Staining the Invisible: Immunohistochemistry for Early Detection of Mismatch Repair Deficiency in Pediatric High‐Grade Brain Tumors

Constitutional mismatch repair deficiency (CMMRD) is a rare autosomal recessive cancer predisposition syndrome, affecting primarily individuals from consanguineous families, leading to multiple childhood cancers, particularly high-grade central nervous system (CNS) tumors. We retrospectively analyzed 21 pediatric brain tumor samples for mismatch repair (MMR) protein expression via immunohistochemistry (IHC). One patient (4.7%) with anaplastic astrocytoma showed loss of MSH6. CMMRD was confirmed in this case via genetic testing in a sibling. IHC is a practical, low-cost screening tool, especially in resource-limited settings. Routine IHC for MMR proteins in pediatric high-grade CNS tumors may facilitate early CMMRD detection, optimize treatment, and support genetic counseling.