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