Difference between revisions of "Meningioma"

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*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>
*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>
*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===
===Prognosis===
*Most are benign - usu. a good prognosis.
*Most are benign - usu. a good prognosis.
**May be malignant - bad 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===
===Genetics===
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*+/-Hyperostosis.
*+/-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>
**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==
==Microscopic==
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Image:Meningioma_-_brain_invasion_-_intermed_mag.jpg | Meningioma with brain invasion - 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)
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>
</gallery>
www:
www:
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<gallery>
<gallery>
File:Psammomatous_meningioma.jpg | Numerous psammoma bodies (WC/jensflorian)
File:Psammomatous_meningioma.jpg | Numerous psammoma bodies (WC/jensflorian)
File:NP psammomatous meningioma 0002.jpg | Psammomatous meningioma after EDTA treatment (WC)
</gallery>
</gallery>


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=====Metaplastic meningioma=====
=====Metaplastic meningioma=====
*Much talked about... but very rare.
*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:  
Microscopic:  
*Cartilage or bone formation.
*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====
====Grade II====
=====Brain invasive meningioma=====  
=====Brain invasive meningioma=====  
*Invades the brain.
*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:
Images:
*[http://moon.ouhsc.edu/kfung/jty1/Composites/FNA0IE18-Meningioma-Invasion.htm Meningioma with brain invasion (ouhsc.edu)].
*[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=====
=====Clear cell meningioma=====
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*[http://path.upmc.edu/cases/case373.html Rhabdoid meningioma - case 1 - several images (upmc.edu)].
*[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)].
*[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===
===Histologic grading===
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==IHC==
==IHC==
*EMA +ve.<ref name=Ref_PSNP13>{{Ref PSNP|13}}</ref>
*EMA +ve (approx. 90%).<ref name=Ref_PSNP13>{{Ref PSNP|13}}</ref>
*Other CKs usually -ve.
*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==
==Molecular==
Non-syndromal meningiomas may show SMO and AKT mutations.<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>
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:
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>
*[[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>
*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>
*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>===
===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 +ve - [[schwannoma]].
*S-100 strong +ve - [[schwannoma]].
**+ve in ~80% of fibrous meningiomas.
**+ve in ~80% of fibrous meningiomas.
*CD34 +ve - [[solitary fibrous tumour]].
*CD34 +ve - [[solitary fibrous tumour]].
**+ve in ~60% of [[fibrous meningioma]]s.
**+ve in ~60% of [[fibrous meningioma]]s.
*STAT6 nuclear +ve: [[solitary fibrous tumour]].
*STAT6 nuclear +ve: [[solitary fibrous tumour]].
*[[EMA]] +ve in ~30% of hemangiopericytoma.
*[[EMA]] +ve in ~30% of [[solitary fibrous tumour]]/[[hemangiopericytoma]].
*Claudin-1 - new kid on the block: +ve in meningioma, but low [[sensitivity]].
*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>
* 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]]
* [[Pulmonary meningothelial-like nodule]]

Latest revision as of 14:13, 19 September 2022

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]

  • Sphenoid wing meningioma (WC/Hellerhoff)

  • Brain displacement by meningioma (AFIP)

  • Macroscopy (Всеволод Лучанский (vvray))

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

  • Meningioma - high mag. (WC)

  • Meningioma - intermed. mag. (WC)

  • Meningioma with brain invasion - intermed. mag. (WC)

  • Meningioma with brain invasion - high mag. (WC)

  • Whorls in meningioma. (WC)

  • Whorls in meningioma. (WC)

  • Meningioma annotated. (WC)

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]

  • Syncytial appearance, whorl formations (WC/jensflorian)

  • Psammoma body (WC/Netha Hussain)

  • Onion bulb formation in smear (WC/jensflorian)

  • Meningioma HPS stain (WC/Nephron)

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.

  • Fibrous meingioma (WC)

  • EMA staining (WC/marvin 101)

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

  • Low power (WC/KGH)

  • Intermed magnification (WC/KGH)

  • Mitosis in a transitional meningioma (WC/jensflorian)

Psammomatous meningioma

Microscopic:

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

  • Numerous psammoma bodies (WC/jensflorian)

  • Psammomatous meningioma after EDTA treatment (WC)

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

  • Angiomatous meningioma (WC/jensflorian)

Microcystic meningioma

Microscopic:

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

DDx:

  • Clear cell meningioma
  • Hemangioblastoma

  • Microcyts (WC/jensflorian)

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:

  • Secretory granules (WC/jensflorian)

  • PAS-positive secretory granules (WC/jensflorian)

  • Smear with secretory granules (WC/jensflorian)

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.

