Pancreatic Ductal Adenocarcinoma with Atypical Genomic Profile: A Case of Long-Term Survival with KRAS-Wildtype, Microsatellite Instability and High Tumor Mutational Burden.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies, typically associated with late-stage diagnosis and limited survival despite advances in systemic therapy. Long-term survival in metastatic PDAC is exceedingly rare, and treatment strategies are limited by the intrinsic resistance of the tumor to standard therapies. However, emerging evidence suggests that molecular subtypes may exhibit distinct biological behaviors and may be amenable to new therapeutic options.

CASE PRESENTATION: We report the remarkable long-term survival of a 43-year-old male with a blank medical history, diagnosed with metastatic PDAC in 2018. The patient presented with postprandial upper abdominal discomfort that progressed to obstructive jaundice, leading to the discovery of a pancreatic head mass with metastatic lymphadenopathy. Despite the poor prognosis typically associated with metastatic PDAC, the patient achieved significant disease control through FOLFIRINOX chemotherapy and underwent surgical resection following complications from vascular involvement. Next-generation sequencing (NGS) revealed a rare KRAS-wildtype tumor with microsatellite instability (MSI) and a high tumor mutational burden (TMB). Moreover, a long-standing suspicion of Lynch syndrome could finally be confirmed.

CONCLUSION: This case highlights the potential impact of personalized treatment and molecular tumor profiling in reshaping the outlook for PDAC patients.