title: Pathology of intrahepatic cholangiocarcinoma.
abstract: Intrahepatic cholangiocarcinoma (iCC) is a primary carcinoma of the liver with increasing significance and major pathogenic, clinical and therapeutic challenges. Classically, it arises from malignant transformation of cholangiocytes bordering small portal bile duct (BD) to second-order segmental large BDs. It has three major macroscopic growth pattern [mass-forming (MF), periductal infiltrative (PI), and intraductal growth (IG)] and histologically is a desmoplastic stroma-rich adenocarcinoma with cholangiocyte differentiation. Recent data pointed out noteworthy degree of heterogeneity in regards of their epidemiology and risk factors, pathological and molecular features, pathogenesis, clinical behaviors and treatment. Notably, several histological variants are described and can coexist within the same tumor. Several different cells of origin have also been depicted in a fraction of iCCs, amongst which malignant transformation of ductules, of hepatic stem/progenitor cells, of periductal glands or through oncogenic reprogramming of adult hepatocytes. A degree of pathological overlap with hepatocellular carcinoma (HCC) may be observed in a portion of iCC. A series of precursor lesions are today characterized and emphasize the existence of a multistep carcinogenesis process. Overall, these new data have brought up in proposal of new histological or molecular classifications, which could soon replace current anatomic-based classification and could have major impact on establishment of prognosis and on development of novel target treatment approaches.
authors.affiliation: Division of Clinical Pathology, Geneva University Hospital and Faculty of Medicine of Geneva, Geneva, Switzerland.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Vijgen
authors.affiliation: Department of Histopathology, Paris Descartes University, Assistance Publique-Hôpitaux de Paris, Cochin University Hospital, Paris, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Terris
authors.affiliation: Division of Clinical Pathology, Geneva University Hospital and Faculty of Medicine of Geneva, Geneva, Switzerland.
authors.forename: Laura
authors.initials: L
authors.lastname: Rubbia-Brandt
keywords: Intrahepatic cholangiocarcinoma (iCC); cells of origin; immunohistochemistry; macroscopic features; microscopic variants