Pathology and genetics of pancreatic neoplasms with acinar differentiation

Abstract

Pancreatic neoplasms with acinar differentiation, including acinar cell carcinoma, pancreatoblastoma, and carcinomas with mixed differentiation, are distinctive pancreatic neoplasms with a poor prognosis. These neoplasms are clinically, pathologically, and genetically unique when compared to other more common pancreatic neoplasms. Most occur in adults, although pancreatoblastomas usually affect children under 10 years old. All of these neoplasms exhibit characteristic histologic features including a solid or acinar growth pattern, dense neoplastic cellularity, uniform nuclei with prominent nucleoli, and granular eosinophilic cytoplasm. Exocrine enzymes are detectable by immunohistochemistry and, for carcinomas with mixed differentiation, neuroendocrine or ductal lineage markers are also expressed. The genetic alterations of this family of neoplasms largely differ from conventional ductal adenocarcinomas, with only rare mutations in TP53, KRAS, and p16, but no single gene or neoplastic pathway is consistently altered in acinar neoplasms. Instead, there is striking genomic instability, and a subset of cases has mutations in the APC/β-catenin pathway, mutations in SMAD4, RAF gene family fusions, or microsatellite instability. Therapeutically targetable mutations are often present. This review summarizes the clinical and pathologic features of acinar neoplasms and reviews the current molecular data on these uncommon tumors.

Metastatic Renal Cell Carcinoma to the Pancreas: A Review

“…29 Acinar cell carcinoma of the pancreas may look like metastatic chromophobe renal cell carcinoma because both may contain eosinophilic granular cytoplasm. In contrast to the uniform nuclear characteristics of acinar cell carcinoma, 30 the nuclei of chromophobe renal cell carcinoma are often irregular and described as ''raisenoid.'' On immunohistochemistry stains, demonstration of positivity for trypsin and chymotrypsin on immunohistochemistry is more in keeping with an acinar cell carcinoma.…”

“…On immunohistochemistry stains, demonstration of positivity for trypsin and chymotrypsin on immunohistochemistry is more in keeping with an acinar cell carcinoma. 30 Metastatic chromophobe renal cell carcinoma may display neoplastic cells with eosinophilic cytoplasm arranged in a somewhat organoid appearance in association with a delicate vascular network, 29 and thus it may be mistaken for a pancreatic endocrine neoplasm. Attention to nuclear detail differences between pancreatic endocrine neoplasm and chromophobe renal cell carcinoma is useful in segregating these 2 entities.…”

A Pediatric Case of Mixed Acinar-Neuroendocrine Carcinoma

“…Several studies have compared the characteristics of MANEC with those of other malignant pancreatic tumors. MANEC has a wide range of pathological characteristics [9,10]. For example, some mixed acinar-ductal carcinomas exhibit intracellular or stromal mucin as evidence of ductal differentiation, whereas others have separate components of individual glands surrounded by desmoplastic stroma [10].…”

Adult pancreatoblastoma: A case report and review of the literature

“…However, mutations of the adenomatous polyposis coli/β-catenin pathway have been described, and allelic loss on chromosome 11p (Wnt signaling pathway) is the most common type of genetic alteration that has been identified in PB (12,15,26,35,36). Furthermore, numerous paediatric cases of PB have occurred in patients with Beckwith-Wiedemann syndrome and familial adenomatous polyposis (12,15,19,26,32).…”