Surgical Neuropathology in
the Community Hospital
Randall K McGivney D.O. FCAP MBA
Chair, Department of Pathology and Labo...
Grading Systems and
Classifications (WHO 2000/2007)
 Grade I – Benign
 Grade II – Low Grade
 Grade IIII – Anaplastic
 ...
Approach to Brain Biopsies
 Routine H&E
 Clinical History and Imaging
 Immunohistochemistry
 Lineage (Epithelial, Glia...
Call from the FS suite
 Where is the tumor
 Look at the Imaging studies or get the
report
 How old is the patient
 Pri...
Histologic Patterns
 Parenchymal and Cellularity (is it hypercellular)
 Is the mass discrete
 Solid or infiltrative
 I...
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)
 Pleomorp...
Astrocytomas
 Account for 60% of all brain tumors with 5-
7 per 100,000 new cases each year
(increasing in numbers) Men s...
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 Guid...
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, Oligo...
Can send for Molecular Tests
 Astrocytoma
 Trisomy 7
 EGF-R
 MGMT Methylation
 Loss of chromosome
10
 Oligodendrogli...
Prognosis
 Grade
 Grade II 4-7 years
 Grade III 2-4 years
 Grade IV 6 months to a year
 Age
 Younger better
 Perfor...
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
...
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 s...
Tuberous Sclerosis Complex
 Major Criteria
 SEGA
 Cortical tuber
 Subependymal Nodule
 Facial Angiofibromas
 Periung...
Tumors in the Lateral Ventricle or
Foramen of Monro
 Central Neurocytoma
 Subependymoma
 Germinoma
 Choroid Plexus Tum...
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 sp...
Ependymoma
 6-8% of all CNS tumors
 2/3 are in the posterior fossa, 4h ventricle
 3rd
most common brain tumor in childr...
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 m...
Differential Diagnosis of
Ependymoma
 Posterior Fossa
 Medulloblastoma and Pilocytic Astrocytoma
 Spinal Cord
 Hemangi...
Subependymoma
 4th
Ventricle, Lateral Ventricle and Spinal
Cord
 Elderly
 Circumscribed and Low Grade (WHO I)
 Low Cel...
Subependymoma
Astroblastoma
Schwannoma
Hemangioblastoma
Hemangioblastoma
 Posterior Fossa in Adults
 Discrete Mass
 75% Sporadic and 25%
von Hippel Lindau
 Reticulin+, Glycog...
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
 Smal...
Atypical Meningioma (WHO II)
Anaplastic Meningioma
(Malignant WHO III)
 Excessive mitotic rate
>20/10 hpf
 Sarcoma carcinoma
or melanoma like
histolo...
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 Cel...
Medulloblastoma/PNET (WHO IV)
 Medulloblastoma
 Classic
 Desmoplastic
 Nodular
 Cerebellar Neuroblastoma
 Large Cell...
Medulloblastoma
 Children – young adults
 Aggressive natural history
 CSF seeding
 5 year survival 60-70%
with therapy...
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...
