Successfully reported this slideshow.

Ascp08 Baltimore

1,444 views

Published on

  • Be the first to comment

  • Be the first to like this

Ascp08 Baltimore

  1. 1. ASCP Course 1301: Diagnostic Issues in Surgical Neuropathology
  2. 2. Mark L. Cohen, M.D.
  3. 3. Richard A. Prayson, M.D. CLEVELAND CLINIC FOUNDATION
  4. 4. Upon completion of this course, participants should be able to: <ul><li>Describe a rational approach to intraoperative neuropathologic consultation </li></ul><ul><li>Define diagnostic criteria for common surgically encountered neuropathologic lesions </li></ul><ul><li>Generate differential diagnoses for each of these neuropathologic entities </li></ul>
  5. 5. Intraoperative Consultation: What the surgeon wants to know <ul><li>Sampling adequacy </li></ul><ul><ul><li>For eventual diagnosis </li></ul></ul><ul><ul><li>For ancillary studies </li></ul></ul><ul><li>What operation to perform </li></ul><ul><li>Appropriate postoperative treatment </li></ul><ul><li>What to tell the family </li></ul><ul><li>WHAT IS IT ?!? </li></ul>
  6. 6. Intraoperative Consultation: What you should know <ul><li>Age </li></ul><ul><li>Location </li></ul><ul><li>History </li></ul><ul><li>Imaging characteristics </li></ul>
  7. 7. Intraoperative consultation: Gross examination
  8. 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
  9. 9. Smear or Freeze? <ul><li>Why I like smear preparations </li></ul><ul><li>Speed </li></ul><ul><li>Sampling </li></ul><ul><li>Simplicity </li></ul><ul><li>Cytology </li></ul><ul><li>Sterility </li></ul><ul><li>Why RAP likes frozen sections </li></ul><ul><li>Familiarity </li></ul><ul><li>Architecture </li></ul><ul><li>Evaluation time </li></ul>
  10. 10. Who cares what you like? What do other neuropathologists do?
  11. 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. 12. The middle path
  13. 13. IOC: Diagnostic Algorithm The tissue is Abnormal Normal Non-neoplastic Get more tissue Neoplastic Representative? Tumor type Tumor grade
  14. 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
  15. 15. Intraoperative Consultation: Thoughts on age(ing) <ul><li>Low-grade gliomas are sufficiently rare in middle-aged & elderly individuals that their apparent presence during intraoperative consultation is reason for concern </li></ul><ul><li>There are a significant number of low grade gliomas of childhood which appear malignant on first assessment - proceed with caution </li></ul>
  16. 16. Meningioma
  17. 17. Astrocytoma (WHO II)
  18. 18. Recurrent glioma (post-radiation)
  19. 19. Pilocytic astrocytoma
  20. 20. Myxopapillary ependymoma
  21. 21. Oligodendro- glioma
  22. 22. Lymphoma
  23. 23. Demyelination
  24. 24. Medulloblastoma
  25. 25. Off to the cases… Heeeerrrs Richard!!
  26. 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
  27. 27. Oligodendroglioma: Why Should I Care? <ul><li>Biologic Behavior </li></ul><ul><li>Grading: “Double Indemnity” </li></ul><ul><li>Molecular prognostication </li></ul>
  28. 28. Oligodendroglioma: Initial Clues Low “P/C” ratio Arcuate vasculature
  29. 29. Subpial spread Perineuronal satellitosis
  30. 30. Band-like cortical calcifications
  31. 31. “ Germinal centers”
  32. 32. Minigemistocytes
  33. 33. Perinuclear halos (fried-eggs)
  34. 34. What is an oligodendroglioma? L I G O S Astrocytomas
  35. 35. Neurocytoma Clear cell ependymoma Dysembryoplastic neuroepithelial tumor
  36. 36. Central neurocytoma
  37. 37. Neuropil islands Synaptophysin positive
  38. 38. Dysembryoplastic Neuroepithelial Tumor
  39. 39. Absence of satellitosis
  40. 40. Clear Cell Ependymoma
  41. 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. 42. Molecular diagnosis of clear cell gliomas Human Pathology, 2004
  43. 43. Anaplastic oligodendroglioma (WHO III) Some tumors may develop histological features commonly found in glioblastomas..
  44. 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. 45. Small cell glioblastoma Pleomorphic nuclei Brisk mitotic rate Pseudopallisading
  46. 46. Indications for genotyping <ul><li>Anaplastic oligodendrogliomas </li></ul><ul><ul><li>1q/19p loss is a positive prognostic indicator </li></ul></ul><ul><li>AO versus small cell GBM </li></ul><ul><ul><li>intact 1p + EGFR amplification = small cell GBM </li></ul></ul><ul><li>Grade II oligodendroglioma </li></ul><ul><ul><li>Confirmation of diagnosis, if 1p deleted (70%) </li></ul></ul>
