Vacuolated cell pattern of pancreatobiliary adenocarcinoma: a clinicopathological analysis of 24 cases of a poorly recognized distinctive morphologic variant important in the differential diagnosis

Abstract

Pancreatic ductal adenocarcinoma (PDCA) is characterized by well-defined tubular units in the vast majority of the cases; however, variations in this theme do occur. It is important to recognize the morphologic spectrum of PDCA to avoid misdiagnosis especially in small specimens and also in metastatic foci. Here, we document a morphologic variant of PDCA that is characterized by a distinctive pattern of infiltrating cribriform nests in a distinctive “microcystic” or “secretory” pattern. Twenty-four cases of PDCA have been identified in a review of 505 cases diagnosed with PDCA. Histologically, this pattern was characterized by infiltrating nests of tumor cells with large vacuoles and “signet-ring” like appearance imparting a cribriform growth pattern. The vacuoles were one to five cells in size, often merging to form multilocular spaces separated by a thin rim of cell membrane. Many of these spaces contained CA19.9 positive granular secretory material. The nuclei were often pushed to the periphery and compressed in a pattern resembling adipocytes, although the nuclei were often densely hyperchromatic and displayed significant atypia. Especially in biopsies from the peripancreatic fat and peritoneum, these neoplastic cells had been misdiagnosed as degenerating adipocytes, and in the lymph nodes, they had been misinterpreted as lipogranulomas. Clinical findings of the patients were similar to that of conventional PDCA, except higher incidence of history of smoking (83% vs. 60%; p=0.034). In conclusion, vacuolated cell adenocarcinoma is a distinct morphologic variant of PDCA, and the presence of this peculiar pattern in a metastatic site, although not specific, should raise the suspicion of a PDCA.

Intrapancreatic distal common bile duct carcinoma: Analysis, staging considerations, and comparison with pancreatic ductal and ampullary adenocarcinomas

“…Other histologic patterns focally observed in otherwise pancreatobiliary-type DCBDC included a tubulolobular pattern akin to that of invasive lobular carcinoma of the breast (2/47 cases, 4.3%; Figure 4a); a microglandular pattern reminiscent of mesonephric remnants (7/47, 14.9%; Figure 4b); a vacuolated cell pattern, as documented recently in PDAC 31 (2/47, 4.3%; Figure 4c); a clear cell or foamy gland appearance (2/47, 4.3%; Figure 4d); an intestinal-like pattern that demonstrated goblet cells (3/47, 6.4%; Figure 4e); medullary morphology (1/47, 2.1%; Figure 4f); and prominent papilla formation within the invasive glands (1/47, 2.1%).…”

Carcinoma Ex Microcystic Adenoma of the Pancreas

“…The reported variant of pancreatic adenocarcinoma with a vacuolated cell pattern is usually accompanied by more conventional intratumoral histologic patterns of ductal carcinoma, such as individual infiltrating glands, stromal desmoplasia, mucin production, and K-ras gene mutation. 5,16 The overall immunohistophenotype in this case was consistent with a serous cystic tumor, although this tumor was not reactive for other markers that are typically expressed in serous cystadenomas. For example, markers such as MUC 6 and a-inhibin were negative in this case, but they are positive in up to 76% of cases of microcystic adenomas.…”

“…Invasion of the spleen, stomach, soft tissue, duodenal wall, or lymph nodes, and also vascular or perineural invasion, has been observed. 1,5,11,14,15,20,21,25,28,29,31 When present, metastases most commonly occur in the liver. However, the presence of additional serous tumors in other organs does not always equate to metastases from a serous primary, and they may be part of a multicystic process or syndrome such as the von-Hippel-Lindau syndrome.…”

Primary signet ring cell carcinoma of the pancreas: Cytopathology review of a rare entity

“…Pancreatic adenocarcinoma with a vacuolated cell pattern is a recently described variant in literature, but not adopted by the 2010 WHO classification . Tumor cells of this variant are characterized by impressively large vacuoles, coalescing together to create microcystic and cribriform patterns.…”

“…Tumor cells of this variant are characterized by impressively large vacuoles, coalescing together to create microcystic and cribriform patterns. It constitutes about 5% of pancreatic carcinomas according to one study, and exhibits a more aggressive clinical behavior when compared to classical pancreatic ductal adenocarcinoma . These microcystic spaces contain cellular debris and mucin .…”