region]]

==Embryonal tumours==
* [[Atypical teratoid/rhabdoid tumour]] (AT/RT) or (AT-RT)
* [[Medulloblastoma]]
* [[Primitive neuroectodermal tumour]] (PNET)
* [[Embryonal tumour with abundant neuropil and true rosettes]] (ETANTR)

DDx:
* [[Ewing sarcoma]]
* [[Sarcoma with CIC-rearrangement]]

==Peripheral nerve sheath tumours==
{{Main|Peripheral nerve sheath tumours}}
A classification:<ref name=pmid17893219>{{cite journal |author=Wippold FJ, Lubner M, Perrin RJ, Lämmle M, Perry A |title=Neuropathology for the neuroradiologist: Antoni A and Antoni B tissue patterns |journal=AJNR Am J Neuroradiol |volume=28 |issue=9 |pages=1633–8 |year=2007 |month=October |pmid=17893219 |doi=10.3174/ajnr.A0682 |url=http://www.ajnr.org/cgi/reprint/28/9/1633}}</ref>
'''Benign:'''
*[[Schwannoma]].
*[[Neurofibroma]].
*[[Perineurioma]].
*Ganglioneuroma.
**[[Traumatic neuroma]].
'''Malignant:'''
*[[Malignant peripheral nerve sheath tumour]] (MPNST).

===Ganglioneuroma===
:'''Not''' to be confused with ''[[ganglioglioma]]''.
*[[AKA]] ganglioma.<ref>URL: [http://medical-dictionary.thefreedictionary.com/ganglioma http://medical-dictionary.thefreedictionary.com/ganglioma]. Accessed on: 8 November 2010.</ref>
{{Main|Ganglioneuroma}}

==Meningioma==
{{Main|Meningioma}}

==Chordoma==
{{Main|Chordoma}}

==Hemangioblastoma==
{{Main|Hemangioblastoma}}

==CNS lymphoma==
Classification:
*Primary CNS lymphoma.
*Non-primary CNS lymphoma - see ''[[lymphoma]]'' article.

===General - primary CNS===
*Classically periventicular distribution.
*Usually large B cell; can be considered a type of [[diffuse large B cell lymphoma]] (DLBCL).
**Prognosis of CNS (DLBCL) lymphomas worse than nodal (non-CNS) DLBCL.<ref name=pmid19925562>{{cite journal |author=Raoux D, Duband S, Forest F, ''et al.'' |title=Primary central nervous system lymphoma: Immunohistochemical profile and prognostic significance |journal=Neuropathology |volume=30 |issue=3 |pages=232–40 |year=2010 |month=June |pmid=19925562 |doi=10.1111/j.1440-1789.2009.01074.x |url=}}</ref>

===Microscopic===
Features:
*Large cell lymphoma.
**Size = 2x diameter normal lymphocyte.
**Nucleolus - common.
*Perivascular clustering.

====Images====
www:
*[http://frontalcortex.com/?page=image&topic=1&qid=1237 CNS lymphoma (frontalcortex.com)].
*[http://path.upmc.edu/cases/case403.html Primary CNS lymphoma - several images (upmc.edu)].
<gallery>
Image:Primary CNS lymphoma - low mag.jpg | CNS lymphoma - low mag. (WC)
Image:Primary CNS lymphoma - intermed mag.jpg | CNS lymphoma - intermed. mag. (WC)
Image:Primary CNS lymphoma - high mag.jpg | CNS lymphoma - high mag. (WC)
Image:Primary CNS lymphoma - very high mag.jpg | CNS lymphoma - very high mag. (WC)
</gallery>
<gallery>
Image: CNS lymphoma (1) B-cell type.jpg | CNS lymphoma. (WC/KGH)
Image: CNS lymphoma (2) B-cell type.jpg | CNS lymphoma. (WC/KGH)
</gallery>

===IHC===
Can be subclassified in ''GCB (germinal centre B-cell-like)'' and ''non-GCB'' by CD10, Bcl-6, MUM1/IRF-4, and Bcl-2.<ref name=pmid19925562/>

Common pattern:
*[[CD20]] +ve - key stain.
*CD3 -ve.
*Ki-67 ~40%.
*Bcl-6 +ve.
*Bcl-1 -ve.

==Ganglioneuroblastoma==
{{Main|Neuroblastoma}}
===General===
*Uncommon.
*Part of the ''neuroblastic tumours'' group which includes:<ref name=pmid10421272>{{cite journal |author=Shimada H, Ambros IM, Dehner LP, Hata J, Joshi VV, Roald B |title=Terminology and morphologic criteria of neuroblastic tumors: recommendations by the International Neuroblastoma Pathology Committee |journal=Cancer |volume=86 |issue=2 |pages=349–63 |year=1999 |month=July |pmid=10421272 |doi= |url=}}</ref>
**[[Ganglioneuroma]] (benign).
**Ganglioneuroblastoma (intermediate).
**[[Neuroblastoma]] (aggressive).

===Microscopic===
Features:
*Ganglion-like cells with a prominent nucleolus.
*Small undifferentiated cells with scant cytoplasm.
<gallery>
Image:Adrenal Ganglioneuroblastoma LP CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - Low power (SKB)
Image:Adrenal Ganglioneuroblastoma MP CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - Medium power (SKB)
Image:Adrenal Ganglioneuroblastoma HP CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - High power (SKB)
Image:Adrenal Ganglioneuroblastoma HP3 CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - High power (SKB)
Image:Adrenal Ganglioneuroblastoma HP2 CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - High power (SKB)
</gallery>
Images:
*[http://path.upmc.edu/cases/case530.html Ganglioneuroblastoma - several images (upmc.edu)].

===IHC===
*NSE +ve -- small cells.

==Lesions of the sella turcica==
{{Main|Pituitary gland}}
Lesions of the sella turcica, the pituitary gland environs, is a topic for it self. The differential diagnosis for lesions in this area includes:
*[[Pituitary adenoma]].
*[[Craniopharyngioma]].
*[[Rathke cleft cyst]].
*[[Germ cell tumour]].
*[[Meningioma]].
*[[Pilomyxoid astrocytoma]] - in children.

==See also==
*[[Neuropathology]].
*[[Muscle biopsy]].

==References==
{{reflist|2}}

==External links==
*[http://www.neuropathologyweb.org/ Neuropathology (neuropathologyweb.org)].
*[http://www.pathology.vcu.edu/WirSelfInst/tumor-1.html Neuropathology Mini-Course (pathology.vcu.edu)].
*[http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html Neuropathology Mini-Course (pathology.vcu.edu)].

[[Category:Neuropathology]]

Neuropathology tumours

2022-04-13T11:47:26Z

Jensflorian: /* Common neuropathology tumours in a table */ Arabic numerals in WHO grades

[[Image:Gemistocytic Astrocytoma 003.jpg|thumb|right|A brain stem [[astrocytoma]]. (WC)]]
The article covers '''tumours in neuropathology'''. Tumours are a large part of [[neuropathology]]. [[Cytopathology]] of CNS tumours is dealt with in the article ''[[CNS cytopathology]]''.

There are separate articles for ''[[peripheral nerve sheath tumours]]'' and ''[[pituitary gland|pituitary/peri-pituitary lesions]]''.

==Brain tumours - overview==
===Alphabetical===
For overview see [[:Category:Neuropathology_tumours|here]]

===By age group===
====Adult====
Four most common types of brain tumours:<ref>[http://neurosurgery.mgh.harvard.edu/abta/primer.htm http://neurosurgery.mgh.harvard.edu/abta/primer.htm]</ref>
# Metastatic brain tumours (barely edges out primary tumours)
#*[[Lung cancer|Lung]] (most common).
#*[[Invasive breast cancer|Breast]].
#*[[Melanoma]].
#*[[Renal cell carcinoma]] (RCC).
# [[Glioblastoma]] (previously known as ''glioblastoma multiforme'').
# [[Anaplastic astrocytoma]].
# [[Meningioma]].

====Children====
# [[Pilocytic astrocytoma]].
# [[Medulloblastoma]].
# [[Ependymoma]].

===By location===
Certain tumours like to hang-out at certain places:<ref>URL: [http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/files/4ce563fb7e8e48fc9ed8b42e296a7747.gif http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/files/4ce563fb7e8e48fc9ed8b42e296a7747.gif] and [http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html]. Accessed on: 2 November 2010.</ref>
====Cerebrum====
*Cortical based - [[oligodendroglioma]].
*Grey-white junction - metastases.
*White matter - astrocytoma, [[glioblastoma]].
*Periventricular - CNS lymphoma.
*Cystic - [[ganglioglioma]], [[pilocytic astrocytoma]], [[pleomorphic xanthoastrocytoma]].
====Cerebellum====
*Midline/central - [[medulloblastoma]].
*Cystic lesion - pilocytic astrocytoma (younger individual), [[hemangioblastoma]] (older individual).
*Solid lesion (older individual) - [[metastasis]].
====Sella turcica====
* [[Pituitary adenoma]].
* [[Craniopharyngioma]].
less common:
* [[Pituicytoma]].
* [[Granular cell tumour]].
* [[Germinoma]].
* [[Chordoma]]
* Rathke cleft cyst.
* Hypophysitis.
* Xanthogranuloma.
====Spinal cord====
*[[Ependymoma]]
*[[Glioblastoma]]
*[[Meningioma]]
*Carcinoma metastasis
*[[Hemangioblastoma]]
====Filum terminale====
*[[Meningioma]].
*[[Myxopapillary ependymoma]].
*[[Neurofibroma]].
*[[Schwannoma]].
*[[Paraganglioma]].
====Meninges====
* [[Meningioma]].
* [[Solitary fibrous tumour]] / Hemangiopericytoma.
* [[Hemangioblastoma]].
less common:
* [[Melanoma]] / Melanocytoma.
* Lymphoproliferative diseases.
* [[Sarcoidosis]]
* [[Arachnoid cyst]].
* Disseminated oligodendroglial-like leptomeningeal tumour.
* Desmoplastic infantile astrocytoma / ganglioglioma.
* Meningioangiomatosis.
* Calcifying pseudoneoplasm.
====Skull====
* [[Fibrous dysplasia]].
* [[Paget disease]].
* [[Histiocytosis]].
* [[Hemangioma]].
* [[Aneurysmal bone cyst]].
* [[Plasma_cell_neoplasms#Multiple_myeloma|Multiple myeloma]].
====Skull base / Cerebellopontine angle====
* [[Schwannoma]].
* [[Meningioma]].
* [[Dermoid cyst]] / epidermoid cyst.
less common:
* [[Ependymoma]].
* [[Choroid plexus papilloma]].
* [[Glomus tumour]].
* [[Chordoma]].
* [[Chondrosarcoma]].
* [[Olfactory neuroblastoma]].
* [[Endolymphatic sac tumour]].

===Cystic tumours===
DDx:<ref>URL: [http://path.upmc.edu/cases/case320/dx.html http://path.upmc.edu/cases/case320/dx.html]. Accessed on: 14 January 2012.</ref>
*[[Pilocytic astrocytoma]].
*[[Pleomorphic xanthoastrocytoma]].
*[[Ganglioglioma]].
*[[Hemangioblastoma]].
*[[Craniopharyngioma]].<ref>URL: [http://www.pathologyoutlines.com/Cnstumor.html#cystsgeneral http://www.pathologyoutlines.com/Cnstumor.html#cystsgeneral]. Accessed on: 14 January 2012.</ref>

===Primary versus secondary===
*[[AKA]] (primary) brain tumour versus metastatic cancer.
====Primary====
[[Glioma|Glial tumours]]:
*Cytoplasmic processes - '''key feature'''.
**Best seen at highest magnification - usu. ~1 micrometer.
**Processes may branch.
*Ill-defined border/blend with the surrounding brain.

[[Meningioma]]:
*Lesion often dura-based.
*Mesenchymal tumor (often contains collagen).

[[Lymphoma]]:
*Large (lymphoid) cells, ergo usu. not a difficult diagnosis.
**~2x size of resting lymphocyte, nucleoli.
*Lesion predominantly perivascular.

====Secondary====
Carcinomas:
*Well-demarcated border between brain and lesion - '''key feature'''.
*No cytoplasmic processes.
*Usu. have nuclear atypia of malignancy.
**Nuclei often ~3-4x the size of a [[RBC]].
*+/-Glandular arrangement.
*+/-Nucleoli.

