Clinicopathologic and genomic landscape of pancreatic acinar cell carcinoma: A single-center experience.

e16484 Background: Pancreatic acinar cell carcinoma (PACC) is an ultra-rare (~1%) pancreatic malignancy. Management is often extrapolated from pancreatic ductal adenocarcinoma (PDAC) despite distinct molecular drivers. We characterize the clinicopathologic and genomic features of PACC at our center to identify precision oncology targets. Methods: A retrospective review of histologically confirmed PACC at a tertiary academic center was performed. Clinical, radiographic, pathologic, treatment, and outcome data were extracted. Standard of care next-generation sequencing (NGS) results were reviewed, with focus on potentially actionable alterations. Results: Seven patients were identified (median age 64, range 46–70; 57% male). Symptoms included abdominal pain and weight loss; notably, jaundice was absent. Pathologic evaluation demonstrated variable lymph node involvement, lymphovascular and perineural invasion, and occasional mixed acinar neuroendocrine differentiation. NGS was performed in a subset of patients and actionable alterations included 9p21.3 co-deletion (CDKN2A/B and MTAP loss), IZKF1 loss, SEC24D-BRAF fusion, and BAP1 mutation (Table 1). All were KRAS wild-type. Surgical resection was performed in three patients, and FOLFIRINOX chemotherapy was commonly used. Treatment responses varied. A swimmer plot analysis revealed that 2/7 patients had prolonged progression-free survival ( > 90months and > 200months), while the remaining patients had follow-up < 5 years. At the time of data reporting, four patients were alive without disease recurrence and under ongoing surveillance. Conclusions: Our cohort confirms PACC is molecularly distinct from PDAC, characterized by absence of KRAS mutation and high prevalence of targetable alterations. The identification of MTAP loss and BRAF alteration suggests that PACC patients should be prioritized for specific precision medicine trials (e.g., PRMT5 or MAPK inhibitors) rather than traditional PDAC regimens. Early NGS is mandatory to optimize precision treatment in this rare cancer. Patient Age Sex Presenting Symptoms Tumor Location Resection performed NGS Findings MSI Status TMB Potential Target 1 46 F Abdominal pain, nausea, bloating, fatigue Head Yes Not tested Not tested Not tested N/A 2 68 F Pruritis, abdominal pain, appetite loss, constipation/diarrhea Head Yes TP53 mutation; KRAS wild type; CDKN2A/B loss; MTAP loss; SEC24D-BRAF fusion MSS Intermediate BRAF/MEK/PRMT5 inhibitors 3 67 M Abdominal pain Head Attempted (aborted) Not tested Not tested Not tested N/A 4 70 M Flank pain and hematuria Head No Not tested Not tested Not tested N/A 5 86 F Asymptomatic (incidental lab finding) Head No BAP1 mutation MSS 6.6 EZH2 inhibitors 6 55 M Abdominal pain Tail No CDKN2 A/B loss; IKZF1 loss; MTAP loss; KRAS wild type MSS 6.8