背景:胰腺腺泡细胞癌(PACC)是一种罕见的胰腺肿瘤。最近,分子分析显示,PACC显示出高频率的BRCA1/2突变,并且可能被认为是与遗传性乳腺癌和卵巢癌(HBOC)相关的癌症。遗传性癌症,包括HBOC,以多灶性和/或异时性肿瘤为特征。然而,没有种系BRCA1突变的同步和异时PACC的病例报告。
方法:一名58岁男子在56岁时被诊断为同步和异期PACC,并接受了两次手术。第二次手术10个月后,患者出现多发肝转移.吉西他滨联合nab-紫杉醇治疗作为一线化疗。经过七个周期,计算机断层扫描检查显示进行性疾病(PD)。因此,改良FOLFIRINOX(mFFX)作为二线化疗给药。经过19次mFFX循环后,综合癌症基因组分析(CGP)鉴定出一个BRCA1致病变异体,该变异体被证实是种系起源.因此,我们用奥拉帕利治疗了病人;然而,4个月后被诊断为PD.他随后在初次手术后5年零9个月死亡,化疗后3年10个月。根据病人的基因数据,他的家人接受了遗传咨询,然后进行了级联测试。因此,在儿子中检测到相同的gBRCA1致病性变异,并开始对他的HBOC相关癌症进行监测.
结论:我们诊断出一名58岁的男性患者,其PACC具有种系BRCA1致病变异。考虑到PACC可能有BRCA1/2突变负责HBOC,我们需要意识到PACC患者可能存在多灶性和/或异时性肿瘤.此外,PACC患者应该接受基因检查,这将有助于确定血亲的治疗策略和医疗保健。
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.
METHODS: 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.
CONCLUSIONS: 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.