===Common neuropathology tumours in a table===
{| class="wikitable"
|'''Type'''
|'''Key feature(s)'''
|'''Imaging'''
|'''History'''
|'''Notes'''
|'''IHC'''
|'''Images'''
|-
|Normal tissue
|cells regularly spaced, no nuc. atypia
|small lesion? / deep lesion?
|variable
|missed lesion?
|nil
|[[Image:Grey_matter_and_white_matter_-_very_high_mag.jpg |thumb|center|150px|Normal. (WC)]]
|-
|[[Reactive astrocytes]]
|astrocytes with well-demarcated eosinophilic cytoplasm, regular spacing, no nuc. atypia
|small lesion? / deep lesion?
|variable
|missed lesion / close to a lesion; non-specific pathologic process - need more tissue
|nil
|[[Image:Reactive_astrocytes_-_lfb_-_high_mag.jpg|thumb|center|150px|Reactive astrocytes. (WC)]]
|-
|[[Schwannoma]]
|cellular areas (Antoni A), paucicelluar areas (Antoni B), palisading of nuclei (Verocay bodies)
|extra-axial + intradural
|old or young
|need frozen section to Dx, DDx: [[meningioma]]
|S100
|[[Image:Schwannoma_-_Antoni_A_and_B_-_very_high_mag.jpg|thumb|center|150px|Schwannoma. (WC)]]
|-
|[[Meningioma]]
|whorls, psammomatous calcs, nuclear inclusions
|extra-axial + intradural
|old or young
|may be diagnosed on smear, DDx: [[schwannoma]], choroid plexus
|EMA, PR, Ki-67
|[[Image:Meningioma_intermed_mag.jpg |thumb|center|150px|Meningioma. (WC)]]
|-
|[[Astrocytoma, IDH-mutant]] (CNS [[WHO]] grade 2 or grade 3)
|glial processes (esp. on smear), nuclear atypia (typical size var. ~3x, irreg. nuc. membrane, hyperchromasia), no Rosenthal fibres in the core of the lesion †, no microvascular proliferation, no necrosis
|often enhancing (suggests high grade), usu. supratentorial, usu. white matter
|usu. old, occ. young
|common
|IDH-1(R132H)+/-, GFAP+
| [[Image:Anaplastic_astrocytoma_-_very_high_mag_-_cropped.jpg | thumb| center| 150px|High-grade astrocytoma. (WC)]]
|-
|[[Glioblastoma]], IDH-wildtype (CNS [[WHO]] grade 4)
|glial processes (esp. on smear), nuclear atypia (typical size var. ~3x, irreg. nuc. membrane, hyperchromasia), no Rosenthal fibres in the core of the lesion †, microvascular proliferation or necrosis
|often enhancing (suggests high grade), usu. supratentorial, usu. white matter
|usu. old, occ. young
|very common, esp. glioblastoma
|IDH-1+/-, GFAP+
| [[Image:Glioblastoma (1).jpg | thumb| center| 150px|Glioblastoma. (WC)]]
|-
|[[Metastatic brain tumours|Metastasis]]
|sharp interface with brain, often glandular, +/-nucleoli, no glial processes
|often cerebellular, well-circumscribed
|usu. old
|often suspected to have metastatic disease
|[[TTF-1]], CK7, [[CK20]], BRST-2
|[[Image:Metastatic_adenocarcinoma_-_cerebellum_-_very_low_mag.jpg | thumb| center|150px |Metastasis. (WC)]]
|}
† Rosenthal fibres at the periphery of a lesion are a non-specific finding seen in chronic processes.

==Brain metastasis==
{{Main|Brain metastasis}}

==Infiltrative astrocytomas==
{{Main|Astrocytoma}}

===Overview===
*Low-grade (diffuse) astrocytomas (WHO Grade II).
*Anaplastic astrocytomas (WHO Grade III).
*[[Glioblastoma]](WHO Grade IV).
**[[Gliosarcoma]] (WHO Grade IV).
*[[Gliomatosis cerebri]] (Grade III/IV).

Notes:
*Non-infiltrative astrocytomas:
**[[Pilocytic astrocytoma]] (WHO Grade I).
***[[Pilomyxoid astrocytoma]] (WHO Grade II).
**[[Pleomorphic xanthoastrocytoma]] (WHO grade II).
**[[Subependymal giant cell astrocytoma]] (WHO grade I).

===Microscopic===
Features:<ref name=pmid>{{cite journal |author=Rong Y, Durden DL, Van Meir EG, Brat DJ |title='Pseudopalisading' necrosis in glioblastoma: a familiar morphologic feature that links vascular pathology, hypoxia, and angiogenesis |journal=J. Neuropathol. Exp. Neurol. |volume=65 |issue=6 |pages=529–39 |year=2006 |month=June |pmid=16783163 |doi= |url=}}</ref><ref>[http://dictionary.reference.com/browse/palisading http://dictionary.reference.com/browse/palisading]</ref>
*Glial processes - '''key feature'''.
**Thin stringy cytoplasmic processes - best seen at high power in less cellular areas.
*No Rosenthal fibres within the tumour itself.

Images:
*[http://moon.ouhsc.edu/kfung/jty1/opaq/PathQuiz/N0A002-PQ01-M.htm Endothelial proliferation in a GBM (ouhsc.edu)].
*[http://moon.ouhsc.edu/kfung/jty1/neurotest/Q05-Ans.htm Endothelial proliferation (ouhse.edu)].
*[http://path.upmc.edu/cases/case368.html Gemistocytic astrocytoma - several images (upmc.edu)].

Notes:
*Glial vs. non-glial tumours:
**Glial: "blends into brain"/gradual transition to non-tumour brain.
**Non-glial: no glial processes.
*Rosenthal fibres within the tumour... make it into a [[pilocytic astrocytoma]].
**Rosenthal fibres may be seen around a (very) slow growing tumour and represent a reactive process.
*Inflammatory cells and macrophages should prompt consideration of an alternate diagnosis (e.g. [[cerebral infarct]], [[multiple sclerosis]]) - esp. if this is a primary lesion.<ref>URL: [http://path.upmc.edu/cases/case79/dx.html http://path.upmc.edu/cases/case79/dx.html]. Accessed on: 2 January 2012.</ref>

====Grading====
Nuclear pleomorphism present:
*At least grade II (diffuse astrocytoma).

Mitotic figures present:
*At least grade III (anaplastic astrocytoma).

Microvascular proliferation ''or'' necrosis with pseudopalisading tumour cells:
*Grade IV (glioblastoma [[AKA]] glioblastoma multiforme).

Notes:
*Pseudopalisading tumour cells = high tumour cell density adjacent to regions of necrosis; palisade = a fence of poles forming a defensive barrier or fortification.
*WHO Grading is currently based on expected biologiocal behaviour without treatment.
**Grading does not reflect molecular divergent groups within a tumor class or response to therapy (Currently controversies in grading for IDH-mutant astrocytoma vs. IDH-wildtype astrocytoma).<ref>{{Cite journal | last1 = Louis | first1 = DN. | last2 = von Deimling | first2 = A. | title = Grading of diffuse astrocytic gliomas: Broders, Kernohan, Zülch, the WHO… and Shakespeare. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Aug | year = 2017 | doi = 10.1007/s00401-017-1765-z | PMID = 28801693 }}</ref>

====Images====
Glioblastoma:
<gallery>
Image:Glioblastoma_%281%29.jpg | Glioblastoma - pseudopalisading of tumour cells (WC)
Image:Glioblastoma_-_high_mag.jpg | Glioblastoma with fragment of near-normal white matter - high mag. (WC)
</gallery>
Anaplastic astrocytoma:
<gallery>
Image:Anaplastic_astrocytoma_-_very_high_mag_-_cropped.jpg | Anaplastic astrocytoma - very high mag. (WC)
Image:Anaplastic_astrocytoma_-_gfap_-_very_high_mag.jpg | Anaplastic astrocytoma - GFAP - very high mag. (WC)
</gallery>

===IHC===
*GFAP - should stain cytoplasm of tumour cells and the perikaryon (nuclear membrane).
*Ki-67 - usu. high >20% of cells.
*p53 - often +ve.
*[[IDH-1]] (isocitrate dehydrogenase 1).
**+ve in tumours that arose from low-grade gliomas.<ref name=pmid19228619>{{cite journal |author=Yan H, Parsons DW, Jin G, ''et al.'' |title=IDH1 and IDH2 mutations in gliomas |journal=N. Engl. J. Med. |volume=360 |issue=8 |pages=765–73 |year=2009 |month=February |pmid=19228619 |pmc=2820383 |doi=10.1056/NEJMoa0808710 |url=}}</ref>
*[[H3F3A|H3F3A K27M]] -ve
**+ve cases to be classified as [[Astrocytoma#H3.3_K27M_mutated_glioma_of_the_midline|K27 mutated midline glioma]].
*[[ATRX]] -ve in tumors with low-grade precursor(most of them also IDH1/2 mutant).

Notes:
*IDH1 and IDH2 mutations - better survival.<ref name=pmid20975057>{{cite journal |author=Houillier C, Wang X, Kaloshi G, ''et al.'' |title=IDH1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas |journal=Neurology |volume=75 |issue=17 |pages=1560–6 |year=2010 |month=October |pmid=20975057 |doi=10.1212/WNL.0b013e3181f96282 |url=}}</ref>

===Molecular===
See also: [[Molecular_pathology_tests#Neuropathology|Molecular Neuropathology]]

==Gliomas==
{{Main|Glioma}}

Gliomas, glioneuronal tumours and neuronal tumours are often categorized together.

===Astrocytic tumours===
{{Main|Astrocytoma}}

* [[Astrocytoma]], IDH-mutant.
* [[Glioblastoma]], IDH-wildtype.
** [[Gliosarcoma]] (a glioblastoma subtype)

Depreceated:
* Diffuse [[Astrocytoma]]
* [[Anaplastic astrocytoma]]
* [[Gliomatosis cerebri]]
* Spongioblastoma

===Oligodendroglial tumours===
* [[Oligodendroglioma]], IDH-mutant and 1p/19q codeleted.

Depreceated:
* Anaplastic oligodendroglioma
* [[Oligoastrocytoma]]
* Anaplastic oligoastrocytoma

===Pediatric-type diffuse high-grade glioma===
{{Main|Pediatric-type diffuse high-grade glioma}}
* [[Astrocytoma#Diffuse_midline_glioma.2C_H3_K27M_mutant|Diffuse midline glioma H3 K27-mutant]]

===Pediatric-type diffuse low-grade glioma===
{{Main|Pediatric-type diffuse low-grade glioma}}

===Circumscribed astrocytic gliomas===
* [[Pilocytic astrocytoma]] (PA)
** [[Pilomyxoid astrocytoma]] (PMA)
* [[Pleomorphic xanthoastrocytoma]] (PXA)
* [[Subependymal giant cell astrocytoma]] (SEGA)
* [[Neuropathology_tumours#Astroblastoma|Astroblastoma MN1-altered]].
* [[Neuropathology_tumours#Chordoid glioma of the third ventricl|Chordoid glioma]].

