Contributed by Kenneth Clark, MD and Sourav Ray, MD
Published on line in April 2004
A man in his 70s presented with right upper quadrant and left-sided back pain. He underwent a series of evaluations including a CT scan of the abdomen and pelvis, which revealed an incidental soft tissue density in the tail of the pancreas with likely involvement of the splenic hilum tracking along the splenic artery. A subsequent MRI confirmed the soft tissue density in the distal pancreas along with possible splenic vein thrombosis. Distal pancreatectomy, splenectomy, and partial omentectomy were performed and the specimen was sent for histopathologic evaluation.
Received was a 15.0x13.0x10.0cm resection of distal pancreas with attached spleen and portion of splenic artery, and an attached sheet of unremarkable omentum, 30.0x20.0x8.0cm. A vaguely circumscribed firm white tumor, 5.0x4.0x3.0 cm, replaced much of the pancreatic parenchyma, and extended into the peripancreatic soft tissue and infiltrated well into the splenic hilum (Fig. 1). The remainder of the splenic parenchyma was unremarkable. The infiltrate encased much of the splenic artery but upon sectioning did not appear to invade the lumen.
Microscopic examination revealed highly atypical glands composed of pleomorphic cells with abundant clear cytoplasm and well defined cell borders (more than 95% clear cells). Glands were arranged in an infiltrative pattern and surrounded by a densely collagenous desmoplastic stroma. Nuclei were moderately pleomorphic with irregular borders and often were eccentrically placed. Chromatin varied from vesicular to coarsely granular and nucleoli were not prominent. Dense hyaline globules were identified within the lumen of many of the atypical glands and could also be focally seen within the cytoplasm of some of the larger cells (Fig. 2). In portions, the clear cells tracked singly through dense reactive stroma and in other areas came together to form small nests. Multifocal perineural invasion was identified. The splenic artery, pancreatic parenchyma, and soft tissue margins were all free of tumor but malignant cells were seen within 1mm of the periarterial soft tissue margin. The splenic artery was encased by tumor though there was no intraluminal invasion and the artery showed severe calcific atherosclerosis.
The background pancreas showed atrophy along with a spectrum of pancreatic intraepithelial neoplasia (PanIn) from mucinous metaplasia with slight papillary changes (PanIn 1B) to large architecturally complex and atypical glands (PanIn III). The foci of PanIn III were a morphologically heterogenous group of lesions some of which consisted of cells with eosinophilic cytoplasm, some with exclusively clear cytoplasm, and some with areas of eosinophilic and clear cell differentiation within the same gland (Fig. 3). The areas of PanIn III were located entirely within the main tumor mass. Tumor necrosis, multinucleated cells, mitotic figures, and apoptotic bodies were not prominent features.
Mucicarmine stain revealed abundant intraluminal and intracytoplasmic mucin within the neoplastic glands. Immunohistochemically, the cells of interest were positive for the epithelial markers CK7 and CAM5.2 and focally positive for CK20. These cells also expressed monoclonal CEA. Although the tumor cells did sow some positivity for NSE, staining for the neuroendocrine markers synaptophysin and chromogranin were negative as were stains for vimentin, p53, HMB45, and CD10. The hyaline globules seen on H&E stain were strongly positive for PASD and immunohistochemically for alpha-1-antitrypsin (Fig. 4).