Surgical Neuropathology in the Community Hospital

Randall K McGivney D.O. FCAP MBA Chair, Department of Pathology and Laboratory Sciences

MacNeal and Weiss Hospitals Medical Director, Genesis Clinical Laboratory

Grading Systems and Classifications (WHO 2000/2007)

Grade I – Benign Grade II – Low Grade Grade IIII – Anaplastic Grade IV – High Grade Malignant

Approach to Brain Biopsies

Routine H&E Clinical History and Imaging Immunohistochemistry

Lineage (Epithelial, Glial, Meningothelial, Neural or Neuronal)

Proliferation (MIB-1) Molecular (EGFR, p53 etc…)

EM still helpful in CNS but … Molecular Studies (FISH)

Call from the FS suite

Where is the tumor Look at the Imaging studies or get the

report How old is the patient Primary Histologic Appearance on H&E Frozen Section and/or Intraoperative

Crush Smears

Histologic Patterns

Parenchymal and Cellularity (is it hypercellular) Is the mass discrete Solid or infiltrative Is it centered around vessels Is it extra – axial Does it infiltrate the meninges Is it destructive and necrotic Is subtle or does it look normal

Normal Hypercellular - Glioma

Crush Smears

Imaging

Infiltrating Fibrillary Astrocytoma WHO grade II

Crush Prep of Grade II

Who Grading of Astrocytic Tumors

Grade I Pilocytic Astrocytoma Subependymal Giant Cell Astrocytoma (SEGA) Pleomorphic Xanthoastrocytoma (PXA)

Grade II Infiltrating Diffuse Astrocytoma

Grade III Anaplastic Astrocytoma

Grade IV Glioblastoma

Astrocytomas

Account for 60% of all brain tumors with 5-7 per 100,000 new cases each year (increasing in numbers) Men slightly more often than woman

Grade II – 5% usually between 20-45 Grade III – 10% usually between 20-60 Grade IV – 85% usually older 45-70

Image of Grade II

Image of Grade III

Image of Grade IV

MIB – (Ki-67) Proliferation Index

Nuclear Proteins in proliferation phases (G1, G2 and M)

Often asked for Rough Guidelines

Grade II 1-4% Grade III 3-15% Grade IV 8-30%

Grade I Pilocytic Astrocytoma cerebellum in a child

Protoplasmic Astrocytoma Grade II

Gemistocytic Astrocytoma, Grade II

GFAP

GFAP

Astrocytomas Oligodendrogliomas Reactive Brain GFAP is not very helpful in distinguishing

Astrocytomas, Oligodendrogliomas or Reactive Gliosis

Maybe p53 50-60% positivity in low grade astrocytomas but ~ 10% in Oligodendrogliomas

Can send for Molecular Tests

Astrocytoma Trisomy 7 EGF-R MGMT Methylation Loss of chromosome

10

Oligodendroglioma 1p/19q P16 (CDKNA)

Prognosis

Grade Grade II 4-7 years Grade III 2-4 years Grade IV 6 months to a year

Age Younger better

Performance Status Resection

Giant Cell Astrocytoma

Small Cell Astrocytoma

Small Cell GBM (WHO Grade IV)

GFAP + MIB 1 High Aggressive variant

must rule out an Oligodendroglioma

Oligodendroglioma

Oligodendroglioma

30-40 years old Seizures Frontal Lobe Slow growing Survival at 10 years

Grade II ~ 10 years Grade III 2-5 years

5-25% of Gliomas

Anaplastic Oligodendroglioma

Oligodendroglioma with Neurocytic Differentiation

Subependymal Giant Cell Astrocytoma (SEGA)

S100 GFAP

20XCT

SEGA

Low Grade (WHO grade I) Associated with Tuberous Sclerosis

1/5000 SEGA occur in 5-15% of people with tuberous sclerosus

Slow growing in mass in the lateral ventricle

2-30 years ~13 years

Tuberous Sclerosis Complex

Major Criteria SEGA Cortical tuber Subependymal Nodule Facial Angiofibromas Periungual Fibromas Hypomelanotic Macules Shagreen Patch Retinal Hamartomas Cardiac Rhabdomyomas Lymphangiomyomatosis Renal Angiomyolipoma