====Astroblastoma====
*No WHO grade yet.<ref>{{Ref WHOCNS|88}}</ref>
*Very rare superficial tumor of young age.<ref>{{Cite journal | last1 = Narayan | first1 = S. | last2 = Kapoor | first2 = A. | last3 = Singhal | first3 = MK. | last4 = Jakhar | first4 = SL. | last5 = Bagri | first5 = PK. | last6 = Rajput | first6 = PS. | last7 = Kumar | first7 = HS. | title = Astroblastoma of cerebrum: A rare case report and review of literature. | journal = J Cancer Res Ther | volume = 11 | issue = 3 | pages = 667 | month = | year = | doi = 10.4103/0973-1482.140800 | PMID = 26458709 }}</ref>
*Large, cystic. Pushing margin towards CNS.
*Vasocentric growth, plump cells with absence of fibrillary pattern.
*GFAP+ve, Synaptohysin-ve, Olig-2-ve, focally EMA/panCK+ve. MIB-1: 1-18 %.
*Molecular profile overlaps with classical [[CNS-PNET]].
**Gene fusions invoving meningioma gene (MN1)<ref>{{Cite journal | last1 = Sturm | first1 = D. | last2 = Orr | first2 = BA. | last3 = Toprak | first3 = UH. | last4 = Hovestadt | first4 = V. | last5 = Jones | first5 = DT. | last6 = Capper | first6 = D. | last7 = Sill | first7 = M. | last8 = Buchhalter | first8 = I. | last9 = Northcott | first9 = PA. | title = New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs. | journal = Cell | volume = 164 | issue = 5 | pages = 1060-72 | month = Feb | year = 2016 | doi = 10.1016/j.cell.2016.01.015 | PMID = 26919435 }}</ref>

<gallery>
File:Astroblastoma_HE_Specimen.jpg | HE. (WC/jensflorian)
File:Astroblastoma_HE_papillae.jpg | HE. (WC/jensflorian)
File:Astroblastoma.jpg | Astroblastoma (AFIP)
</gallery>

====Chordoid glioma of the third ventricle====
* WHO grade II.
* Slowly growing, non-invasive, in adults.
* Clusters of epithelioid cells in mucinous stroma.
* Lymphocytic infiltrates, adjacent Rosenthal fibers.
* Fibrosis may be present.
* Few mitoses.
* [[GFAP]]+ve, MIB-1 1-3%.
* [[TTF-1]]+ve.
* CD34+ve.
* [[IDH-1]]-ve, [[p53]]-ve.
* PRKCA D463H mutations.<ref>{{Cite journal | last1 = Goode | first1 = B. | last2 = Mondal | first2 = G. | last3 = Hyun | first3 = M. | last4 = Ruiz | first4 = DG. | last5 = Lin | first5 = YH. | last6 = Van Ziffle | first6 = J. | last7 = Joseph | first7 = NM. | last8 = Onodera | first8 = C. | last9 = Talevich | first9 = E. | title = A recurrent kinase domain mutation in PRKCA defines chordoid glioma of the third ventricle. | journal = Nat Commun | volume = 9 | issue = 1 | pages = 810 | month = 02 | year = 2018 | doi = 10.1038/s41467-018-02826-8 | PMID = 29476136 }}</ref>

<gallery>
File:NP op 20201028 009.jpg | Chordoid Glioma. (WC/jensflorian)
</gallery>

===Ependymal tumours===
* [[Subependymoma]]
* [[Myxopapillary Ependymoma]]
* [[Ependymoma]]
* Anaplastic ependymoma

==Choroid plexus tumours==
* [[Choroid plexus papilloma]]
* Atypical choroid plexus papilloma
* [[Choroid plexus carcinoma]]

==Other neuroepithelial tumours==
* [[Neuropathology_tumours#Cribiform_neuroepithelial_tumour|Cribifiorm neuroepithelial tumour]].

===Cribiform neuroepithelial tumour===
AKA: '''CRINET'''.
*Not listed in the current WHO classification.
*First description in 2009.<ref>{{Cite journal | last1 = Hasselblatt | first1 = M. | last2 = Oyen | first2 = F. | last3 = Gesk | first3 = S. | last4 = Kordes | first4 = U. | last5 = Wrede | first5 = B. | last6 = Bergmann | first6 = M. | last7 = Schmid | first7 = H. | last8 = Frühwald | first8 = MC. | last9 = Schneppenheim | first9 = R. | title = Cribriform neuroepithelial tumor (CRINET): a nonrhabdoid ventricular tumor with INI1 loss and relatively favorable prognosis. | journal = J Neuropathol Exp Neurol | volume = 68 | issue = 12 | pages = 1249-55 | month = Dec | year = 2009 | doi = 10.1097/NEN.0b013e3181c06a51 | PMID = 19915490 }}</ref>
*Around ventricles.<ref>{{Cite journal | last1 = Arnold | first1 = MA. | last2 = Stallings-Archer | first2 = K. | last3 = Marlin | first3 = E. | last4 = Grondin | first4 = R. | last5 = Olshefski | first5 = R. | last6 = Biegel | first6 = JA. | last7 = Pierson | first7 = CR. | title = Cribriform neuroepithelial tumor arising in the lateral ventricle. | journal = Pediatr Dev Pathol | volume = 16 | issue = 4 | pages = 301-7 | month = | year = | doi = 10.2350/12-12-1287-CR.1 | PMID = 23495723 }}</ref>
*Young children.<ref>{{Cite journal | last1 = Park | first1 = JY. | last2 = Kim | first2 = E. | last3 = Kim | first3 = DW. | last4 = Chang | first4 = HW. | last5 = Kim | first5 = SP. | title = Cribriform neuroepithelial tumor in the third ventricle: a case report and literature review. | journal = Neuropathology | volume = 32 | issue = 5 | pages = 570-6 | month = Oct | year = 2012 | doi = 10.1111/j.1440-1789.2011.01293.x | PMID = 22239490 }}</ref>
*Small undifferentiated cells arranged in cribriform strands and trabeculae of varying thickness.
*MAP2+ve, Synaptophysin+ve, CK+/-ve. MIB-1: 30%.
*INI-1 loss, but no rhabdoid features and good prognosis.
*Stable genomic profile.<ref>{{Cite journal | last1 = Gessi | first1 = M. | last2 = Japp | first2 = AS. | last3 = Dreschmann | first3 = V. | last4 = Zur Mühlen | first4 = A. | last5 = Goschzik | first5 = T. | last6 = Dörner | first6 = E. | last7 = Pietsch | first7 = T. | title = High-Resolution Genomic Analysis of Cribriform Neuroepithelial Tumors of the Central Nervous System. | journal = J Neuropathol Exp Neurol | volume = 74 | issue = 10 | pages = 970-4 | month = Oct | year = 2015 | doi = 10.1097/NEN.0000000000000239 | PMID = 26352987 }}</ref>

==Neuronal and mixed neuronal/glial tumours==
* [[Desmoplastic infantile astrocytoma]] / ganglioglioma (DIA/DIG)
* [[Dysembryoplastic neuroepithelial tumour]]
* [[Central Neurocytoma]] / Extraventricular [[neurocytoma]]
* Cerebellar liponeurocytoma
* [[Papillary glioneuronal tumour]] (PGNT)
* [[Rosette-forming glioneuronal tumour of the fourth ventricle]] (RGNT)
* Gangliocytoma / Ganglioglioma
* Dysplastic ganglioglioma of the cerebellum ([[Lhermitte-Duclos disease]])
* [[Paraganglioma]]

===Desmoplastic infantile astrocytoma / Desmoplastic infantile ganglioglioma===
* Abbreviated ''DIA'' or ''DIG''.
* ICD-O code: 9412/1
* Large, superficial, cystic tumor of the infancy.
* Biologic course corresponds to WHO grade I.
* Very rare, included in the WHO since 1993.
* Prominent desmoplastic stroma.
* Astrocytic cells within stroma.
**GFAP+.
**MIB-1 usu. 1%.
* Frequent BRAF V600E or V600D mutations.<ref>{{Cite journal | last1 = Wang | first1 = AC. | last2 = Jones | first2 = DTW. | last3 = Abecassis | first3 = IJ. | last4 = Cole | first4 = BL. | last5 = Leary | first5 = SES. | last6 = Lockwood | first6 = CM. | last7 = Chavez | first7 = L. | last8 = Capper | first8 = D. | last9 = Korshunov | first9 = A. | title = Desmoplastic Infantile Ganglioglioma/Astrocytoma (DIG/DIA) are Distinct Entities with Frequent BRAFV600 Mutations. | journal = Mol Cancer Res | volume = | issue = | pages = | month = Jul | year = 2018 | doi = 10.1158/1541-7786.MCR-17-0507 | PMID = 30006355 }}</ref>
*Single case with BRAF indel or BRAF fusion.
<gallery>
File:DIG-histology.jpg | Histopathology of DIG (HE stain)
File:DIG-histology2.jpg | Prominent ganglioid cells in DIG (HE stain)
</gallery>

===Cerebellar liponeurocytoma===
* Previously called ''lipomatous medulloblastoma'' (name changed in WHO 2000).
* Mean age: 50 years.
* As the name states: A tumour of the cerebellum.
** But cases outside cerebellum reported that would qualify.<ref>{{Cite journal | last1 = Gupta | first1 = K. | last2 = Salunke | first2 = P. | last3 = Kalra | first3 = I. | last4 = Vasishta | first4 = RK. | title = Central liponeurocytoma: case report and review of literature. | journal = Clin Neuropathol | volume = 30 | issue = 2 | pages = 80-5 | month = | year = | doi = | PMID = 21329617 }}</ref>
* WHO grade II <ref>{{Cite journal | last1 = Nishimoto | first1 = T. | last2 = Kaya | first2 = B. | title = Cerebellar liponeurocytoma. | journal = Arch Pathol Lab Med | volume = 136 | issue = 8 | pages = 965-9 | month = Aug | year = 2012 | doi = 10.5858/arpa.2011-0337-RS | PMID = 22849747 }}</ref> (upgraded from WHO grade I in 2007)<ref>{{Cite journal | last1 = Brat | first1 = DJ. | last2 = Parisi | first2 = JE. | last3 = Kleinschmidt-DeMasters | first3 = BK. | last4 = Yachnis | first4 = AT. | last5 = Montine | first5 = TJ. | last6 = Boyer | first6 = PJ. | last7 = Powell | first7 = SZ. | last8 = Prayson | first8 = RA. | last9 = McLendon | first9 = RE. | title = Surgical neuropathology update: a review of changes introduced by the WHO classification of tumours of the central nervous system, 4th edition. | journal = Arch Pathol Lab Med | volume = 132 | issue = 6 | pages = 993-1007 | month = Jun | year = 2008 | doi = 10.1043/1543-2165(2008)132[993:SNUARO]2.0.CO;2 | PMID = 18517285 }}</ref>
*ICD-O code: 9506/1

====Histo====
* Advanced neuronal and lipomatous differentiation.
* Neurocytes: round to oval nuclei with clear cytoplasm.
* Quite cellular.
* Mitoses almost absent.

====IHC====
* [[GFAP]] +/-ve (focal).
* [[MAP2]] +ve.
* Synaptophysin +ve.
* NeuN +ve.
* MIB-1: usu 1-3%.

====Molecular====
* Distinct methylation profile.
* Recurent losses on 2p and Chr. 14.<ref>{{Cite journal | last1 = Capper | first1 = D. | last2 = Stichel | first2 = D. | last3 = Sahm | first3 = F. | last4 = Jones | first4 = DTW. | last5 = Schrimpf | first5 = D. | last6 = Sill | first6 = M. | last7 = Schmid | first7 = S. | last8 = Hovestadt | first8 = V. | last9 = Reuss | first9 = DE. | title = Practical implementation of DNA methylation and copy-number-based CNS tumor diagnostics: the Heidelberg experience. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Jul | year = 2018 | doi = 10.1007/s00401-018-1879-y | PMID = 29967940 }}</ref>

<gallery>
File:Cerebellar liponeurocytoma.jpg | Liponeurocytoma, HE (WC/Marvin101).
File:Liponeurocytoma Synaptophysin.jpg | Liponeurocytoma, Synapto (WC/Marvin101).
File:Cerebellar Liponeurocytoma HE.jpg | Liponeurocytoma, HE (WC/jensflorian).
File:Cerebellar Liponeurocytoma Synaptophysin.jpg | Liponeurocytoma, Synapto (WC/jensflorian).
</gallery>

====DDx====
* [[Medulloblastoma]]
* [[Neurocytoma]]

===Gangliocytoma===
* Grade I WHO neuronal tumour.
** ICD-O code: 9492/0
* Groups of irregular large neurons.
* Non-neoplastic, reticulin-rich glial stroma.

