Pancreatic Neuroendocrine Tumor in Lynch Syndrome: Expanding the Tumor Spectrum of Mismatch Repair Deficiency

Lynch syndrome is an autosomal dominant hereditary cancer syndrome caused by germline mutations in DNA mismatch repair genes. Currently, Lynch syndrome has well-established associations with colorectal and endometrial cancers. However, a definitive association between Lynch syndrome and pancreatic neuroendocrine tumors (P-NETs) remains unestablished. Herein, we report the case of a 38-year-old male with a maternal family history of Lynch syndrome who presented with hypoglycemia, abdominal pain, and diarrhea. Imaging revealed a 5.6 cm pancreatic tail mass with hepatic, lymph node, and osseous metastases. Synchronous sigmoid adenocarcinoma was identified during admission. Germline testing confirmed a pathogenic MLH1 mutation, and liver biopsy of the P-NET demonstrated loss of MLH1 and PMS2 expression. The patient was treated with capecitabine and temozolomide (CAPTEM) chemotherapy, pembrolizumab, long-acting repeatable octreotide (octreotide LAR), and diazoxide for hypoglycemia management. Disease progression with spinal epidural extension necessitated palliative radiation and intravenous immunoglobulin for severe thrombocytopenia. This case highlights the expanding phenotypic spectrum of Lynch syndrome and suggests that P-NETs may represent a rare but clinically significant manifestation. Early recognition of this association supports comprehensive genetic testing, enables the use of precision immunotherapy, and underscores the need for expanded surveillance strategies in patients with atypical tumor profiles.