This document summarizes an educational course on diagnostic issues in surgical neuropathology. It provides an overview of common intraoperative consultation procedures, techniques, and considerations. It then reviews diagnostic criteria, differentials, and clinical details for several common neuropathological lesions encountered during surgery, including oligodendroglioma, primary CNS lymphoma, demyelinating lesions, and medulloblastoma. The goal of the course is to help participants develop skills in intraoperative consultation, diagnosis, and differential development.

1. ASCP Course 1301: Diagnostic Issues in Surgical Neuropathology

2. Mark L. Cohen, M.D.

3. Richard A. Prayson, M.D. CLEVELAND CLINIC FOUNDATION

7. Intraoperative consultation: Gross examination

8. Cardinal ordinances of neuropathologic IOC NEVER Process all of the abnormal appearing tissue ALWAYS Include portions of the softest, darkest regions of the specimen

10. Who cares what you like? What do other neuropathologists do?

11. 92 Neuropathologists (from 14 countries) prefer: J Neurosurg 1999;91:454 90% H&E stain 1/3 Touch prep 2/3 Crush/Smear Cytologic method 70% Both FS & cytology 10% Cytology only 20% Frozen only

12. The middle path

13. IOC: Diagnostic Algorithm The tissue is Abnormal Normal Non-neoplastic Get more tissue Neoplastic Representative? Tumor type Tumor grade

14. IOC: Common Pathologic Diagnoses 5 Inflammatory 5 Abscess 5 CNS lymphoma 15 Meningioma 15 Metastatic carcinoma 15 Low-grade glioma 40 High-grade glioma Percentage of cases Diagnosis

16. Meningioma

17. Astrocytoma (WHO II)

18. Recurrent glioma (post-radiation)

19. Pilocytic astrocytoma

20. Myxopapillary ependymoma

21. Oligodendro- glioma

22. Lymphoma

23. Demyelination

24. Medulloblastoma

25. Off to the cases… Heeeerrrs Richard!!

26. Case 6: Oligodendroglioma (WHO II) These slowly growing neoplasms often manifest after several years of preoperative epileptic seizures and have a favorable prognosis regarding time till recurrence

28. Oligodendroglioma: Initial Clues Low “P/C” ratio Arcuate vasculature

29. Subpial spread Perineuronal satellitosis

30. Band-like cortical calcifications

31. “ Germinal centers”

32. Minigemistocytes

33. Perinuclear halos (fried-eggs)

34. What is an oligodendroglioma? L I G O S Astrocytomas

35. Neurocytoma Clear cell ependymoma Dysembryoplastic neuroepithelial tumor

36. Central neurocytoma

37. Neuropil islands Synaptophysin positive

38. Dysembryoplastic Neuroepithelial Tumor

39. Absence of satellitosis

40. Clear Cell Ependymoma

41. IHC in clear cell gliomas Positive Negative +/- Vimentin Positive Negative Weak EMA Rare Strong Rare Neu-N Rare Strong Weak Synapto Weak Rare +/- GFAP Clear cell ependymoma Neurocytoma Oligodendro- glioma Antigen

42. Molecular diagnosis of clear cell gliomas Human Pathology, 2004

43. Anaplastic oligodendroglioma (WHO III) Some tumors may develop histological features commonly found in glioblastomas..

44. Molecular subtyping of histologically-defined AOs 1.5 6 6 > 10 Survival (years) 18% 33% 100% 100% Response rate Temporal Ring-enhanced Temporal Ring-enhanced Frontal Parietal Frontal Parietal Imaging 1p intact Other (e.g. EGFR amp) 1p intact P53 mutation 1p loss other 1p/19q loss only Molecular genetics

45. Small cell glioblastoma Pleomorphic nuclei Brisk mitotic rate Pseudopallisading

49. Supratentorial, periventricular, often multiple Meningeal, ocular disease in ~20%

50. Modest peritumoral edema Marked response to steroids

51. Primary CNS Lymphoma: Intraoperative Consultation Smear Crush

52. Pre-operative steroids = “Ghost tumor”

53. Angiocentric & angioinvasive

54. “ Reticulin cell sarcoma”

55. No Satellitosis

58. Hen’s teeth: Metastatic DLBCL

59. Primary dural lymphoma

60. Intravascular lymphomatosis

61. Case 8: Tumor-like demyelinating lesion

62. Worrisome feature #1: Hypercellularity

63. Worrisome feature #2: Pleomorphism

64. Worrisome feature #3: Mitoses

65. Worrisome feature #4: Microvascular proliferation

66. Worrisome feature #5: Degeneration

67. Helpful feature #1: Inflammation

68. Helpful feature #2: Low N/C ratios

69. Helpful feature #3: Demarcation

70. Helpful feature #4: Xanthomatous histiocytes

71. Helpful features #5: Creutzfeldt astrocytes

72. Differential Diagnosis: Glioma

73. Differential Diagnosis: Liquefactive necrosis

74. Differential Diagnosis: Progressive multifocal leukoencephalopathy

75. TLDL: Immunohistochemistry Anti-CD68 Anti-GFAP

77. Case 9: Medulloblastoma A malignant, invasive embyonal tumor of the cerebellum with preferential manifestation in children, predominant neuronal differentiation, and an inherent tendency to metastasize via CSF pathways

78. Medulloblastoma vs. PNET

80. “ Classic” medulloblastoma (60%) 5-year, event-free survival = 80%

81. Desmoplastic medulloblastoma (10%) Anti-synaptophysin Reticulin-free “pale islands” NBCCS/PTCH

82. Medulloblastoma with extensive nodularity (< 5%) Predominantly < 3 years of age

83. Large cell/anaplastic medulloblastoma (25%) Moderate anaplasia (15%) Severe anaplasia (10%) 5-year survival = 65% 5-year survival = 50%

86. References

87. References

88. References