===Ganglioglioma===
:'''Not''' to be confused with ''[[ganglioneuroma]]''.
====General====
*Gangliolioma: Grade I WHO mixed neuronal-glial tumour (ICD-O code: 9505/1).
*Anaplastic ganglioglioma: Grade III (ICD-O: 9505/3)
*Rare (approx. 0.5% of all CNS tumors).
*Usu. temporal lobe.
*Predominantly children (mean age: 9 years).
*Recognized as a cause of [[epilepsy]].<ref name=pmid12125968>{{Cite journal | last1 = Im | first1 = SH. | last2 = Chung | first2 = CK. | last3 = Cho | first3 = BK. | last4 = Lee | first4 = SK. | title = Supratentorial ganglioglioma and epilepsy: postoperative seizure outcome. | journal = J Neurooncol | volume = 57 | issue = 1 | pages = 59-66 | month = Mar | year = 2002 | doi = | PMID = 12125968 }}</ref>
*Favourable prognosis (survival rates up to 97%)
**Insufficient data für anaplastic ganglioglioma.

====Macroscopic====
*Circumscribed lesion.
*Usu. contrast enhancing.
*Solid, but intracortical cysts may be present.
*Little mass effect.

====Microscopic====
Features:
*Dysplastic neurons.
**Out of regular architecture / abnormal location.
**Cytomegaly
**Clustering
**Binucleated (very occassionally).
*Atypical glia.
*Eosinophilic granular bodies.
*Calcification.
*Prominent capillary network.
*Lymphocytic cuffing.
*May contain some reticulin.
*Glial component may resemble:
**Fibrillary astrocytoma.
**Oligodendroglioma.
**Pilocytic astrocytoma.

Anaplastic ganglioglioma:
*Brisk mitotic activity
*Necrosis

====IHC====
*Neurons:
**[[MAP2]] +ve
**Synaptophysin +ve
** Neurofilament +ve
*Glia:
**CD34+/-ve
*BRAF V600E +ve (approx. 25%, mainly ganglion cells).

====Molecular====
*BRAF V600E-mutated(approx. 25%).
*IDH1/2 wt.
*No 1p/19q codeletion.
*Usu. Chr. 7 gain.
*CDKN2A deletions in anaplastic ganglioglioma.

====DDx:====
*[[DNT]].
*[[Oligodendroglioma]].
*Trapped cortical neurons in diffuse astrocytoma.
*Papillary glioneuronal tumor.
*Dysembryoplastic neuroepithelial tumor.

====Images====
<gallery>
File:Ganglioglioma lymphocytic cuffing PAS.jpg | Lymphocytic cuffing in ganglioglioma (WC/jensflorian)
File:Ganglioglioma calcification.jpg | Calcification in ganglioglioma (WC/jensflorian)
File:Ganglioglioma Cd34 x200.jpg | CD34 immunostain in ganglioglioma (WC/jensflorian)
File:Anaplastic ganglioglioma HE.jpg | Pleomorphic ganglion cells in ganglioglioma (WC/jensflorian)
</gallery>
*[http://path.upmc.edu/cases/case142.html Ganglioglioma - case 1 (upmc.edu)].
*[http://path.upmc.edu/cases/case282.html Ganglioglioma - case 2 (upmc.edu)].

===Lhermitte-Duclos disease===
*Abbreviated ''LDD''.
*[[AKA]] ''dysplastic cerebellar gangliocytoma''.<ref name=pmid20060133>{{Cite journal | last1 = Yağci-Küpeli | first1 = B. | last2 = Oguz | first2 = KK. | last3 = Bilen | first3 = MA. | last4 = Yalçin | first4 = B. | last5 = Akalan | first5 = N. | last6 = Büyükpamukçu | first6 = M. | title = An unusual cause of posterior fossa mass: Lhermitte-Duclos disease. | journal = J Neurol Sci | volume = 290 | issue = 1-2 | pages = 138-41 | month = Mar | year = 2010 | doi = 10.1016/j.jns.2009.12.010 | PMID = 20060133 }}</ref>
*[[AKA]] ''dysplastic gangliocytoma of the cerebellum''.
{{Main|Lhermitte-Duclos disease}}
<gallery>
File:Dysplastic_gangliocytoma_lhermitte_duclos.jpg | Dysplastic gangliocytoma (low mag).
</gallery>

===Papillary glioneuronal tumour===
* Abbreviated ''PGNT''.
* A benign, supratentorial tumor of childhood.
** Biologic course corresponds to WHO grade I.
** Before WHO 2000, considered a [[Ganglioglioma]] variant.
*Prominent pseudopapillary architecture.
*Neurocytes to medium-sized ganglion cells.
*GFAP+ core, GFAP- layer
*Rosenthal fibers, Eosinophilic Granular bodies and lymphocytic cuffing may be present.
<gallery>
File:PGNT_HE_stain.jpg | PGNT (HE) (WC/jensflorian)
</gallery>

===Rosette-forming glioneuronal tumour of the fourth ventricle===
* Abbreviated ''RGNT''.
* Provisional ICD-O code: 9509/1
* A rare benign infratentorial tumour of the midline of children and adults.
* Biologic course corresponds to WHO grade I.
* Glial component corresponds to [[pilocytic astrocytoma]].
* Neurocytic rosettes.
* Eosinopil fibrillary cores / pseudorosettes.
* GFAP+ in fibrillary areas, Syn+ in rosettes.
* Neurocytic cells: MAP2+
* MIB-1 usu. below 3%.
<gallery>
File:Histology RGNT HE.jpg | RGNT, HE stain (WC/jensflorian).
File:RGNT HE 2.jpg | RGNT, higher magnification (WC/jensflorian).
</gallery>

===Polymorphous low-grade tumor of the young (PLNTY)===
* [[Pediatric-type diffuse low-grade glioma#Diffuse low-grade glioma, MAPK pathway-altered|Polymorphous low-grade tumor of the young (PLNTY)]]

==Pineal tumours==
{{Main|Pineal gland}}

* [[Pineocytoma]]
* [[Pineal parenchymal tumour of intermediate differentiation]]
* [[Pineoblastoma]]
* [[Papillary tumour of the pineal region]]

==Embryonal tumours==
* [[Atypical teratoid/rhabdoid tumour]] (AT/RT) or (AT-RT)
* [[Medulloblastoma]]
* [[Primitive neuroectodermal tumour]] (PNET)
* [[Embryonal tumour with abundant neuropil and true rosettes]] (ETANTR)

DDx:
* [[Ewing sarcoma]]
* [[Sarcoma with CIC-rearrangement]]

==Peripheral nerve sheath tumours==
{{Main|Peripheral nerve sheath tumours}}
A classification:<ref name=pmid17893219>{{cite journal |author=Wippold FJ, Lubner M, Perrin RJ, Lämmle M, Perry A |title=Neuropathology for the neuroradiologist: Antoni A and Antoni B tissue patterns |journal=AJNR Am J Neuroradiol |volume=28 |issue=9 |pages=1633–8 |year=2007 |month=October |pmid=17893219 |doi=10.3174/ajnr.A0682 |url=http://www.ajnr.org/cgi/reprint/28/9/1633}}</ref>
'''Benign:'''
*[[Schwannoma]].
*[[Neurofibroma]].
*[[Perineurioma]].
*Ganglioneuroma.
**[[Traumatic neuroma]].
'''Malignant:'''
*[[Malignant peripheral nerve sheath tumour]] (MPNST).

===Ganglioneuroma===
:'''Not''' to be confused with ''[[ganglioglioma]]''.
*[[AKA]] ganglioma.<ref>URL: [http://medical-dictionary.thefreedictionary.com/ganglioma http://medical-dictionary.thefreedictionary.com/ganglioma]. Accessed on: 8 November 2010.</ref>
{{Main|Ganglioneuroma}}

==Meningioma==
{{Main|Meningioma}}

==Chordoma==
{{Main|Chordoma}}

==Hemangioblastoma==
{{Main|Hemangioblastoma}}

==CNS lymphoma==
Classification:
*Primary CNS lymphoma.
*Non-primary CNS lymphoma - see ''[[lymphoma]]'' article.

===General - primary CNS===
*Classically periventicular distribution.
*Usually large B cell; can be considered a type of [[diffuse large B cell lymphoma]] (DLBCL).
**Prognosis of CNS (DLBCL) lymphomas worse than nodal (non-CNS) DLBCL.<ref name=pmid19925562>{{cite journal |author=Raoux D, Duband S, Forest F, ''et al.'' |title=Primary central nervous system lymphoma: Immunohistochemical profile and prognostic significance |journal=Neuropathology |volume=30 |issue=3 |pages=232–40 |year=2010 |month=June |pmid=19925562 |doi=10.1111/j.1440-1789.2009.01074.x |url=}}</ref>

===Microscopic===
Features:
*Large cell lymphoma.
**Size = 2x diameter normal lymphocyte.
**Nucleolus - common.
*Perivascular clustering.

====Images====
www:
*[http://frontalcortex.com/?page=image&topic=1&qid=1237 CNS lymphoma (frontalcortex.com)].
*[http://path.upmc.edu/cases/case403.html Primary CNS lymphoma - several images (upmc.edu)].
<gallery>
Image:Primary CNS lymphoma - low mag.jpg | CNS lymphoma - low mag. (WC)
Image:Primary CNS lymphoma - intermed mag.jpg | CNS lymphoma - intermed. mag. (WC)
Image:Primary CNS lymphoma - high mag.jpg | CNS lymphoma - high mag. (WC)
Image:Primary CNS lymphoma - very high mag.jpg | CNS lymphoma - very high mag. (WC)
</gallery>
<gallery>
Image: CNS lymphoma (1) B-cell type.jpg | CNS lymphoma. (WC/KGH)
Image: CNS lymphoma (2) B-cell type.jpg | CNS lymphoma. (WC/KGH)
</gallery>

===IHC===
Can be subclassified in ''GCB (germinal centre B-cell-like)'' and ''non-GCB'' by CD10, Bcl-6, MUM1/IRF-4, and Bcl-2.<ref name=pmid19925562/>

Common pattern:
*[[CD20]] +ve - key stain.
*CD3 -ve.
*Ki-67 ~40%.
*Bcl-6 +ve.
*Bcl-1 -ve.

==Ganglioneuroblastoma==
{{Main|Neuroblastoma}}
===General===
*Uncommon.
*Part of the ''neuroblastic tumours'' group which includes:<ref name=pmid10421272>{{cite journal |author=Shimada H, Ambros IM, Dehner LP, Hata J, Joshi VV, Roald B |title=Terminology and morphologic criteria of neuroblastic tumors: recommendations by the International Neuroblastoma Pathology Committee |journal=Cancer |volume=86 |issue=2 |pages=349–63 |year=1999 |month=July |pmid=10421272 |doi= |url=}}</ref>
**[[Ganglioneuroma]] (benign).
**Ganglioneuroblastoma (intermediate).
**[[Neuroblastoma]] (aggressive).

===Microscopic===
Features:
*Ganglion-like cells with a prominent nucleolus.
*Small undifferentiated cells with scant cytoplasm.
<gallery>
Image:Adrenal Ganglioneuroblastoma LP CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - Low power (SKB)
Image:Adrenal Ganglioneuroblastoma MP CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - Medium power (SKB)
Image:Adrenal Ganglioneuroblastoma HP CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - High power (SKB)
Image:Adrenal Ganglioneuroblastoma HP3 CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - High power (SKB)
Image:Adrenal Ganglioneuroblastoma HP2 CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - High power (SKB)
</gallery>
Images:
*[http://path.upmc.edu/cases/case530.html Ganglioneuroblastoma - several images (upmc.edu)].

===IHC===
*NSE +ve -- small cells.

==Lesions of the sella turcica==
{{Main|Pituitary gland}}
Lesions of the sella turcica, the pituitary gland environs, is a topic for it self. The differential diagnosis for lesions in this area includes:
*[[Pituitary adenoma]].
*[[Craniopharyngioma]].
*[[Rathke cleft cyst]].
*[[Germ cell tumour]].
*[[Meningioma]].
*[[Pilomyxoid astrocytoma]] - in children.

==See also==
*[[Neuropathology]].
*[[Muscle biopsy]].

==References==
{{reflist|2}}

==External links==
*[http://www.neuropathologyweb.org/ Neuropathology (neuropathologyweb.org)].
*[http://www.pathology.vcu.edu/WirSelfInst/tumor-1.html Neuropathology Mini-Course (pathology.vcu.edu)].
*[http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html Neuropathology Mini-Course (pathology.vcu.edu)].

