S100P, von Hippel-Lindau gene product, and IMP3 serve as a useful immunohistochemical panel in the diagnosis of adenocarcinoma on endoscopic bile duct biopsy.

Histopathologic distinction between benign and malignant bile duct epithelial lesions on endoscopic biopsies can be extremely challenging because of limited material, crush artifact, and compounding inflammatory and/or reactive changes particularly after stent placement. In this study, a total of 72 endoscopic bile duct biopsies, including 40 adenocarcinomas and 32 benign cases, were immunohistochemically examined for the expression of S100P, von Hippel-Lindau gene product (pVHL), and IMP3 to evaluate their diagnostic value. The results showed that 36 adenocarcinomas (90%) exhibited strong nuclear and cytoplasmic staining for S100P, of which 30 (83.3%) showed diffuse immunoreactivity. Intermediate to strong cytoplasmic staining for IMP3 was demonstrated in 31 tumors (77.5%) (15 diffuse, 16 focal). Completely negative staining for pVHL was observed in 37 adenocarcinomas. In the remaining 3 tumors, focal (1) or diffuse (2) membranous and cytoplasmic pVHL immunoreactivity was detected. Twenty-eight tumors (70%) showed a S100P+/IMP3+/pVHL- staining pattern, 6 (15%) with a S100P+/IMP3-/pVHL- pattern, and 2 (5%) with a S100P-/IMP3+/pVHL- pattern. All 32 benign biopsies were completely negative for IMP3 with the exception of 2 cases with focal dysplasia where focal immunoreactivity was observed. Thirty benign biopsies (93.8%) were positive for pVHL with a diffuse staining pattern observed in 28 cases (93.3%). Eight benign biopsies (25%) showed focal S100P positivity. Twenty-two benign biopsies (68.8%) displayed a S100P-/IMP3-/pVHL+ staining pattern. In conclusion, an immunohistochemical panel consisting of S100P, pVHL, and IMP3 can be helpful in distinguishing adenocarcinoma from reactive epithelial changes on challenging bile duct biopsies. The findings of focal S100P and/or IMP3 expression with reciprocal loss of pVHL immunoreactivity in a few benign biopsies suggest a use of these markers in the detection of early epithelial dysplasia that may be beyond histologic recognition.