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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.



  • 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.


  • 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]


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


  • 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]


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.


  • May involute into benign sclerotic tissue.[16]
  • Thick-walled blood vessels -> think schwannoma.




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.


  • Syncytial, nuclear clearing (pseudoinclusions).
  • Whorls, Onion bulb formations.
  • Few psammoma bodies.


  • 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


  • 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.


  • Vascular malformatons
  • Hemangioblastoma
Microcystic meningioma


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


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


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


  • Combined KLF4 K409Q and TRAF7 mutations.[20]



Lymphoplasmacyte-rich meningioma


  • Lymphocytes.
  • Plasma cells.


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.


  • 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]


Clear cell meningioma


  • Usu. spinal cord.[25]


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


  • SMARCE1 mutations.[26]


Chordoid meningioma
  • Chordoma-like.



Grade III

Papillary meningioma


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


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


Other morphological variants

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

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

Histologic grading


  • 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.


  • Grade II soft criteria memory device HMNs: hypercellular, macronucleoli, NC ratio increased, necrosis, sheeting.


  • EMA +ve (approx. 90%).[30]
  • PR +ve (approx. 75%, expression decreases from grade I to III).
  • SSTR2A +ve (approx. 95%).
  • S100 variable (up to 35% cases, usually patchy).[31]
  • SOX10 -ve.
  • GFAP -ve.
  • CD34 usu. -ve (approx 8% cases positive).
  • CD13 +ve.[32]
  • Other CKs usually -ve (approx 6% cases positive, mostly secretory meningiomas).


Non-syndromal meningiomas may show AKT1/TRAF7, SMO, KLF4/TRAF7, and PIK3CA mutations (1/3 of cases).[33]

  • 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. [34]

Intraventricular meningiomas have NF2 mutations. [35]

Several inherited diseases are associated with meningiomas:

Methylation profiling distinguishes two major groups with six distinct clinically relevant methylation classes.[41]

DDx of meningioma & IHC[42]

A standard work-up

  • Ki-67 >5-10% - predicts re-occurrence.[45]
  • PR (progesterone receptor) +ve in > 80% of meningiomas.[46]
    • Loss of PR staining predicts recurrence.
    • Strong association with tumour grade:[47]
      • Low WHO grade tumours usu. +ve.
      • High WHO grade tumours usu. -ve.

See also


  1. Rogers, L.; Barani, I.; Chamberlain, M.; Kaley, TJ.; McDermott, M.; Raizer, J.; Schiff, D.; Weber, DC. et al. (Oct 2014). "Meningiomas: knowledge base, treatment outcomes, and uncertainties. A RANO review.". J Neurosurg: 1-20. doi:10.3171/2014.7.JNS131644. PMID 25343186.
  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.
  3. Wiemels, J.; Wrensch, M.; Claus, EB. (Sep 2010). "Epidemiology and etiology of meningioma.". J Neurooncol 99 (3): 307-14. doi:10.1007/s11060-010-0386-3. PMID 20821343.
  4. Shankar, GM.; Abedalthagafi, M.; Vaubel, RA.; Merrill, PH.; Nayyar, N.; Gill, CM.; Brewster, R.; Bi, WL. et al. (04 2017). "Germline and somatic BAP1 mutations in high-grade rhabdoid meningiomas.". Neuro Oncol 19 (4): 535-545. doi:10.1093/neuonc/now235. PMID 28170043.
  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.
  6. Katz, LM.; Hielscher, T.; Liechty, B.; Silverman, J.; Zagzag, D.; Sen, R.; Wu, P.; Golfinos, JG. et al. (Apr 2018). "Loss of histone H3K27me3 identifies a subset of meningiomas with increased risk of recurrence.". Acta Neuropathol. doi:10.1007/s00401-018-1844-9. PMID 29627952.
  7. URL: Accessed on: 26 October 2010.
  8. Kimonis, VE.; Mehta, SG.; Digiovanna, JJ.; Bale, SJ.; Pastakia, B.. "Radiological features in 82 patients with nevoid basal cell carcinoma (NBCC or Gorlin) syndrome.". Genet Med 6 (6): 495-502. doi:10.109701.GIM.0000145045.17711.1C. PMID 15545745.
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  11. Ikeda, D.; Chiocca, EA. (Oct 2012). "Editorial: dural tail sign.". J Neurosurg 117 (4): 643-4. doi:10.3171/2012.2.JNS12266. PMID 22839655.
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  16. URL: Accessed on: 3 November 2010.
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  19. URL: Accessed on: 12 October 2011.
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