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.

The surgical management of metastatic pancreatic acinar cell carcinoma and associated pancreatic panniculitis—A case report and literature review

“…Finally, pancreatic ACCs are well known to be associated with germline mutations of the BRCA2 gene [ 21 ]. Thus, patients diagnosed with pancreatic ACC should be referred for genetic counselling and tested for BRCA2 mutations.…”

Survival outcomes in men with a positive family history of prostate cancer: a registry based study

“…pancreatic, breast, ovarian). These cancers may also be relevant in investigating genes that confer lifetime risks of prostate cancer, such as BRCA1 and BRCA2 [ 22 – 24 ]. The demographic and clinical differences between the groups may confound the observations made.…”

The contemporary trend in worsening prognosis of pancreatic acinar cell carcinoma: A population-based study

“…One of the features of ACC is the expression of pancreatic enzymes, such as pancreatin, chymotrypsin, and lipase, which are stored in the larger cytoplasmic proenzyme granules [3]. Most patients have no specific symptoms, except those with excessive lipase secretion (about 15% of patients), who may develop symptoms of lipomemeitis such as joint pain, subcutaneous fat necrosis/nodules [3][4][5]. Thus, 50-60% of patients have advanced or metastasis disease at the time of diagnosis, resulting in a low survival rate and poor overall survival (OS) [4].…”

“…Most patients have no specific symptoms, except those with excessive lipase secretion (about 15% of patients), who may develop symptoms of lipomemeitis such as joint pain, subcutaneous fat necrosis/nodules [3][4][5]. Thus, 50-60% of patients have advanced or metastasis disease at the time of diagnosis, resulting in a low survival rate and poor overall survival (OS) [4]. Another reason for the poor prognosis is the lack of standardized treatment for ACC.…”

“…Due to the rarity of ACC, prospective studies are generally not readily available. Most of the existing studies are small samples, single-center retrospective case reports or case series [2,4,[7][8][9][10], making it difficult to obtain meaningful hypotheses about the clinical characteristics and treatment of ACC patients. To the best of our knowledge, only three studies have reported ACC based on large public databases [11][12][13].…”