surgical neuropathology in the community hospital
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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
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Grading Systems and Classifications (WHO 2000/2007)
Grade I – Benign Grade II – Low Grade Grade IIII – Anaplastic Grade IV – High Grade Malignant
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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)
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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
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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
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Normal Hypercellular - Glioma
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Crush Smears
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Imaging
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Infiltrating Fibrillary Astrocytoma WHO grade II
Crush Prep of Grade II
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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
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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
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Image of Grade II
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Image of Grade III
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Image of Grade IV
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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%
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Grade I Pilocytic Astrocytoma cerebellum in a child
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Protoplasmic Astrocytoma Grade II
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Gemistocytic Astrocytoma, Grade II
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GFAP
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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
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Can send for Molecular Tests
Astrocytoma Trisomy 7 EGF-R MGMT Methylation Loss of chromosome
10
Oligodendroglioma 1p/19q P16 (CDKNA)
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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
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Giant Cell Astrocytoma
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Small Cell Astrocytoma
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Small Cell GBM (WHO Grade IV)
GFAP + MIB 1 High Aggressive variant
must rule out an Oligodendroglioma
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Oligodendroglioma
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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
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Anaplastic Oligodendroglioma
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Oligodendroglioma with Neurocytic Differentiation
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Subependymal Giant Cell Astrocytoma (SEGA)
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S100 GFAP
20XCT
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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
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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
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Tumors in the Lateral Ventricle or Foramen of Monro
Central Neurocytoma Subependymoma Germinoma Choroid Plexus Tumors Meningioma
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SEGA
Complete Surgical Excision Can recur Not usually treated with chemo and
radiation
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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
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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
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Myxopapillary ependymoma, Grade I
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Gross of Ependymoma
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Ependymoma Grade II
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Anaplastic Ependymoma
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Anaplastic Ependymoma
GFAP S-100
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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
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Differential Diagnosis of Ependymoma
Posterior Fossa Medulloblastoma and Pilocytic Astrocytoma
Spinal Cord Hemangioblastoma, Glioma, Pilocystic
Filum Terminale Paraganglioma, Lipoma and Schwannoma
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Subependymoma
4th Ventricle, Lateral Ventricle and Spinal Cord
Elderly Circumscribed and Low Grade (WHO I) Low Cellularity Microcysts
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Subependymoma
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Astroblastoma
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Schwannoma
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Hemangioblastoma
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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+/-
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Meningioma
Meningioma (WHO I) Atypical (WHO II) Anaplastic - Malignant
(WHO III)
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Prognostic Variables in Meningioma
Extent of surgical resection
Histologic Grade Age Gender Location
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Atypical Meningioma (WHO II)
High Mitotic Rate >4/10 hpf
At least 3 of the following Sheeting Macronucleoli Small Cells Hypercellularity Necrosis
Brian invasion
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Atypical Meningioma (WHO II)
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Anaplastic Meningioma (Malignant WHO III)
Excessive mitotic rate >20/10 hpf
Sarcoma carcinoma or melanoma like histology
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Papillary Meningioma (WHO III)
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Chordoid Meningioma (WHO II)
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Chordoid Meningioma (WHO II)
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Predisposition
Neurofibromatosis 2 (NF2) Radiation Trauma (maybe) Syndromes
Cowden’s Gorlin’s Nevoid Basal Cell Li Fraumeni Turcot/Gardner VHL
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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
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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
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Desmoplastic Medulloblastoma
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Large Cell Anaplastic Medulloblastoma
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Cerebellar Lipo neurocytoma
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Cerebellar Lipo neurocytoma WHO II
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Central Neurocytoma WHO II
Central Mass near foramen of Monro discrete central mass
Hydrocephalus causes symptoms
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Central Neurocytoma WHO II
Synaptophysin
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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