Brain Pathology Case of the Month - April 2019


2009 sample: Diffuse, Grade II astrocytoma, IDH-mutant, 1p/19q-intact
2017 sample: Anaplastic, Grade III oligoastrocytoma (OA) with a dual genotype


According to the 2016 WHO Central Nervous System tumour classification, which integrated molecular biology and histology into diagnosis, nearly all of the IDH mutant gliomas are classified as either astrocytomas -IDH mutant, or oligodendrogliomas- IDH mutant and 1p/19q co-deletion. The diagnosis of oligoastrocytoma is strongly discouraged. Despite this, true oligoastrocytomas consisting of histologically and molecularly distinct astrocytic and oligodendroglial tumour populations have been reported, albeit rarely, with only 5 cases of oligoastrocytomas supported by the molecular findings (1,2,3,4). The present case, to the best of our knowledge, is the first to be extensively analyzed by a large targeted NGS panel (Supplementary Data). This molecular profiling allowed us to identify different tumor cell subpopulations in the different morphological areas. The presence of the same IDH2 mutation in the 2009 and in both areas of the 2017 samples at similar allelic frequencies indicates that this is a driver event in the tumor. As proposed by many authors and the 2016 WHO, we can assume that OAs come from an IDH mutant cell of origin, but later during tumorigenesis develop cytologically distinct subpopulations, as observed in the present case. Indeed, the variation of allelic frequencies for TP53 mutations and the difference in ATRX and CIC mutations is consistent with the presence of molecularly distinct tumor cell subpopulations. The presence of CIC mutation and 1p19q co-deletion in the tumor block of the 2017 sample is consistent with the diagnosis of an oligodendroglial tumor. In contrast, the absence of CIC mutation, 1p19q co-deletion, and ATRX IHC expression in the 2009 sample and in the infiltrating cells of 2017 sample is consistent with the diagnosis of an astrocytic tumor. This is also supported by the detection of ATRX deletion in the 2009 sample. Different hypotheses on the evolution of the tumor can be formulated. We cannot elucidate whether the two morphological components were already present in the 2009 tumor, or whether these two components evolved due to tumoral progression in 2017. It should be noted that this is the first description of a diagnosis of OA at recurrence. In conclusion, this case revealed the difficulties of diagnosing tumors with mixed morphologies and dual genotypes, when applying the 2016 WHO classification.


  1. Barresi V, Lionti S, Valori L, Gallina G, Caffo M and Rossi S (2017) Dual-Genotype diffuse low grade glioma: Is it really time to abandon oligoastrocytoma as a distinct entity? J Neuropath Exp Neurol 76: 342-346.
  2. Huse JT, Diamond EL, Wang L and Rosenblum MK (2015) Mixed glioma with molecular features of composite oligodendroglioma and astrocytomla: a true oligoastrocytoma? Acta Neuropathol 129: 151-3
  3. Qu M, Olofsson T, Sigurdardottir S, You C, Kalimo H, Nister M et al (2007) Genetically distinct astrocytic and oligodendroglial components in oligoastrocytomas. Acta Neuropathol 113: 129-36.
  4. WilcoxP, Li CC, Lee M, Shivalingam B, Brennan J, Suter CM et al (2015) Oligoastrocytomas: throwing the baby out with the bathwater? Acta Neuropathol 129: 147-9

Contributed by Laetitia Lebrun, Marie Le Mercier, Barbara Melendez, Isabelle Salmon, Nicky D'Haene

International Society of Neuropathology