Synchronous supratentorial and infratentorial oligodendrogliomas with incongruous IDH1 mutations, a case report

Abstract

Infratentorial oligodendrogliomas, a rare pathological entity, are generally considered metastatic lesions from supratentorial primary tumors. Here, we report the case of a 23-year-old man presenting with a histopathologically confirmed right precentral gyrus grade 2 oligodendroglioma and a concurrent pontine grade 3 oligodendroglioma. The pontine lesion was biopsied approximately a year after the biopsy of the precentral lesion due to disease progression despite 4 cycles of procarbazine-CCNU-vincristine (PCV) chemotherapy and stable supratentorial disease. Histology and genetic analysis of the pontine biopsy were consistent with grade 3 oligodendroglioma, and comparison of the two lesions demonstrated common 1p/19q co-deletions and TERT promoter mutations but distinct IDH1 mutations, with a non-canonical IDH1 R132G mutation identified in the infratentorial lesion and a R132H mutation identified in the cortical lesion. Initiation of Temozolomide led to complete response of the supratentorial lesion and durable disease control, while Temozolomide with subsequent radiation therapy of 54 Gy in 30 fractions resulted in partial response of the pontine lesion. This case report supports possible distinct molecular pathogenesis in supratentorial and infratentorial oligodendrogliomas and raises questions about the role of different IDH1 mutant isoforms in explaining treatment resistance to different chemotherapy regimens. Importantly, this case suggests that biopsies of all radiographic lesions, when feasible and safe, should be considered in order to adequately guide management in multicentric oligodendrogliomas.

The Role of Genetic Analysis in Distinguishing Multifocal and Multicentric Glioblastomas: An Illustrative Case

“…Agopyan-Miu et al [ 12 ] reported a patient with synchronous supratentorial and infratentorial oligodendrogliomas. They resected the lesions sequentially and subjected them to genetic analysis.…”

2021 updates to the World Health Organization classification of adult-type and pediatric-type diffuse gliomas: a clinical practice review

“…In addition to the frontal lobe, other locations in the cerebrum include the temporal, parietal or rarely occipital lobe. Very rare case reports describe oligodendrogliomas arising in the posterior fossa, brainstem or demonstrating diffuse involvement of multiple bilateral brain areas in a gliomatosis cerebri pattern (26)(27)(28). Recurrent disease is more likely to show leptomeningeal or intraventricular spread (27,29,30).…”

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“…One speculation is that the right parietal lesion is a secondary lesion derived from the frontal tumor. The different IDH mutations may suggest an evolved trajectory resulting in more invasive clones able to metastasize transmission (8,10). In this case, glioma cells in the parietal lesion probably possess a more remarkable ability to metastasize through cerebrospinal fluid or cortical tract fibers.…”

“…The simultaneous presence of multiple foci, remarkably homologous foci with different histopathologic compositions, is rare in all types of gliomas (7). Based on radiologic and/or pathologic features, complicating lesions can be divided into multifocal and multicentric categories (8). Multicentric gliomas fail to differentiate due to genetic defects in stem cells, resulting in defective, highly proliferative cell populations that form tumor centers (9).…”

“…Multicentric gliomas fail to differentiate due to genetic defects in stem cells, resulting in defective, highly proliferative cell populations that form tumor centers (9). Multifocal gliomas, on the other hand, represent the presence of multiple tumor foci that are differentially associated and have consistent genetic variants (8). Due to this rarity, the underlying molecular relationships of synchronous lesions are poorly understood.…”