A Case of Adenocarcinoma of Unknown Primary Site in a Lynch Syndrome Patient Responds to Ipilimumab/Nivolumab

Background Adenocarcinomas of unknown primary site are exceedingly rare in patients with Lynch syndrome. Case Presentation We report the case of a 32‐year‐old woman with Lynch syndrome and metastatic adenocarcinoma of unknown primary site. She was found to carry a pathogenic MLH1 deletion and subsequently presented with adenocarcinoma identified in umbilical hernia repair tissue. Diagnostic evaluation revealed liver, spleen, and lymph node metastases. Liver and splenic mass biopsies confirmed metastatic adenocarcinoma with MLH1 and PMS2 deficiency and an elevated tumor mutational burden of 20.1. Despite extensive imaging, endoscopic, and surgical evaluation, no primary site was identified. Treatment with four cycles of combined ipilimumab and nivolumab resulted in a sustained partial response (PR). The patient was rendered NED after a hepatic metastasectomy and remains in complete remission on monthly nivolumab maintenance. Conclusions This case demonstrates the clinical benefit of combined immune checkpoint inhibition in mismatch repair–deficient adenocarcinoma of unknown primary site in a patient with Lynch syndrome.