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