Diagnostic accuracy of an immunohistochemical panel to distinguish intrahepatic cholangiocarcinoma from bile duct adenoma.

Background & Objectives: Differential diagnosis between intrahepatic cholangiocarcinoma (ICC), an aggressive liver tumour, and bile duct adenoma (BDA), an indolent lesion, is fundamental but sometimes challenging, particularly for well-differentiated ICC. Morphological analysis alone is often not sufficient to achieve a correct diagnosis. Several immunohistochemical markers have been proposed to improve the diagnostic performance, but all of them, taken singularly, showed low sensitivity and are not used in clinical practice. Moreover, only a few studies focused on the differential diagnosis between ICC and BDA, so far. The aim of this study was to investigate the diagnostic performance of a 3-marker panel, including p53, p16INK4a, and S100P, to evaluate whether their combination might help to distinguish ICC from BDA. Methods: Fifty-two surgically resected liver nodules (30 ICCs and 22 BDAs) were retrospectively selected and stained with p53, p16INK4a, and S100P. p53 was considered positive when a strong nuclear immunoreaction was observed, while p16INK4a and S100P positivity was both nuclear and cytoplasmic. An algorithm was built and its diagnostic performance analysed. Results: As expected, despite their perfect specificity (100%), all the evaluated markers showed a low sensitivity when considered singularly (56.7%, 26.6%, 23.4%, for p53, p16INK4a, S100P, respectively). On the contrary, the algorithm based on the sequential use of p53, p16INK4a, and S100P, showed a sensitivity of 73.4%, a specificity of 100% and an overall accuracy of 84.6%. Conclusion: The adopted 3-marker algorithm is helpful in differentiating ICC from BDA. Further larger studies are needed to validate the proposed algorithm.