[[Category:Neuropathology]]

High-grade astrocytoma with piloid features

2022-04-13T11:44:48Z

Jensflorian: Category

'''High-grade astrocytoma with piloid features''' is a rare [[Glioma|glial]] tumor which often requires methylation analyis to secure diagnosis. There is currently no definitive grading, but clinical behaviour suggests WHO CNS grade 3.

=Clinical=
*Rare (1-3% of all brain tumor in adults).
*Usu. posterior fossa (75%).
*Supratentorial or spinal locations possible.
*Imaging may be similiar to [[Glioblastoma]].
*5-year OS: 50%.

=Histology=
*Often so variable, so molecular testing is essential to secure diagnosis.
*Astrocytic nature of tumor cells.
*Frequent mitoses.
*Elongated glial tumor cell processes ("piloid").
*Rosenthal fibers or eosinophilic granular bodies.
*Perivascular lymphocytic cuffing.
*Necrosis may be present.

=IHC=
*[[GFAP]]+ve.
*ATRX: nuclear loss in approx. 40%.

=Molecular=
*DNA Methylation profile of high-grade astrocytoma with piloid features is essential for diagnosis.
*MAPK genes often altered (NF1, BRAF fusion, FGFR1, KRAS).
*CDKN2A/B homozygous deletion.
*CDK4 amplification.
*TERT promotor mutations are rare.
*Absence of IDH1/2 hotspot mutation.

=DDx:=
*[[Glioblastoma]]
*[[Pleomorphic xanthoastrocytoma]]

=See also=
*[[Astrocytoma]].
*[[Neuropathology_tumours#Infiltrative_astrocytomas]]

{{Reflist|2}}

[[Category:Diagnosis]]

High-grade astrocytoma with piloid features

2022-04-13T11:43:49Z

Jensflorian: Create

Astrocytoma

2022-04-13T11:28:33Z

Jensflorian: fix link

An '''astrocytoma''' is a neoplasm thought to be derived from an [[neurohistology|astrocyte]]. Astrocytomas/Glioblastomas are most common type of glial tumours and grouped together with [[Oligodendroglioma]] and glioneuronal tumours in the current WHO brain tumor classficiation. Some (often circumscribed) astrocytic tumors and pediatric tumours are biologically different from adult-onset diffuse astrocytomas. An overview of other CNS tumours is found in the ''[[CNS tumours]]'' article.

=Categorization=
Astrocytomas can be categorized in serveral ways.
* Common vs. uncommon tumours.
* Adult vs. pediatric tumours.
* Circumscribed vs. diffusely growing astrocytomas.

Until 2016 WHO classification, roman numerals I-IV were used for grading. The current 2021 WHO classification uses arabic numbering 1-4 for CNS WHO grading instead.

=Overview=
These astrocytic tumors are frequently diagnosed in neuropathology practice:
{| class="wikitable sortable"
! Name
! Type
! Age
! Variants / Patterns / Other designations
! Image
|-
| Astrocytoma, IDH mutant WHO CNS grade 2
| diffuse
| adults
| Diffuse, protoplasmatic, fibrillar or gemistocytic astrocytoma.
| [[File:Astrocytoma whoII HE.jpg|thumb|center|150px]]
|-
| Astrocytoma, IDH mutant WHO CNS grade 3
| diffuse
| adults
| Anaplastic astrocytoma, gliomatosis cerebri
| [[File:Anaplastic_astrocytoma_-_very_high_mag.jpg|thumb|center|150px]]
|-
| Astrocytoma, IDH mutant WHO CNS grade 4
| diffuse
| adults
|
| [[File:IDH1_GBM_20x.jpg|thumb|center|150px]]
|-
| Glioblastoma, WHO CNS grade 4
| diffuse
| adults
| small cell, epitheloid/rhabdoid, with PNET componet, with granular cell component, giant cell, gliosarcoma
| [[File:Glioblastoma_(1).jpg|thumb|center|150px]]
|-
| Diffuse midline glioma, H3 K27M-mutant, WHO CNS grade 4
| diffuse
| children
|
| [[File:K27M mutant diffuse glioma of the midline.jpg|thumb|center|150px]]
|-
|-
| Pilocytic astrocytoma, WHO CNS grade 1
| circumscribed
| children
| pilomyxoid astrocytoma, anaplastic pilocytic astrocytoma
| [[File:Rosenthal_HE_40x.jpg|thumb|center|150px]]
|-
| Pleomorphic xanthoastrocytoma, WHO CNS grade 2 (PXA)
| circumscribed
| young adults
|
| [[File:PXA_HE_x20.jpg|thumb|center|150px]]
|-
| Pleomorphic xanthoastrocytoma, WHO CNS grade 3 (PXA)
| circumscribed
| young adults
| Anaplastic PXA.
| [[File:Anaplastic_pxa_histology.jpg|thumb|center|150px]]
|-
| Subependymal giant cell astrocytoma, WHO CNS grade 1 (SEGA)
| circumscribed
| young adults
| SEGA in tuberous sclerosis
| [[File:SEGA_HE.jpg|thumb|center|150px]]
|}

=Adult-type astrocytomas=
*[[Astrocytoma, IDH-mutant]].
*[[Glioblastoma]], IDH wildtype.
*High-grade astrocytoma with piloid features.
*[[Pleomorphic xanthroastrocytoma]].
*[[Subependymal giant cell astrocytoma]].
*[[Chordoid glioma]].

=Pediatric-type astrocytomas=
*[[Pilocytic astrocytoma]].
*[[Pediatric-type diffuse high-grade glioma]].
*[[Pediatric-type diffuse low-grade glioma]].
*[[Astroblastoma]].

=Common Astrocytomas=
==Pilocytic astrocytoma==
* Benign, cystic, infratentorial.
* Classic childhood tumor, surgically resectable.
* Circumscribed astrocytic glioma
* Variant: [[Pilomyxoid astrocytoma]]
{{Main|Pilocytic astrocytoma}}

==Astrocytoma, IDH mutant==
* Astrocytoma, IDH mutant are less common than glioblastoma.
* Grade 2-4 depends on histological and molecular criteria:
{{Main|Astrocytoma, IDH-mutant}}

=== Astrocytoma, IDH mutant grade 2===
* Formerly designated as Diffuse astrocytoma Grade II.
* Typically seen in adults.
* Usually shows progression to astrocytoma IDH mutant, grade 4.

===Astrocytoma, IDH mutant grade 3===
* Formerly designated Anaplastic astrocytoma Grade III.
* Typically seen in adults.
* Increased cellularity, cell atypia and mitotic activity.
* Lacks endothelial proliferations and necrosis of glioblastoma.

===Astrocytoma, IDH mutant grade 4===
* Formerly called Glioblastoma, IDH mutant.
* Endothelial proliferations and necrosis indistinguishable from glioblastoma.
* Homozygous CDKN2A deletion qualifies grade 2 and grade 3 astrocytomas as grade 4 tumor.

==Glioblastoma==
* Most common malignant brain tumor peaking around 65 years.
* Prognosis very poor.
* Variant: [[Giant cell glioblastoma]]
* Variant: [[Gliosarcoma]]
{{Main|Glioblastoma}}

=Uncommon Astrocytomas=
==Diffuse astrocytoma, MYB- or MYBL-altered==
* Pediatric-type diffuse low-grade glioma.
* Associated with epileptic seizures.
* Excellent prognosis.
{{Main|Diffuse astrocytoma, MYB- or MYBL-altered}}

==Subependymal giant cell astrocytoma==
* Intraventricular benign tumor of adolescents.
* Associated with [[Tuberous sclerosis]].
{{Main|Subependymal giant cell astrocytoma}}

==Pleomorphic xanthroastrocytoma (PXA)==
* Kids & young adults usually with good prognosis.
* Large lipidized cells mimicking a malignant tumor
{{Main|Pleomorphic xanthoastrocytoma}}

==Diffuse midline glioma, H3 K27-altered==
* High-grade astrocytic neoplasm associated with midline structures (thalamus, brain stem, spinal cord).
* Mostly in children and adolescents.
* Includes diffuse intrinsic pontine gliomas (DPIG).

{{Main|Diffuse midline glioma, H3 K27-altered}}

==Diffuse hemispheric glioma, H3 G34-mutant==
* Infiltrative hemispheric glioma of young adults.
* Glioblastoma-like appearance (CNS WHO grade 4 tumor).
* Newly defined entity in WHO 2021 classification.
* H3F3A missense mutation G34R or G34V.
{{Main|Diffuse hemispheric glioma, H3 G34-mutant}}

==Gliomatosis cerebri==
* Depreceated entity.
* Was used for extensively diffusely growing astrocytic neoplasms.
**Introduced in 1938 as a post-mortem diagnosis.<ref>SAMUEL NEVIN - GLIOMATOSIS CEREBRI, DOI: http://dx.doi.org/10.1093/brain/61.2.170 170-191 First published online: 1 June 1938</ref>
**Since 2016 it is no longer considered a distinct entity.<ref>{{Cite journal | last1 = Johnson | first1 = DR. | last2 = Guerin | first2 = JB. | last3 = Giannini | first3 = C. | last4 = Morris | first4 = JM. | last5 = Eckel | first5 = LJ. | last6 = Kaufmann | first6 = TJ. | title = 2016 Updates to the WHO Brain Tumor Classification System: What the Radiologist Needs to Know. | journal = Radiographics | volume = 37 | issue = 7 | pages = 2164-2180 | month = | year = | doi = 10.1148/rg.2017170037 | PMID = 29028423 }}</ref><ref>{{Cite journal | last1 = Herrlinger | first1 = U. | last2 = Jones | first2 = DT. | last3 = Glas | first3 = M. | last4 = Hattingen | first4 = E. | last5 = Gramatzki | first5 = D. | last6 = Stuplich | first6 = M. | last7 = Felsberg | first7 = J. | last8 = Bähr | first8 = O. | last9 = Gielen | first9 = GH. | title = Gliomatosis cerebri: no evidence for a separate brain tumor entity. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Oct | year = 2015 | doi = 10.1007/s00401-015-1495-z | PMID = 26493382 }}</ref>
* More than 3 lobes have to be involved, us. bilateral (radiology required).
* biologic behaviour corresponds to WHO III (ICD-O: 9381/3)
* Based on presence / absence of a solid component authors propose two types:<ref>{{Cite journal | last1 = Seiz | first1 = M. | last2 = Tuettenberg | first2 = J. | last3 = Meyer | first3 = J. | last4 = Essig | first4 = M. | last5 = Schmieder | first5 = K. | last6 = Mawrin | first6 = C. | last7 = von Deimling | first7 = A. | last8 = Hartmann | first8 = C. | title = Detection of IDH1 mutations in gliomatosis cerebri, but only in tumors with additional solid component: evidence for molecular subtypes. | journal = Acta Neuropathol | volume = 120 | issue = 2 | pages = 261-7 | month = Aug | year = 2010 | doi = 10.1007/s00401-010-0701-2 | PMID = 20514489 }}</ref>
** GC type 1: classic diffuse growth, without IDH1/2 mutation.
** GC type 2: with a solid portion, mostly IDH1 mutant.
* Genetic studies indicate strong overlap with diffuse astrocytic gliomas, oligodendrogliomas and glioblastoma.

==Gliosarcoma==
===General===
*Considered to be a variant of [[glioblastoma]] by WHO.<ref name=pmid19618114>{{cite journal |author=Han SJ, Yang I, Tihan T, Prados MD, Parsa AT |title=Primary gliosarcoma: key clinical and pathologic distinctions from glioblastoma with implications as a unique oncologic entity |journal=J. Neurooncol. |volume=96 |issue=3 |pages=313–20 |year=2010 |month=February |pmid=19618114 |pmc=2808523 |doi=10.1007/s11060-009-9973-6 |url=}}</ref>
*Rare ~ 200 cases reported in the literature.<ref name=pmid19618114/>
*Definition: gliosarcoma = glioblastoma + sarcomatous component.<ref name=pmid20415184>{{cite journal |author=Ayadi L, Charfi S, Khabir A, ''et al.'' |title=[Cerebral gliosarcoma: clinico-pathologic study of 8 cases] |language=French |journal=Tunis Med |volume=88 |issue=3 |pages=142–6 |year=2010 |month=March |pmid=20415184 |doi= |url=}}</ref>
*Usual location (like glioblastoma): temporal lobe.
*Prognosis is similiar to [[glioblastoma]].<ref>{{Cite journal | last1 = Frandsen | first1 = J. | last2 = Orton | first2 = A. | last3 = Jensen | first3 = R. | last4 = Colman | first4 = H. | last5 = Cohen | first5 = AL. | last6 = Tward | first6 = J. | last7 = Shrieve | first7 = DC. | last8 = Suneja | first8 = G. | title = Patterns of care and outcomes in gliosarcoma: an analysis of the National Cancer Database. | journal = J Neurosurg | volume = | issue = | pages = 1-6 | month = Jun | year = 2017 | doi = 10.3171/2016.12.JNS162291 | PMID = 28621623 }}</ref>
** Age below 65 years is prognostic.

