Acinar Cell Carcinoma of the Pancreas: Overview of Clinicopathologic Features and Insights into the Molecular Pathology

Abstract

Acinar cell carcinomas (ACCs) of the pancreas are rare pancreatic neoplasms accounting for about 1-2% of pancreatic tumors in adults and about 15% in pediatric subjects. They show different clinical symptoms at presentation, different morphological features, different outcomes, and different molecular alterations. This heterogeneous clinicopathological spectrum may give rise to difficulties in the clinical and pathological diagnosis with consequential therapeutic and prognostic implications. The molecular mechanisms involved in the onset and progression of ACCs are still not completely understood, although in recent years, several attempts have been made to clarify the molecular mechanisms involved in ACC biology. In this paper, we will review the main clinicopathological and molecular features of pancreatic ACCs of both adult and pediatric subjects to give the reader a comprehensive overview of this rare tumor type.

Keywords: acinar cell carcinoma; immunohistochemistry; molecular pathology; morphology; pancreas.

Figure 1

Macroscopic appearance of a well circumscribed and large acinar cell carcinoma of the pancreatic head.

Figure 2

At scan magnification, most acinar cell carcinomas appear highly cellular with a lobular architecture and scant fibrous stroma. Abundant necrosis (right) is frequently observed. These morphological features can help in the differential diagnosis with the more common ductal adenocarcinoma that is generally less cellular, shows abundant fibrous stroma without or with focal necrosis.

Figure 3

Acinar cell carcinomas may have different histological features. The acinar architectural pattern (A) is characterized by cells forming structures resembling normal pancreatic acini, sometimes with minute lumens. Cells are in a monolayer with basally located nuclei and have a moderate amount of granular eosinophilic cytoplasm. The glandular pattern (B) is characterized by proliferation of cells, sometimes arranged in multiple layers, forming glandular structures. The trabecular pattern (C) is characterized by trabecular structures formed by ribbons of cells strongly resembling the morphology of pancreatic neuroendocrine tumors. The solid pattern (D) is characterized by large sheets of poorly differentiated cells without lumens that generally show large nuclei with dispersed chromatin and prominent nucleoli.

Figure 4

Uncommon histological features of pancreatic acinar cell carcinomas include oncocytic cells (A), spindle cells (B), pleomorphic cells (C), and clear cells (D).

Figure 5

Mixed acinar-neuroendocrine carcinomas (MANECs) are composed of both acinar and neuroendocrine components and each must represent at least 30% of the tumor tissue. The neuroendocrine component is very difficult to identify morphologically on H&E stained sections (A). The use of immunohistochemistry employing antibodies directed against general neuroendocrine [(B) chromogranin A] and acinar markers [(C) BCL10] is mandatory for the diagnosis.

Figure 6

(A) Mixed acinar-ductal adenocarcinoma is a neoplasm showing both acinar (top right corner) and ductal differentiation. Neoplastic glands are generally surrounded by a desmoplastic stroma similarly to ordinary ductal adenocarcinomas. The acinar component is easily identifiable using acinar cell markers including BCL10 (B).

Figure 7

At the ultrastructural level, tumor cells contain large electron-dense granules, abundant rough endoplasmic reticulum, well-developed Golgi complexes, and some mitochondria.

Figure 8

Antibodies directed against trypsin (A) and BCL10 (B) are the best in terms of sensitivity in detecting acinar cell carcinoma. The immunoreactivity is cytoplasmic and strong.

Figure 9

Acinar cell carcinomas frequently show scattered chromogranin A-positive neuroendocrine cells (A), but for the diagnosis of MANEC they must represent at least 30% of the tumor tissue (see Figure 5). Acinar cell carcinomas may also express cytokeratin 7 (B) and cytokeratin 19 (C), which are traditionally known markers of ductal adenocarcinomas. PDX1 immunoreactivity (D) is observed in about 90% of cases, while nuclear positivity for β-catenin (E) in about 15% of cases. Strong nuclear immunoreactivity for p53 (F) can be found in about 30% of carcinomas and its prognostic meaning is not clear, to date.

Figure 10

Acinar cell carcinoma in a 1-year-old boy characterized by a trabecular growth (A) resembling that of a pancreatic neuroendocrine tumor. However, tumor cells are strongly immunoreactivity for trypsin (B).