Pancreatic acinar cell carcinoma: A review on molecular profiling of patient tumors

Abstract

Pancreatic carcinomas with acinar differentiation are rare, accounting for 1%-2% of adult pancreatic tumors; they include pancreatic acinar cell carcinoma (PACC), pancreatoblastoma, and carcinomas of mixed differentiation. Patients with PACC have a prognosis better than pancreatic ductal adenocarcinomas but worse than pancreatic neuroendocrine tumors. Reports of overall survival range from 18 to 47 mo. A literature review on PACCs included comprehensive genomic profiling and whole exome sequencing on a series of more than 70 patients as well as other diagnostic studies including immunohistochemistry. Surgical resection of PACC is the preferred treatment for localized and resectable tumors. The efficacy of adjuvant treatment is unclear. Metastatic PACCs are generally not curable and treated with systemic chemotherapy. They are moderately responsive to chemotherapy with different regimens showing various degrees of response in case reports/series. Most of these regimens were developed to treat patients with pancreatic ductal adenocarcinomas or colorectal adenocarcinomas. Review of PACC’s molecular profiling showed a number of gene alterations such as: SMAD4, BRAF, BRCA2, TP53, RB1, MEN1, JAK-1, BRCA-1, BRCA-2, and DNA mismatch repair abnormalities. PACCs had multiple somatic mutations with some targetable with available drugs. Therefore, molecular profiling of PACC should be an option for patients with refractory PACC.

Response of germline BRCA2-mutated advanced pancreatic acinar cell carcinoma to olaparib

“…Among these, the BRCA2 mutation, the major breast cancer susceptibility gene, has been widely studied in breast and ovarian cancers, and accounts for 4% to 43% in relevant research. [ 19 – 24 ] A woman who carries a germline BRCA2 mutation could be 5 times more likely to have breast cancer than one who does not carry the mutation. Similarly, men who have the BRCA2 mutations are 8.6 times more likely to develop a prostate malignancy and 2.13- to 21.7-fold more likely to develop pancreatic carcinoma.…”

Pancreatic acinar cell carcinoma—case report and literature review

“…Acinar cell carcinoma (ACC) represents approximately 1% of all pancreatic neoplasms, which primarily occur in late adulthood [ 8 , 9 ], with a male to female ratio of 3.6:1 [ 10 ]. Most patients with pancreatic ACC have no specific symptoms, and the non-specific clinical symptoms include weight loss (52%), abdominal pain (32%), nausea and vomiting (20%), melena (12%), weakness, anorexia or diarrhea (8%) [ 11 ].…”

Successful BRAF/MEK inhibition in a patient with BRAFV600E-mutated extrapancreatic acinar cell carcinoma

“…Distinguishing this uncommon presentation from metastatic PAC is mandatory for appropriate therapy and prognostification (Agaimy et al 2011). Although the clinical course tends to be more favorable in comparison to PDACs, unresectable or metastatic disease is still associated with a poor prognosis and overall survival ranges between 18 and 47 mo (Al-Hader et al 2017). Despite recent work on the molecular pathogenesis, these tumors are still poorly understood.…”

“…Immunohistochemistry revealed DCC reduction or loss, MYC amplification, and increased epidermal growth factor receptor (EGFR) expression in major subgroups of 57 tumor samples investigated (Bergmann et al 2014). Sequencing analyses identified mutations in TP53, ARID1A, BRAF, SMAD4, BRCA1, BRCA2, CDKN2A, CTNNB1, RB1, MEN1, MYC, JAK1, APC, GNAS, and FAT (Furlan et al 2014;Jiao et al 2014;Al-Hader et al 2017;Jakel et al 2017;La Rosa et al 2018) as well as enrichment of mutational signatures linked to tobacco exposition or defective DNA repair mechanisms in some cases (Jakel et al 2017). Mismatch repair deficiency has been reported in up to 14% of cases (Al-Hader et al 2017).…”