Answer: Small cell carcinoma

Histology: This neoplasm is composed of back-to-back cells with prominent nuclear molding. The nuclear to cytoplasmic ratio is high, the chromatin is dispersed, and numerous mitoses are present. The neoplastic cells immunolabel for synaptophysin, chromogranin and CD56. Immunolabeling for pancytokeratin is positive in a dot-like pattern.

Discussion: Small cell carcinomas of the gallbladder are rare epithelial neoplasms. Maitra et al. recently reported 12 cases. The mean age at diagnosis was 69 years, and the male-to-female ratio was 5:7. Three-fourths of the carcinomas had metastasized or extended locally beyond the gallbladder at surgery. Survival was uniformly poor, with a mean survival of only 11 months. Of interest, half the small cell carcinomas were combined with other neoplasms such as an adenocarcinoma. In the case we present here, the cytokeratin immunostain highlighted islands of positivity suggestive of a better differentiated component in the background. In the series reported by Maitra, immunolabeling was usually positive for chromogranin (focal), neuron-specific enolase, and Leu-7. At the molecular level they found a high frequency of p53 (75%) and p16INK4a (33%) abnormalities, and a low frequency of deleted in pancreatic carcinoma-4 inactivation (0%) and KRAS2 codon 12 mutations (17%).

Reference(s):
– A. Maitra et al., Small cell carcinoma of the gallbladder: a clinicopathologic, immunohistochemical, and molecular pathology study of 12 cases. Am J Surg Pathol. 2001 May;25(5):595-601.