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.

Keywords: Molecular profiling; Pancreatic acinar cell carcinoma; Targeted therapy.

Figure 1

Different histological forms of pancreatic acinar cell carcinomas. A: A case of PACC displaying nested to glandular growth patterns (HE 40 ×); B: Higher magnification of the same tumor in Panel A showing monotonous cells with eosinophilic/granular cytoplasm with well-defined cell borders and uniform nuclei with minimal atypia and prominent nucleoli (HE 200 ×); C: Tumor from a different patient showing a predominantly sheet-like growth with no distinct pattern (HE 40 ×). D: Higher magnification of the same tumor in C showing uniform cells with eosinophilic granular cytoplasm (prominent zymogen granules) with minimal pleomorphism (HE 200 ×). Inset: mitotic figures were identified throughout the tumor (HE 400 ×).