  47. 47. Caveat emptor : All 1p deletions are not created equal <ul><li>Whole 1p deletion associated with whole 19q deletion </li></ul><ul><ul><li>Typical oligodendroglial morphology with good overall and progression free survival </li></ul></ul><ul><li>Distal 1p36 deletion associated with intact or completely absent chromosome 19 </li></ul><ul><ul><li>More frequently seen in astrocytic tumors, and characterizes a particularly aggressive group of gliomas </li></ul></ul><ul><li>FISH with 1p36 probe will not distinguish these two forms of 1p deletion </li></ul>
  48. 48. Case 7: Primary CNS Lymphoma (the 5% tumor) <ul><li>5% of primary intracranial neoplasms </li></ul><ul><ul><li>Median age = 55 </li></ul></ul><ul><li>5% of AIDS patients, usually late-stage </li></ul><ul><ul><li>3600-fold relative risk, median age = 40 </li></ul></ul><ul><li>5% of post-transplant patients </li></ul><ul><ul><li>50% confined to CNS </li></ul></ul><ul><li>5% of congenital immunodeficiencies </li></ul><ul><ul><li>Median age = 10 </li></ul></ul>
  49. 49. Supratentorial, periventricular, often multiple Meningeal, ocular disease in ~20%
  50. 50. Modest peritumoral edema Marked response to steroids
  51. 51. Primary CNS Lymphoma: Intraoperative Consultation Smear Crush
  52. 52. Pre-operative steroids = “Ghost tumor”
  53. 53. Angiocentric & angioinvasive
  54. 54. “ Reticulin cell sarcoma”
  55. 55. No Satellitosis
  56. 56. <ul><li>Subclassification and analysis of proliferative activity appears to be of no practical importance </li></ul>Anti-CD20
  57. 57. Primary CNS Lymphoma: Prognosis <ul><li>Excellent initial response rate </li></ul><ul><li>Cerebral recurrence is typical </li></ul><ul><li>Median survival (treated) </li></ul><ul><ul><li>4 months (including AIDS) </li></ul></ul><ul><ul><li>9 months (immunocompetent) </li></ul></ul><ul><ul><li>2 years (tertiary care/clinical trials) </li></ul></ul>
  58. 58. Hen’s teeth: Metastatic DLBCL
  59. 59. Primary dural lymphoma
  60. 60. Intravascular lymphomatosis
  61. 61. Case 8: Tumor-like demyelinating lesion
  62. 62. Worrisome feature #1: Hypercellularity
  63. 63. Worrisome feature #2: Pleomorphism
  64. 64. Worrisome feature #3: Mitoses
  65. 65. Worrisome feature #4: Microvascular proliferation
  66. 66. Worrisome feature #5: Degeneration
  67. 67. Helpful feature #1: Inflammation
  68. 68. Helpful feature #2: Low N/C ratios
  69. 69. Helpful feature #3: Demarcation
  70. 70. Helpful feature #4: Xanthomatous histiocytes
  71. 71. Helpful features #5: Creutzfeldt astrocytes
  72. 72. Differential Diagnosis: Glioma
  73. 73. Differential Diagnosis: Liquefactive necrosis
  74. 74. Differential Diagnosis: Progressive multifocal leukoencephalopathy
  75. 75. TLDL: Immunohistochemistry Anti-CD68 Anti-GFAP
  76. 76. TLDL: Outcome <ul><li>Resolution </li></ul><ul><li>Progression to MS </li></ul><ul><li>Rarely paraneoplastic </li></ul><ul><li>Rarely develop CNS lymphoma </li></ul>
  77. 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. 78. Medulloblastoma vs. PNET
  79. 79. <ul><li>One-third of pediatric posterior fossa tumors </li></ul><ul><li>Peak incidence = age 7 </li></ul><ul><li>70% are younger than 16 </li></ul><ul><li>Comprises 1% of adult primary CNS tumors </li></ul><ul><li>80% between ages 21 and 40 </li></ul><ul><li>Rarely occurs beyond age 50 </li></ul><ul><li>WHO IV (Classic, Desmoplastic, LC/A, MBEN) </li></ul>
  80. 80. “ Classic” medulloblastoma (60%) 5-year, event-free survival = 80%
  81. 81. Desmoplastic medulloblastoma (10%) Anti-synaptophysin Reticulin-free “pale islands” NBCCS/PTCH
  82. 82. Medulloblastoma with extensive nodularity (< 5%) Predominantly < 3 years of age
  83. 83. Large cell/anaplastic medulloblastoma (25%) Moderate anaplasia (15%) Severe anaplasia (10%) 5-year survival = 65% 5-year survival = 50%
  84. 84. <ul><li>Local </li></ul><ul><li>Supratentorial metastases </li></ul><ul><li>Leptomeningeal dissemination </li></ul><ul><li>Extraneural metastases </li></ul>Medulloblastoma: Recurrence
  85. 85. Upon completion of this course, participants should be able to: <ul><li>Describe a rational approach to intraoperative neuropathologic consultation </li></ul><ul><li>Define diagnostic criteria for common surgically encountered neuropathologic lesions </li></ul><ul><li>Generate differential diagnoses based upon these neuropathologic entities </li></ul>
  86. 86. References
  87. 87. References
  88. 88. References

×