===Microscopic===
Features:
*[[Glioblastoma]].
*Sarcomatous component (one of the following):<ref name=pmid19618114/><ref name=pmid20415184/>
**Fibroblastic.
**Cartilaginous.
**Osseous.
**Smooth muscle.
**Striated muscle.
**Adipocyte.

====Images====
<gallery>
Image:Gliosarcoma_Histopathology_200x_EVG.jpg | Gliosarcoma - elastica van Giesson. (WC)
</gallery>
www:
*[http://path.upmc.edu/cases/case169/micro.html Gliosarcoma - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case361.html Gliosarcoma - case 2 - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case367.html Gliosarcoma - case 3 - several images (upmc.edu)].

===IHC===
*GFAP +ve -- astrocytic component.<ref name=pmid9736406>{{Cite journal | last1 = Horiguchi | first1 = H. | last2 = Hirose | first2 = T. | last3 = Kannuki | first3 = S. | last4 = Nagahiro | first4 = S. | last5 = Sano | first5 = T. | title = Gliosarcoma: an immunohistochemical, ultrastructural and fluorescence in situ hybridization study. | journal = Pathol Int | volume = 48 | issue = 8 | pages = 595-602 | month = Aug | year = 1998 | doi = | PMID = 9736406 }}</ref>
**Spindle cell component -ve.<ref>URL: [http://path.upmc.edu/cases/case361.html http://path.upmc.edu/cases/case361.html]. Accessed on: 15 January 2012.</ref>

Gliosarcoma with smooth muscle component (gliomyosarcoma):<ref name=pmid21393877>{{Cite journal | last1 = Khanna | first1 = M. | last2 = Siraj | first2 = F. | last3 = Chopra | first3 = P. | last4 = Bhalla | first4 = S. | last5 = Roy | first5 = S. | title = Gliosarcoma with prominent smooth muscle component (gliomyosarcoma): a report of 10 cases. | journal = Indian J Pathol Microbiol | volume = 54 | issue = 1 | pages = 51-4 | month = | year = | doi = 10.4103/0377-4929.77324 | PMID = 21393877 }}</ref>
*SMA +ve.
*Factor VIII +ve.

==Gliofibroma==
* Very rare indolent tumor in children <ref>{{Cite journal | last1 = Deb | first1 = P. | last2 = Sarkar | first2 = C. | last3 = Garg | first3 = A. | last4 = Singh | first4 = VP. | last5 = Kale | first5 = SS. | last6 = Sharma | first6 = MC. | title = Intracranial gliofibroma mimicking a meningioma: a case report and review of literature. | journal = Clin Neurol Neurosurg | volume = 108 | issue = 2 | pages = 178-86 | month = Feb | year = 2006 | doi = 10.1016/j.clineuro.2004.11.021 | PMID = 16412839 }}</ref>
* Usually not dura-based (DD: Desmoplastic infantile astrocytoma)
* Glial tumor with non-neoplastic fibromatous component.

=See also=
*[[CNS tumours]].

=References=
{{Reflist|2}}

[[Category:Neuropathology]]

Astrocytoma

2022-04-13T11:26:59Z

Jensflorian: link

An '''astrocytoma''' is a neoplasm thought to be derived from an [[neurohistology|astrocyte]]. Astrocytomas/Glioblastomas are most common type of glial tumours and grouped together with [[Oligodendroglioma]] and glioneuronal tumours in the current WHO brain tumor classficiation. Some (often circumscribed) astrocytic tumors and pediatric tumours are biologically different from adult-onset diffuse astrocytomas. An overview of other CNS tumours is found in the ''[[CNS tumours]]'' article.

=Categorization=
Astrocytomas can be categorized in serveral ways.
* Common vs. uncommon tumours.
* Adult vs. pediatric tumours.
* Circumscribed vs. diffusely growing astrocytomas.

Until 2016 WHO classification, roman numerals I-IV were used for grading. The current 2021 WHO classification uses arabic numbering 1-4 for CNS WHO grading instead.

=Overview=
These astrocytic tumors are frequently diagnosed in neuropathology practice:
{| class="wikitable sortable"
! Name
! Type
! Age
! Variants / Patterns / Other designations
! Image
|-
| Astrocytoma, IDH mutant WHO CNS grade 2
| diffuse
| adults
| Diffuse, protoplasmatic, fibrillar or gemistocytic astrocytoma.
| [[File:Astrocytoma whoII HE.jpg|thumb|center|150px]]
|-
| Astrocytoma, IDH mutant WHO CNS grade 3
| diffuse
| adults
| Anaplastic astrocytoma, gliomatosis cerebri
| [[File:Anaplastic_astrocytoma_-_very_high_mag.jpg|thumb|center|150px]]
|-
| Astrocytoma, IDH mutant WHO CNS grade 4
| diffuse
| adults
|
| [[File:IDH1_GBM_20x.jpg|thumb|center|150px]]
|-
| Glioblastoma, WHO CNS grade 4
| diffuse
| adults
| small cell, epitheloid/rhabdoid, with PNET componet, with granular cell component, giant cell, gliosarcoma
| [[File:Glioblastoma_(1).jpg|thumb|center|150px]]
|-
| Diffuse midline glioma, H3 K27M-mutant, WHO CNS grade 4
| diffuse
| children
|
| [[File:K27M mutant diffuse glioma of the midline.jpg|thumb|center|150px]]
|-
|-
| Pilocytic astrocytoma, WHO CNS grade 1
| circumscribed
| children
| pilomyxoid astrocytoma, anaplastic pilocytic astrocytoma
| [[File:Rosenthal_HE_40x.jpg|thumb|center|150px]]
|-
| Pleomorphic xanthoastrocytoma, WHO CNS grade 2 (PXA)
| circumscribed
| young adults
|
| [[File:PXA_HE_x20.jpg|thumb|center|150px]]
|-
| Pleomorphic xanthoastrocytoma, WHO CNS grade 3 (PXA)
| circumscribed
| young adults
| Anaplastic PXA.
| [[File:Anaplastic_pxa_histology.jpg|thumb|center|150px]]
|-
| Subependymal giant cell astrocytoma, WHO CNS grade 1 (SEGA)
| circumscribed
| young adults
| SEGA in tuberous sclerosis
| [[File:SEGA_HE.jpg|thumb|center|150px]]
|}

=Adult-type astrocytomas=
*[[Astrocytoma, IDH-mutant]].
*[[Glioblastoma]], IDH wildtype.
*High-grade astrocytoma with piloid features.
*[[Pleomorphic xanthroastrocytoma]].
*[[Subependymal giant cell astrocytoma]].
*[[Chordoid glioma]].

=Pediatric-type astrocytomas=
*[[Pilocytic astrocytoma]].
*[[Pediatric-type diffuse high-grade glioma]].
*[[Pediatric-type diffuse low-grade glioma]].
*[[Astroblastoma]].

=Common Astrocytomas=
==Pilocytic astrocytoma==
* Benign, cystic, infratentorial.
* Classic childhood tumor, surgically resectable.
* Circumscribed astrocytic glioma
* Variant: [[Pilomyxoid astrocytoma]]
{{Main|Pilocytic astrocytoma}}

==Astrocytoma, IDH mutant==
* Astrocytoma, IDH mutant are less common than glioblastoma.
* Grade 2-4 depends on histological and molecular criteria:
{{Main|Astrocytoma, IDH mutant}}

=== Astrocytoma, IDH mutant grade 2===
* Formerly designated as Diffuse astrocytoma Grade II.
* Typically seen in adults.
* Usually shows progression to astrocytoma IDH mutant, grade 4.

===Astrocytoma, IDH mutant grade 3===
* Formerly designated Anaplastic astrocytoma Grade III.
* Typically seen in adults.
* Increased cellularity, cell atypia and mitotic activity.
* Lacks endothelial proliferations and necrosis of glioblastoma.

===Astrocytoma, IDH mutant grade 4===
* Formerly called Glioblastoma, IDH mutant.
* Endothelial proliferations and necrosis indistinguishable from glioblastoma.
* Homozygous CDKN2A deletion qualifies grade 2 and grade 3 astrocytomas as grade 4 tumor.

==Glioblastoma==
* Most common malignant brain tumor peaking around 65 years.
* Prognosis very poor.
* Variant: [[Giant cell glioblastoma]]
* Variant: [[Gliosarcoma]]
{{Main|Glioblastoma}}

=Uncommon Astrocytomas=
==Diffuse astrocytoma, MYB- or MYBL-altered==
* Pediatric-type diffuse low-grade glioma.
* Associated with epileptic seizures.
* Excellent prognosis.
{{Main|Diffuse astrocytoma, MYB- or MYBL-altered}}

==Subependymal giant cell astrocytoma==
* Intraventricular benign tumor of adolescents.
* Associated with [[Tuberous sclerosis]].
{{Main|Subependymal giant cell astrocytoma}}

==Pleomorphic xanthroastrocytoma (PXA)==
* Kids & young adults usually with good prognosis.
* Large lipidized cells mimicking a malignant tumor
{{Main|Pleomorphic xanthoastrocytoma}}

==Diffuse midline glioma, H3 K27-altered==
* High-grade astrocytic neoplasm associated with midline structures (thalamus, brain stem, spinal cord).
* Mostly in children and adolescents.
* Includes diffuse intrinsic pontine gliomas (DPIG).

{{Main|Diffuse midline glioma, H3 K27-altered}}

==Diffuse hemispheric glioma, H3 G34-mutant==
* Infiltrative hemispheric glioma of young adults.
* Glioblastoma-like appearance (CNS WHO grade 4 tumor).
* Newly defined entity in WHO 2021 classification.
* H3F3A missense mutation G34R or G34V.
{{Main|Diffuse hemispheric glioma, H3 G34-mutant}}

==Gliomatosis cerebri==
* Depreceated entity.
* Was used for extensively diffusely growing astrocytic neoplasms.
**Introduced in 1938 as a post-mortem diagnosis.<ref>SAMUEL NEVIN - GLIOMATOSIS CEREBRI, DOI: http://dx.doi.org/10.1093/brain/61.2.170 170-191 First published online: 1 June 1938</ref>
**Since 2016 it is no longer considered a distinct entity.<ref>{{Cite journal | last1 = Johnson | first1 = DR. | last2 = Guerin | first2 = JB. | last3 = Giannini | first3 = C. | last4 = Morris | first4 = JM. | last5 = Eckel | first5 = LJ. | last6 = Kaufmann | first6 = TJ. | title = 2016 Updates to the WHO Brain Tumor Classification System: What the Radiologist Needs to Know. | journal = Radiographics | volume = 37 | issue = 7 | pages = 2164-2180 | month = | year = | doi = 10.1148/rg.2017170037 | PMID = 29028423 }}</ref><ref>{{Cite journal | last1 = Herrlinger | first1 = U. | last2 = Jones | first2 = DT. | last3 = Glas | first3 = M. | last4 = Hattingen | first4 = E. | last5 = Gramatzki | first5 = D. | last6 = Stuplich | first6 = M. | last7 = Felsberg | first7 = J. | last8 = Bähr | first8 = O. | last9 = Gielen | first9 = GH. | title = Gliomatosis cerebri: no evidence for a separate brain tumor entity. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Oct | year = 2015 | doi = 10.1007/s00401-015-1495-z | PMID = 26493382 }}</ref>
* More than 3 lobes have to be involved, us. bilateral (radiology required).
* biologic behaviour corresponds to WHO III (ICD-O: 9381/3)
* Based on presence / absence of a solid component authors propose two types:<ref>{{Cite journal | last1 = Seiz | first1 = M. | last2 = Tuettenberg | first2 = J. | last3 = Meyer | first3 = J. | last4 = Essig | first4 = M. | last5 = Schmieder | first5 = K. | last6 = Mawrin | first6 = C. | last7 = von Deimling | first7 = A. | last8 = Hartmann | first8 = C. | title = Detection of IDH1 mutations in gliomatosis cerebri, but only in tumors with additional solid component: evidence for molecular subtypes. | journal = Acta Neuropathol | volume = 120 | issue = 2 | pages = 261-7 | month = Aug | year = 2010 | doi = 10.1007/s00401-010-0701-2 | PMID = 20514489 }}</ref>
** GC type 1: classic diffuse growth, without IDH1/2 mutation.
** GC type 2: with a solid portion, mostly IDH1 mutant.
* Genetic studies indicate strong overlap with diffuse astrocytic gliomas, oligodendrogliomas and glioblastoma.

