Abstract
Constitutional biallelic mismatch repair deficiency CMMR-D is a rare childhood cancer predisposition syndrome. Detection of CMMR-D in pediatric HGG is crucial and can improve patient outcome due to the fact that CMMR-D is responsive to immune checkpoint inhibitors like Nivolumab. A 5 years old girl not known to have any medical illness before presented KFMC (a tertiary pediatric cancer center in Saudi Arabia) with history of headache, vomiting, left eye squint and lethargy. Parents are first degree relatives with strong family history of malignancy. Her brother died at the age of 8 years with refractory non-Hodgkin lymphoma. Imaging showed large intra-axial left frontal complex mass. GTR achieved and pathology revealed glioblastoma. She received radiation and TMZ therapy but her tumor relapsed quickly. Molecular testing performed and revealed germline pathogenic mutation in MSH6 gene which confirmed the diagnosis of CMMRD. After the first 6 doses of Nivolumab, imaging showed regression of the tumor with very good tolerance of the therapy. We tried to avoid doing early MRI scanning as long as our patient continued to be clinically stable to avoid misinterpretation of initial immunotherapy-specific tumor flare. Unanswered question is the optimal duration of immunotherapy. We are planning to continue Nivolumab therapy as long she continues her excellent general condition in the absence of significant progression or severe toxicity with the possibility of second surgical excision in the future if the tumor become more localized.