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Case Study 61
Kenneth Clark, MD
Question 1
• This is a 31-year-old asymptomatic man
who was found to have papilledema on a
routine ophthalmologic examination. He
was subsequently sent for an MRI.
• Describe the MRI findings.
Answer
• A large, well-circumscribed cystic lesion with a
mural nodule of the left parietal-occipital lobe.
The mural nodule shows diffuse homogeneous
contrast enhancement. The cystic component
shows hyperintense signal on T2. No FLAIR
signal is seen.
Question 2
• What is the differential diagnosis of a cystic
lesion with a mural nodule?
Answer
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Ganglioglioma
Hemangioblastoma
Pilocytic astrocytoma
Pleomorphic Xanthoastrocytoma
Question 3
• The lesion was biopsied and submitted for
an intra-operative evaluation. Describe the
intra-operative smear. How would you
report to the surgeon?
• Click here to see the smear
Answer
• The smear shows a polymorphous cellular neoplasm
comprised of small and large cells in a dense glial
background. The small cells show ovoid-to-elongated
hyperchromatic nuclei with angular nuclear contours,
evenly distributed chromatin and indistinct cytoplasm;
many of these cells show thin processes. The large cells
show more abundant cytoplasm, finely stippled
chromatin and prominent nucleoli; numerous markedly
enlarged and multinucleated forms are seen. These cells
also show processes. The background numerous
globules of dense eosinophilic material. No mitotic
figures are seen.
• A. Neoplastic
• B. Defer to permanent sections, favor ganglioglioma
Question 4
• The lesion was resected and submitted for
pathologic examination. Describe the findings.
• Click here to see the H&E slide
Answer
• Sections show a neuroglial tumor comprised of
neoplastic astrocytes and neurons. The majority of
astrocytes show nuclear pleomorphism with angular
contours, hyperchromasia and scant amounts of light
eosinophilic cytoplasm; sparse scattered gemistocytes
are also seen. The neurons show markedly enlarged
nuclei with significant contour irregularities, prominent
nucleoli, marked variation in size and shape, and
moderate amounts of pale pink flocculent cytoplasm.
Numerous bi-nucleate and giant multinucleate forms are
seen. No mitotic activity is seen. The background shows
very abundant granular eosinophilic bodies and
occasional Rosenthal fibers in the more purely glial
areas. There is significant degenerative nuclear atypia
in the larger cells both glial and neuronal.
Question 5
• What is your differential diagnosis based on
these findings?
Answer
• Ganglioglioma, WHO grade 1
• Pleomorphic Xanthoastrocytoma (PXA)
– Large cells show flocculent cytoplasm, many giant
multinucleate cells have astrocytic appearance, and
eosinophilic granular bodies/Rosenthal fibers are
numerous; although unlikely, pleomorphic
xanthoastrocytoma (PXA) needs to be ruled out
Question 6
• What immunohistochemical stains would you
order to firmly establish the diagnosis?
Answer
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GFAP (identify glial component)
Synaptophysin (identify neuronal component)
NeuN (identify neoplastic neuronal component)
IDH1
Ki67 (proliferation index)
Reticulin (abundant fibers with pericellular
staining in PXA, not ganglioglioma)
• Click to view GFAP, Synaptophysin, NeuN,
IDH1, Ki67, Reticulin
Question 7
• Based on the H&E and immunohistochemical
findings (see below), what is your final
diagnosis?
• GFAP – strong staining of glial tumor cells; negative in large and
giant multinucleated cells
• NeuN – highlights non-neoplastic neurons in adjacent cortex;
negative in neuronal cells and giant cells within the tumor
• IDH1 – negative
• Synaptophysin – stains the cytoplasm of large and multinucleated
tumor cells
• Ki67 - the proliferative index is less than 2%.
• Reticulin – low background deposition in majority of tumor; rich
perivascular deposition; no conclusive pericellular deposition
Answer
• Ganglioglioma, WHO grade 1
Question 8
• Where do the majority of gangliogliomas
typically occur?
Answer
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Temporal Lobe – 86%
Frontal Lobe – 7%
Parietal Lobe – 3%
Occipital Lobe – 3%
Other Areas – 1%
• The predominant temporal lobe
involvement explains the common
association of ganglioglioma and epilepsy
Question 9
• How typical are the neuroradiologic
findings in this case?
Answer
• The neuroradiology in this case are classic
for ganglioglioma. MRI typically shows a
well-circumscribed, T1-weighted
hypointense/T2-weighted hyperintense
lesion with a mural nodule that shows
contrast enhancement (variable).
Question 10
• Are there genetic abnormalities associated with
ganglioglioma?
Answer
• Only about 1/3 of gangliogliomas show a
cytogenetic abnormality. Of these, gain of
chromosome 7 and partial loss of chromosome
9p are the most common.
• Recent studies have shown BRAF mutations in
approximately 20% of gangliogliomas, 10% of
pilocytic astrocytomas and almost 70% of PXAs;
this may be useful in diagnostically challenging /
borderline cases.
Question 11
• What is the prognosis of ganglioglioma?
Answer
• Generally, gangliogliomas are considered
benign lesions with 7.5-year recurrence-free
survival rates approaching 95%. However,
anaplastic change in the glial component is
known to occur (mitotic activity, endothelial
hyperplasia, necrosis). In these transformed
lesions Ki67 indices are high and p53 clonality
may be present.
References
• Schindler G, et al. Analysis of BRAF V600E mutation in 1,320
nervous system tumors reveals high mutation frequencies in
pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar
pilocytic astrocytoma (2011). Acta Neuropathol. 121(3):397-405.
• Louis D, Ohgaki H, Wiestler O, Cavanee W. WHO Classification of
Tumours of the Central Nervous System. IARC: Lyon 2007.
• Prayson R, et al. Cortical architectural abnormalities and MIB1
immunoreactivity in gangliogliomas: a study of 60 patients with
intracranial tumors (1995). J Neuropathol Exp Neurol. 54:513-520.
• Squire J, et al. Molecular cytogenetic analysis of glial tumors using
spectral karyotyping and comparative genomic hybridization (2001).
Mol Diagn. 6:93-108.