Clinical analysis of synchronous double primary hepatocellular carcinoma and intrahepatic cholangiocarcinoma_West China Medical Journal

Authors：

WU Qiuji ¹ , XIONG Moli ² , WANG Xinyuan ¹ , LU Changli ² , LI Chuan ³ , CHEN Weixia ⁴ , WEN Tianfu ³ ,  LI Qiu ¹ , Liver Cancer MDT of West China Hospital of Sichuan University

1. Department of Abdominal Tumor, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
3. Department of Hepatic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
4. Center for Medical Imaging, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

LI Qiu, Email: fbqiu9@163.com

Keywords：

Double primary; Hepatocellular carcinoma; Intrahepatic cholangiocarcinoma; Imaging; Pathology

DOI：

10.7507/1002-0179.201902092

Video：

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Objective To explore the clinical, imaging, and pathological features of patients with synchronous double primary hepatocellular carcinoma and intrahepatic cholangiocarcinoma (sdpHCC-ICC), to enhance our understanding of the disease and reduce the rate of misdiagnosis and missed diagnosis.Methods The clinical, imaging, and pathological data of patients who were histologically confirmed as sdpHCC-ICC in West China Hospital of Sichuan University between January 1st 2014 and December 31st 2018 were studied retrospectively.Results A total of 11 patients with sdpHCC-ICC were screened for the study, of which 10 were male and 1 was female. The median age of patients was 55.6 years (ranged from 47 to 73 years). Eight patients were chronically infected with hepatitis B virus. Both increased alpha-fetoprotein and carbohydrate antigen 19-9 were observed in 8 patients. Contrast enhanced CT was performed in 8 cases, color doppler ultrasound in 4 cases, enhanced MRI in 3 cases, and contrast-enhanced ultrasound in 1 case. Among them, one solitary lesion was found in 2 patients, and two or more lesions were observed in 9 patients. Most of the patients had typical imaging performance of hepatocellular carcinoma (HCC): 8 patients showed strong enhancement of HCC during the hepatic arterial phase and progressive hyper-attenuation on venous and delayed phases, 1 patient showed peripheral rim enhancement in the arterial phase of intrahepatic cholangiocarcinoma (ICC) in another lesion could be observed at the same time. None of the 11 patients with sdpHCC-ICC was diagnosed accurately before operation. All patients underwent surgical treatment. HCC lesions were distributed in all parts of the liver, while ICC lesions were located in the right lobe of the liver in 10 cases. The median diameter of HCC and ICC was 3.5 cm and 2.1 cm, respectively. All of them were confirmed by hematoxylin-eosin staining and immunohistochemistry.Conclusions The clinical characteristics of sdpHCC-ICC are usually atypical. It is difficult to make an accurate preoperative diagnosis. Tumor markers may be valuable to the diagnosis of sdpHCC-ICC. The definite diagnosis of sdpHCC-ICC depends on pathological examination.

Citation： WU Qiuji, XIONG Moli, WANG Xinyuan, LU Changli, LI Chuan, CHEN Weixia, WEN Tianfu, LI Qiu, Liver Cancer MDT of West China Hospital of Sichuan University. Clinical analysis of synchronous double primary hepatocellular carcinoma and intrahepatic cholangiocarcinoma. West China Medical Journal, 2019, 34(3): 309-314. doi: 10.7507/1002-0179.201902092 Copy

