FINAL DIAGNOSIS: ACINAR CELL CARCINOMA OF THE PANCREAS
Acinar cell carcinoma of the pancreas is a rare neoplasm, comprising 1-2 % of exocrine pancreatic tumors (Solcia E et al., 1997). The tumor most commonly occurs in middle-aged or elderly Caucasian men. Patients may present with vague abdominal pain, or the mass may be found incidentally. Patients (up to 15%) can also present with widespread subcutaneous fat necrosis, polyarthritis, and eosinophilia (Schmid's triad) due to increased circulating lipase secreted by the tumor (Solcia E et al., 1997, Ashley SW and Lauwers GY, 2002).
Acinar cell carcinomas can involve the head or tail of the pancreas. They are usually well-circumscribed, partly encapsulated, pink to tan, homogeneous fleshy mass, averaging 11 cm in greatest diameter, occasionally demonstrating extensive hemorrhage and necrosis (Solcia E et al., 1997, Klimstra DS et al., 1992). Microscopically, most tumors are highly cellular with minimal stroma and lack the stromal desmoplasia commonly seen with ductal adenocarcinomas. Four patterns of growth have been described (Klimstra DS et al.): acinar, solid, trabecular and glandular. The acinar pattern is present in most tumors, often admixed with trabecular and glandular patterns; the solid pattern is also often seen. The tumor cells resemble normal pancreatic acinar cells. The nuclei are round to oval, with only mild pleomorphism and single prominent nucleoli. The cytoplasm tends to be abundant, eosinophilic, and granular due to zymogen granules, which are PAS-positive and diastase-resistant, but in the solid tumors, PAS positivity may be scant. Mitotic activity is variable, form rare mitoses to >50 per 10 hpf.
In the present case, the differential diagnosis, based on morphology, included an acinar cell carcinoma and a pancreatic endocrine tumor because the pattern of growth was mostly solid with rare areas of acinar-type structures. However, the lack of classic "salt and pepper" chromatin distribution and the presence of prominent single nucleoli are unusual for endocrine neoplasms (See Fig. 5).
Since normal pancreatic acinar cells secrete pancreatic enzymes, the most useful histochemical and/or immunohistochemical stains for acinar cell carcinoma are for the pancreatic enzymes, such as trypsin, chymotrypsin, amylase, elastase, and lipase. When the neoplastic cells exhibit nuclear polarity, these stains usually demonstrate positivity in the apical portions of the cells, while the stains are more focal and usually restricted to single cells in tumors with solid patterns (See Fig. 11). Tumor cells that are positive for synaptophysin and chromogranin A can be found in 30-50% of cases (Notohara K et al., 2000 and Hoorens A et al., 1993). Usually they occur in tumors with a solid pattern, where they are scattered throughout the tissue (Solcia E et al., 1997). Although only a small number of cases with synaptophysin immunohistochemistry have been reported, the diffuse positive staining for synaptophysin in our case appears to be uncommon for acinar cell carcinoma and is a potential pitfall, thus emphasizing the need to perform the stains to demonstrate positivity for at least one pancreatic enzyme.
Ultrastructural studies of acinar cell carcinomas have demonstrated a resemblance to normal pancreatic acinar cells with well-developed endoplasmic reticulum and zymogen granules (mean diameter 400-500nm), which are commonly oriented toward the luminal space. An interesting finding in acinar cell carcinomas is the presence of membrane-bound filamentous inclusions, which are thought to be within the spectrum of zymogen granules (Tucker JA et al., 1994, Chong JM et al.,1996, and Ordonez NG et al., 2000). Similar inclusions have only rarely been identified in endocrine tumors (Ordonez NG et al., 2001), therefore, these inclusions may serve as an ultrastructural marker in the diagnosis of acinar cell carcinomas.
Acinar cell carcinomas are aggressive tumors and most patients die from their cancer within a mean of 18 months after diagnosis and a 5 year survival of 5.9%; however, the overall survival is better than pancreatic ductal adenocarcinoma (Klimstra DS et al.). Younger patients (less than 60 years old) and patients with tumors less than 10 cm tend to have longer survival than patients over 60 years or with larger tumors. Patients who present with symptoms of elevated lipase do much worse (mean survival 8.8 months). Resection is the treatment of choice, with or without chemoradiation therapy, and metastases may be present at the time of diagnosis.
In summary, we presented a case of pancreatic acinar cell carcinoma with an almost exclusively solid growth pattern. While the tumor showed some immunophenotypic evidence of endocrine cell differentiation, clinical, histologic, and electron microscopic features, along with the positive immunostaining for trypsin, were all consistent with acinar cell carcinoma.