Pancreatic acinar cell carcinoma (pACC) is a rare and aggressive malignancy that lacks standardized diagnostic and therapeutic guidelines. It typically presents at an advanced stage, with nonspecific symptoms and large tumors, often exceeding 5 cm and sometimes metastatic. Traditional biomarkers such as CA19-9 and CEA are elevated in fewer than 20 percent of cases (n=40), underscoring the limited utility of conventional diagnostics and the need for further molecular profiling.
This study integrates clinical characteristics, biomarker trends, genomic alterations, and treatment patterns based on case reports and retrospective studies (2008–2025), along with original analyses of SEER and cBioPortal datasets. Statistical methods included generalized linear models, ANOVA, and Tukey’s HSD post-hoc tests.
Genomic analysis revealed several amplifications more frequent in pACC than in pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine tumors (PNETs), including ELOC (p=0.0001 vs. PDAC), ELF3 (p=0.0014 vs. PDAC), AGO2 and RECQL4 (both p<0.001 vs. PDAC and PNET), and MYC (p=0.0045 vs. PNET). TEK deep deletions (p=0.026 vs. PNET) may compromise angiogenesis and contribute to tumor progression.
Mutations in tumor suppressor and immune-regulatory genes were also observed. PTEN, TP53, and MEN1 mutations were significantly more common in pACC than in PDAC (p<0.001), while CTNNB1 and MEN1 were more frequent compared to PNETs (p<0.05). RB1 mutations occurred less often in pACC than in both PDAC and PNET (p<0.05). ZNRF3 and HLA-C mutations appeared unique to pACC, suggesting distinct immune evasion mechanisms. Structural variants involving BRAF (p<0.001) and SND1-BRAF (p=0.0015) were also more frequent in pACC.
SEER data revealed racial and ethnic differences in pACC incidence, with Non-Hispanic White individuals exhibiting higher rates than Black, Asian, or Hispanic populations. Survival varied by sequencing of radiation and surgery, as well as whether intervention recommendations were documented.
These findings highlight the distinct molecular and clinical landscape of pACC, underscoring the need for comprehensive genomic profiling to inform early detection and personalized treatment strategies.