This case was originally published in 2018. The information provided in this case was accurate and correct at the time of initial program release. Any changes in terminology since the time of initial publication may not be reflected in this case.
Clinical History
A 34-year-old man with intractable epilepsy since age 21 years had a lesion in the left inferolateral temporal lobe with focal calcifications by neuroimaging. No exact diagnosis had been established. The mass had not changed significantly over the years; however, on the last MRI obtained it appeared to have focal enhancement (Image A and Image B). A nodule of abnormal tissue containing calcific material (see scanned virtual slide) was excised without complications. After recovery from surgery, the patient is nearly seizure-free.
Tissue Site
Lateral left temporal lobe
Whole Slide Image
The whole slide image provided is an H&E stained slide of the lateral left temporal lobe from a tumor resection.
Questions
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What is the BEST diagnosis?
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Astrocytoma, WHO grade II
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Focal cortical dysplasia, ILAE type IIb
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Ganglioglioma, WHO grade I
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Oligodendroglioma, WHO grade II
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Pilocytic astrocytoma, WHO grade I
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This image (Neurofilament, IHC stain) demonstrates what feature of this case?
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Endothelial proliferation in multiple vessels
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Multiple perivascular leukocytic aggregates
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Normal morphology of the amygdala
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Poorly oriented, dysmorphic neuronal forms
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Tumor cell infiltration of the cerebral cortex
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Pending molecular confirmation, the IHC stains shown for BRAF V600E, IDH1 R132H, and ATRX indicate which of the following?
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All genes are mutated.
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ATRX and BRAF are mutated; IDH1 is wildtype.
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BRAF is mutated; the others are wildtype.
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IDH1 is mutated; the others are wildtype.
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All genes are wildtype.
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Discussion and Diagnosis
Ganglioglioma is a low-grade neoplasm, WHO grade I, that typically presents with seizures rather than as an expansile intracranial mass. It is the most common mixed glioneuronal neoplasm and the most common tumor causing longstanding temporal lobe epilepsy. It can present clinically at any age, but the majority does so before age 30 years. On imaging studies ganglioglioma can be either cystic or solid, and approximately 30% of cases will have associated calcific material. While ganglioglioma can develop at any level of the CNS, it is predominantly a lesion of the cerebral cortex and favors the temporal lobe (Image A and Image B). Over 90% of gangliogliomas behave in an indolent fashion, and surgical resection is often curative.
Histologically, ganglioglioma is comprised of oligodendroglial and/or astrocytic glia and admixed dysplastic and maloriented neurons with dendritic abnormalities and lack of normal cortical lamination (Image C, Image D, and Image E). Mitoses are rare or absent, and the Ki67 labelling index is very low (Image F). Gangliogliomas may exhibit meningeal infiltration and subpial spread (see scanned virtual slide) and may contain eosinophilic granular bodies, Rosenthal fibers, and abundant reticulin. Anaplastic ganglioglioma, WHO grade III, shows features such as cellular atypia, pleomorphism, and prominent mitotic figures.
The most common genetic abnormality in gangliogliomas is the BRAF V600E mutation (Image G) with a reported 20% to 60% incidence, although KIAA1549-BRAF fusion occurs rarely. These abnormalities are not specific for ganglioglioma. The majority of gangliogliomas exhibit CD34 expression on both tumor blood vessels and tumor cells (Image H). It is important to note that IDH1/2 mutations (Image I), ATRX mutations (Image J), and/or 1p/19q chromosomal codeletions preclude the diagnosis of ganglioglioma.
The differential diagnosis of ganglioglioma can be a challenge. Pilocytic astrocytoma (PA) typically does not contain dysplastic neurons. While PA typically does have a BRAF genetic abnormality, it is most commonly the formation of transforming fusion product, KIAA1549-BRAF. Low-grade diffuse astrocytomas and oligodendrogliomas may entrap neurons and mimic ganglioglioma. Molecular genetic analysis can be most helpful in distinguishing these tumors. Low-grade diffuse astrocytomas usually have IDH mutations and may have ATRX mutations, but they only rarely harbor the BRAF V600E mutation. Oligodendrogliomas have both IDH mutations and 1p/19q codeletions which are not found in gangliogliomas. Moreover, in both of these low-grade diffuse glial neoplasms the entrapped neurons are not dysplastic, enlarged, or multinucleate. Focal cortical dysplasia (FCD) may show large, maloriented, dysplastic neurons but typically lacks hypercellularity and does not harbor neoplastic glial elements.
Ganglioglioma, WHO grade I
Take Home Points
- The presence of enlarged, maloriented, dysmorphic neurons admixed with neoplastic glial elements is the cardinal histological feature of ganglioglioma, WHO grade I.
- BRAF V600E mutation is the most common genetic abnormality in ganglioglioma.
- Mutations in IDH1/2, ATRX, and/or codeletion of 1p/19q preclude the diagnosis of ganglioglioma.
- Over 90% of ganglioglioma patients have long-term recurrence-free survival after complete resection.
- An anaplastic (WHO grade III) variant of ganglioglioma does exist.
References
- Brat DJ. Neuronal and mixed neuronal-glial tumours. In: Love S, Budka H, Ironside JW, Perry A, eds. Greenfield’s Neuropathology. 9th edition. 2015;1727-30.
- Compton JJ, Laack NN, Eckel LJ, Schomas DA, Giannini C, Meyer FB. Long-term outcomes for low-grade intracranial ganglioglioma: 30-year experience from the Mayo Clinic. J Neurosurg. 2012;117:825-30.
- Louis DN, Ohgaki H, Wiestler OD, et al. WHO Classification of Tumours of the Central Nervous System. Revised 4th edition. Lyon, France: IARC; 2016:138-41.
Answer Key
- What is the BEST diagnosis?
- A. Astrocytoma, WHO grade II
- B. Focal cortical dysplasia, ILAE type IIb
- C. Ganglioglioma, WHO grade I
- D. Oligodendroglioma, WHO grade II
- E. Pilocytic astrocytoma, WHO grade I
- This image (Neurofilament, IHC stain) demonstrates what feature of this case?
- A. Endothelial proliferation in multiple vessels
- B. Multiple perivascular leukocytic aggregates
- C. Normal morphology of the amygdala
- D. Poorly oriented, dysmorphic neuronal forms
- E. Tumor cell infiltration of the cerebral cortex
- Pending molecular confirmation, the IHC stains shown for BRAF V600E, IDH1 R132H, and ATRX indicate which of the following?
- A. All genes are mutated.
- B. ATRX and BRAF are mutated; IDH1 is wildtype.
- C. BRAF is mutated; the others are wildtype.
- D. IDH1 is mutated; the others are wildtype.
- E. All genes are wildtype.