Minor Criteria Multiple Dermal enamel Pits Hamartomatous Rectal

Polyps Bone Cysts Gingival Fibromas Non renal hamartomas Retinal achromic patch Confetti skin Multiple Renal Cysts White Matter radial

migration lines

Tumors in the Lateral Ventricle or Foramen of Monro

Central Neurocytoma Subependymoma Germinoma Choroid Plexus Tumors Meningioma

SEGA

Complete Surgical Excision Can recur Not usually treated with chemo and

radiation

Ependymoma

Tumor in children and young adults originate in the walls of the cerebral or posterior fossa ventricles or spinal canal Subependymoma, WHO Grade I Myxopapillary Ependymoma, WHO Grade I Ependymoma, WHO Grade II Anaplastic Ependymoma, WHO Grade III

Ependymoma

6-8% of all CNS tumors 2/3 are in the posterior fossa, 4h ventricle 3rd most common brain tumor in children 50% of them occur in the first 2 decades 30% occur in children less than 3 years Most frequent neuroepithelial tumor in the

spinal cord

Myxopapillary ependymoma, Grade I

Gross of Ependymoma

Ependymoma Grade II

Anaplastic Ependymoma

Anaplastic Ependymoma

GFAP S-100

Grading of Ependymomas

Poor Outcomes Hypercellularity Vascular Proliferation Mitoses >4/10 hpf Necrosis

2 or more – Anaplastic Ependymoma Ho, et al Journal of Neuro-Oncology 2001, 5:77

Differential Diagnosis of Ependymoma

Posterior Fossa Medulloblastoma and Pilocytic Astrocytoma

Spinal Cord Hemangioblastoma, Glioma, Pilocystic

Filum Terminale Paraganglioma, Lipoma and Schwannoma

Subependymoma

4th Ventricle, Lateral Ventricle and Spinal Cord

Elderly Circumscribed and Low Grade (WHO I) Low Cellularity Microcysts

Subependymoma

Astroblastoma

Schwannoma

Hemangioblastoma

Hemangioblastoma

Posterior Fossa in Adults Discrete Mass 75% Sporadic and 25%

von Hippel Lindau Reticulin+, Glycogen+,

Fat+, Inhibin+, S100+, NSE+, CD10-, Cytokeratin -, EMA- and GFAP+/-

Meningioma

Meningioma (WHO I) Atypical (WHO II) Anaplastic - Malignant

(WHO III)

Prognostic Variables in Meningioma

Extent of surgical resection

Histologic Grade Age Gender Location

Atypical Meningioma (WHO II)

High Mitotic Rate >4/10 hpf

At least 3 of the following Sheeting Macronucleoli Small Cells Hypercellularity Necrosis

Brian invasion

Atypical Meningioma (WHO II)

Anaplastic Meningioma (Malignant WHO III)

Excessive mitotic rate >20/10 hpf

Sarcoma carcinoma or melanoma like histology

Papillary Meningioma (WHO III)

Chordoid Meningioma (WHO II)

Chordoid Meningioma (WHO II)

Predisposition

Neurofibromatosis 2 (NF2) Radiation Trauma (maybe) Syndromes

Cowden’s Gorlin’s Nevoid Basal Cell Li Fraumeni Turcot/Gardner VHL

Medulloblastoma/PNET (WHO IV)

Medulloblastoma Classic Desmoplastic Nodular Cerebellar Neuroblastoma Large Cell Anaplastic Medullomyoblastoma Melanotic

Medullo(neuro)-epithelioma Ependymoblastoma Pineoblastoma Supratentorial PNET

Neuroblastoma Ganglioneuroblastoma

Atypical Teratoid/Rhabdoid tumor

Medulloblastoma

Children – young adults Aggressive natural

history CSF seeding 5 year survival 60-70%

with therapy Radiation helps but

detrimental to native CNS Favorable and

unfavorable variants

Desmoplastic Medulloblastoma

Large Cell Anaplastic Medulloblastoma

Cerebellar Lipo neurocytoma

Cerebellar Lipo neurocytoma WHO II

Central Neurocytoma WHO II

Central Mass near foramen of Monro discrete central mass

Hydrocephalus causes symptoms

Central Neurocytoma WHO II

Synaptophysin

Neurocytoma

Can have Extra-ventricular Neurocytoma Neuronal markers Positive

Synaptophysin, NSE, MAP-2, Chromogranin Usually central low grade near foramen of

Monro Favorable differentiate from Oligodendroglioma,

Clear Cell Ependymoma and Cerebellar Lipo neurocytoma