Difference between revisions of "Pituitary gland"

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Pituitary gland (view source)

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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>
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).
*Anterior pituitary ([[AKA]] adenohypophysis, pars distalis).
*Posterior pituitary (AKA neurohypophysis, neural pituitary).
*Posterior pituitary (AKA neurohypophysis, neural pituitary, pars nervosa).


=Function=
=Function=
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Mnemonic: "Go Look For The Adenoma Please" = GH, LH, FSH, TSH, ACTH, 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===
===Posterior===
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*Less cellular.
*Less cellular.
**Usually more cellular in perivascular location.
**Usually more cellular in perivascular location.
Image: [http://www.ouhsc.edu/histology/Glass%20slides/38_09.jpg Herring bodies (ouhsc.edu)].


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=
=DDx for sella turcica lesions=
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**Classically: visual field defects (bitemporal hemianopsia).
**Classically: visual field defects (bitemporal hemianopsia).
**Others (increased intracranial pressure): headache, nausea, vomiting.
**Others (increased intracranial pressure): headache, nausea, vomiting.
**Tumor of adults.


Classification:
Classification:
#Microadenoma <= 1 cm.
#Microadenoma <= 1 cm.
#Macroadenoma > 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:
Notes:
*May be classified by what they secrete. ''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.
  ''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====
====Familial pituitary adenomas====
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*Loss of fibrous stroma.
*Loss of fibrous stroma.
**The cells of a normal (anterior) pituitary are nested.
**The cells of a normal (anterior) pituitary are nested.
*Basophilic cells (corticotrophs).
*Eosinophilic cells(somatotrophs).


Notes:
Notes:
*Smears very well.<ref>MUN. 24 November 2010.</ref>
*Smears very well.<ref>MUN. 24 November 2010.</ref>
The WHO 2017 Classification of tumours of endocrine organs recoginizes following tumours:<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>
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Adenoma 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====
====Images====
<gallery>
<gallery>
Image:Nonfunctioning_pituitary_adenoma_%281%29.jpg | Pituitary adenoma - non-functioning. (WC)
Image:Nonfunctioning_pituitary_adenoma_%281%29.jpg | Pituitary adenoma - non-functioning. (WC/KGH)
Image:Pituitary_adenoma_%281%29_GH_production.jpg | Pituitary adenoma - GH producing. (WC)
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>
</gallery>
www:
*[http://path.upmc.edu/cases/case6.html Pituitary adenoma - crappy pictures (upmc.edu)].
*[http://path.upmc.edu/cases/case556.html Pituitary adenoma - case 2 - several images (upmc.edu)].


===Stains===
===Stains===
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*LH.
*LH.
*FSH.
*FSH.
*TSH.
*TSH - [[Hyperthyroidism]]
*GH.
*GH - [[Acromegaly]].
*Prolactin.
*Prolactin -Galactorrhea, Amenorrhea, Gynecomastia. Golgi staining pattern in sparsely granulated cases.
*ACTH - Cushing disease.
*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==
==Rathke cleft cyst==
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==Craniopharyngioma==
==Craniopharyngioma==
{{Main|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==
==Autoimmune hypophysitis==
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*Rare.
*Rare.
*Autoantigens are unknown.
*Autoantigens are unknown.
*May occur in pregnancy.
*May be misdiagnosed as a nonsecreting adenoma.
*May be misdiagnosed as a nonsecreting adenoma.


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


=See also=
=See also=
Jensflorian
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