Pancreatic Neoplasms With Acinar Differentiation: A Review of Pathologic and Molecular Features

Abstract

Context.— Pancreatic acinar lesions encompass a broad spectrum of malignant tumors and benign reactive processes affecting both adults and children, with clinical, pathologic, and molecular features that are distinct from more common ductal neoplasms. Accurate morphologic diagnosis and molecular assessment of these uncommon neoplasms is critical for effective patient care. Objective.— To review the clinical, pathologic, and molecular features of pancreatic neoplasms with acinar differentiation, the most common of which is acinar cell carcinoma but which also includes mixed carcinomas with acinar components, cystic acinar lesions, and pancreatoblastoma. Data Sources.— We assessed the current primary literature, as well as recently updated diagnostic manuals. Conclusions.— Pancreatic acinar neoplasms are a morphologically and molecularly heterogeneous group of diseases that are characterized by acinar differentiation of at least a subset of the neoplastic cells, defined either morphologically (granular cytoplasm, single prominent nucleoli) or immunohistochemically. Squamoid nests are a key morphologic feature of pancreatoblastoma. Alterations in WNT signaling and chromosomal 11p loss are common molecular features of both acinar cell carcinoma and pancreatoblastoma. Targetable molecular alterations in acinar carcinoma include BRAF rearrangements and DNA repair defects, including mismatch repair deficiency and BRCA pathway defects. For practicing pathologists, morphologic recognition of such acinar neoplasms is critical, and in the future, molecular diagnostics to identify lesions susceptible to targeted therapy will likely form an important component of patient care.

Case Report: Two Cases of Metastatic Pancreatoblastoma in Adults: Efficacy of Folfirinox and Implication of the Wnt/β-Catenin Pathway in Genomic Analysis

“…Pathologically, these tumors are considered as part of the "pancreatic carcinomas with acinar differentiation, " with acinar cell carcinomas and carcinomas of mixed differentiation (11). Squamoid nests are the key morphologic feature of pancreatoblastoma; a neuroendocrine component is frequently found (12). On IHC, a very distinctive feature is the abnormal nuclear and cytoplasmic localization of β-catenin, usually restricted to the squamoid nests (12).…”

“…Squamoid nests are the key morphologic feature of pancreatoblastoma; a neuroendocrine component is frequently found (12). On IHC, a very distinctive feature is the abnormal nuclear and cytoplasmic localization of β-catenin, usually restricted to the squamoid nests (12).…”

Molecular alterations in pancreatic tumors

“…Intriguingly, a genome-wide analysis identified no recurrent point mutations in ACCs[ 124 ]. Microsatellite instability was detected in a fraction of ACC ranging from 7% to 14% of cases[ 127 ]. ACC with MSI did not exhibit distinct morphological or clinical features[ 128 ].…”

Optimizing Chemotherapy of Pancreatic Acinar Cell Carcinoma: Our Experiences and Pooled Analysis of Literatures

“…Although acinar cells represent over 80% of the pancreas, pancreatic acinar cell carcinoma (PACC) is rare, accounting for approximately 1% of primary pancreatic neoplasms [1]. Recent studies demonstrated that PACC was quite different from pancreatic ductal cell carcinoma (PDCC) in clinical, pathologic and molecular features and had a signi cantly better survival [2][3][4]. Therapeutic strategy of PACC should be distinguished [1,5,6].…”