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

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2024-08-26 DOI:10.1002/cnr2.70007

Tomohiro Kubo, Yuki Ikeda, Joji Muramatu, Kazuma Ishikawa, Makoto Yoshida, Kazuharu Kukita, Masafumi Imamura, Shintaro Sugita, Akihiro Sakurai, Kohichi Takada

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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 3 years 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.

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胚系 BRCA1 基因突变的同步性和近同步性胰腺尖状细胞癌的长期存活率

背景：胰腺尖细胞癌（PACC）是一种罕见的胰腺肿瘤。最近，分子分析表明，PACC显示出高频率的BRCA1/2突变，很可能被认为是与遗传性乳腺癌和卵巢癌（HBOC）相关的癌症。包括 HBOC 在内的遗传性癌症的特点是多灶性和/或隐性肿瘤。然而，目前还没有关于种系BRCA1突变的同步和近同步PACC的病例报告：病例：一名 58 岁的男性在 56 岁时被诊断为同步和近同步性 PACC，并接受了两次手术。第二次手术后 10 个月，患者出现多发性肝转移。吉西他滨加纳布紫杉醇疗法作为一线化疗。七个周期后，计算机断层扫描检查发现疾病进展（PD）。因此，二线化疗采用了改良 FOLFIRINOX（mFFX）。经过19个周期的mFFX治疗后，综合癌症基因组图谱（CGP）发现了一个BRCA1致病变异体，并证实该变异体为种系来源。因此，我们用奥拉帕尼对患者进行了治疗；然而，4个月后，他被诊断为肺结核。随后，他在初次手术 5 年 9 个月后死亡，化疗 3 年 10 个月后死亡。根据患者的基因数据，他的家人接受了基因咨询，随后进行了级联检测。结果，在其子体内检测到了相同的 gBRCA1 致病变体，并开始对其进行 HBOC 相关癌症的监测：结论：我们诊断出一名 58 岁男性患有同步和近同步 PACC，并伴有种系 BRCA1 致病变异。考虑到PACC很可能与导致HBOC的BRCA1/2基因突变有关，我们需要注意PACC患者中可能存在多灶和/或间期肿瘤。此外，PACC 患者应接受基因检查，这将有利于确定治疗策略和血亲的医疗保健。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.