Malignant Transformation in Von-Meyenburg Complexes: Histologic and Immunohistochemical Clues With Illustrative Cases

Benign developmental defects known as Von-Meyenburg complexes (VMCs) have been postulated to progress to cholangiocarcinoma (CC) in rare instances. Although a gradual, sequential histologic transition from VMCs to CC has been described in some of these cases, the underlying genetic mechanism is yet to be elucidated. Here, we review the literature to put together a report on the clinicopathologic features and immunohistochemical changes associated with such transformation. We also review the documented association between CC and p16 inactivation, and discuss a possible role for this mechanism to contribute in VMCs to CC progression. In addition, using 2 illustrative cases encountered at our institute, we provide morphologic and immunohistochemical clues that can be used to detect such progression from hamartoma to malignancy. These cases and the accompanying review of literature further solidify the association between VMCs and CC.