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ASCP Course 1301: Diagnostic Issues in Surgical Neuropathology
Mark L. Cohen, M.D.
Richard A. Prayson, M.D.
CLEVELAND CLINIC FOUNDATION
Upon completion of this course, participants should be able to:
1. Describe a rational approach to intraoperative neuropathologic consultation
2. Define diagnostic criteria for common surgically encountered neuropathologic lesions
3. Generate differential diagnoses for each of these neuropathologic entities
Intraoperative Consultation: What the surgeon wants to know
1. Sampling adequacya. For eventual diagnosisb. For ancillary studies
2. What operation to perform3. Appropriate postoperative
treatment4. What to tell the family5. WHAT IS IT ?!?
Intraoperative Consultation: What you should know
• Age• Location• History• Imaging
characteristics
Intraoperative consultation: Gross examination
Cardinal ordinances of neuropathologic IOC
NEVER
Process all of the abnormal appearing tissue
ALWAYS Include portions of the
softest, darkest regions of the specimen
Smear or Freeze?
Why I like smear
preparations•Speed•Sampling•Simplicity•Cytology•Sterility
Why RAP likes frozen
sections• Familiarity• Architecture• Evaluation
time
Who cares what you like?
What do other neuropathologists do?
92 Neuropathologists (from 14 countries) prefer:
Frozen only 20%
Cytology only 10%
Both FS & cytology 70%
Cytologic method
Crush/Smear 2/3
Touch prep 1/3
H&E stain 90%J Neurosurg 1999;91:454
The middle path
IOC: Diagnostic Algorithm
The tissue is
AbnormalNormal
Non-neoplasticGet more tissue Neoplastic
Representative? Tumor type
Tumor grade
IOC: Common Pathologic Diagnoses
Diagnosis Percentage of cases
High-grade glioma 40
Low-grade glioma 15
Metastatic carcinoma
15
Meningioma 15
CNS lymphoma 5
Abscess 5
Inflammatory 5
Intraoperative Consultation: Thoughts on age(ing)
Low-grade gliomas are sufficiently rare in middle-aged & elderly individuals that their apparent presence during intraoperative consultation is reason for concern
There are a significant number of low grade gliomas of childhood which appear malignant on first assessment - proceed with caution
Meningioma
Astrocytoma(WHO II)
Recurrent glioma(post-radiation)
Pilocytic astrocytoma
Myxopapillaryependymoma
Oligodendro-glioma
Lymphoma
Demyelination
Medulloblastoma
Off to the cases…
Heeeerrrs Richard!!
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
Oligodendroglioma: Why Should I Care?
1. Biologic Behavior 2. Grading: “Double Indemnity”3. Molecular prognostication
Oligodendroglioma: Initial Clues
Low “P/C” ratio Arcuate vasculature
Subpial spread
Perineuronal satellitosis
Band-like cortical calcifications
“Germinal centers”
Minigemistocytes
Perinuclear halos (fried-eggs)
LIGOS
Astrocytomas
What is an oligodendroglioma?
Neurocytoma
Clear cellependymoma
Dysembryoplasticneuroepithelial tumor
Central neurocytoma
Neuropil islands Synaptophysin positive
Dysembryoplastic Neuroepithelial Tumor
Absence of satellitosis
Clear Cell Ependymoma
IHC in clear cell gliomas
Antigen Oligodendro-glioma
Neurocytoma Clear cellependymoma
GFAP +/- Rare Weak
Synapto Weak Strong Rare
Neu-N Rare Strong Rare
EMA Weak Negative Positive
Vimentin +/- Negative Positive
Molecular diagnosis of clear cell gliomas
Human Pathology, 2004
Anaplastic oligodendroglioma (WHO III)
Some tumors may develop histological features commonly found in glioblastomas..
