A Case Report of Lynch Syndrome: Clinical Course and Literature Review

Lynch syndrome (LS) is a hereditary cancer predisposition syndrome caused by germline defects in DNA mismatch repair (MMR) genes. While colorectal cancer is its most common manifestation, small bowel adenocarcinoma (SBA) remains a rare occurrence and often presents with nonspecific symptoms, contributing to delayed diagnosis. We present the case of a 76-year-old woman with Lynch syndrome who initially presented with anorexia, fatigue, and abdominal pain. Initial gastroscopy and colonoscopy were unrevealing. However, with progressive symptoms and rising tumor markers, further evaluation with positron emission tomography–computed tomography (PET-CT) and double-balloon enteroscopy led to the diagnosis of moderately differentiated duodenal adenocarcinoma. Immunohistochemical analysis confirmed microsatellite instability (MSI). Given her personal and family history of colorectal neoplasms, a clinical diagnosis of Lynch syndrome was established. The patient exhibited poor tolerance to platinum-based chemotherapy and was subsequently treated with a programmed cell death protein 1 (PD-1) inhibitor, resulting in transient clinical improvement. In the later course, her illness was complicated by exacerbation of pre-existing Sjögren’s syndrome and severe opportunistic infections, culminating in acute respiratory distress syndrome and multiorgan failure, ultimately leading to death. This case highlights the elevated risk of multiple primary malignancies in Lynch syndrome, the diagnostic challenges associated with SBA, and the pivotal role of MSI status in guiding immunotherapy. It also underscores the need for careful monitoring of immune-related adverse events, particularly in patients with underlying autoimmune diseases.