meningiomas: current classification and molecular …
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MENINGIOMAS: CURRENT MENINGIOMAS: CURRENT CLASSIFICATION AND CLASSIFICATION AND
MOLECULAR FEATURESMOLECULAR FEATURES
Arie Perry, M.D.
ARACHNOIDAL CAP CELLSARACHNOIDAL CAP CELLS
Martin SchmidtVirchows Arch
170:429,1902
Yamashima T et. al. Mod Pathol, 1:224, 1988
PROPOSED FUNCTIONSPROPOSED FUNCTIONS
Structural Barrier with Cellular Wrapping/Ensheathing– Part of CNS-CSF and blood-CSF barriers– Part of choroid plexus stroma (tela choroidea)– Ensheath proximal portion of nerve roots
Conduit for CSF drainage/absorption– Help regulate intracranial pressure– Participate in CSF homeostasis
Production of collagen and ECM proteins (fibroblast-like)
Epithelial-like/Secretory Functions– Intercellular desmosomes and other junctions– Secrete major CSF proteins (e.g. prostaglandin D-synthase,
IGF-II, IGFBP-II, apo-E, 2-microglobulin, etc.)– Secrete glioneuronal differentiation and proliferation factors
Monocyte-like Functions
PROPOSED FUNCTIONSPROPOSED FUNCTIONS
y– HLA-DR expression– Participation in foreign-body reactions and meningeal
rheumatoid nodules
Trophic Support for Glial and Neuronal Cells Reactive Processes (e.g. meningothelial
hyperplasia)
MENINGIOMA (WHO I)MENINGIOMA (WHO I)
PROGNOSTIC VARIABLESPROGNOSTIC VARIABLES
Extent of surgical resectionHistologic grade Patient Age Patient Age Patient Gender Tumor location
(e.g. AVP)
REGIONAL MULTICENTRICITYREGIONAL MULTICENTRICITYBorovich B, Doron Y; J Neurosurg 64:58Borovich B, Doron Y; J Neurosurg 64:58--63, 198663, 1986
Radial dural strips in 14 meningiomas and 10 controls from convexity
Meningothelial nests only in meningiomasg y g Field effect? Explanation for unexpected recurrences
and multiple meningiomas
CLONALITY OF MULTIPLE MENINGIOMAS CLONALITY OF MULTIPLE MENINGIOMAS Stangl AP et al., J Neurosurg 86:853Stangl AP et al., J Neurosurg 86:853--58, 199758, 1997
35 meningiomas with NF2mutations derived from 10 patients
6/10 patients had clonal mutation in all 6/10 patients had clonal mutation in all tumors
?CSF spread (vs. intradural)
CLASSIFICATION/GRADING SCHEME: CLASSIFICATION/GRADING SCHEME: WHO 2007WHO 2007
WHO I = Benign WHO II = Atypicalyp WHO III = Anaplastic
MENINGIOMA GRADINGMENINGIOMA GRADING
Atypical (WHO II)– High mitotic index (≥4/10 HPF)– Presence of at least 3 of 5 variables: sheeting,
macronucleoli, small cells, hypercellularity, necrosis
Anaplastic (Malignant) (WHO III)– Excessive mitotic index (≥20/10 HPF)– Sarcoma, carcinoma, or melanoma-like histology
Perry A et al., Am J Surg Pathol 21: 1455, 1997Perry A et al., Cancer 85:2046, 1999
100100
9090
8080
7070
6060
5050 Anaplastic n = 23
Atypical, n = 156
Benign, n=464
RecurrenceRecurrence--free Survival in 643 Patientsfree Survival in 643 Patientswith Primary Meningiomawith Primary Meningioma
cen
tce
nt
5050
4040
3030
2020
1010
00
00 11 22 33 44 55 66 77 88 99 1010
p < 0.001
Anaplastic, n = 23
Pe
rcP
erc
100100
9090
8080
7070
6060
5050
Atypical, n = 156
Benign, n=464
Overall Survival in 643 PatientsOverall Survival in 643 Patientswith Primary Meningiomawith Primary Meningioma
cen
tce
nt
5050
4040
3030
2020
1010
00
00 11 22 33 44 55 66 77 88 99 1010
p < 0.001
Anaplastic, n = 23
Pe
rcP
erc
GRADE VS. GENDER/AGEGRADE VS. GENDER/AGEPerry A et al., Am J Surg Pathol 21: 1455, 1997Perry A et al., J Neuropathol Exp Neurol, 2001
WHO I WHO II/III
Male 68% 32%Female 88% 12%
Pediatric/NF2 40% 60%Adult/Sporadic 80% 20%
P<0.001
RUSSIAN SERIES: 271 MENINGIOMASRUSSIAN SERIES: 271 MENINGIOMAS
Korshunov A, et al., Int J Cancer 104:728, 2003
ATYPICAL MENINGIOMA (WHO II)ATYPICAL MENINGIOMA (WHO II)
BRAIN INVASIVE MENINGIOMABRAIN INVASIVE MENINGIOMA
GFAP
BRAIN INVASIVE MENINGIOMABRAIN INVASIVE MENINGIOMA
WHO 2007
CLEAR CELL MENINGIOMA (WHO II)CLEAR CELL MENINGIOMA (WHO II)
PAS
PASD
CHORDOID MENINGIOMA (WHO II)CHORDOID MENINGIOMA (WHO II) ANAPLASTIC MENINGIOMA (WHO III)ANAPLASTIC MENINGIOMA (WHO III)
p 6 mo.
Ki-67>20%
PAPILLARY MENINGIOMA (WHO III)PAPILLARY MENINGIOMA (WHO III)
RHABDOID MENINGIOMA (WHO III)RHABDOID MENINGIOMA (WHO III)
VIM
LYMPHOPLASMACYTELYMPHOPLASMACYTE--RICH MENINGIOMARICH MENINGIOMA
ONCOCYTIC MENINGIOMAONCOCYTIC MENINGIOMA
AMA
EMBOLIZED MENINGIOMASEMBOLIZED MENINGIOMAS