Intrahepatic Cholangiocarcinomas Have Histologically and... : The American Journal of Surgical Pathology (original) (raw)

Original Articles

Intrahepatic Cholangiocarcinomas Have Histologically and Immunophenotypically Distinct Small and Large Duct Patterns

Sigel, Carlie S. MD*; Drill, Esther MS†; Zhou, Yi MD, PhD‡; Basturk, Olca MD*; Askan, Gokce MD*; Pak, Linda M. MD§; Vakiani, Efsevia MD, PhD*; Wang, Tao MD*; Boerner, Thomas MD∥; Do, Richard K.G. MD, PhD¶; Simpson, Amber L. PhD∥; Jarnagin, William MD∥; Klimstra, David S. MD*

Departments of *Pathology

†Epidemiology and Biostatistics

∥Surgery

¶Radiology, Memorial Sloan Kettering Cancer Center, New York, NY

‡Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC

§Department of Surgery, Brigham and Women’s Hospital, Boston, MA

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Conflicts of Interest and Source of Funding: Supported in part by the Cancer Center Support Grant of the National Institutes of Health/National Cancer Institute under award number P30CA008748 and Cycle for Survival. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Carlie S. Sigel, MD, 1275 York Ave., New York, NY 10065 (e-mail: [email protected]).

Abstract

Intrahepatic cholangiocarcinomas are histologically heterogenous. Using a cohort of 184 clinically defined, resected intrahepatic cholangiocarcinomas, we retrospectively classified the histology into 4 subtypes: large duct (LD), small duct (SD) (predominantly tubular [SD1] or predominantly anastomosing/cholangiolar, [SD2]), or indeterminate. Then, we tested the 4 subtypes for associations with risk factors, patient outcomes, histology, and immunophenotypic characteristics. SD was the most common (84%; 24% SD1 and 60% SD2) with lower proportions of LD (8%), and indeterminate (8%). Primary sclerosing cholangitis was rare (2%), but correlated with LD (_P_=0.005). Chronic hepatitis, frequent alcohol use, smoking, and steatosis had no histologic association. LD was associated with mucin production (P<0.001), perineural invasion (_P_=0.002), CA19-9 staining (_P_<0.001), CK7+, CK19+, CD56− immunophenotype (_P_=0.005), and negative albumin RNA in situ hybridization (_P_<0.001). SD was histologically nodular (_P_=0.019), sclerotic (_P_<0.001), hepatoid (_P_=0.042), and infiltrative at the interface with hepatocytes (_P_<0.001). Albumin was positive in 71% of SD and 18% of LD (_P_=0.0021). Most albumin positive tumors (85%) lacked extracellular mucin (_P_<0.001). S100P expression did not associate with subtype (_P_>0.05). There was no difference in disease-specific or recurrence-free survival among the subtypes. Periductal infiltration and American Joint Committee on Cancer eighth edition pT stage predicted survival by multivariable analysis accounting for gross configuration, pT stage, and histologic type. pT2 had worse outcome relative to other pT stages. Significant differences in histology and albumin expression distinguish LD from SD, but there is insufficient evidence to support further subclassification of SD.