Acinar cell carcinoma of the pancreas is a rare entity, accounting for <2% of pancreatic malignances.1 It often presents in older patients, though around 6% of cases are reported in the pediatric population.2 The most common clinical presentation is abdominal pain, though a small percentage of acinar cell carcinoma can release digestive enzymes such as lipase or alpha fetoprotein, leading to fat necrosis and arthralgia.3,4 Overall, acinar cell carcinoma is an aggressive disease and carries a poor prognosis with 5 year survival reported to be from anywhere between <10-45%.5-7 Metastatic disease at the time of presentation is seen in around 60% of patients.6 Grossly the tumors are well circumscribed, but large and bulky with fibrous septa and frequent necrosis or hemorrhage.2

Cytologic smears are typically highly cellular with loosely cohesive clusters of cells. Cells form a vague acinar pattern, recapitulating normal pancreatic acini. The cells are cytologically bland with abundant delicate granular cytoplasm and large round nuclei. Nuclei are eccentrically located and often have prominent nucleoli. The background is distinctive in that there are abundant loose zymogen granules and abundant naked nuclei.1

Acinar cell carcinoma has distinct positivity for pancreatic enzymes, especially trypsin. Chymotrypsin, anti-chymotrypsin, lipase, and phospholipase A2 are also positive but less specific. PAS positive (diastase resistant) cytoplasmic granules are also present.1 Weak positivity for synaptophysin or chromogranin may be seen, as in this case. BCL10 is expressed in normal acini, and positivity for BCL10 is useful in distinguishing acinar cell carcinoma.8 In our case, the specimen was positive for chymotrypsin.
The molecular pathogenesis of acinar cell carcinoma has not been entirely delineated. 50% have loss of chromosome 11p, so this locus may play an important role. Additionally, losses of TP53, APC, and SMAD4 loci have been reported along with gains of 3p and CTNNB1 loci.2 Overall, sequencing has revealed a large number of mutations present, with no single common gene mutated in more than 30% of acinar cell carcinomas.9 Microsatellite instability has also been identified in up to 10% of cases.2

Acinar cell carcinoma can be a diagnostically difficult due to its rarity and its resemblance to normal pancreatic acini as well as morphologic overlap with other solid and cellular neoplasms of the pancreas, including solid psuedopapillary neoplasm and pancreatic neuroendocrine tumor. The distinction between acinar cell carcinoma and pancreatic ductal adenocarcinoma is also important.

Benign acinar cells are typically present on fine-needle aspirations of the pancreas, but occur in normal proportion with other normal pancreatic components. Acinar cell carcinoma, in contrast, will be highly cellular and comprise a disproportionally large component of the smear. Benign acinar cells appear morphologically similar to acinar cell carcinoma, but will have smaller nuclei and inconspicuous nuclei. The background associated with benign pancreatic acini will also be cleaner and lack the abundance of stripped nuclei and zymogen granules.1

Solid pseudopapillary neoplasm of the pancreas appears cellular on cytologic preparations with loosely cohesive clusters and single cells. Pseudopapillary formations with tumor cells clinging to central vessels will also be present. Hyalinized material is often seen in the background and in association with cell groups. Individual cells have delicate clear cytoplasm that may contain round PAS positive hyaline globules. Nuclei are eccentrically placed and occasionally have grooves or pseudoinclusions. Nuclear staining with beta-catenin is the key diagnostic marker.1 Nuclear E-cadherin and cytoplasmic CD10 are also present. Synaptophysin may show focal positivity.

Pancreatic neuroendocrine neoplasms also yield cellular smears with loosely cohesive cell groups and single cells. Cell groups may have a pseudorosette arrangement. The individual cells are monotonous with delicate granular cytoplasm and round eccentrically placed nuclei. Chromatin will appear finely stippled with a characteristic salt and pepper appearance on Papanicolaou stain. Pancreatic neuroendocrine tumors will be positive for synaptophysin, chromogranin, and CD56.1

Pancreatic ductal adenocarcinomas yield variably cellular smears with an increased proportion of pancreatic ductal cells. Ductal cell groups display architectural atypia including nuclear crowding and overlapping. Nuclear atypia will also be present and include pleomorphism, irregular nuclear membranes, and increased nuclear to cytoplasmic ratios. The cytoplasm is often foamy appearing and mucicarmine positive intracytoplasmic mucin is sometimes appreciable. Single isolated malignant cells are also present. Chromatin appears coarse, and nucleoli are often visible. Necrosis may be seen in the background. Pancreatic ductal adenocarcinoma is positive for CK7 and shows accumulation of p53 and loss of SMAD4 on immunohistochemical stains.1