  • Ossified meningioma, HE stain. (WC/jensflorian)

  • Metaplastic meningioma with xanthomatous changes. (WC/jensflorian)

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:

  • Finger-like protrusions, HE (WC/jensflorian)

  • Brain invasive meningooma (WC/Nephron)

Clear cell meningioma

Epidemiology:

  • Usu. spinal cord.[25]

Microscopic:

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

  • Clear cell meningioma, HE (WC/jensflorian)

Molecular:

  • SMARCE1 mutations.[26]

Images:

Chordoid meningioma
  • Chordoma-like.

Microscopic:

  • Chordoid meningioma - HE (WC/jensflorian)

  • Chordoid meningioma - alcian blue (WC/jensflorian)


Image:

Grade III

Papillary meningioma

Microscopic:

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

  • Papillary meningioma (WC/jensflorian)

  • Papillary meningioma (WC)

Rhabdoid meningioma

Microscopic:

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

  • Rhabdoid meningioma. (WC/Marvin 101)

  • Frozen section (WC/jensflorian)

www:

Other morphological variants

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

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

  • Whorling-sclerosing features in meningioma (HE/jensflorian)

  • Meningioma with rosette-forming features (HE/jensflorian)

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 (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).

Molecular

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

References

  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: http://moon.ouhsc.edu/kfung/jty1/neurotest/Q13-Ans.htm. 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.
  9. ↑ Lee, CW.; Tan, TC. (Feb 2014). "Meningioma associated with Gorlin's syndrome.". J Clin Neurosci 21 (2): 349-50. doi:10.1016/j.jocn.2013.02.033. PMID 24100109.
  10. ↑ URL: http://path.upmc.edu/cases/case702.html. Accessed on: 2 February 2012.
  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.
  12. ↑ Wen, M.; Jung, S.; Moon, KS.; Pei, J.; Lee, KH.; Jin, SG.; Li, SY.; Ryu, HH. (Dec 2014). "Immunohistochemical profile of the dural tail in intracranial meningiomas.". Acta Neurochir (Wien) 156 (12): 2263-73. doi:10.1007/s00701-014-2216-4. PMID 25238986.
  13. ↑ Aoki, S.; Sasaki, Y.; Machida, T.; Tanioka, H.. "Contrast-enhanced MR images in patients with meningioma: importance of enhancement of the dura adjacent to the tumor.". AJNR Am J Neuroradiol 11 (5): 935-8. PMID 2120998.
  14. ↑ Qi, ST.; Liu, Y.; Pan, J.; Chotai, S.; Fang, LX. (Oct 2012). "A radiopathological classification of dural tail sign of meningiomas.". J Neurosurg 117 (4): 645-53. doi:10.3171/2012.6.JNS111987. PMID 22839654.
  15. ↑ Goyal, N.; Kakkar, A.; Sarkar, C.; Agrawal, D.. "Does bony hyperostosis in intracranial meningioma signify tumor invasion? A radio-pathologic study.". Neurol India 60 (1): 50-4. doi:10.4103/0028-3886.93589. PMID 22406780.
  16. ↑ URL: http://radiographics.rsna.org/content/23/3/785.long. Accessed on: 3 November 2010.
  17. ↑ 17.0 17.1 Perry, Arie; Brat, Daniel J. (2010). Practical Surgical Neuropathology: A Diagnostic Approach: A Volume in the Pattern Recognition series (1st ed.). Churchill Livingstone. pp. 194. ISBN 978-0443069826.
  18. ↑ Sahm, F.; Bissel, J.; Koelsche, C.; Schweizer, L.; Capper, D.; Reuss, D.; Böhmer, K.; Lass, U. et al. (Nov 2013). "AKT1E17K mutations cluster with meningothelial and transitional meningiomas and can be detected by SFRP1 immunohistochemistry.". Acta Neuropathol 126 (5): 757-62. doi:10.1007/s00401-013-1187-5. PMID 24096618.
