Pancreatic acinar cell carcinoma demonstrates marked clinical heterogeneity and recurrent actionable genomic...

Pancreatic acinar cell carcinoma (PACC) is a rare pancreatic malignancy with a molecular profile distinct from pancreatic ductal adenocarcinoma (PDAC) but is commonly treated using extrapolated paradigms.

We retrospectively identified patients with histologically confirmed PACC at a tertiary academic center and abstracted clinical, pathologic, treatment, and outcome data. Next-generation sequencing (NGS) was reviewed for microsatellite status, tumor mutational burden, and actionable genomic alterations.

Seven patients were identified (median age, 64 years; 57% male). Most presented with metastatic disease (71%), yet outcomes were heterogeneous, including prolonged progression-free survival exceeding 7 years and 16 years in select patients. Carbohydrate antigen 19-9 (CA 19-9) was normal in all cases, and jaundice was absent despite frequent pancreatic head involvement. All tumors were KRAS wild-type. NGS revealed recurrent alterations including CDKN2A/B and MTAP co-deletion, BRAF fusion, IKZF1 loss, and BAP1 mutation. Tumors were microsatellite stable with low-to-intermediate tumor mutational burden. One patient received matched targeted therapy through a precision oncology trial.

PACC demonstrates substantial clinical heterogeneity with a subset of patients exhibiting prolonged survival despite metastatic disease. Recurrent actionable genomic alterations support routine molecular profiling and prioritization for biomarker-driven trials. These findings challenge extrapolation from PDAC and support a precision oncology framework for this ultra-rare malignancy.