Fetal gut–like differentiation in gallbladder cancer

Summary Adenocarcinomas showing fetal gut–like (enteroblastic) differentiation can arise in a variety of organs and are frequently accompanied by an elevated serum α -fetoprotein (AFP) level. However, no study has investigated fetal gut–like differentiation in gallbladder cancer in detail. Herein, we performed morphological and immunohistochemical analyses of fetal gut–like differentiation in 49 consecutive gallbladder cancer cases. The expression of Sal-like protein 4 (SALL4), an embryonic stem cell marker reported to represent fetal gut–like differentiation, as well as other oncofetal proteins, including glypican-3 (GPC3) and AFP, was assessed. We found 1 case of fetal gut–like adenocarcinoma that coexisted with conventional-type adenocarcinoma. The fetal gut–like adenocarcinoma component revealed diffuse immunoreactivity for SALL4 and partial positivity for AFP, whereas the conventional-type adenocarcinoma component was negative. We also found 2 poorly differentiated adenocarcinomas with hepatoid morphology and 1 clear cell carcinoma, none of which showed SALL4 positivity. In other conventional-type adenocarcinomas, focal immunoreactivity for SALL4 and GPC3 was occasionally observed. The overall positivity rates for SALL4 and GPC3 were 12.2% (6/49) and 16.3% (8/49), respectively. SALL4 and GPC3 expression was not associated with clinicopathological factors, including T category, lymphovascular invasion, and lymph node metastases. In conclusion, fetal gut–like adenocarcinoma was found in 2% of our gallbladder cancer series. We conclude that fetal gut–like adenocarcinoma is a distinct histological subtype of gallbladder cancer, characterized by SALL4 expression.