Histopathology

Large nodules of cells are separated by hypocellular fibrous bands. The desmo-plastic stroma characteristic of ductal adenocarcinomas is generally absent. Tumour necrosis may occur and is generally infarct-like in appearance. Within the tumour cell islands, there is an abundant fine microvasculature. Several architectural patterns have been described. The most characteristic is the acinar pattern, with neoplastic cells arranged in small glandular units; there are numerous small lumina within each island of cells giving a cribriform appearance. In some instances, the lumina are more dilated, resulting in a glandular pattern, although separate glandular structures surrounded by stroma are usually not encountered. A number of the micro-

Fig. 10.27 Acinar cell carcinoma. The hypodense lobulated tumour occupies the tail of the pancreas.

glandular tumours previously reported as 'microadenocarcinoma' were more recently shown to have been acinar cell carcinomas (see chapter on miscellaneous carcinomas). The second most common pattern in acinar cell carcinomas is the solid pattern: solid nests of cells lacking luminal formations are separated by small vessels. Within these nests, cellular polarization is generally not evident, but there may be an accentuation of polarization at the interface with the vessels, resulting in basal nuclear localization in these regions and a palisading of nuclei along the microvascula-ture. In rare instances, a trabecular arrangement of tumour cells may be present, with exceptional cases also showing a gyriform appearance {936}. The neoplastic cells contain minimal to moderate amounts of cytoplasm that may be more abundant in cells lining lumina. The cytoplasm varies from amphophilic to eosinophilic and is characteristically granular, reflecting the presence of zymogen granules. In many instances, however, only minimal cyto-plasmic granularity may be detectable. The nuclei are generally round to oval and relatively uniform, with marked nuclear pleomorphism being exceptional. A single, prominent, central nucleolus is a characteristic finding but not invariably present. The mitotic rate is variable (mean 14 per 10 high power fields, range 0 to > 50 per 10 high power fields). Zymogen granules are weakly positive with PAS staining, and resistant to diastase. Mucin production is generally not detectable with mucicarmine or Alcian blue stains and, if present, is limited to the luminal membrane in acinar or glandular formations. The histochemical stain for butyrate esterase can be used to identify active lipase within the tumour cells {936, 938}. Due to the scarcity of zymogen granules in many examples of acinar cell carcinoma, histochemical stains are relatively insensitive for documenting acinar differentiation, and very focal staining may be difficult to interpret with confidence.

Immunohistochemistry

Immunohistochemical identification of pancreatic enzyme production is helpful in confirming the diagnosis of acinar cell carcinoma. Antibodies against trypsin, chymotrypsin, lipase, and elastase have all been used {739, 810, 936, 1282}. Both

Fig. 10.28 An acinar cell carcinoma (AC) lies near the spleen (SP). The tumour's cut surface is lobulat-ed.

trypsin and chymotrypsin are detectable in over 95% of cases; lipase is less commonly identified (approximately 70% of cases) {936}. Pancreatic stone protein is also commonly expressed {739}. In solid areas, immunohistochemical staining for enzymes may show diffuse cytoplasmic positivity, whereas the reaction product is restricted to the apical cytoplasm in aci-nar areas.

Immunohistochemical markers of endocrine and ductal differentiation may also be detected in acinar cell carcinomas, generally in a minor cell population {739, 936}. Scattered individual cells stain for chromogranin or synaptophysin are found in over one third of lesions. Over half exhibit focal CEA and B72.3 expression {739, 936}. Uncommonly, there is immunohistochemical positivity for alpha-fetoprotein, generally in cases associated with elevations in serum alpha-feto-protein {819}.

Ultrastructure

Electron microscopy provides further evidence of enzyme production {675, 408, 936, 1978}. Exocrine secretory features are consistently found, with abundant rough endoplasmic reticulum arranged in parallel arrays and relatively abundant

Fig. 10.29 Acinar cell carcinoma showing well differentiated acinar structures.

mitochondria. Cellular polarization is generally evident, with basal basement membranes and apical lumina. Adjacent cells are joined by tight junctions. Although the distribution varies from cell to cell, most acinar cell carcinomas exhibit electron dense zymogen granules. In polarized cells, they are located in the apical cytoplasm, and the secretory contents may be seen within the luminal spaces where granules have fused with the apical membrane. The size range of zymogen granules in acinar cell carcinomas (1251000 nm) is somewhat greater than that found in non-neoplastic acinar cells (2501000 nm). In addition to typical zymogen granules, a second granule type, the irregular fibrillary granule, is detected ultrastructurally in many cases {302, 936, 938, 1477}. It has been suggested that irregular fibrillary granules may represent a recapitulation of the fetal zymogen granules, although attempts to document the presence of pancreatic enzymes within them by immunohistochemistry have been unconvincing {936, 938, 1032}.

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