Pancreatic acinar cell carcinoma demonstrates marked clinical heterogeneity and recurrent actionable genomic alterations
9 affiliations
- 1Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, United States
- 2Department of Internal Medicine, Division of Medical Oncology, University of Kansas Medical Center, Westwood, KS, United States
- 3Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, United States
- 4Department of Hematology and Oncology, Wake Forest School of Medicine, Winston-Salem, NC, United States
- 5Department of Internal Medicine, Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, United States
- 6Department of Cancer Biology, University of Kansas Medical Center, Kansas City, KS, United States
- 7Department of Surgery, University of Kansas Medical Center, Kansas City, KS, United States
- 8Division of Gastroenterology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, United States
- 9Division of Gastroenterology and Hepatology, University of Kansas Medical Center, Kansas City, KS, United States
Abstract
Background: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
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BibTeX
@article{farhoud2026pancreatic,
title = {{Pancreatic acinar cell carcinoma demonstrates marked clinical heterogeneity and recurrent actionable genomic alterations}},
author = {Noor Farhoud and Raed Al-Rajabi and Joaquina Baranda and Haoran Li and Ameer Hamza and Wei Zhang and Ravi Paluri and Ashish Manne and Prasad Dandawate and Subhrajit Saha and Timothy Schmitt and Sean Kumer and Clay King and Mojtaba Olyaee and Amit Rastogi and Reza Hejazi and Weijing Sun and Anup Kasi},
journal = {Frontiers in Cell and Developmental Biology},
year = {2026},
month = oct,
doi = {10.3389/fcell.2026.1913398},
url = {https://doi.org/10.3389/fcell.2026.1913398},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Pancreatic acinar cell carcinoma demonstrates marked clinical heterogeneity and recurrent actionable genomic alterations
AU - Noor Farhoud
AU - Raed Al-Rajabi
AU - Joaquina Baranda
AU - Haoran Li
AU - Ameer Hamza
AU - Wei Zhang
AU - Ravi Paluri
AU - Ashish Manne
AU - Prasad Dandawate
AU - Subhrajit Saha
AU - Timothy Schmitt
AU - Sean Kumer
AU - Clay King
AU - Mojtaba Olyaee
AU - Amit Rastogi
AU - Reza Hejazi
AU - Weijing Sun
AU - Anup Kasi
PY - 2026
DA - 2026/10/13
JO - Frontiers in Cell and Developmental Biology
DO - 10.3389/fcell.2026.1913398
UR - https://doi.org/10.3389/fcell.2026.1913398
AB - Background: 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. Methods: 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. Results: 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. Conclusion: 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.
SN - 2296-634X
ER -