Germline Biallelic Mismatch Repair Deficiency in Childhood Glioblastoma and Implications for Clinical Management.

Neurology India 2022 Mar-Apr

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We report a case of a 9-year-old boy with glioblastoma with a past history of colon cancer. Germline bi-allelic DNA-mismatch repair deficiency was diagnosed by a lack of immunohistochemical staining for PMS2 in the tumor and normal tissue. Family history was lacking. Sequencing confirmed compound heterozygous PMS2 mutations. A second hit in the DNA-polymerase-ε gene led to complete DNA-replication repair deficiency. This contributed to an ultra-hypermutated phenotype. Temozolomide was excluded from the treatment. PD-1 immunotherapy at recurrence contributed to extending post-relapse survival up to 11 months. Challenges included managing initial immune "flare" related to "pseudo-progression" and access to drug. Family screening diagnosed the sibling with Lynch syndrome. This is the first report of a child with a brain tumor treated with immunotherapy from India. Our report supports the routine inclusion of immunohistochemistry for mismatch repair proteins in the evaluation of pediatric high-grade glioma as this may directly impact the clinical care of these children and families.

Citation

Avijeet K Mishra, Rimpa B Achari, Lateef Zameer, Gopal Achari, Anisha Gehani, Paromita Roy, Sumedha Sudhaman, Vanessa Bianchi, Melissa Edwards, Saugata Sen, Reghu K Sukumaran, Arpita Bhattacharyya, Uri Tabori, Anirban Das. Germline Biallelic Mismatch Repair Deficiency in Childhood Glioblastoma and Implications for Clinical Management. Neurology India. 2022 Mar-Apr;70(2):772-774