Surgical Neuropathology in the Community Hospital
Surgical Neuropathology in the Community Hospital
Surgical Neuropathology in the Community Hospital
Surgical Neuropathology in the Community Hospital
Surgical Neuropathology in the Community Hospital
Surgical Neuropathology in the Community Hospital
Surgical Neuropathology in the Community Hospital
Surgical Neuropathology in the Community Hospital
Surgical Neuropathology in the Community Hospital
Surgical Neuropathology in the Community Hospital
Surgical Neuropathology in the Community Hospital
Surgical Neuropathology in the Community Hospital
Surgical Neuropathology in the Community Hospital
Surgical Neuropathology in the Community Hospital
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Surgical Neuropathology in the Community Hospital

  1. 1. 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
  2. 2. Grading Systems and Classifications (WHO 2000/2007)  Grade I – Benign  Grade II – Low Grade  Grade IIII – Anaplastic  Grade IV – High Grade Malignant
  3. 3. 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)
  4. 4. 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
  5. 5. 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
  6. 6. Normal Hypercellular - Glioma
  7. 7. Crush Smears
  8. 8. Imaging
  9. 9. Infiltrating Fibrillary Astrocytoma WHO grade II Crush Prep of Grade II
  10. 10. 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
  11. 11. 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
  12. 12. Image of Grade II
  13. 13. Image of Grade III
  14. 14. Image of Grade IV
  15. 15. 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%
  16. 16. Grade I Pilocytic Astrocytoma cerebellum in a child
  17. 17. Protoplasmic Astrocytoma Grade II
  18. 18. Gemistocytic Astrocytoma, Grade II
  19. 19. GFAP
  20. 20. 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
  21. 21. Can send for Molecular Tests  Astrocytoma  Trisomy 7  EGF-R  MGMT Methylation  Loss of chromosome 10  Oligodendroglioma  1p/19q  P16 (CDKNA)
  22. 22. 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
  23. 23. Giant Cell Astrocytoma
  24. 24. Small Cell Astrocytoma
  25. 25. Small Cell GBM (WHO Grade IV)  GFAP +  MIB 1 High  Aggressive variant must rule out an Oligodendroglioma
  26. 26. Oligodendroglioma
  27. 27. 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
  28. 28. Anaplastic Oligodendroglioma
  29. 29. Oligodendroglioma with Neurocytic Differentiation
  30. 30. Subependymal Giant Cell Astrocytoma (SEGA)
  31. 31. S100 GFAP 20XCT
  32. 32. 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
  33. 33. 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
  34. 34. Tumors in the Lateral Ventricle or Foramen of Monro  Central Neurocytoma  Subependymoma  Germinoma  Choroid Plexus Tumors  Meningioma
  35. 35. SEGA  Complete Surgical Excision  Can recur  Not usually treated with chemo and radiation
  36. 36. 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
  37. 37. 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
  38. 38. Myxopapillary ependymoma, Grade I
  39. 39. Gross of Ependymoma
  40. 40. Ependymoma Grade II
  41. 41. Anaplastic Ependymoma
  42. 42. Anaplastic Ependymoma GFAP S-100
  43. 43. 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
  44. 44. Differential Diagnosis of Ependymoma  Posterior Fossa  Medulloblastoma and Pilocytic Astrocytoma  Spinal Cord  Hemangioblastoma, Glioma, Pilocystic  Filum Terminale  Paraganglioma, Lipoma and Schwannoma
  45. 45. Subependymoma  4th Ventricle, Lateral Ventricle and Spinal Cord  Elderly  Circumscribed and Low Grade (WHO I)  Low Cellularity  Microcysts
  46. 46. Subependymoma
  47. 47. Astroblastoma
  48. 48. Schwannoma
  49. 49. Hemangioblastoma
  50. 50. 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+/-
  51. 51. Meningioma  Meningioma (WHO I)  Atypical (WHO II)  Anaplastic - Malignant (WHO III)
  52. 52. Prognostic Variables in Meningioma  Extent of surgical resection  Histologic Grade  Age  Gender  Location
  53. 53. Atypical Meningioma (WHO II)  High Mitotic Rate >4/10 hpf  At least 3 of the following  Sheeting  Macronucleoli  Small Cells  Hypercellularity  Necrosis  Brian invasion
  54. 54. Atypical Meningioma (WHO II)
  55. 55. Anaplastic Meningioma (Malignant WHO III)  Excessive mitotic rate >20/10 hpf  Sarcoma carcinoma or melanoma like histology
  56. 56. Papillary Meningioma (WHO III)
  57. 57. Chordoid Meningioma (WHO II)
  58. 58. Chordoid Meningioma (WHO II)
  59. 59. Predisposition  Neurofibromatosis 2 (NF2)  Radiation  Trauma (maybe)  Syndromes  Cowden’s  Gorlin’s Nevoid Basal Cell  Li Fraumeni  Turcot/Gardner  VHL
  60. 60. 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
  61. 61. 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
  62. 62. Desmoplastic Medulloblastoma
  63. 63. Large Cell Anaplastic Medulloblastoma
  64. 64. Cerebellar Lipo neurocytoma
  65. 65. Cerebellar Lipo neurocytoma WHO II
  66. 66. Central Neurocytoma WHO II  Central Mass near foramen of Monro discrete central mass  Hydrocephalus causes symptoms
  67. 67. Central Neurocytoma WHO II Synaptophysin
  68. 68. 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

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