Small-cell carcinoma of the gallbladder - a clinicopathological, immunohistochemical and flow cytometric study of 15 cases.

Small cell carcinoma (SC) of the gallbladder is an uncommon tumor, and not enough information of this tumor has been previously reported. The SCs in this series occured in nine women and six men (mean age; 64.5 years). Histologically, they consisted of small atypical cells with scanty cytoplasm, hyperchromatic nuclei and inconspicuous nucleoli growing in sheets and cords. Two tumors contained neoplastic glands similar to those of well-differentiated adenocarcinoma and a histological transition between SC and adenocarcinoma was seen in one of the two tumors. Argyrophil granules were present in 10 tumors. The tumor cells were immunoreactive to epithelial markers (epithelial membrane antigen: 12/14; AE1/AE3: 12/14; CAM 5.2: 9/14; carcinoembryonic antigen: 7/14) and neuroendocrine markers (neuron specific enolase: 11/14; chromagranin A: 4/14; Leu 7: 10/14; adrenocorticotrophic hormone: 6/14). Abnormalities in tumor suppressor gene p53 expression were found in 9 of 14 SCs by using monoclonal antibody PAb 1801. Flow cytometry revealed aneuploidy in 7 (78%) of 9 in the SC and 26 (40%) of 65 in the adenocarcinoma. The survival curve of the SCs was less favorable than that of papillary adenocarcinoma and well differentiated adenocarcinoma in pTNM stage 2-4 (P=0.0027, P=0.0017, respectively). These results suggested that the SCs of the gallbladder arose from common primitive cells capable of endocrine and epithelial differentiation, while most SCs (78%) showed DNA aneuploid by flow cytometry and their prognosis was worse than that of differentiated adenocarcinoma of the gallbladder.