  19. ↑ URL: http://moon.ouhsc.edu/kfung/jty1/Com04/Com405-1-Diss.htm. Accessed on: 12 October 2011.
  20. ↑ Reuss, DE.; Piro, RM.; Jones, DT.; Simon, M.; Ketter, R.; Kool, M.; Becker, A.; Sahm, F. et al. (Mar 2013). "Secretory meningiomas are defined by combined KLF4 K409Q and TRAF7 mutations.". Acta Neuropathol 125 (3): 351-8. doi:10.1007/s00401-013-1093-x. PMID 23404370.
  21. ↑ URL: http://moon.ouhsc.edu/kfung/jty1/Com04/Com405-1-Diss.htm. Accessed on: 3 January 2012.
  22. ↑ Baumgarten, P.; Gessler, F.; Schittenhelm, J.; Skardelly, M.; Tews, DS.; Senft, C.; Dunst, M.; Imoehl, L. et al. (Sep 2016). "Brain invasion in otherwise benign meningiomas does not predict tumor recurrence.". Acta Neuropathol 132 (3): 479-81. doi:10.1007/s00401-016-1598-1. PMID 27464983.
  23. ↑ Brokinkel, B.; Hess, K.; Mawrin, C. (Apr 2017). "Brain invasion in Meningiomas - Clinical considerations and impact of neuropathological evaluation: A systematic Review.". Neuro Oncol. doi:10.1093/neuonc/nox071. PMID 28419308.
  24. ↑ Pizem, J.; Velnar, T.; Prestor, B.; Mlakar, J.; Popovic, M.. "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.". Clin Neuropathol 33 (5): 354-63. doi:10.5414/NP300750. PMID 25034703.
  25. ↑ Perry, Arie; Brat, Daniel J. (2010). Practical Surgical Neuropathology: A Diagnostic Approach: A Volume in the Pattern Recognition series (1st ed.). Churchill Livingstone. pp. 200. ISBN 978-0443069826.
  26. ↑ Smith, MJ.; Wallace, AJ.; Bennett, C.; Hasselblatt, M.; Elert-Dobkowska, E.; Evans, LT.; Hickey, WF.; van Hoff, J. et al. (Dec 2014). "Germline SMARCE1 mutations predispose to both spinal and cranial clear cell meningiomas.". J Pathol 234 (4): 436-40. doi:10.1002/path.4427. PMID 25143307.
  27. ↑ Zunarelli, E.; Tallarico, E.; Valentini, A.; Maiorana, A. (2010). "Oncocytic meningioma: study of eight new cases and analysis of 13 reported cases.". Pathology 42 (6): 587-9. doi:10.3109/00313025.2010.508740. PMID 20854082.
  28. ↑ Haberler, C.; Jarius, C.; Lang, S.; Rössler, K.; Gruber, A.; Hainfellner, JA.; Budka, H. (Feb 2002). "Fibrous meningeal tumours with extensive non-calcifying collagenous whorls and glial fibrillary acidic protein expression: the whorling-sclerosing variant of meningioma.". Neuropathol Appl Neurobiol 28 (1): 42-7. PMID 11849562.
  29. ↑ Liverman, C.; Mafra, M.; Chuang, SS.; Shivane, A.; Chakrabarty, A.; Highley, R.; Hilton, DA.; Byrne, NP. et al. (Aug 2015). "A clinicopathologic study of 11 rosette-forming meningiomas: a rare and potentially confusing pattern.". Acta Neuropathol 130 (2): 311-3. doi:10.1007/s00401-015-1456-6. PMID 26106026.
  30. ↑ Perry, Arie; Brat, Daniel J. (2010). Practical Surgical Neuropathology: A Diagnostic Approach: A Volume in the Pattern Recognition series (1st ed.). Churchill Livingstone. pp. 13. ISBN 978-0443069826.
  31. ↑ "The prognostic role of the immunohistochemical expression of S100 in meningiomas". J Cancer Res Clin Oncol. July 2022. doi:10.1007/s00432-022-04186-9. PMID 35838837.
  32. ↑ "CD13 is a useful tool in the differential diagnosis of meningiomas with potential biological and prognostic implications". Virchows Arch 480 (6): 1223–1230. June 2022. doi:10.1007/s00428-022-03304-9. PMC 9184408. PMID 35212813. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9184408/.
  33. ↑ Clark, VE.; Erson-Omay, EZ.; Serin, A.; Yin, J.; Cotney, J.; Ozduman, K.; Avşar, T.; Li, J. et al. (Mar 2013). "Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO.". Science 339 (6123): 1077-80. doi:10.1126/science.1233009. PMID 23348505.
