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.
An 11-year-old boy was admitted after presenting with progressive mental status change and nausea for two weeks. Cranial imaging showed a right parieto-occipital mass (Image A). He underwent subtotal resection of the lesion.
Brain, right parieto-occipital region
Whole Slide Image
The whole slide image provided is an H&E stained slide of the right parieto-occipital region of the brain from a craniotomy.
What is the BEST diagnosis?
Anaplastic pleomorphic xanthoastrocytoma
Atypical teratoid/rhabdoid tumor
Which of the following is typical for this neoplasm?
BRAF V600E mutations are detected in half of cases tested.
Deletions of hSNF5/INI1 on chromosome 22 are common.
Eosinophilic granular bodies are found in most cases.
Most cases occur in children younger than 18 years old.
Tumor cells are often positive for IDH1 R132H by IHC.
The neoplasm is characterized by which of the following?
Eosinophilic granular bodies, perivascular lymphocytes, and intercellular reticulin
Loss of INI1 expression; desmin negative
Melan A, HMB45, and S100 positivity
Patchy EMA, somatostatin receptor type 2A, and PR positivity
Vimentin and variably GFAP-positive epithelioid cells with necrosis
Discussion and Diagnosis
The diagnosis is epithelioid glioblastoma, WHO grade IV. Microscopic examination shows a hypercellular malignancy consisting of a mixture of spindled and epithelioid/rhabdoid cells (Image B and Image C). The spindled cells are arranged in fascicles or sheets with elongated hyperchromatic nuclei, scant cytoplasm, indistinct cellular borders, and varying amounts of intercellular collagen (Image D). Loose or packed aggregates of epithelioid/rhabdoid cells are found between spindled areas (Image E), and they vary from small and histiocytoid with vesicular nuclei and prominent nucleoli (Image F) to large and round with eccentric nuclei indented by globular eosinophilic cytoplasm (Image G). Transition between spindled and epithelioid/rhabdoid areas may be abrupt or gradual, and some cells show intermediate histology. Mitotic figures, geographic necrosis, and infiltrating mononuclear inflammatory cells are identified (Image H), but no eosinophilic granular bodies or dysplastic neurons are detected. IHC shows that a minority of neoplastic cells have GFAP-positive cytoplasm (Image I). All neoplastic cells have vimentin-positive cytoplasm without globoid cytoplasmic accentuation. Tumor cells stain negatively for cytokeratin AE1, S100 protein, desmin, and IDH1 R132H mutant protein. Nuclear expression of INI1 (SMARCB1 or BAF47) is retained in all neoplastic cells (Image J). IHC with BRAF VE1 is equivocal. However, DNA sequencing detects a BRAF V600E mutation in this case.
The histologic differential diagnosis of epithelioid glioblastoma includes giant cell glioblastoma, anaplastic pleomorphic xanthoastrocytoma (PXA), atypical teratoid/rhabdoid tumor (AT/RT), metastatic melanoma, carcinoma, and rhabdomyosarcoma. The distinguishing feature of giant cell glioblastoma is the presence of large tumor cells with big nuclei, macronucleoli, and voluminous cytoplasm. Similar giant cells are seen in PXA with most cases of PXA also exhibiting eosinophilic granular bodies. Approximately two-thirds of PXAs have been found to have BRAF V600E mutations. One recent report suggested that epithelioid glioblastoma and anaplastic PXA may be the same entity based on their molecular abnormalities, histologic features, and clinical picture. IHC provides a clear distinction between epithelioid glioblastoma and AT/RT, as the latter shows loss of INI1 nuclear expression. Finally, varying IHC panels can help distinguish epithelioid glioblastoma from metastatic melanoma, carcinoma, and rhabdomyosarcoma.
Epithelioid glioblastoma is a rare variant (<2%) of glioblastoma that has been reported primarily in the cerebrum of both children and adults (aged 10 to 82 years in the largest series to date, with a majority being younger than 30 years old). Neuroimaging studies typically show intra-axial masses with solid and cystic components and relatively circumscribed borders. Characteristic histopathologic and molecular abnormalities are such that epithelioid glioblastoma has been recognized as a distinct nosologic entity in the 2016 update of WHO Classification of CNS Tumours. One series defined epithelioid glioblastoma as having an epithelioid component in >30% to 40% of tumor cells. Importantly, GFAP immunoreactivity in tumor cells is highly variable, often very focal and patchy when positive. About half of epithelioid glioblastomas tested harbor activating BRAF V600E mutations. Strong BRAF VE1 immunoreactivity (in both epithelioid and spindled tumor cells) has been reported to correlate well with BRAF V600E mutations detected by DNA sequencing, but high background staining can make interpretation of BRAF VE1 difficult. No cases reported thus far have shown complete loss of INI1 nuclear expression. A minor subset of reported cases showed EGFR amplification and/or PTEN loss. Rare cases have been found to have IDH1/2 mutations. Pediatric epithelioid glioblastoma has rarely been reported to harbor both BRAF V600E and H3F3A K27M mutations. Epithelioid glioblastoma is generally regarded as an aggressive malignancy with high risk of hemorrhage and leptomeningeal spread in pediatric patients; however, rare long term survivors have been reported.
Take Home Points
- Epithelioid glioblastoma contains both spindled and epithelioid/rhabdoid cells.
- Although epithelioid glioblastoma can be seen at all ages, the majority of patients are under 30 years old.
- GFAP immunoreactivity in epithelioid glioblastomas is highly variable.
- BRAF V600E mutations are found in about half of epithelioid glioblastomas.
- Alexandrescu S, Korshunov A, Lai SH, et al. Epithelioid glioblastomas and anaplastic epithelioid pleomorphic xanthoastrocytomas - same entity or first cousins? Brain Pathol. 2016;26:215-23.
- Broniscer A, Tatevossian RG, Sabin ND, et al. Clinical, radiological, histological, and molecular characteristics of pediatric epithelioid glioblastoma. Neuropathol Appl Neurobiol. 2014;40:327-36.
- Kleinschmidt-DeMasters BK, Aisner DL, Foreman NK. BRAF VE1 immunoreactivity patterns in epithelioid glioblastomas positive for BRAF V600E mutation. Am J Surg Pathol. 2015;39:528-40.
- Kleinschmidt-DeMasters BK, Aisner DL, Birks DK, et al. Epithelioid GBMs show a high percentage of BRAF V600E mutation. Am J Surg Pathol. 2013;37:685-98.
- Takahashi Y, Akahane T, Sawada T, et al. Adult classic glioblastoma with a BRAF V600E mutation. World J Surg Oncol. 2015;13:100-4.
- What is the BEST diagnosis?
- A. Anaplastic pleomorphic xanthoastrocytoma
- B. Atypical teratoid/rhabdoid tumor
- C. Epithelioid glioblastoma
- D. Metastatic melanoma
- E. Rhabdoid meningioma
- Which of the following is typical for this neoplasm?
- A. BRAF V600E mutations are detected in half of cases tested.
- B. Deletions of hSNF5/INI1 on chromosome 22 are common.
- C. Eosinophilic granular bodies are found in most cases.
- D. Most cases occur in children younger than 18 years old.
- E. Tumor cells are often positive for IDH1 R132H by IHC.
- The neoplasm is characterized by which of the following?
- A. Eosinophilic granular bodies, perivascular lymphocytes, and intercellular reticulin
- B. Loss of INI1 expression; desmin negative
- C. Melan A, HMB45, and S100 positivity
- D. Patchy EMA, somatostatin receptor type 2A, and PR positivity
- E. Vimentin and variably GFAP-positive epithelioid cells with necrosis