Molecular subtyping of histologically-defined AOs
Molecular
genetics
1p/19q lossonly
1p lossother
1p intactP53
mutation
1p intactOther (e.g. EGFR amp)
Imaging FrontalParietal
FrontalParietal
TemporalRing-
enhanced
TemporalRing-
enhanced
Response
rate
100% 100% 33% 18%
Survival(years)
> 10 6 6 1.5
Pleomorphic nucleiBrisk mitotic ratePseudopallisading
Small cell glioblastoma
Indications for genotyping
• Anaplastic oligodendrogliomas– 1q/19p loss is a positive prognostic
indicator
• AO versus small cell GBM– intact 1p + EGFR amplification = small
cell GBM
• Grade II oligodendroglioma– Confirmation of diagnosis, if 1p deleted
(70%)
Caveat emptor: All 1p deletions are not created equal
• Whole 1p deletion associated with whole 19q deletion– Typical oligodendroglial morphology with good
overall and progression free survival• Distal 1p36 deletion associated with intact
or completely absent chromosome 19– More frequently seen in astrocytic tumors, and
characterizes a particularly aggressive group of gliomas
• FISH with 1p36 probe will not distinguish these two forms of 1p deletion
Case 7: Primary CNS Lymphoma (the 5% tumor)
• 5% of primary intracranial neoplasms – Median age = 55
• 5% of AIDS patients, usually late-stage – 3600-fold relative risk, median age =
40• 5% of post-transplant patients
– 50% confined to CNS• 5% of congenital immunodeficiencies
– Median age = 10
Supratentorial, periventricular, often multiple
Meningeal, ocular disease in ~20%
Modest peritumoral edema
Marked response to steroids
Primary CNS Lymphoma: Intraoperative Consultation
Smear
Crush
Pre-operative steroids = “Ghost tumor”
Angiocentric & angioinvasive
“Reticulin cell sarcoma”
No Satellitosis
Subclassification and analysis of proliferative
activity appears to be of no practical importance
Anti-CD20
Primary CNS Lymphoma: Prognosis
•Excellent initial response rate•Cerebral recurrence is typical•Median survival (treated)
–4 months (including AIDS)–9 months (immunocompetent)–2 years (tertiary care/clinical trials)
Hen’s teeth: Metastatic DLBCL
Primary dural lymphomaPrimary dural lymphoma
Intravascular lymphomatosis
Case 8: Tumor-like demyelinating lesion
Worrisome feature #1: Hypercellularity
Worrisome feature #2: Pleomorphism
Worrisome feature #3: Mitoses
Worrisome feature #4: Microvascular proliferation
Worrisome feature #5: Degeneration
Helpful feature #1: Inflammation
Helpful feature #2: Low N/C ratios
Helpful feature #3: Demarcation
Helpful feature #4: Xanthomatous histiocytes
Helpful features #5: Creutzfeldt astrocytes
Differential Diagnosis: Glioma
Differential Diagnosis: Liquefactive necrosis
Differential Diagnosis: Progressive multifocal leukoencephalopathy
Anti-CD68
Anti-GFAP
TLDL: Immunohistochemistry
TLDL: Outcome
•Resolution•Progression to MS•Rarely paraneoplastic•Rarely develop CNS lymphoma
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
Medulloblastoma vs. PNET
One-third of pediatric posterior fossa tumors
Peak incidence = age 770% are younger than 16Comprises 1% of adult primary CNS tumors
80% between ages 21 and 40 Rarely occurs beyond age 50
WHO IV (Classic, Desmoplastic, LC/A, MBEN)
5-year, event-free survival = 80%
“Classic” medulloblastoma (60%)
Desmoplastic medulloblastoma (10%)
Anti-synaptophysin
Reticulin-free “pale islands”
NBCCS/PTCH
Predominantly < 3 years of age
Medulloblastoma with extensive nodularity (< 5%)
Large cell/anaplastic medulloblastoma (25%)
Moderate anaplasia (15%) Severe anaplasia (10%)
5-year survival = 65% 5-year survival = 50%
• Local• Supratentorial
metastases• Leptomeningeal
dissemination• Extraneural
metastases
Medulloblastoma: Recurrence
Upon completion of this course, participants should be able to:
• Describe a rational approach to intraoperative neuropathologic consultation
• Define diagnostic criteria for common surgically encountered neuropathologic lesions
• Generate differential diagnoses based upon these neuropathologic entities
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