==Gliosarcoma==
===General===
*Considered to be a variant of [[glioblastoma]] by WHO.<ref name=pmid19618114>{{cite journal |author=Han SJ, Yang I, Tihan T, Prados MD, Parsa AT |title=Primary gliosarcoma: key clinical and pathologic distinctions from glioblastoma with implications as a unique oncologic entity |journal=J. Neurooncol. |volume=96 |issue=3 |pages=313–20 |year=2010 |month=February |pmid=19618114 |pmc=2808523 |doi=10.1007/s11060-009-9973-6 |url=}}</ref>
*Rare ~ 200 cases reported in the literature.<ref name=pmid19618114/>
*Definition: gliosarcoma = glioblastoma + sarcomatous component.<ref name=pmid20415184>{{cite journal |author=Ayadi L, Charfi S, Khabir A, ''et al.'' |title=[Cerebral gliosarcoma: clinico-pathologic study of 8 cases] |language=French |journal=Tunis Med |volume=88 |issue=3 |pages=142–6 |year=2010 |month=March |pmid=20415184 |doi= |url=}}</ref>
*Usual location (like glioblastoma): temporal lobe.
*Prognosis is similiar to [[glioblastoma]].<ref>{{Cite journal | last1 = Frandsen | first1 = J. | last2 = Orton | first2 = A. | last3 = Jensen | first3 = R. | last4 = Colman | first4 = H. | last5 = Cohen | first5 = AL. | last6 = Tward | first6 = J. | last7 = Shrieve | first7 = DC. | last8 = Suneja | first8 = G. | title = Patterns of care and outcomes in gliosarcoma: an analysis of the National Cancer Database. | journal = J Neurosurg | volume = | issue = | pages = 1-6 | month = Jun | year = 2017 | doi = 10.3171/2016.12.JNS162291 | PMID = 28621623 }}</ref>
** Age below 65 years is prognostic.

===Microscopic===
Features:
*[[Glioblastoma]].
*Sarcomatous component (one of the following):<ref name=pmid19618114/><ref name=pmid20415184/>
**Fibroblastic.
**Cartilaginous.
**Osseous.
**Smooth muscle.
**Striated muscle.
**Adipocyte.

====Images====
<gallery>
Image:Gliosarcoma_Histopathology_200x_EVG.jpg | Gliosarcoma - elastica van Giesson. (WC)
</gallery>
www:
*[http://path.upmc.edu/cases/case169/micro.html Gliosarcoma - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case361.html Gliosarcoma - case 2 - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case367.html Gliosarcoma - case 3 - several images (upmc.edu)].

===IHC===
*GFAP +ve -- astrocytic component.<ref name=pmid9736406>{{Cite journal | last1 = Horiguchi | first1 = H. | last2 = Hirose | first2 = T. | last3 = Kannuki | first3 = S. | last4 = Nagahiro | first4 = S. | last5 = Sano | first5 = T. | title = Gliosarcoma: an immunohistochemical, ultrastructural and fluorescence in situ hybridization study. | journal = Pathol Int | volume = 48 | issue = 8 | pages = 595-602 | month = Aug | year = 1998 | doi = | PMID = 9736406 }}</ref>
**Spindle cell component -ve.<ref>URL: [http://path.upmc.edu/cases/case361.html http://path.upmc.edu/cases/case361.html]. Accessed on: 15 January 2012.</ref>

Gliosarcoma with smooth muscle component (gliomyosarcoma):<ref name=pmid21393877>{{Cite journal | last1 = Khanna | first1 = M. | last2 = Siraj | first2 = F. | last3 = Chopra | first3 = P. | last4 = Bhalla | first4 = S. | last5 = Roy | first5 = S. | title = Gliosarcoma with prominent smooth muscle component (gliomyosarcoma): a report of 10 cases. | journal = Indian J Pathol Microbiol | volume = 54 | issue = 1 | pages = 51-4 | month = | year = | doi = 10.4103/0377-4929.77324 | PMID = 21393877 }}</ref>
*SMA +ve.
*Factor VIII +ve.

==Gliofibroma==
* Very rare indolent tumor in children <ref>{{Cite journal | last1 = Deb | first1 = P. | last2 = Sarkar | first2 = C. | last3 = Garg | first3 = A. | last4 = Singh | first4 = VP. | last5 = Kale | first5 = SS. | last6 = Sharma | first6 = MC. | title = Intracranial gliofibroma mimicking a meningioma: a case report and review of literature. | journal = Clin Neurol Neurosurg | volume = 108 | issue = 2 | pages = 178-86 | month = Feb | year = 2006 | doi = 10.1016/j.clineuro.2004.11.021 | PMID = 16412839 }}</ref>
* Usually not dura-based (DD: Desmoplastic infantile astrocytoma)
* Glial tumor with non-neoplastic fibromatous component.

=See also=
*[[CNS tumours]].

=References=
{{Reflist|2}}

[[Category:Neuropathology]]

Ependymoma

2022-04-12T12:56:50Z

Jensflorian: /* Classic ependymoma */ DDx

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Ependymoma_H%26E.jpg
| Width =
| Caption = Ependymoma grade II WHO. [[H&E stain]]
| Synonyms =
| Micro = Perivascular pseudorosettes, ependymal rosettes
| Subtypes = Tanycytic, Clear cell, Papillary, Cellular
| LMDDx = [[Subependymoma]], [[Glioblastoma]], [[Pilocytic astrocytoma]], [[Oligodendroglioma]]
| Stains =
| IHC = GFAP +ve
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site =
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence =
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis = intermediate to poor (WHO Grades II & III)
| Other =
| ClinDDx =
| Tx =
}}

'''Ependymoma''' is a [[neuropathology tumour]].

==General==
*Called the forgotten glial tumour.
*Anatomic location is essential for tumor diagnosis.

Epidemiology:<ref name=Ref_PBoD8_1334>{{Ref PBoD8|1334}}</ref>
*Usual site:
**Adults: usually spinal cord.
**Children: usually posterior fossa.
*May be associated with [[neurofibromatosis type 2]].

There are currently eight main ependymal tumors:<ref name=Ref_WHOCNS_74>{{Ref WHOCNS|74}}</ref>
#Supratentorial ependymoma, ZFTA-fusion positive
#Supratentorial ependymoma, YAP1-fusion positive
#Posterior fossa ependymoma group A
#Posterior fossa ependymoma group B
#Spinal ependymoma
#Spinal ependymoma, MYCN-amplified
#[[Myxopapillary ependymoma]]
#[[Subependymoma]]

Ependymoma (not otherwise specified).

*Depreceated terminologies:
**Papillary ependymoma.
**Clear cell ependymoma.
**Tanycytic ependymoma.
**Cellular ependymoma.
**Ependymoma, RELA fusion-positive.<ref>{{Cite journal | last1 = Parker | first1 = M. | last2 = Mohankumar | first2 = KM. | last3 = Punchihewa | first3 = C. | last4 = Weinlich | first4 = R. | last5 = Dalton | first5 = JD. | last6 = Li | first6 = Y. | last7 = Lee | first7 = R. | last8 = Tatevossian | first8 = RG. | last9 = Phoenix | first9 = TN. | title = C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. | journal = Nature | volume = 506 | issue = 7489 | pages = 451-5 | month = Feb | year = 2014 | doi = 10.1038/nature13109 | PMID = 24553141 }}</ref><ref>{{Cite journal | last1 = Pietsch | first1 = T. | last2 = Wohlers | first2 = I. | last3 = Goschzik | first3 = T. | last4 = Dreschmann | first4 = V. | last5 = Denkhaus | first5 = D. | last6 = Dörner | first6 = E. | last7 = Rahmann | first7 = S. | last8 = Klein-Hitpass | first8 = L. | title = Supratentorial ependymomas of childhood carry C11orf95-RELA fusions leading to pathological activation of the NF-κB signaling pathway. | journal = Acta Neuropathol | volume = 127 | issue = 4 | pages = 609-11 | month = Apr | year = 2014 | doi = 10.1007/s00401-014-1264-4 | PMID = 24562983 }}</ref> This is now called Supratentorial ependymoma, ZFTA-fusion positive.
**Anaplastic ependymoma.

==Gross==
*Usually discrete and enhancing.
*Ventricular location, but also within the spinal cord.
*Dissemination possible.
*[[Myxopapillary ependymoma]] classically at [[filum terminale]].
*[[Subependymoma]] typically seen in IVth ventricle.
<gallery>
File:AFIP405711R-EPENDYMOMA.jpg | Radiology (AFIP)
File:AFIP405713G-EPENDYMOMA.jpg | Ependymoma in the fourth ventricle (AFIP)
File:Ependymoma in the fourth ventricle.jpg | Gross (AFIP)
</gallery>

==Microscopic==
==="Classic" ependymoma===
*Come in two CNS WHO grades: 2 and 3.
*Usu. sharply demarcated from surrounding brain parenchyma.
Features:
*Cells have a "tadpole-like" morphology.
**May also be described as ''ice cream cone-shaped''.<ref>[http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html]</ref>
*'''Rosettes''' = circular nuclear free zones/cells arranged in a pseudoglandular fashion; comes in two flavours in ependymoma:
**''Perivascular pseudorosettes'' = (tumour) cells arranged around a blood vessel; nuclei of cells distant from the blood vessel, i.e. rim of cytoplasm (from tumour cells) surround blood vessel (nucleus-free zone); more common than ependymal rosette... but less specific.
**''Ependymal rosette'' ([[AKA]] ''true ependymal rosette'') = rosette has an empty space at the centre - '''key feature'''.
*Nuclear features monotonous, i.e. "boring".<ref>MUN. 6 Oct 2009.</ref>
**There is little variation in size, shape and staining.
*Hyalinized vessels.
*Calcification.
*Rare cases with cartilagineous metaplasia.<ref>{{Cite journal | last1 = Wang | first1 = X. | last2 = Zhang | first2 = S. | last3 = Ye | first3 = Y. | last4 = Chen | first4 = Y. | last5 = Liu | first5 = X. | title = Ependymoma with cartilaginous metaplasia might have more aggressive behavior: a case report and literature review. | journal = Brain Tumor Pathol | volume = 29 | issue = 3 | pages = 172-6 | month = Jul | year = 2012 | doi = 10.1007/s10014-011-0079-4 | PMID = 22228122 }}</ref>
*Branching capillaries usu. only in supratentorial ependymomas.

