Foamy gland pattern of pancreatic ductal adenocarcinoma - A deceptively benign-appearing variant

Pathologic diagnosis of pancreatic adenocarcinoma is frequently a challenge , particularly in small biopsies, frozen sections, and in metastatic foci. Here we report a deceptively benign-appearing and morphologically distincti ve pattern of ductal adenocarcinoma with prominent microvesicular cytoplasm , giving the cells a foamy appearance similar to that described in the pros tate (Am J Surg Pathol 1996;20:419). This variant, which we refer to as foa my gland pattern (FGP), was frequently misdiagnosed in frozen sections or b iopsies and its pathologic stage underestimated in surgical specimens. Hist ologically, the diagnostic features were: (1) white and crisply foamy, "mic rovesicular" cytoplasm; (2) often basally located and compressed, hyperchro matic nuclei reminiscent of endocervical glands (and so-called "adenoma mal ignum") or gastric foveolar glands; (3) irregular nuclear contours forming wrinkled (raisinoid) nuclei in some areas; and (4) a distinctive chromophil ic condensation of the cytoplasmic material in the luminal aspect of the ce lls forming a brush border-like zone (BLZ). Histochemically, this BLZ was p ositive for mucicarmine, alcian blue, and high iron diamine, but not PAS. T he remainder of the cytoplasm was negative for all these stains. In contras t, benign mucinous ducts, which constitute the major differential diagnosis , had more homogeneous acidophilic cytoplasm, lacked BLZ, and showed cytopl asmic staining with PAS. Immunohistochemically, the tumor cells were diffus ely and strongly positive for CEA and cytokeratin 8 whereas B72.3 staining was focal and weak. MUC1 staining was largely confined to the BLZ. MUC2 was negative. P53 staining was detected in 16 of the 20 cases studied and was strong and diffuse in five. K-ras mutation was detected in 6 of 8 cases stu died. The clinical findings in the 20 patients in this study (4 pure and 16 mixed with usual ductal carcinoma) did not appear to differ significantly from those of ordinary ductal adenocarcinoma of the pancreas. Eleven patien ts were men and nine were women; the mean age was 62 years and the mean tum or size was 4.4 cm. Follow-up information was available in 17 patients of w hom 7 were alive at an average follow up of 23 months (range, 7-104 mos), a nd 10 were dead of disease at a median follow up of 15 months (range, 4-42 mos). The median survival of the four patients with pure FGP was 18 months. The median survival did not appear to be significantly longer than that of the patients with resectable ordinary ductal adenocarcinoma in the authors ' experience (109 patients, median survival of 12 mos, p = 0.48). In conclu sion, foamy gland pattern of invasive pancreatic ductal carcinoma is morpho logically distinctive and is prone to misdiagnosis as a benign process. The pathologic stage is often underestimated as a result of the lack of its re cognition and misinterpretation as mucinous ducts. Careful attention to its microscopic features is adequate for accurate diagnosis. Histochemical and immunohistochemical stains are useful in confirming the diagnosis of malig nancy in challenging cases.