Highlighting the importance and clinical utility of testing
A 46-year-old man presented with seizures and was found to have a right temporal lobe ring-enhancing tumor. The patient underwent tumor resection at Mayo Clinic.
- The resected specimen showed a high-grade infiltrating glioma composed by monomorphous tumor cells with round nuclei and high nuclear-to-cytoplasmic ratio. Mitotic activity was brisk and microcalcifications were focally present. Microvascular proliferation and necrosis were observed. Immunohistochemical studies excluded the most common IDH1 mutation (p.R132H), while ATRX protein expression was retained.
- The diagnoses considered included: 1) IDH-wild-type small-cell glioblastoma; 2) IDH-mutant glioblastoma; or 3) IDH-mutant and 1p/19q co-deleted anaplastic oligodendroglioma.
- Neuro-oncology next-generation sequencing (NGS) panel was consistent with the absence of an IDH mutation and revealed a TERT promoter mutation.
- Chromosomal microarray showed intact 1p/19q status, EGFR amplification associated with gain of chromosome 7, loss of chromosome 10, CDKN2A/B homozygous loss, and gain of chromosomes 19 and 20.
- The overall genetic findings, in conjunction with the morphology, led to the final integrated diagnosis of IDH-wild-type small-cell glioblastoma (WHO grade IV).
- Small-cell glioblastoma is a subtype of IDH-wild-type glioblastoma that morphologically overlaps with anaplastic oligodendroglioma due to the nuclear regularity, high nuclear-to-cytoplasmic ratio, microcalcifications, and lack of cellular pleomorphism.
- TERT promoter mutations are characteristic of both IDH-wild-type glioblastoma and IDH-mutant oligodendroglioma, which is molecularly defined by the concurrent presence of an IDH mutation and 1p/19q co-deletion. The finding of a TERT promoter mutation in the absence of an IDH mutation, as seen in this case, is consistent with an integrated diagnosis of IDH-wild-type glioblastoma.
- Frequent molecular features of small-cell glioblastoma include EGFR amplification (~70%) and losses of chromosome 10 (>95%), as observed in this case.1