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Glioma arising in the setting of mismatch repair deficiency—rare or are we missing it?

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Abstract

Germline mutations in mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS2) can be mono-allelic or biallelic, resulting in a Lynch syndrome (LS) or constitutional mismatch repair deficiency (CMMRD) syndrome respectively. Glioma arising in the setting of MMR deficiency is uncommon. We describe two pediatric patients with high-grade glioma (HGG) and associated MMR protein deficiency. On histomorphology both cases showed HGG with astrocytic morphology and prominent multinucleated tumor cells. On immunohistochemistry, the first case was negative for IDH1 p.R132H showed loss of ATRX and p53 positivity. The second case was positive for IDH1 p.R132H and p53, but showed retained expression of ATRX. The histomorphology in both cases and additionally IDH mutation with retained ATRX in the second case, prompted us to test for MMR protein deficiency which was carried out by immunohistochemistry (IHC). One case revealed an immunostaining pattern suggestive of CMMRD while the other was suggestive of LS. Both the cases showed good response to surgery and radio-chemotherapy in the follow-up available. Our cases highlight the importance of testing for MMR proteins by simple IHC, in the setting of appropriate clinical scenario, histopathological and immunohistochemical findings. The recognition of these tumors is extremely important to guide further treatment and prompt family screening.

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Authors and Affiliations

  1. Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, Karnataka, India

    Aditi Goyal, Shilpa Rao & Vani Santosh

  2. Department of Neurosurgery, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, Karnataka, India

    Nishanth Sadashiva

  3. Department of Radiation Oncology, Sri Shankara Cancer Hospital and Research Centre, Bengaluru, India

    Karthik S Rishi

  4. Department of Pathology, Health Care Global (HCG) Cancer Hospital, Bengaluru, India

    Veena Ramaswamy

Authors
  1. Aditi Goyal
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  2. Shilpa Rao
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  3. Karthik S Rishi
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  4. Veena Ramaswamy
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  5. Nishanth Sadashiva
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  6. Vani Santosh
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Contributions

All authors contributed to the case report. All authors (A.G., S.R., K.R., V.R., N.S. and V.S.) were involved in working up the cases and providing thorough information about the cases. The first draft of the manuscript was written by A.G.; and S.R. and V.S. commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Vani Santosh.

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Goyal, A., Rao, S., Rishi, K. et al. Glioma arising in the setting of mismatch repair deficiency—rare or are we missing it?. Childs Nerv Syst 40, 233–237 (2024). https://doi.org/10.1007/s00381-023-06158-x

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