Small cell carcinoma of the gallbladder - A clinicopathologic, immunohistochemical, and molecular pathology study of 12 cases

Small cell carcinomas of the gallbladder are unusual neoplasms that have be en characterized only recently. The authors describe the clinical, histopat hologic, immunohistochemical, and molecular features of 12 small cell carci nomas of the gallbladder. The mean age at diagnosis was 69 years, and the m ale-to-female ratio was 5:7. The neoplasms had an average size of 3 cm, and 90% showed invasion of the muscularis propria and perimuscular connective tissue. Seventy-five percent of the carcinomas had metastasized or extended locally beyond the gallbladder at surgery. Survival was uniformly poor, wi th a mean survival of 10.7 months (range, 3-25 months). Half the small cell carcinomas were combined with other neoplasms. Four had foci of adenocarci noma, one contained areas of squamous differentiation, and another had a co mponent of carcinosarcoma. Immunohistochemical analysis showed focal reacti vity for chromogranin (six of six cases), neuron-specific enolase (six of s ix cases), and Leu-7 (three of three cases). The molecular changes in small cell carcinomas were similar to those of adenocarcinomas occurring at this site, with a high frequency of p53 (75%) and p16(INK4a) (33%) abnormalitie s, and a low frequency of deleted in pancreatic carcinoma-4 inactivation (0 %) and K-ras codon 12 mutations (17%). In contrast to pulmonary small cell carcinomas, p16(INK4a) function appears to be abrogated more frequently in these carcinomas.