Pancreatic acinar cell carcinoma is associated with BRCA2 germline mutations: a case report and literature review

Abstract

Acinar cell carcinoma (ACC) is a rare pancreatic neoplasm with dismal prognosis. Insights into the molecular basis of ACC can pave the way for the application of more effective, personalized therapies and detection of patients with hereditary predisposition. Molecular analysis revealed a germline BRCA2 (and CHEK2) mutation in a patient with a rare pancreatic ACC with extensive intraductal growth. Somatic loss of the wild-type BRCA2 allele in the tumor indicated the causal relationship of ACC with the germline defect. A thorough literature review identified another nine ACCs associated with germline BRCA2 mutation and two ACCs associated with germline BRCA1 mutation, resulting in a prevalence of BRCA1/2 germline mutations in almost 7% of ACCs. Moreover, somatic BRCA1/2 alterations are reported in 16% of sporadic ACCs. Overall, about one fifth (22%) of all pancreatic ACCs exhibit BRCA1/2 deficiency. This study underscores the important role of BRCA1/2 mutations in pancreatic ACC. All ACC patients should undergo genetic testing for BRCA1/2 mutations to identify carriers of pathogenic variants. This will allow to select patients that can benefit from targeted therapies directed against BRCA1/2-deficient tumors and is also crucial as a referral to genetic screening for the relatives of affected individuals carrying germline BRCA1/2 alterations. Abbreviations: ACC: acinar cell carcinoma; HBOC: Hereditary Breast and Ovarian Cancer; LOH: loss of heterozygosity; PARP: poly (ADP-ribose) polymerase; PDAC: pancreatic ductal adenocarcinoma; PP: pancreatic panniculitis; SD: standard deviation; WES: whole-exome sequencing.

Keywords: Acinar cell carcinoma of the pancreas; germline mutation; somatic mutation.

Figure 1.

Fine needle aspiration cytology showed a highly cellular specimen consisting of a monotonous population of single cells and clusters of cells with a moderate amount of basophilic cytoplasm (a). The nuclei are round to oval with moderate anisonucleosis and a single prominent nucleolus (arrows) (b). Histologically the tumor showed extensive intraductal growth in the main pancreatic duct (PD) and side branches (SB) (c). The tumor was composed of uniform cells with granular cytoplasm and nucleoli with a single prominent nucleolus (arrows), forming small lumina (d). Immunohistochemically, the tumor cells were strongly positive for BCL10 (e) and negative for Chromogranin A (f). Note the opposite staining patterns in the adjacent islets of Langerhans (arrows). PD, pancreatic duct; SB, side branch of pancreatic duct.