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4.	Koh KC, Lee H, Choi MS, et al. Clinicopathologic features and prognosis of combined hepatocellular cholangiocarcinoma. Am J Surg, 2005, 189(1): 120-125.
5.	Allen RA, Lisa JR. Combined liver cell and bile duct carcinoma. Am J Pathol, 1949, 25(4): 647-655.
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12.	Goodman ZD, Ishak KG, Langloss JM, et al. Combined hepatocellular- cholangiocarcinoma. A histologic and immunohistochemical study. Cancer, 1985, 55(1): 124-135.
13.	Wakasa T, Wakasa K, Shutou T, et al. A histopathological study on combined hepatocellular and cholangiocarcinoma: cholangiocarcinoma component is originated from hepatocellular carcinoma. Hepatogastroenterology, 2007, 54(74): 508-513.
14.	Cao J, Huang L, Liu CF, et al. Double primary hepatic cancer (hepatocellular carcinoma and intrahepatic cholangiocarcinoma) in a single patient: a clinicopathologic study of 35 resected cases. J Gastroenterol Hepatol, 2013, 28(6): 1025-1031.
15.	Garancini M, Goffredo P, Pagni F, et al. Combined hepatocellular-cholangiocarcinoma: a population-level analysis of an uncommon primary liver tumor. Liver Transplantation, 2014, 20(8): 952-959.
16.	周彦明, 杨甲梅, 李滨, 等. 原发性肝脏双肿瘤: 附五例. 中华肝胆外科杂志, 2009, 15(6): 451-452.
17.	Sanada Y, Shiozaki S, Aoki H, et al. A clinical study of 11 cases of combined hepatocellular-cholangiocarcinoma assessment of enhancement patterns on dynamics computed tomography before resection. Hepatol Res, 2005, 32(3): 185-195.
18.	Gera S, Ettel M, Acosta-Gonzalez G, et al. Clinical features, histology, and histogenesis of combined hepatocellular-cholangiocarcinoma. World J Hepatol, 2017, 9(6): 300-309.
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20.	Poultsides GA, Zhu AX, Choti MA, et al. Intrahepatic cholangiocarcinoma. Surg Clin, 2010, 90(4): 817-837.
21.	李小龙, 潘虎晓, 施国明, 等. 基于单中心的双原发性肝细胞肝癌和肝内胆管癌术后疗效影响因素分析. 中国临床医学, 2018, 25(4): 518-525.
22.	Zhang BH, Yang BH, Tang ZY. Randomized controlled trial of screening for hepatocellular carcinoma. J Cancer Res Clin Oncol, 2004, 130(7): 417-422.
23.	粟立红, 朱新宇, 张缭云. 肝内胆管癌的诊断策略. 临床肝胆病杂志, 2017, 33(1): 180-183.
24.	Khan SA, Thomas HC, Davidson BR, et al. Cholangiocarcinoma. Lancet, 2005, 366(9493): 1303-1314.
25.	Bridgewater J, Galle PR, Khan SA, et al. Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma. J Hepatol, 2014, 60(6): 1268-1289.
26.	蔡珍华, 吴婷. 血清CA19-9对肝胆胰疾病的临床诊断价值. 胃肠病学和肝病学杂志, 2013, 22(11): 1155-1158.
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30.	唐啸, 张莹. 肝内周围型胆管细胞癌的CT和MRI诊断研究. 医学影像学杂志, 2013, 23(2): 217-219.
31.	李伟. 肝内周围型胆管细胞癌CT和MRI的诊断价值研究. 世界临床医学, 2016, 10(19): 214.
32.	吴向嵩, 刘颖斌. 肝内胆管细胞癌手术治疗策略的进展. 中华消化外科杂志, 2016, 15(11): 1131-1134.
33.	王晓耘, 王健东. 肝癌淋巴结转移手术治疗进展. 中国实用外科杂志, 2015, 35(4): 454-456.
34.	Wu C, Bai DS, Jiang GQ, et al. Synchronous double cancers of primary hepatocellular carcinoma and intrahepatic cholangiocarcinoma: a case report and review of the literature. World J Surg Oncol, 2014, 12: 337.
35.	Jeng KS, Sheen IS, Jeng WJ, et al. Activation of the sonic hedgehog signaling pathway occurs in the CD133 positive cells of mouse liver cancer Hepa 1-6 cells. Onco Targets Ther, 2013, 6: 1047-1055.
36.	Massani M, Stecca T, Fabris L, et al. Isolation and characterization of biliary epithelial and stromal cells from resected human cholangiocarcinoma: a novel in vitro model to study tumor-stroma interactions. Oncol Rep, 2013, 30(3): 1143-1148.

