Transcript Case Study 59

Case Study 59
Kenneth Clark, MD
Question 1
• This is a 40-year-old woman who 2004 had a
right temporal lobe tumor resected which was
signed out as a WHO grade 2
oligodendroglioma. On follow-up surveillance
MRI she was found to have a new lesion since
her last exam (2 years).
• Describe the MRI findings (films of original lesion
also provided for comparison).
Answer
• 2004 – Fairly well circumscribed, T1
hypointense, non-contrast enhancing lesion with
subtle FLAIR signal near temporal pole.
• 2011 – Postoperative changes from remote right
temporal lobe oligodendroglioma resection. New
irregular region of ring-enhancement posterior to
resection bed with adjacent area of FLAIR signal
immediately adjacent to posterior aspect of
resection cavity anterior to region of
enhancement.
Question 2
• What is the differential diagnosis of a ringenhancing lesion?
Answer
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Gliomas (high-grade)
Radiation necrosis
Abscess
Infarct
Demyelination
Metastases
Question 3
• The lesion was resected and submitted for
pathological examination. Describe the
histologic findings.
• Click here to view the slide
Answer
• Sections show an infiltrating glial tumor with
predominantly oligodendroglial morphology (round nuclei
with perinuclear clearing). There is also a subset of
tumor cells that show astrocytic morphology with larger
hyperchromatic nuclei with irregular nuclear contours
and ill-defined eosinophilic cytoplasm. In many regions
cells appear gemistocytic with small eccentric nuclei,
sharp cell borders and homogeneous glassy eosinophilic
cytoplasm. Scattered mitoses can be seen. Multifocal
glomeruloid endothelial proliferation is seen. Many of the
vessels have sclerotic hyalinizing basement membranes.
In the most cellular area of tumor a small focus of
incomplete necrosis without palisading is seen.
Question 4
• What is your diagnostic impression?
Answer
• Recurrent glioma, high grade, with
oligodendroglial and astrocytic morphologies
Question 5
• What immunohistochemical stains would you
order to further characterize this lesion?
Answer
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GFAP
IDH1
EGFR
P53
Ki67
• Click to see GFAP, IDH1, EGFR, p53, Ki67
Question 6
• The immunohistochemical findings support
the impression of oligoastrocytoma. Would
any molecular studies be useful in better
characterizing this neoplasm? If so, which
studies?
Answer
• Fluorescence In Situ Hybridization (FISH)
– 1p/19q deletion
– P16 deletion
– EGFR amplification
• LOH
– 1p, 19q, 9p (p16), 10q (PTEN), 17p (Tp53)
• IDH1 mutational analysis
Question 7
• Molecular studies show the following results:
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1p/19q – NO deletion
74% p16 deletion by FISH (hemizygous)
No EGFR amplification
100% 9p deletion by PCR (LOH)
100% p53 deletion by PCR (LOH)
33% 10q deletion by PCR (LOH)
Positive for IDH1 mutation (p.R132H, c.395G>A)
• How would you interpret these?
Answer
• The absence of 1p/19q deletion is seen in 5070% of oligoastrocytomas and less than 10% of
pure oligodendrogliomas
• P53 mutation is commonly seen in
oligoastrocytomas, while rare in pure
oligodendrogliomas
• 10q loss (PTEN) is also more frequently seen in
oligoastrocytomas, rare in pure oligos
• EGFR amplification is rare in both tumors
• Taken together, these molecular data support
the diagnosis of high grade oligoastrocytoma.
Question 8
• The tumor does show focal necrosis. Is it a
grade 3 or 4 (glioblastoma)
Answer
• The tumor shows numerous mitoses, clear
endothelial proliferation and foci of necrosis;
likewise it would formally meet the criteria for
glioblastoma, WHO Grade 4. However, the
patient has received radiation therapy and the
necrosis seen isn’t typical (non-palisading,
incomplete) of a glioblastoma. The extent to
which the necrosis can be attributed to radiation
vasculopathy is unclear but a reasonable
possibility. Because of this it could still be
classified as a Grade 3 lesion as it is in the
oligodendroglial lineage.
Question 9
• What is the significance of the IDH1 mutation?
Answer
• Mutations of the isocitrate dehydrogenase
enzyme isoform 1 (IDH1) have recently been
identified in a high percentage of infiltrating glial
neoplasms. Approximately 90% of all IDH1
mutations affect amino amino acid 132 (R132H).
Although the mutational analysis is not needed
for the diagnosis of glioma in this case, it is a
useful prognostic marker as patients who harbor
the mutation have better clinical outcomes than
those without. IDH1 is particularly useful in small
biopsies of low cellularity which are difficult to
interpret.
Question 10
• What is the prognosis of this patient?
Answer
• Anaplastic oligoastrocytoma has a median
survival of 2.8 years and 5- and 10-year
survival rates of 36% and 9%, respectively
following resection and radiation only. The
addition of chemotherapy increases the
median survival to almost 50 months.
Question 11
• Two factors have shown to have independent
prognostic implications – necrosis and 1p
deletion
• Necrosis – Anaplastic oligoastroctyomas with
necrosis are associated with worse outcomes
than those without, leading some to classify any
oligoastrocytoma with necrosis as “glioblastoma
with oligodendroglial component”
• 1p deletion – Independently associated with
increased progression-free and overall survival
References
• Louis D, Ohgaki H, Wiestler O, Cavanee W. WHO Classification of
Tumours of the Central Nervous System. IARC: Lyon 2007.
• Yan H, et al. IDH1 and IDH2 Mutations in Gliomas (2009). N Engl J
Med.360:765-773.
• Eoli M, et al. Reclassification of oligoastrocytomas by loss of
heterozygosity studies (2006). Int J Cancer. 119:84-90.
• Miller C, Dunham C, Scheithauer B, Perry A. Significance of
necrosis is grading of oligodendroglial neoplasms: A
clinicopathologic and genetic study of 1093 newly-diagnosed high
grade gliomas (2006). J Clin Oncol. 24:5419-5426.
• Mueller W, et al. Genetic signature of oligoastrocytomas correlates
with tumor location and denotes distinct molecular subsets (2002).
Am J Pathol. 161:313-319.