Phenotypic diversity of intrahepatic and extrahepatic cholangiocarcinoma on aspiration cytology and core needle biopsy: case series and review of the literature

BACKGROUND: Cholangiocarcinoma (CC) represents approximately 10% of primary liver malignancies and can mimic metastatic adenocarcinoma. METHODS: The authors retrospectively reviewed the cytopathology files at the University of Texas Medical Branch to identify patients who were diagnosed with intrahepatic or extrahepatic CC by aspiration cytology between 1995 and 2004. Brush cytology specimens of extrahepatic CC were excluded. All diagnoses were confirmed as CC by clinical, imaging, and histopathologic findings and by chart review. RESULTS: Cytopathology files from 13 patients with CC diagnosed by FNA were retrieved. The male:female ratio was 5:8, and the patients ranged in age from 29 years to 74 years (mean age, 59 years). In 12 of 13 patients, aspirates were obtained by ultrasound guidance; and, in 1 patient, computed tomography guidance was used. Three patients had aspirates only, 10 patients also had core biopsies, and 1 patient had cell block preparations. The phenotypic distribution of CC according to the World Health Organization (WHO) histologic classification was 9 adenocarcinoma (intrahepatic), not otherwise specified (NOS) (69%); 2 gastric foveolar type (extrahepatic) CCs (15%); 1 intestinal type (extrahepatic) CC (8%); and 1 sarcomatous/spindle cell type (intrahepatic) CC (8%). One adenocarcinoma, NOS was well differentiated CC with bland tubular architecture, and one was pleomorphic. Ancillary histochemical and immunochemical stains were performed on 5 of 13 specimens, which included 4 core biopsies and 1 aspirate with Mucicarmine positivity (3 specimens), carcinoembryonic antigen positivity (3 specimens), and a cytokeratin 7 (CK7)-positive/CK20-negative pattern (2 specimens). The 1 sarcomatous/spindle cell type CC was chromogranin-negative and low molecular weight keratin (cell adhesion molecule 5.2)-positive, which excluded metastatic carcinoid. CONCLUSIONS: Classification of intrahepatic and extrahepatic CC in aspiration cytology specimens was achieved in a reliable manner concordant with the WHO histologic classification. Special types of CC with bland nuclear features posed a diagnostic challenge on cytologic evaluation, particularly the well differentiated CC with tubular architecture and the gastric foveolar type CC with mucin-producing tumor cells. The addition of core biopsy and/or ancillary studies, such as histochemical and immunochemical stains, were helpful in reaching the correct diagnosis.