Abstract 4875: Clinical importance and clarification of the WHO subclassification of combined hepatocellular and cholangiocarcinoma
Authors: NAKAYAMA Hisashi , TAKAYAMA Tadatoshi , Midorikawa Yutaka , Sugitani Masahiko 
Published: August 2019

Abstract
Introduction: Combined hepatocellular and cholangiocarcinoma, classical type (Comb HCC-CCC) is defined as a single tumor, in which hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are clearly differentiated. However, combined hepatocellular-cholangiocarcinoma with stem-cell features, cholangiolocellular type (CoCC) was added to the WHO Classification in 2010. This has caused a great deal of confusion and raised many questions for clinicians and pathologists. The aim of this study was to answer these questions and evaluate the clinical importance of the WHO classification. Subjects: The subjects were 1,002 patients with primary liver cancer who underwent hepatectomy from 2010 to 2016, including 931 with HCC, 6 with Comb HCC-CCC, 50 with ICC, and 15 with CoCC. Pathological evaluation using immunohistochemical staining was mainly used for CoCC. Results: The CoCC cases had similar serum total bilirubin and serum albumin to those in other types of hepatic cancer, but with a low ICGR15 level. AFP, PIVKA-II, and CEA were 4.4 (1.3 - 3,689) ng/mL, 18 (9 - 15,933) mAU/mL, and 3.8 (0.2 - 33) ng/mL, respectively. In preoperative CT diagnosis of CoCC, HCC, Comb HCC-CCC, and ICC were diagnosed in 20%, 40%, and 40% of the cases, respectively, suggesting difficulty with this diagnosis. The resected specimen showed the number of tumors (1 [1 - 16]), tumor diameter (4 [1.7 - 12] cm), microscopic-portal venous invasion (43%), microscopic venous invasion (36%), and cirrhosis (22%), suggesting a higher level of invasion to vascular channels compared to other types of cancer. In pathological findings, both transitional HCC and cholangiocarcinoma were found in HE staining, in addition to fibrosis and necrosis in the tumor. Among the subjects, 40%, 100%, 100%, and 100% had biliary cell markers of positive CD117 (c-Kit), positive CD56 (NCAM), positive CK7, and positive CK19, respectively, in addition to high expression of neural cell adhesion molecules. Levels of hepatocytes (10%) and glypican 3 (25%) were low. Cumulative survival was lower than that in other types of liver cancer, with 1- and 3-year survival rates of 67% and 57%, respectively. [Conclusion] The development mechanism of Comb HCC-CCC is thought to be genetic transformation of HCC or ICC, while that of CoCC with stem-cell features is believed to be cancerization of stem cells. However, stem-cell features are just characteristics, and thus do not serve as definitive evidence for stem cell-derived cancer. In addition, since there are various types of CoCC in Comb HCC-CCC, actual classification is extremely difficult in many cases. The clinical importance of clear differentiation between Comb HCC-CCC and CoCC is unclear, and thus the WHO classification of these tumors may be in a transition period.
Citation Format: Hisashi NAKAYAMA, Tadatoshi TAKAYAMA, Yutaka Midorikawa, Masahiko Sugitani. Clinical importance and clarification of the WHO subclassification of combined hepatocellular and cholangiocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4875.