Meningioma

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Meningioma
Diagnosis in short

Meningioma. HPS stain.

LM whorled appearance, calcification - 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)
LM DDx schwannoma, solitary fibrous tumour, hemangiopericytoma, others
IHC EMA +ve, keratins usu. -ve, CD34 -ve/+ve, S-100 -ve (usu.), PR +ve (-ve in more aggressive ones)
Site see CNS tumours

Syndromes neurofibromatosis 2, nevoid basal cell carcinoma syndrome

Clinical history +/-radiation
Prevalence common
Radiology extra-axial, intradural lesion, dural tail sign (on MRI)
Prognosis usually benign, dependent on grade
Clin. DDx dependent on site - see CNS tumours
Treatment surgical removal

Meningioma a very common tumour in neuropathology.

General

Prevalence

  • Most common primary brain tumour.[1]
  • May be caused by prior radiation.[2]
  • Women develop meningioma twice as likely as men.[3]
  • 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.[4]
    • Presence of TERT promotor mutation.[5]
    • Loss of H3K27me3.[6]

Genetics

Quick overview

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
Miningioma (1) transitional type.jpg
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
Brain invasion meningioma.jpg
Anaplastic, WHO III 20 or more mitoses/10 HPF, morphologiy similiar to carcinoma or sarcoma rhabdoid, papillary
Mitoses anaplastic meningioma.jpg

Gross/Radiology

  • Extra-axial, intradural.
    • Can be extradural - very rare.[10]
  • Dural tail sign (DTS) on MRI.[11][12]
    • Enhancement of dura adjacent to the mass lesion - commonly seen (~70% of cases).[13]
    • May be subclassified radiologically - predictive of grading.[14]
  • +/-Hyperostosis.
    • Associated with invasion into the skull in ~20% of cases.[15]

Microscopic

Features (memory device WCN):

  • Whorled appearance - key feature.
  • Calcification, 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.[16]
  • Thick-walled blood vessels -> think schwannoma.

DDx:

Images

www:

Morphologic subtypes

  • Many subtypes exist.[17]
  • 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.[18]
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.
Transitional meningioma
  • AKA mixed.
  • Common.
  • Lobular and fasicular growth patterns coexist.
  • Usu. a mixture of meningeothelial and fibromatous meningioma
Psammomatous meningioma

Microscopic:

  • Psammoma bodies dominate over tumor cells.
    • Irregular calcifications (confluent psammoma bodies).
  • Usually found in spinal cord.
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
Microcystic meningioma

Microscopic:

  • Cystic appearance.
  • Increased cytologic pleomorphism of the elongated cells.

DDx:

  • Clear cell meningioma
  • Hemangioblastoma
Secretory meningioma
  • Associated with brain edema; may have a worse outcome.

Microscopic:[19]

  • Eosinophilic intracytoplasmic inclusions that are CEA +ve and PAS +ve.

Molecular:

  • Combined KLF4 K409Q and TRAF7 mutations.[20]

DDx:

Images:

Lymphoplasmacyte-rich meningioma

Microscopic:

  • Lymphocytes.
  • Plasma cells.

Images:

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.

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.[22][23][24]

Images:

Clear cell meningioma

Epidemiology:

  • Usu. spinal cord.[25]

Microscopic:

  • Clear cells - contain glycogen (PAS +ve).

Molecular:

  • SMARCE1 mutations.[26]

Images:

Chordoid meningioma
  • Chordoma-like.

Microscopic:


Image:

Grade III

Papillary meningioma

Microscopic:

  • discohesive meningothelial tumour cells around a fibrovascular core.
  • perivascular pseudorosettes.
Rhabdoid meningioma

Microscopic:

  • Rhabdoid appearance (abundant cytoplasm).
    • Cross-striations.

www:

Other morphological variants

These are currently not listed in the WHO as separate entities.

  • Oncocytic.[27]
  • Whorling-sclerosing.[28]
  • Rosette-forming.[29]

Histologic grading

Grading:[17]

  • 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):
    1. Brain-invasive meningioma.
      • Invasion of meningioma into brain.
        • Meninogioma with entraped GFAP +ve tissue.
    2. 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:
        1. Sheeting architecture.
        2. High NC ratio clusters; clusters of "lymphocyte-like" cells.
        3. Hypercellularity.
        4. Macronucleoli.
        5. Necrosis not caused by treatment, e.g. radiation or embolization.
    3. 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.[30]
  • Other CKs usually -ve.

Molecular

Non-syndromal meningiomas may show SMO and AKT mutations.[31]

Several inherited diseases are associated with meningiomas:

Methylation profiling distinguishes two major groups with six distinct clinically relevant methylation classes.[36]


DDx of meningioma & IHC[37]

A standard work-up

  • Ki-67 >5-10% - predicts re-occurrence.[40]
  • PR (progesterone receptor) +ve in > 80% of meningiomas.[41]
    • Loss of PR staining predicts recurrence.
    • Strong association with tumour grade:[42]
      • Low WHO grade tumours usu. +ve.
      • High WHO grade tumours usu. -ve.

See also

References

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  2. Baldi, I.; Engelhardt, J.; Bonnet, C.; Bauchet, L.; Berteaud, E.; Grüber, A.; Loiseau, H. (Sep 2014). "Epidemiology of meningiomas.". Neurochirurgie. doi:10.1016/j.neuchi.2014.05.006. PMID 25249493.
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  5. Sahm, F.; Schrimpf, D.; Olar, A.; Koelsche, C.; Reuss, D.; Bissel, J.; Kratz, A.; Capper, D. et al. (May 2016). "TERT Promoter Mutations and Risk of Recurrence in Meningioma.". J Natl Cancer Inst 108 (5). doi:10.1093/jnci/djv377. PMID 26668184.
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