Glioblastoma IDH wild-type (radiation induced)

Case contributed by Dr Bruno Di Muzio


Patient treated for a medulloblastoma 30 years ago (resection and neuroaxis radiation).

Patient Data

Age: 50 years
Gender: Male

There is a mass in the left precentral gyrus with thick and nodular peripheral enhancement with adjacent white matter high FLAIR signal with no mass-effect on the lateral ventricles and no midline shift. There is a small amount of diffusion restriction which appears related to the anteromedial wall. Spectroscopy demonstrated slight reduction in NAA and slight elevation of choline with no significant lactate rise. The peripheral enhancing component has increased cerebral blood volume.

No further contrast enhancing lesion.

Prominent periventricular white matter high FLAIR signal. Prior posterior fossa craniotomy. A large focus of calcification is seen in the left cerebellar hemisphere. Further focal calcification or cavernoma is seen in the right temporal parietal region as well as further scattered tiny areas of susceptibility artefact. These are stable when compared to previous examinations. Ex-vacuo dilatation of the left lateral ventricle again demonstrated.

IMPRESSION: Overall, findings favor tumor with increased cerebral blood flow and peripheral diffusion restriction concerning for high-grade glioma. Metastasis is a less likely differential diagnosis.

MICROSCOPIC DESCRIPTION: The sections show fragments of unremarkable cerebral cortex and white matter and separate fragments of a densely hypercellular glial tumor. Tumor cells are a mixture of pleomorphic, astrocytic and oligodendroglial cells arranged in diffuse sheets. Scattered mitotic figures are identified and there are several foci of microvascular proliferation with multilayering of atypical cells around vessel lumena. Scattered small foci of necrosis are also seen.

IMMUNOHISTOCHEMISTRY: GFAP positive in tumor astrocytes; negative in oligodendroglial cells Nogo A positive in tumor oligodendrocytes; negative in tumor astrocytes. Nestin positive (high) IDH-1 R132H negative (not mutated) ATRX negative (likely mutated) MGMT negative (likely methylated) p53 negative p16 negative Topoisomerase labeling index: Approximately 35% The features are of glioblastoma multiforme with an oligodendroglioma component (WHO Grade IV).

DIAGNOSIS: Brain tumor: Glioblastoma multiforme with an oligodendroglioma component (WHO Grade IV).

Note: Although this tumor is entirely consistent with IDH wild-type molecular subtype, strictly speaking, to conclusively establish this, IDH would need to be sequenced to ensure that a non-IDH1 R132H mutation was present. In practice, an IDH1 R132H negative tumor in an individual of 50-years-of-age the possibility of this being IDH mutant low. Generally, it is felt that sequencing is unnecessary over the age of 55 as the rate of non-R132H mutations is <1%, and not recommended by the WHO classification of CNS tumors (2016). 

Case Discussion

This patient received radiation therapy as part of a treatment for medulloblastoma when he was an adolescent. More than 30 years after this treatment brain imaging shows a diffuse cerebral atrophy as a post radiation treatment effect and a left frontal lobe tumor corresponding to a glioblastoma

Although the patient has all the requisites to fit his new tumor as a radiation-induced glioma, the lesion could also represent a de novo tumor. 

Cahan et al 1 have defined radiation-induced malignancies as those tumors which fulfill the following criteria: 

  • tumor in a previously irradiated area
  • sufficient latency time between the original and new tumors
  • new tumor must have a distinct histology from the original
  • no history of disease predisposing to tumor development
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Case information

rID: 34943
Published: 18th Mar 2015
Last edited: 14th Aug 2019
Tag: rmh
Inclusion in quiz mode: Included

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