Epithelioid glioblastoma

Epithelioid glioblastoma is a classic variant of glioblastoma (along with gliosarcoma and giant cell glioblastoma) only recently added to recognised in the current (2021) WHO classification of CNS tumours as part of the 2016 update ¹⁴. 

Terminology

Whether or not epithelioid glioblastomas are distinct from rhabdoid glioblastomas is at present unclear, however, the latter term should be avoided and is not recognised in the current WHO classification ^2,3. 

It is important to note that true epithelial differentiation of glioblastomas (typically squamous) is very rarely seen in adults but is distinct from epithelioid glioblastoma ². 

Epidemiology

Unlike run-of-the-mill glioblastomas that are usually encountered in older adults, epithelioid glioblastomas have a predilection for young adults and children ^1,3. 

Pathology

Epithelioid glioblastoma are WHO grade IV4 tumours ³. Interestingly, they sometimes co-exist with pleomorphic xanthoastrocytomas, however, their exact relationship is at present unclear ³. 

Microscopic appearance

These tumours are heterogeneous with large epithelioid cells that have abundant eosinophilic cytoplasm, vesicular chromatin, and prominent nucleoli. These cells are reminiscent of melanoma cells. Rhabdoid cells are also sometimes encountered ¹.

Immunophenotype

Immunohistochemistry demonstrates a mixture of astrocytic and epithelial markers ³: 

• vimentin: positive
• S100: positive
• GFAP: positive but patchy
• EMA: variable
• cytokeratins: variable

Genetics

Approximately 50% of cases of epithelioid glioblastoma have BRAF V600E mutations ^1-3. 

Radiographic features

Epithelioid glioblastomas most frequently present as diencephalic or less frequently superficial cerebral hemispheric masses ^1,2. Haemorrhage and leptomeningeal seeding are probably fairly common at the time of diagnosis ². 

These tumours are indistinguishable for glioblastoma on imaging, with enhancement, necrosis and diffusion restriction present in the vast majority of tumours ². 

Treatment and prognosis

Epithelioid glioblastomas are aggressive tumours with poor prognosis, even worse than ordinary glioblastomas ³. In one series the median survival was only 169 days ². 

These tumours also sometimes demonstrate systemic metastases, a very uncommon occurrence for other primary brain tumours ². 

Differential diagnosis

In children the main differential is atypical teratoid / rhabdoid/rhabdoid tumour (AT/RT), distinguished by universal lack of INI1 expression in AT/RT ².