Massive/Mass-forming Ductular Reaction Associated With Vascular Occlusion in Various Underlying Basic Liver Diseases

Massive/mass-forming ductular reaction of the liver (MDR) is occasionally in the differential diagnosis with true bile duct tumors. Our diagnostic histomorphological and immunohistochemical study of 14 cases from a consultant collective of 2970 cases follows the appearance of MDR with regard to various underlying liver diseases and the conditions of pathologic perfusion. We describe MDR measuring up to 7 cm in localized form or affecting up to 70% of the parenchyma in subacute liver necrosis. MDR developed in the context of severe inflammatory liver diseases and liver cirrhosis, as well as in colocalization with true malignant neoplasms such as hepatocellular carcinoma, epithelioid hemangioendothelioma, and hepatic angiosarcoma. In all cases, MDR was associated with intra- or directly perilesional thrombotic or tumorous obliteration of intrahepatic portal or hepatic veins or liver sinusoids. In end-stage liver cirrhosis, it was additionally associated with fibrotic occlusion of the portoseptal vascular bed. Further key diagnostic features of this hypoperfused, extensive parenchymal transformation included a monolayered network of small cytokeratin 7-, cytokeratin 19-, and CD56-positive ductules with fingertip-like endings, low proliferative activity (<3% Ki-67-positive cells), and embedded in a loose stroma. The pre-existing lobular architecture, including portal tracts or cirrhotic remodeling, was preserved. In conclusion, MDR of the liver is a rare, confluent pluriacinar and sometimes pseudo-tumorous transformation of the liver parenchyma that is associated with altered liver perfusion. Clinically and histomorphologically, it can mimic a true biliary neoplasm.