| CASE REPORT |
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| Year : 2022 | Volume
: 70
| Issue : 2 | Page : 772--774 |
Germline Biallelic Mismatch Repair Deficiency in Childhood Glioblastoma and Implications for Clinical Management
Avijeet K Mishra1, Rimpa B Achari2, Lateef Zameer3, Gopal Achari4, Anisha Gehani5, Paromita Roy3, Sumedha Sudhaman6, Vanessa Bianchi6, Melissa Edwards6, Saugata Sen5, Reghu K Sukumaran1, Arpita Bhattacharyya1, Uri Tabori7, Anirban Das8
1 Department of Pediatric Hematology and Oncology, Tata Medical Center, Kolkata, West Bengal, India
2 Department of Radiation Oncology, Tata Medical Center, Kolkata, West Bengal, India
3 Department of Histopathology, Tata Medical Center, Kolkata, West Bengal, India
4 Department of Neurosurgery, Tata Medical Center, Kolkata, West Bengal, India
5 Department of Radiology, Tata Medical Center, Kolkata, West Bengal, India
6 Peter Gilgan Center for Research and Learning, The Hospital for Sick Children, Toronto, Canada
7 Division of Hematology and Oncology; Peter Gilgan Center for Research and Learning, The Hospital for Sick Children, Toronto, Canada
8 Department of Pediatric Hematology and Oncology, Tata Medical Center, Kolkata, West Bengal, India; Division of Hematology and Oncology; Peter Gilgan Center for Research and Learning, The Hospital for Sick Children, Toronto, Canada
Correspondence Address:
Dr. Anirban Das
Consultant, Pediatric Hematology/Oncology, Tata Medical Center. 14, Major Arterial Road (EW), Rajarhat, New Town, Kolkata - 700 160, West Bengal
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0028-3886.344608
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.
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