Clinicopathologic characterization of gallbladder graft-versus-host disease in the pediatric population.

Graft-versus-host disease (GVHD) is a common and important complication of allogenic hematopoietic cell transplantation (HCT). The cardinal histologic feature of GVHD in the gastrointestinal tract is the presence of apoptotic bodies. To date, no study has evaluated the pathologic characteristics of gallbladder GVHD (GB-GVHD). In this study we sought to describe their clinicopathologic features in a cohort of pediatric patients and compared them to a control group composed of 10 and 15 recent cases of acute and chronic cholecystitis, respectively. A total of 6 GB-GVHD cases were included, 5 cholecystectomies and 1 autopsy case(s), presenting in 2 boys and 4 girls, with a mean age of 6.7 years (1.5-18.6). The median days post-transplant to presentation was 261 (40-699) and all cases had GVHD involving other organs. GB-GVHD compared to the control groups was significantly associated with a younger age (p=0.019), presence of apoptotic bodies and higher number of apoptotic bodies in 10 continuous mucosal folds and in 100 and 500 epithelial cells (all p<0.001), and increased number of intraepithelial lymphocytes per 100 epithelial cells (p<0.001). All patients were treated for GVHD with half of them achieving treatment response. Besides the autopsy case, all patients are alive with a median follow-up time of 45 months (4-212). The cause of death for the autopsy case was sepsis due to Pseudomonas aeruginosa. In our experience, the presence of both increased apoptotic bodies and intraepithelial lymphocytes in the gallbladder of HCT patients should raise concern for GB-GVHD.