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 26-year-old woman went to her physician complaining of the onset of new headaches. After two months, she complained of worsening, unremitting head pain. Her physician ordered a CT scan which disclosed hydrocephalus and a mass in the suprasellar/third ventricular area.
Tissue Site
Third ventricle
Whole Slide Image
The whole slide image provided is an H&E stained slide of the hypothalamus from a resection.
Questions
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What is the BEST diagnosis?
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Craniopharyngioma
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Glioblastoma, IDH-wildtype
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Granular cell tumor of the sellar region
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Pilocytic astrocytoma
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Pituicytoma
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What additional information would help support your diagnosis?
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BRAF analysis for fusion
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Confirmation of 1p/19q codeletion
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Evidence of EGFR amplification
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Next-generation sequencing (NGS) for IDH1/2 mutations
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Strong nuclear expression of TTF1
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Assuming that the histological features shown are representative of the neoplasm, what WHO grade should be assigned?
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Grade I
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Grade II
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Grade III
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Grade IV
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This entity is not assigned a WHO grade
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Discussion and Diagnosis
The diagnosis in this case is pilocytic astrocytoma of the third ventricle, WHO grade I. Pilocytic astrocytomas are typically well-demarcated, low-grade glial neoplasms that can be encountered at different sites in the CNS. They account for almost one third of the CNS tumors in the pediatric population, but their incidence drops markedly in adult years. In children they are most common in the posterior fossa, often associated with a cyst. However, at any age they can occur in the third ventricle, optic nerve, cerebral hemispheres, and rarely in the brainstem and spinal cord. They are usually slow-growing masses that produce clinical signs due to compression of adjacent structures or blockage of CSF flow. If the tumor is amenable to surgical removal, then gross total resection is often curative. Rare, aggressive pilocytic astrocytomas with anaplasia have been described with increased mitotic counts, foci of tumor necrosis, anaplastic cellular features, and infiltration of the surrounding parenchyma.
The MRI images shown for this case are T1-weighted, post gadolinium infusion (Image A and Image B). A complex mass with enhancing and nonenhancing components is seen filling the suprasellar cistern, third ventricle, interpeduncular cistern, and a portion of the prepontine cistern. The margins of the mass are well defined, and there is no evidence of infiltration of the cerebral parenchyma that borders the mass. These findings are distinct from what would be expected in a high-grade, diffuse astrocytic neoplasm. There is moderate ventriculomegaly limited to the lateral ventricles, which is consistent with obstruction of CSF flow and would account for the patient’s symptoms. In this age group, these findings would be consistent with a third ventricular pilocytic astrocytoma but do not exclude craniopharyngioma, pituicytoma, or granular cell tumor. On MRI imaging, pilocytic astrocytomas are most frequently hypointense or isointense with gray matter on T1-weighted images and hyperintense on T2-weighted images.
The smear preparation (Image C) shows relatively uniform tumor cells with no nuclear pleomorphism and a moderate amount of cytoplasm with fine filamentous, “piloid” processes. In high-grade astrocytic neoplasms, more pleomorphism, irregular astrocytic forms, and possibly background necrotic debris would be expected. Craniopharyngioma would show squamous-type cells. Granular cell tumor would have polygonal tumor cells with a moderate amount of granular, eosinophilic cytoplasm.
The H&E-stained, paraffin-embedded tissue shows histological features diagnostic of pilocytic astrocytoma. There are foci of Rosenthal fibers in the tumor (Image D), and the histological appearance is that of a moderately cellular astrocytic tumor with regular nuclei, no mitoses, and pilocytic cells growing in sheets (Image D and Image E). In the areas shown there is no biphasic pattern with alternating densely cellular and loosely cellular areas, nor are there the microcysts characteristic of these neoplasms. IHC for GFAP (Image F and Image G) demonstrates strong tumor cell positivity. It is of interest that in some areas of the tumor there is well-developed endothelial proliferation (Image F); however, in pilocytic astrocytomas endothelial proliferation has no prognostic or diagnostic significance. The Ki67 (MIB-1) nuclear labelling index is low (Image H), consistent with a low-grade neoplasm. Other IHC results help support the diagnosis of pilocytic astrocytoma. IHC for mutated IDH-1 R132H is negative (Image I), as expected. The IHC for BRAF V600E mutation is negative here (Image J), but that mutation is present in a small percentage of pilocytic astrocytomas.
BRAF gene fusions and mutations are the most common molecular alterations in pilocytic astrocytomas, causing abnormalities in the MAPK signaling pathway which contribute to the etiology of the neoplasm. The most common genetic abnormality is a duplication of 7q34, which contains BRAF, with a tandem duplication resulting in a transforming fusion gene, KIAA1549-BRAF. This abnormality is present in over 70% of pilocytic astrocytomas, especially pediatric posterior fossa tumors.
Pilocytic astrocytoma, WHO grade I
Take Home Points
- While pilocytic astrocytomas constitute one third of the glial neoplasms in the pediatric population under 14 years of age, they do occur much less frequently in adults with a peak incidence in the 20s.
- Abnormalities of BRAF are the predominant molecular alterations in pilocytic astrocytomas.
- The most frequent BRAF-related genetic abnormality in pilocytic astrocytomas is the KIAA1549-BRAF gene fusion. Other BRAF gene fusions and a number of BRAF mutations have been documented but are much less frequent.
- Pilocytic astrocytomas are most often a grade I lesion; however, increased mitotic rate, tumor necrosis, anaplastic features, and invasion of adjacent brain may indicate more aggressive behavior.
References
- Collins VP, Jones DTW, Giannini C. Pilocytic astrocytoma: pathology, molecular mechanisms and markers. Acta Neuropathol. 2015;129:775-88.
- Fleichter M, Hewer E, Knecht U, et al. Adult anaplastic pilocytic astrocytoma – a diagnostic challenge? A case series and literature review. Clin Neurol Neurosurg. 2016;147:98-104.
- Louis DN, Ohgaki H, Wiestler OD, et al. WHO Classification of Tumours of the Central Nervous System. Revised 4th edition. Lyon, France: IARC; 2016:80-9.
- Reis G, Tihan T. Practical molecular pathologic diagnosis of pilocytic astrocytomas. Surg Pathol Clin. 2015;8(1):63-71.
Answer Key
- What is the BEST diagnosis?
- A. Craniopharyngioma
- B. Glioblastoma, IDH-wildtype
- C. Granular cell tumor of the sellar region
- D. Pilocytic astrocytoma
- E. Pituicytoma
- What additional information would help support your diagnosis?
- A. BRAF analysis for fusion
- B. Confirmation of 1p/19q codeletion
- C. Evidence of EGFR amplification
- D. Next-generation sequencing (NGS) for IDH1/2 mutations
- E. Strong nuclear expression of TTF1
- Assuming that the histological features shown are representative of the neoplasm, what WHO grade should be assigned?
- A. Grade I
- B. Grade II
- C. Grade III
- D. Grade IV
- E. This entity is not assigned a WHO grade