  34. ↑ "Single-cell DNA sequencing reveals order of mutational acquisition in TRAF7/AKT1 and TRAF7/KLF4 mutant meningiomas". Acta Neuropathol 144 (4): 799–802. October 2022. doi:10.1007/s00401-022-02485-6. PMID 35984495.
  35. ↑ "Intraventricular meningiomas frequently harbor NF2 mutations but lack common genetic alterations in TRAF7, AKT1, SMO, KLF4, PIK3CA, and TERT". Acta Neuropathol Commun 7 (1): 140. August 2019. doi:10.1186/s40478-019-0793-4. PMC 6716845. PMID 31470906. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6716845/.
  36. ↑ Fontaine, B.; Rouleau, GA.; Seizinger, BR.; Menon, AG.; Jewell, AF.; Martuza, RL.; Gusella, JF. (1991). "Molecular genetics of neurofibromatosis 2 and related tumors (acoustic neuroma and meningioma).". Ann N Y Acad Sci 615: 338-43. PMID 2039155.
  37. ↑ Smith, MJ.; O'Sullivan, J.; Bhaskar, SS.; Hadfield, KD.; Poke, G.; Caird, J.; Sharif, S.; Eccles, D. et al. (Mar 2013). "Loss-of-function mutations in SMARCE1 cause an inherited disorder of multiple spinal meningiomas.". Nat Genet 45 (3): 295-8. doi:10.1038/ng.2552. PMID 23377182.
  38. ↑ van den Munckhof, P.; Christiaans, I.; Kenter, SB.; Baas, F.; Hulsebos, TJ. (Feb 2012). "Germline SMARCB1 mutation predisposes to multiple meningiomas and schwannomas with preferential location of cranial meningiomas at the falx cerebri.". Neurogenetics 13 (1): 1-7. doi:10.1007/s10048-011-0300-y. PMID 22038540.
  39. ↑ Aavikko, M.; Li, SP.; Saarinen, S.; Alhopuro, P.; Kaasinen, E.; Morgunova, E.; Li, Y.; Vesanen, K. et al. (Sep 2012). "Loss of SUFU function in familial multiple meningioma.". Am J Hum Genet 91 (3): 520-6. doi:10.1016/j.ajhg.2012.07.015. PMID 22958902.
  40. ↑ Sievers, P.; Chiang, J.; Schrimpf, D.; Stichel, D.; Paramasivam, N.; Sill, M.; Gayden, T.; Casalini, B. et al. (Nov 2019). "YAP1-fusions in pediatric NF2-wildtype meningioma.". Acta Neuropathol. doi:10.1007/s00401-019-02095-9. PMID 31734728.
  41. ↑ Sahm, F.; Schrimpf, D.; Stichel, D.; Jones, DT.; Hielscher, T.; Schefzyk, S.; Okonechnikov, K.; Koelsche, C. et al. (Mar 2017). "DNA methylation-based classification and grading system for meningioma: a multicentre, retrospective analysis.". Lancet Oncol. doi:10.1016/S1470-2045(17)30155-9. PMID 28314689.
  42. ↑ Hahn HP, Bundock EA, Hornick JL (February 2006). "Immunohistochemical staining for claudin-1 can help distinguish meningiomas from histologic mimics". Am. J. Clin. Pathol. 125 (2): 203–8. doi:10.1309/G659-FVVB-MG7U-4RPQ. PMID 16393681. http://ajcp.ascpjournals.org/content/125/2/203.full.pdf.
  43. ↑ Agaimy, A.; Buslei, R.; Coras, R.; Rubin, BP.; Mentzel, T. (Jul 2014). "Comparative study of soft tissue perineurioma and meningioma using a five-marker immunohistochemical panel.". Histopathology 65 (1): 60-70. doi:10.1111/his.12366. PMID 24393170.
  44. ↑ Grunberg, SM. (1991). "The role of progesterone receptors in meningioma.". Cancer Treat Res 58: 127-37. PMID 1683782.
  45. ↑ Croul, SE. 8 November 2010.
  46. ↑ Takei, H.; Buckleair, LW.; Powell, SZ. (Feb 2008). "Immunohistochemical expression of apoptosis regulating proteins and sex hormone receptors in meningiomas.". Neuropathology 28 (1): 62-8. doi:10.1111/j.1440-1789.2007.00852.x. PMID 18021195.
  47. ↑ Tao, Y.; Liang, G.; Li, Z.; Wang, Y.; Wu, A.; Wang, H.; Lu, Y.; Liu, Z. et al. (May 2012). "Clinical features and immunohistochemical expression levels of androgen, estrogen, progesterone and Ki-67 receptors in relationship with gross-total resected meningiomas relapse.". Br J Neurosurg. doi:10.3109/02688697.2012.685780. PMID 22616825.
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