Clinically aggressive early-onset pancreatic ductal adenocarcinoma with KRAS wild-type status: A case report

Pancreatic ductal adenocarcinoma (PDAC) represents one of the most lethal and challenging gastrointestinal (GI) malignancies. Predominant driver mutations for this cancer include KRAS, which is present in >90% of cases, alongside inactivating mutations in various tumor suppressor genes, such as CDKN2A, TP53 and SMAD4. The present case report explores a case of early onset pancreatic cancer in a 45-year-old patient with cancer antigen 19-9 (CA 19-9) levels within the minimal range, a finding typically associated with advanced disease. Specifically, the tumor exhibited an atypical somatic molecular profile, characterized by mutations in the ERBB2, MSH3, MUC1/MUC16 genes and the absence of KRAS mutations (KRAS wild type), which is an uncommon occurrence in PDAC. The presence of liver metastases and vascular invasion at diagnosis, coupled with the lack of response to standard FOLFIRINOX treatment, underscored the aggressiveness of the disease and highlighted the need to explore novel targeted therapies. The patient underwent surgery and has maintained a favorable response to date. This case of PDAC in a relatively young patient underscored a distinctive molecular profile that especially lacked KRAS mutations whilst featuring alterations in ERBB2, MSH3 and MUC1/MUC16, potentially indicating a unique subgroup with unique biological and treatment responses. Additionally, CA19-9 levels within the minimal range suggest the need to identify alternative novel biomarkers with adequate sensitivity and specificity. This is because in >80% PDAC cases with stage II disease and beyond, CA-19-9 levels are elevated. The rarity of the present case, combined with the rapid progression despite FOLFIRINOX treatment, suggests that additional human epidermal growth factor receptor 2-targeted therapies may be necessary during disease progression.