Meningeal tumor pathology Define the role of mitotic activity in meningioma grading Discuss the effect of preoperative embolization on meningioma grading Name and grade the aggressive meningioma variants Why are CNS melanocytic tumors and supratentorial hemangioblastomas no longer classified as meningiomas? Compare the behavior of anaplastic meningiomas, hemangiopericytomas, and solitary fibrous tumors

“Meningioma cells recapitulate their lepidic function”

Epithelial Membrane Antigen (EMA)

Meningioma: Behavior ~90% are WHO Grade I Excellent 5-year survival 20% recur within 10 years (GTR) ~10% are “Atypical” (WHO Grade II) 5-year recurrence = 40%, mortality = 20% ~2% are “Anaplastic” (WHO Grade III ) median survival = 1.5 years

Meningioma: WHO I Variants Traditional Meningothelial, fibrous, transitional, psammomatous, angiomatous Deceptive Microcystic, metaplastic, secretory Questionable Lymphoplasmacyte-rich

Microcystic meningioma (FS: “Glioma”)

Metaplastic meningiomas

Secretory meningioma – may cause marked cerebral edema

Meningioma: Grading Atypical (WHO Grade II) Anaplastic (WHO Grade III) High mitotic index (>4/10hpfs) or 3 of 5: Architectural loss, hypercellularity, macronucleoli, small cell differentiation, necrosis or Brain invasion Anaplastic (WHO Grade III) Excessive mitotic activity (>20/10hpfs) or Loss of meningothelial differentiation (“sarcomatous, carcinomatous, or melanomatous differentiation”)

Atypical meningioma (WHO II) Hypercellularity Architectural loss (“sheeting”) N E C R O S I Small cell differentiation

Caveat emptor

WHO II – Brain Invasion

Not Brain Invasion

Meningioma: Grading Atypical (WHO Grade II) Anaplastic (WHO Grade III) High mitotic index (>4/10hpfs) or 3 of 5: Architectural loss, hypercellularity, macronucleoli, small cell differentiation, necrosis or Brain invasion Anaplastic (WHO Grade III) Excessive mitotic activity (>20/10hpfs) or Loss of meningothelial differentiation (“sarcomatous, carcinomatous, or melanomatous differentiation”)

Anaplastic menigioma

Aggressive meningioma variants WHO Grade II Chordoid meningioma Clear cell meningioma WHO Grade III Papillary meningioma Rhabdoid meningioma * The aggressive pattern should comprise >50% of the tumor volume

Chordoid meningioma

Clear cell menigioma

Clear cell v microcystic menigioma

Mengiomas with clear cells meningioma Microcystic Age Predilection Young adults Older Adults Typical location CP angle Spinal Convexity Histo- chemistry Intracellular glycogen Extracellular glycoprotein Behavior Aggressive Benign

Papillary meningioma

Rhabdoid meningioma

Ex-meningiomas Melanocytic meningioma Angioblastic meningioma Now Meningeal Melanocytoma Angioblastic meningioma Now Hemangioblastoma Hemangiopericytic meningioma Now Hemangiopericytoma, and maybe Solitary Fibrous Tumor

Meningeal melanocytoma

Immunocytochemistry Meningiomas EMA - positive S100 – positive in 10% HMB-45 - negative Melanocytomas EMA – negative S100 – positive HMB-45 – positive

Case History 25 year-old man with two months of headache following automobile accident, now with double vision Family and personal history of “moles and skin lesions” Left frontal lobe mass

Brat, DJ et al. Am J Surg Path 23: 745, 1999 CNS Melanocytic Tumors Melanocytoma Melanocytic tumor, ID Primary melanoma Metatstatic melanoma Tight nests >50% No Invasion Yes Epithelioid cells Rare Most Nucleoli Indistinct Prominent Mitoses 0-1/10hpf 1-3/10hpf 2-15/ 10hpf 7-35/ 10hpf Necrosis ~20% ~90% Brat, DJ et al. Am J Surg Path 23: 745, 1999

17-73 Mean = 51 53,67,68 15-71 Mean=43 2/3 spinal 1/3 ST, 1PF CNS Melanocytic Tumors Melanocytoma Melanotic tumor, ID Primary Malignant melanoma Age 17-73 Mean = 51 53,67,68 15-71 Mean=43 Location 2/3 spinal 1/3 ST, 1PF PF,conus, pineal ~equal dist: Spinal,PF,ST Recurrence None Poor f/u All STR 1/5 GTR* * 1 to 3 year follow-up

33 years later…

Cerebellar hemangioblastoma

Cerebellar & ST hemangioblastoma FS (“Glioma”)

Mengiomas with clear cells meningioma Microcystic Hemangio- blastoma Age Predilection Young adults Older Adults Depends on VHL status Typical location CP angle Spinal Convexity Cerebellum Histo- chemistry Intracellular glycogen Extracellular glycoprotein lipid Immunohisto- EMA + Inhibin -- EMA – Inhibin + Behavior Aggressive Benign

Hemangioblastoma: Anti-inhibin IHC

Meningeal hemangiopericytoma

Solitary fibrous tumor Anti-CD34 Anti-bcl2

HPC SFT Hyalinization Rare, Focal Diffuse Mitoses Common Rare EMA Negative CD34 Weak Strong Bcl-2 Recurrence (GTR) 80% None Metastasis 30% 5yr survival 70% 100%

Meningeal tumor pathology Define the role of mitotic activity in meningioma grading Discuss the effect of preoperative embolization on meningioma grading Name and grade the aggressive meningioma variants Why are CNS melanocytic tumors and supratentorial hemangioblastomas no longer classified as meningiomas? Compare the behavior of anaplastic meningiomas, hemangiopericytomas, and solitary fibrous tumors