Biology Over Imaging: Duodenal Adenocarcinoma Recurrence Presenting as a Pancreatic Head Mass in Lynch Syndrome

Duodenal adenocarcinoma (DA) is a rare gastrointestinal malignancy with an increased incidence in patients with Lynch syndrome (LS). Although recurrence following resection is recognised, patterns of relapse are typically predictable, most commonly involving the liver, lymph nodes, or peritoneum. Presentation as a pancreatic mass is exceedingly uncommon and poses a significant diagnostic and treatment challenge. We report the case of a 47-year-old man with PMS2-associated LS who underwent curative resection for DA in 2021. Four years later, he presented with a pancreatic head mass that demonstrated radiological features consistent with a locally advanced (LA) primary pancreatic ductal adenocarcinoma (PDAC). Initial clinical and imaging findings strongly supported this diagnosis. The patient underwent six months of neoadjuvant chemotherapy with significant tumour regression, leading to pancreaticoduodenectomy. Unexpectedly, the final histopathological evaluation revealed the lesion to be a recurrence of the original DA rather than a new PDAC. This report highlights a rare and misleading pattern of recurrence in LS, where tumour biology overrides conventional anatomical assumptions. It underscores the importance of maintaining diagnostic vigilance in patients with hereditary cancer syndromes and supports an aggressive, multidisciplinary approach, including neoadjuvant therapy, even in cases initially presumed to represent locally advanced PDAC. Recognition of such atypical presentations is essential not only for optimising management but also for reinforcing the central role of tumour biology in guiding diagnosis, therapeutic decision-making, and future research in hereditary malignancies.