IgG4-related hepatobiliary disease (IgG4-HBD), which encompasses IgG4-related sclerosing cholangitis (IgG4-SC), IgG4-related hepatopathy and IgG4-related cholecystitis, belongs to a larger family of disorders called IgG4-related disease (IgG4-RD), which is a multisystemic fibroinflammatory condition with characteristic histopathological features that can involve many different organ systems. 1,2

Histologic examination plays a crucial role in diagnosing IgG4-RD due to its histopathological features, distinguishing it from other illnesses with similar clinical presentations. Since treatment and management of these diseases vary significantly, accurate diagnosis is essential. In the past, under-recognition and misdiagnosis of IgG4-RD have led to unnecessary tissue resections and inappropriate medical therapy. 3, 4, 5, 6 However, with increasing awareness of IgG4-RD, histologic confirmation through tissue biopsies has become prevalent to avoid unnecessary life-altering surgeries. While not all histopathological features may be present on limited biopsy samples, the current article aims to discuss anticipated histologic features for diagnosing IgG4-HBD on biopsy and potential histologic mimickers. Accurate diagnosis or at least suggestion of IgG4-RD is crucial, and biopsy can also help determine disease extent and severity, monitor treatment response, and evaluate disease progression. Hence, this article reviews clinical and pathologic features of IgG-RD of the biliary tract and liver, emphasizing histomorphologic features that can be seen in tissue biopsy material.