Germline BRCA1-Mutated Synchronous and Metachronous Pancreatic Acinar Cell Carcinoma With Long-Term Survival

Sep 21, 2026

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Pancreatic acinar cell carcinoma (PACC) is a rare pancreatic neoplasm. Molecular studies indicate frequent BRCA1/2 mutations and a connection to hereditary breast and ovarian cancer (HBOC), in which cancers often present multifocal and/or metachronous patterns. A 58-year-old man developed synchronous and metachronous PACC, multiple liver metastases, progressed after gemcitabine plus nab-paclitaxel, and then received modified FOLFIRINOX. Comprehensive genomic profiling confirmed a germline BRCA1 pathogenic variant and guided subsequent olaparib therapy, while cascade testing initiated HBOC surveillance in relatives.

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Case

Cancer Reports CASE REPORT OPEN ACCESS Germline BRCA1-Mutated Synchronous and Metachronous Pancreatic Acinar Cell Carcinoma With Long-Term Survival Tomohiro Kubo1 | Yuki Ikeda1 | Joji Muramatu1 | Kazuma Ishikawa1 | Makoto Yoshida1 | Kazuharu Kukita2 | Masafumi Imamura2 | Shintaro Sugita3 | Akihiro Sakurai4 | Kohichi Takada1 1Department of Medical Oncology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan | 2Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan | 3Department of Surgical Pathology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan | 4Department of Medical Genetics and Genomics, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan Correspondence: Kohichi Takada ([ktakada@sapmed.ac.jp](ktakada@sapmed.ac.jp)) Received: 30 April 2024 | Revised: 29 July 2024 | Accepted: 10 August 2024 Keywords: germline BRCA1 mutation | HBOC | pancreatic acinar cell carcinoma | synchronous and metachronous tumor ABSTRACT Background: Pancreatic acinar cell carcinoma (PACC) is a rare pancreatic neoplasm. Recently, molecular analysis revealed that PACC shows a high frequency of the BRCA1/2 mutation and is likely to be considered a cancer associated with hereditary breast and ovarian cancer (HBOC). Hereditary cancers, including HBOC, are characterized by multifocal and/or metachronous tumors. However, no case reports exist of germline BRCA1-mutated synchronous and metachronous PACC. Case: A 58-year-old man was diagnosed with synchronous and metachronous PACC at the age of 56 and underwent two surgeries. Ten months after the second surgery, the patient developed multiple liver metastases. Gemcitabine plus nab-paclitaxel therapy was administered as first-line chemotherapy. After seven cycles, computed tomography examination revealed progressive disease (PD). Therefore, modified FOLFIRINOX (mFFX) was administered as second-line chemotherapy. After 19 cycles of mFFX, comprehensive cancer genomic profiling (CGP) identified a BRCA1 pathogenic variant that was confirmed to be germline origin. Accordingly, we treated the patient with olaparib; however, he was diagnosed with PD after 4 months. He subsequently died 5 years and 9 months after the initial surgery, and 3years and 10 months after chemotherapy. Based on the genetic data of the patients, his family members received genetic counseling followed by cascade testing. Consequently, the same gBRCA1 pathogenic variant was detected in the son and his surveillance for HBOC-related cancers was initiated. Conclusion: We diagnosed a 58-year-old man with a synchronous and metachronous PACC with germline BRCA1 pathogenic variant. Considering that PACC is likely to have BRCA1/2 mutations responsible for HBOC, we need to be aware of the possible presence of multifocal and/or metachronous tumors in patients with PACC. Additionally, patients with PACC should undergo genetic examinations, which would be beneficial in determining treatment strategies and health care for blood relatives. 1 | Introduction Pancreatic acinar cell carcinoma (PACC) accounts for approximately 1% of pancreatic neoplasms and is considered a relatively rare tumor [1] . Several differences exist, in terms of biological behaviors and gene signatures, between PACC and pancreatic ductal adenocarcinoma (PDAC) . Recent reports have shown that PACC has a distinctive mutational landscape [2–5] . PACC exhibits a higher frequency of BRCA1/2 mutations compared to PDAC and is more likely to be an This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC. Cancer Reports, 2024; 7:e70007 [https://doi.org/10.1002/cnr2.70007](https://doi.org/10.1002/cnr2.70007) 1 o

FAQs

What makes germline BRCA1–mutated PACC clinically important in this case?

The report highlights an HBOC-associated PACC with synchronous and metachronous tumors and later confirmed a germline BRCA1 pathogenic variant. This supports awareness of multifocal/metachronous disease patterns and the need for genetic evaluation.

How was the patient treated after progression on first-line chemotherapy?

After gemcitabine plus nab-paclitaxel led to progressive disease, the patient received modified FOLFIRINOX as second-line chemotherapy. Comprehensive genomic profiling then identified a germline BRCA1 variant, leading to olaparib treatment.

What role did genetic counseling and testing play for the patient’s family?

Following identification of the germline BRCA1 pathogenic variant, family members received genetic counseling and cascade testing. The son carried the same variant and initiated surveillance for HBOC-related cancers.

Sep 21, 2026

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