Distinct histomorphological features are associated with IDH1 mutation in intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma has known histological heterogeneity. Mutations in IDH1 (mIDH1) define a molecular subclass of intrahepatic cholangiocarcinoma and IDH-targeted therapies are in development. Characterizing mIDH1 ICC histomorphology is of clinical interest for efficient identification. Resected ICCs with targeted next-generation sequencing by MSK-IMPACT were selected. Clinical data were obtained. By slide review, blinded to IDH status, data were collected for histology type, mucin production, necrosis, fibrosis, cytoplasm cell shape (low cuboidal, plump cuboidal/polygonal, and columnar), and architectural pattern (anastomosing, tubular, compact tubular, and solid). A tumor was considered architecturally heterogeneous if no dominant pattern represented ≥75% of the tumor. Parameters were compared between mIDH1and IDH wild-type controls. In the examined cohort (113 ICC: 29 mIDH1 and 84 IDH wild-type), all IDH1-mutant tumors were of small duct-type histology, thus analysis was limited to 101 small duct-type tumors. mIDH1cases were more likely to have plump cuboidal/polygonal shape (P = .014) and geographic-type fibrosis (P = .005), while IDH1 wild-type were more likely to have low cuboidal shape (P = .005). Both groups were predominantly architecturally heterogeneous with no significant difference in the distribution of architectural patterns. Plump cuboidal/polygonal cell shape and a geographic-type pattern of intra-tumoral fibrosis are more often seen in mIDH1compared to IDH wild-type tumors; however, IDH1 mutation is not associated with a distinct histoarchitectural pattern.