1. 中国临床肿瘤学会(CSCO). 原发性肝癌诊疗指南2018.v1. [2019-01-01]. http://www.csco.org.cn/.
2. Altekruse SF, Fau-Dickie SA, Fau-Mcglynn LA, et al. Histological classification of liver and intrahepatic bile duct cancers in SEER registries. J Registry Manag, 2011, 38(4): 201-205.
3. Tang D, Nagano H, Nakamura M, et al. Clinical and pathological features of Allen’s type C classification of resected combined hepatocellular and cholangiocarcinoma: a comparative study with hepatocellular carcinoma and cholangiocellular carcinoma. J Gastrointest Surg, 2006, 10(7): 987-998.
4. Koh KC, Lee H, Choi MS, et al. Clinicopathologic features and prognosis of combined hepatocellular cholangiocarcinoma. Am J Surg, 2005, 189(1): 120-125.
5. Allen RA, Lisa JR. Combined liver cell and bile duct carcinoma. Am J Pathol, 1949, 25(4): 647-655.
6. Hamilton SR, Aaltonen LA. 世界卫生组织肿瘤分类及诊断标准系列: 消化系统肿瘤病理学和遗传学. 虞积耀, 崔全才, 译. 北京: 人民卫生出版社, 2006.
7. 王玉兰, 杜经丽, 韦立新, 等. 肝细胞癌胆管癌并存6例临床病理分析. 诊断病理学杂志, 2009, 16(2): 92-95.
8. Komuta M, Govaere O, Vandecaveye V, et al. Histological diversity in cholangiocellular carcinoma reflects the different cholangiocyte phenotypes. Hepatology, 2012, 55(6): 1876-1888.
9. Watanabe T, Sakata J, Ishikawa T, et al. Synchronous development of HCC and CCC in the same subsegment of the liver in a patient with type C liver cirrhosis. World J Hepatol, 2009, 1(1): 103-109.
10. Li AJ, Ma SL, Pawlik T, et al. Surgical treatment of double primary liver cancer: an observational study for a rare type of tumor. Medicine (Baltimore), 2016, 95(32): e4412.
11. Fukukura Y, Taguchi J, Nakashima O, et al. Combined hepatocellular and cholangiocarcinoma: correlation between CT findings and clinicopathological features. J Comput Assist Tomogr, 1997, 21(1): 52-58.
12. Goodman ZD, Ishak KG, Langloss JM, et al. Combined hepatocellular- cholangiocarcinoma. A histologic and immunohistochemical study. Cancer, 1985, 55(1): 124-135.
13. Wakasa T, Wakasa K, Shutou T, et al. A histopathological study on combined hepatocellular and cholangiocarcinoma: cholangiocarcinoma component is originated from hepatocellular carcinoma. Hepatogastroenterology, 2007, 54(74): 508-513.
14. Cao J, Huang L, Liu CF, et al. Double primary hepatic cancer (hepatocellular carcinoma and intrahepatic cholangiocarcinoma) in a single patient: a clinicopathologic study of 35 resected cases. J Gastroenterol Hepatol, 2013, 28(6): 1025-1031.
15. Garancini M, Goffredo P, Pagni F, et al. Combined hepatocellular-cholangiocarcinoma: a population-level analysis of an uncommon primary liver tumor. Liver Transplantation, 2014, 20(8): 952-959.
16. 周彦明, 杨甲梅, 李滨, 等. 原发性肝脏双肿瘤: 附五例. 中华肝胆外科杂志, 2009, 15(6): 451-452.
17. Sanada Y, Shiozaki S, Aoki H, et al. A clinical study of 11 cases of combined hepatocellular-cholangiocarcinoma assessment of enhancement patterns on dynamics computed tomography before resection. Hepatol Res, 2005, 32(3): 185-195.
18. Gera S, Ettel M, Acosta-Gonzalez G, et al. Clinical features, histology, and histogenesis of combined hepatocellular-cholangiocarcinoma. World J Hepatol, 2017, 9(6): 300-309.
19. 俞顺章, 郑莹, 吴春晓, 等. 上海市肝细胞癌防治40年. 中华流行病学杂志, 2013, 34(6): 637-641.
20. Poultsides GA, Zhu AX, Choti MA, et al. Intrahepatic cholangiocarcinoma. Surg Clin, 2010, 90(4): 817-837.
21. 李小龙, 潘虎晓, 施国明, 等. 基于单中心的双原发性肝细胞肝癌和肝内胆管癌术后疗效影响因素分析. 中国临床医学, 2018, 25(4): 518-525.
22. Zhang BH, Yang BH, Tang ZY. Randomized controlled trial of screening for hepatocellular carcinoma. J Cancer Res Clin Oncol, 2004, 130(7): 417-422.
23. 粟立红, 朱新宇, 张缭云. 肝内胆管癌的诊断策略. 临床肝胆病杂志, 2017, 33(1): 180-183.
24. Khan SA, Thomas HC, Davidson BR, et al. Cholangiocarcinoma. Lancet, 2005, 366(9493): 1303-1314.
25. Bridgewater J, Galle PR, Khan SA, et al. Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma. J Hepatol, 2014, 60(6): 1268-1289.
26. 蔡珍华, 吴婷. 血清CA19-9对肝胆胰疾病的临床诊断价值. 胃肠病学和肝病学杂志, 2013, 22(11): 1155-1158.
27. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: hepatobiliary cancers. (Version 1.2019). [2019-01-01]. https://www.nccn.org.
28. 周纯武, 赵心明. 肿瘤影像诊断图谱. 2版. 北京: 人民卫生出版社, 2018: 998.
29. Fabrega-Foster K, Ghasabeh MA, Pawlik TM, et al. Multimodality imaging of intrahepatic cholangiocarcinoma. Hepatobiliary Surg Nutr, 2017, 6(2): 67-78.
30. 唐啸, 张莹. 肝内周围型胆管细胞癌的CT和MRI诊断研究. 医学影像学杂志, 2013, 23(2): 217-219.
31. 李伟. 肝内周围型胆管细胞癌CT和MRI的诊断价值研究. 世界临床医学, 2016, 10(19): 214.
32. 吴向嵩, 刘颖斌. 肝内胆管细胞癌手术治疗策略的进展. 中华消化外科杂志, 2016, 15(11): 1131-1134.
33. 王晓耘, 王健东. 肝癌淋巴结转移手术治疗进展. 中国实用外科杂志, 2015, 35(4): 454-456.
34. Wu C, Bai DS, Jiang GQ, et al. Synchronous double cancers of primary hepatocellular carcinoma and intrahepatic cholangiocarcinoma: a case report and review of the literature. World J Surg Oncol, 2014, 12: 337.
35. Jeng KS, Sheen IS, Jeng WJ, et al. Activation of the sonic hedgehog signaling pathway occurs in the CD133 positive cells of mouse liver cancer Hepa 1-6 cells. Onco Targets Ther, 2013, 6: 1047-1055.
36. Massani M, Stecca T, Fabris L, et al. Isolation and characterization of biliary epithelial and stromal cells from resected human cholangiocarcinoma: a novel in vitro model to study tumor-stroma interactions. Oncol Rep, 2013, 30(3): 1143-1148.

West China Medical Journal

Clinical analysis of synchronous double primary hepatocellular carcinoma and intrahepatic cholangiocarcinoma

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