Acinar Cell Carcinoma of the Pancreas.

A 50-year-old white man presented with hyperglycemia and a 6-month history of changes in bowel habits, bloating, epigastric pain that radiated to his back, an 11.3kg weight loss, and ultimately dark brown urine and jaundice. He underwent an abdominal computer-assisted tomographic scan and endoscopic retrograde cholangiopancreatography, which revealed a pancreatic mass. A stent was placed in the ampulla, and he was referred for surgical evaluation of the pancreatic mass. A radical pancreaticoduodenectomy (Whipple procedure) was performed. The common bile duct was 1 cm in diameter. Three peri-pancreatic lymph nodes were enlarged up to 4 cm in diameter The lymph nodes were difficult to dissect because of fibrosis to adjacent structures. Within the head of the pancreas, a firm nodular mass was identified. The remaining pancreas had a rocklike consistency.

The surgical specimen consisted of the distal portion of the stomach, proximal portion of duodenum, and proximal portion of pancreas with attached gallbladder and cystic duct. The cut surface of the enlarged peripancreatic lymph nodes showed a nodular area of effacement. The nodes were tan-pink and had confluent areas of hemorrhage and necrosis. There was a tumor within the head of the pancreas, 1.6 cm in diameter, that was located medial to the common bile duct. The cut surface had an appearance similar to that of the enlarged lymph node. A total of 17 lymph nodes were dissected, 3 of which were positive for tumor metastases.

Microscopically, the tumor was strikingly cellular and divided into lobulations by thin fibrous strands. The tumor extended into adjacent pancreatic tissue in a scalloped nodular configuration. While there were areas displaying uniform solid nests of tumor cells, the regular "acinar" with back-to-back glandular arrangement was a predominant pattern throughout the tumor (Figure, A). The tumor cells had a granular eosinophilic cytoplasm. The nuclei were basal in orientation, hyperchromatic, and showed slight variability in size and shape. The mitotic count was low ([is less than] 1/10 high-power fields). There was a positive periodic acid-Schiff reaction following diastase digestion within apical cytoplasmic tips (Figure, B). Mucicarmine was sparsely positive. Staining for neuroendocrine markers, including chromogranin, synaptophysin, glucagon, somatostatin, gastrin, and vasoactive intestinal peptide, was negative. Electron microscopy showed acinar structures with short microvilli. Within the apical tips were numerous, single membrane-bound, variably electron-dense granules that ranged in size from 300 to 500 nm (Figure, C). A diagnosis of acinar cell carcinoma (ACC) was rendered.

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Acinar cell carcinoma is a pancreatic epithelial tumor that occasionally can have a neuroendocrine component. It is an uncommon tumor, representing only 1% to 2% of all exocrine tumors of the pancreas. While acinar tumor cells are reminiscent of cells found in a low-grade neuroendocrine tumor, a neuroendocrine immunohistochemical workup rarely reveals positive results. These tumor cells usually stain for 1 of the tumor markers of exocrine pancreas, such as trypsin, lipase, chymotrypsin, and phospholipase [A.sub.2]. Keratin CAM 5.2 is present in all acinar tumor cells.[1] Rarely, ACCs stain for carcinoembryonic antigen and [Alpha]-fetoprotein. Positivity to synaptophysin and chromogranin have been found in up to one fourth of these tumors. Some ACC cells also stain for somatostatin and glucagon.[2]

On electron microscopy, large electron-dense granules (400-500 nm, with a range of 170-1800 nm) are identified within the apical portion of these acinar complexes. While some of these granules are zymogen, occasionally neuroendocrine secretory granules may be identified (75-350 nm). Some authors refer to these tumors as "acinar-endocrine cell tumors."[1]

Differential diagnoses include endocrine tumors, solid pseudopapillary tumors, pancreatoblastoma, and ductal adenocarcinoma. It is important to distinguish ACCs from the more common low-grade neuroendocrine tumors, as the latter have a better prognosis and oncologic management differs significantly. Absence of acinar differentiation, lack of periodic acid-Schiff positivity, a uniform nuclear morphology, and fibrous stroma favor a neuroendocrine tumor. Solid pseudopapillary tumors, which occur almost exclusively in young women, have a favorable prognosis. They are grossly characterized by cysts and hemorrhage, and have a solid and pseudopapillary histologic pattern.[1] Solid pseudopapillary tumors are reported to stain positively with CD56 and CD10, and are negative for chromogranin. On the other hand, ACCs are CD56 negative and focally positive with CD10.[3] Pancrea-toblastoma has an acinar histology, but in addition will display areas of squamoid bodies. Ductal adenocarcinomas are positive for mucicarmine; usually positive for M1, carcinoembryonic antigen, and CA 19-9; and negative for pancreatic enzymes. On electron microscopy, ductal adenocarcinoma cells contain mucin and lack zymogen granules.[1]

In summary, ACC of the pancreas is a rare tumor that may mimic the histologic appearance of the more common, but less aggressive, low-grade neuroendocrine tumor and solid pseudopapillary tumor, or the more ominous ductal adenocarcinoma and pancreatoblastoma. Inclusion of these entities in the differential diagnosis of ACCs and systematic identification of their clinical and pathologic features will greatly aid in arriving at the correct diagnosis.

We thank Raoul Fresco MD, PhD, for his expertise in electron microscopy and Oscar H. Izquierdo for preparation of the composite images.

References

[1.] Solcia E, Capella C, Kloppel G. Tumors of the Pancreas. Washington, DC: Armed Forces Institute of Pathology; 1997:103-114. Atlas of Tumor Pathology; 3rd series, fascicle 20.

[2.] Klimstra DS, Heffess CS, Oertel JE, Rosai J. Acinar cell carcinoma of the pancreas: a clinicopathologic study of 28 cases. Am J Surg Pathol. 1992;16:815-837.

[3.] Notohara K, Hamazaki S, Tsukuyama C, et al. Solid-pseudopapillary tumor of the pancreas: immunohistochemical localization of neuroendocrine markers and CD 10. Am J Surg Pathol. 2000;24:1361-1371.

Accepted for publication February 13, 2001.

From the Department of Pathology, Loyola University Medical Center, Maywood, III.

Reprints: Grace G. Hartman, MD, Department of Pathology, Loyola University Medical Center, 2160 S First Ave, Maywood, IL 60153 (email: [e-mail]).