DDx (supratentorial and posterior fossa ependymoma):
*[[Subependymoma]].
*[[Glioblastoma]] (GBM).
*Gliomas with BCOR internal tandem duplication.
*[[Astroblastoma]], MN1-altered.
**Invasive border = GBM; circumscribed border of lesion = ependymoma.
*[[Oligodendroglioma]] (Clear cell ependymoma))

DDx (spinal ependymoma):
*[[Pilocytic astrocytoma]] (Tanycytic ependymoma)
*Diffuse midline glioma, H3 K27-altered
*Small cell glioblastoma (MYCN-amplified spinal ependymoma)

====Images====
www:
*[http://www.flickr.com/photos/ckrishnan/3862487821/in/photostream Ependymoma (flickr.com)].
*[http://www.ajnr.org/cgi/content-nw/full/27/3/488/F10 Ependymoma - ependymal rosettes (ajnr.org)].
*[http://path.upmc.edu/cases/case95/micro.html Anaplastic ependymoma - case 1 (upmc.edu)].
*[http://path.upmc.edu/cases/case324.html Anaplastic ependymoma - case 2 (upmc.edu)].
<gallery>
File:AFIP405736M-EPENDYMOMA.jpg | Ependymoma smear. (AFIP)
File:AFIP405715M-EPENDYMOMA.jpg | Perivascular pseudorosettes in a ependymoma. (AFIP)
Image:Ependymoma_intermed_mag.jpg | Ependymoma - intermed. mag. (WC)
Image:Ependymoma_low_intermed_mag.jpg | Ependymoma - low mag. (WC)
File:Ependymoma_H%26E.jpg | Ependymoma - high mag. (WC/Sbrandner)
File:Ependymoma_true_ependymal_rosettes_and_pseudorosettes.jpg | True ependymal and pseudorosettes in a ependymoma. (WC/jensflorian)
File:Ependymal_linings_ependymoma_HE.jpg | Ependymal linings in a ependymoma. (WC/jensflorian)
File:Ependymoma_GFAP.jpg| GFAP IHC in a ependymoma. (WC/Sbrandner)
File:EMA_ependymoma_periluminal.jpg | Periluminal EMA positivity in a ependymoma. (WC/jensflorian)
File:Ependymoma_EMA.jpg | Dot-like EMA immunreactivity n a ependymoma. (WC/Marvin101)
File:Tanycytic ependymoma HE.jpg | Tanycytic morphology in ependymoma must not confused with [[pilocytic astrocytoma]]. (WC/jensflorian)
File:Tanicytic_ependymoma_x10.jpg | Tanycytic morphology in ependymoma - low mag. (WC/jensflorian)
File:Papillary_Ependymoma.jpg | Papillary morphology in ependymoma - low mag. (WC/jensflorian)
File:Papillary_ependymoma_HE_x40.jpg | Papillary morphology in ependymoma - intermed. mag. (WC/jensflorian)
File:Clear_cell_ependymoma_HE.jpg | Clear cell morphology in ependymoma may mimic [[oligodendroglioma]]. (WC/jensflorian)
File:HE_anaplastic_epedymomas_mitoses_pleomorphism.jpg | Brisk mitotic activity in a anaplastic ependymoma. (WC/jensflorian)
File:Cartilaginous metaplasia ependymoma.jpg|Metaplastic transformation in an anaplastic ependymoma. (WC/jensflorian)
File:Ependymoma_L1CAM_IHC.jpg | L1CAM immunohistochemistry indicates presence of ZFTA-fusion.
File:Ependymoma_NFkappaB_IHC.jpg | Nuclear NFkappaB IHC indicates presence of ZFTA-fusion.
</gallery>

===Grading===
Easy:
*Subependymoma = CNS WHO grade 1.
*Myxopapillary ependymoma = CNS WHO grade 2.

Not so easy:
All other ependymomas: WHO CNS Grade 2 vs. Grade 3 depends on:
*Cellular density.
*Mitoses (no clear cut-off).
*Necrosis (not prognostic).
*Microvascular proliferation.
*Poor interobserver reliability<ref>{{Cite journal | last1 = Ellison | first1 = DW. | last2 = Kocak | first2 = M. | last3 = Figarella-Branger | first3 = D. | last4 = Felice | first4 = G. | last5 = Catherine | first5 = G. | last6 = Pietsch | first6 = T. | last7 = Frappaz | first7 = D. | last8 = Massimino | first8 = M. | last9 = Grill | first9 = J. | title = Histopathological grading of pediatric ependymoma: reproducibility and clinical relevance in European trial cohorts. | journal = J Negat Results Biomed | volume = 10 | issue = | pages = 7 | month = May | year = 2011 | doi = 10.1186/1477-5751-10-7 | PMID = 21627842 }}</ref>

Notes:
*Many tumours fall between grade 2 and grade 3.
*Rare cases with sarcomatous or cartilaginous components.<ref>{{Cite journal | last1 = Vajtai | first1 = I. | last2 = Kuhlen | first2 = D. | last3 = Kappeler | first3 = A. | last4 = Mariani | first4 = L. | last5 = Zimmermann | first5 = A. | last6 = Paulus | first6 = W. | title = Rapid spontaneous malignant progression of supratentorial tanycytic ependymoma with sarcomatous features - "Ependymosarcoma". | journal = Pathol Res Pract | volume = 206 | issue = 7 | pages = 493-8 | month = Jul | year = 2010 | doi = 10.1016/j.prp.2009.07.013 | PMID = 19853384 }}</ref><ref>{{Cite journal | last1 = Boukas | first1 = A. | last2 = Joshi | first2 = A. | last3 = Jenkins | first3 = A. | last4 = Holliman | first4 = D. | title = Extensive cartilaginous metaplasia of recurrent posterior fossa ependymoma: case report and review of the literature. | journal = Pediatr Neurosurg | volume = 49 | issue = 2 | pages = 93-8 | month = | year = 2013 | doi = 10.1159/000356931 | PMID = 24401698 }}</ref>

==IHC==
*Reticulin-ve.
*GFAP+ve.
*MIB1 (usu low).
*[[IDH-1]]-ve.
*EMA (dots and rings).<ref>{{Cite journal | last1 = Hasselblatt | first1 = M. | last2 = Paulus | first2 = W. | title = Sensitivity and specificity of epithelial membrane antigen staining patterns in ependymomas. | journal = Acta Neuropathol | volume = 106 | issue = 4 | pages = 385-8 | month = Oct | year = 2003 | doi = 10.1007/s00401-003-0752-8 | PMID = 12898159 }}</ref>
**Widespread and strong EMA expression is indicative of YAP1-fused ependymoma.
*Olig2-ve.<ref>{{Cite journal | last1 = Švajdler | first1 = M. | last2 = Rychlý | first2 = B. | last3 = Mezencev | first3 = R. | last4 = Fröhlichová | first4 = L. | last5 = Bednárová | first5 = A. | last6 = Pataky | first6 = F. | last7 = Daum | first7 = O. | title = SOX10 and Olig2 as negative markers for the diagnosis of ependymomas: An immunohistochemical study of 98 glial tumors. | journal = Histol Histopathol | volume = 31 | issue = 1 | pages = 95-102 | month = Jan | year = 2016 | doi = 10.14670/HH-11-654 | PMID = 26287936 }}</ref>
*H3K27me3 nuclear loss in Posterior fossa group A ependymoma (nuclear loss is diagnostic).<ref>{{Cite journal | last1 = Panwalkar | first1 = P. | last2 = Clark | first2 = J. | last3 = Ramaswamy | first3 = V. | last4 = Hawes | first4 = D. | last5 = Yang | first5 = F. | last6 = Dunham | first6 = C. | last7 = Yip | first7 = S. | last8 = Hukin | first8 = J. | last9 = Sun | first9 = Y. | title = Immunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Jul | year = 2017 | doi = 10.1007/s00401-017-1752-4 | PMID = 28733933 }}</ref>
*L1CAM in supratentorial tumors (expression indicates ZFTA fusion).<ref>{{Cite journal | last1 = Parker | first1 = M. | last2 = Mohankumar | first2 = KM. | last3 = Punchihewa | first3 = C. | last4 = Weinlich | first4 = R. | last5 = Dalton | first5 = JD. | last6 = Li | first6 = Y. | last7 = Lee | first7 = R. | last8 = Tatevossian | first8 = RG. | last9 = Phoenix | first9 = TN. | title = C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. | journal = Nature | volume = 506 | issue = 7489 | pages = 451-5 | month = Feb | year = 2014 | doi = 10.1038/nature13109 | PMID = 24553141 }}</ref>
*p65 nuclear +ve in ZFTA-fused ependymoma.

==Molecular==
Two distinct molecular subgroups exist in the posterior fossa:<ref>{{Cite journal | last1 = Witt | first1 = H. | last2 = Mack | first2 = SC. | last3 = Ryzhova | first3 = M. | last4 = Bender | first4 = S. | last5 = Sill | first5 = M. | last6 = Isserlin | first6 = R. | last7 = Benner | first7 = A. | last8 = Hielscher | first8 = T. | last9 = Milde | first9 = T. | title = Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma. | journal = Cancer Cell | volume = 20 | issue = 2 | pages = 143-57 | month = Aug | year = 2011 | doi = 10.1016/j.ccr.2011.07.007 | PMID = 21840481 }}</ref>
* Group A ependymomas:
**typically found in children.
**laterally.
**relatively unfavorable clinical outcome.
**CpG island methylator phenotype.<ref>{{Cite journal | last1 = Mack | first1 = SC. | last2 = Witt | first2 = H. | last3 = Piro | first3 = RM. | last4 = Gu | first4 = L. | last5 = Zuyderduyn | first5 = S. | last6 = Stütz | first6 = AM. | last7 = Wang | first7 = X. | last8 = Gallo | first8 = M. | last9 = Garzia | first9 = L. | title = Epigenomic alterations define lethal CIMP-positive ependymomas of infancy. | journal = Nature | volume = 506 | issue = 7489 | pages = 445-50 | month = Feb | year = 2014 | doi = 10.1038/nature13108 | PMID = 24553142 }}</ref>
**Loss of H3K27me.<ref>{{Cite journal | last1 = Panwalkar | first1 = P. | last2 = Clark | first2 = J. | last3 = Ramaswamy | first3 = V. | last4 = Hawes | first4 = D. | last5 = Yang | first5 = F. | last6 = Dunham | first6 = C. | last7 = Yip | first7 = S. | last8 = Hukin | first8 = J. | last9 = Sun | first9 = Y. | title = Immunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Jul | year = 2017 | doi = 10.1007/s00401-017-1752-4 | PMID = 28733933 }}</ref>
* Group B ependymomas:
**typically adults.
**midline.
**relatively favorable clinical outcomes.
**gene expression profiles similar to that of spinal cord ependymomas.
**increased Chromosomal 1q gains. <ref>{{Cite journal | last1 = Korshunov | first1 = A. | last2 = Witt | first2 = H. | last3 = Hielscher | first3 = T. | last4 = Benner | first4 = A. | last5 = Remke | first5 = M. | last6 = Ryzhova | first6 = M. | last7 = Milde | first7 = T. | last8 = Bender | first8 = S. | last9 = Wittmann | first9 = A. | title = Molecular staging of intracranial ependymoma in children and adults. | journal = J Clin Oncol | volume = 28 | issue = 19 | pages = 3182-90 | month = Jul | year = 2010 | doi = 10.1200/JCO.2009.27.3359 | PMID = 20516456 }}</ref>

Supratentorial ependymomas have also a distinct profile:
*70 % of these ependymomas are ZFTA-fusion positive and have recurrent gene fusions mostly involving RELA<ref>{{Cite journal | last1 = Parker | first1 = M. | last2 = Mohankumar | first2 = KM. | last3 = Punchihewa | first3 = C. | last4 = Weinlich | first4 = R. | last5 = Dalton | first5 = JD. | last6 = Li | first6 = Y. | last7 = Lee | first7 = R. | last8 = Tatevossian | first8 = RG. | last9 = Phoenix | first9 = TN. | title = C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. | journal = Nature | volume = 506 | issue = 7489 | pages = 451-5 | month = Feb | year = 2014 | doi = 10.1038/nature13109 | PMID = 24553141 }}</ref>
**EPHB2 amplifications and CDKN2A deletions in a subset of these tumors<ref>{{Cite journal | last1 = Philip-Hollingsworth | first1 = S. | last2 = Hollingsworth | first2 = RI. | last3 = Dazzo | first3 = FB. | title = Host-range related structural features of the acidic extracellular polysaccharides of Rhizobium trifolii and Rhizobium leguminosarum. | journal = J Biol Chem | volume = 264 | issue = 3 | pages = 1461-6 | month = Jan | year = 1989 | doi = | PMID = 2912966 }}</ref>
*6-8% are YAP1-fusion positive, mostly MAMLD1 as fusion partner.
Note: Molecular subgroups have no treatment implications (at the moment).

==See also==
*[[Subependymoma]].
*[[Myxopapillary ependymoma]].
*[[Neuropathology tumours]].

==References==
{{Reflist|1}}

[[Category:Diagnosis]]
[[Category:Neuropathology tumours]]