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©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
Clinicopathological characteristics and surgical outcomes of sarcomatoid hepatocellular carcinoma
Jian-Ping Wang, Zhi-Gang Yao, Ya-Wen Sun, Xi-Han Liu, Feng-Kai Sun, Cun-Hu Lin, Fu-Xin Ren, Bei-Bei Lv, Shuai-Jun Zhang, Yang Wang, Fan-Ying Meng, Shun-Zhen Zheng, Wei Gong, Jun Liu
Jian-Ping Wang, Fan-Ying Meng, Shun-Zhen Zheng, Wei Gong, Jun Liu, Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong Province, China
Jian-Ping Wang, Fan-Ying Meng, Shun-Zhen Zheng, Wei Gong, Jun Liu, Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
Zhi-Gang Yao, Cun-Hu Lin, Bei-Bei Lv, Shuai-Jun Zhang, Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
Ya-Wen Sun, Cancer Prevention and Control Research Office of Shandong Province, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, Shandong Province, China
Xi-Han Liu, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong Province, China
Feng-Kai Sun, Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
Fu-Xin Ren, Shandong Medical Imaging Research Institute, Shandong University, Jinan 250021, Shandong Province, China
Yang Wang, Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
Author contributions: Wang JP and Liu J designed the study; Yao ZG, Lin CH, Lv BB and Zhang SJ collected and analyzed the pathological data; Ren FX and Wang Y collected and analyzed the imaging data; Liu XH, Sun FK, Meng FY, Zheng SZ and Gong W collected and analyzed the clinical data; Sun YW performed statistical analyses; Wang JP drafted the manuscript; Liu J supervised the study and revised the manuscript.
Supported by Shandong Provincial Natural Science Foundation, China, No. ZR2014HP065 and No. ZR2017BH072; National Natural Science Foundation of China, No. 81373172 and No. 81770646; and Shandong Key R& D Program, No. 2015GGB14099 and No. 2017GSF218038.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Shandong Provincial Hospital.
Informed consent statement: Patients were not required to give informed consent for this study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: The authors have no conflict-of interest to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Jun Liu, MD, PhD, Professor, Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324 Jingwu Road, Jinan 250021, Shandong Province, China. dr_liujun1967@126.com
Received: March 11, 2020
Peer-review started: March 11, 2020
First decision: April 8, 2020
Revised: April 24, 2020
Accepted: July 14, 2020
Article in press: July 14, 2020
Published online: August 7, 2020
ARTICLE HIGHLIGHTS
Research background
Hepatocellular carcinoma (HCC) is the sixth most common type of cancer and the fourth leading cause of cancer-related death worldwide. Sarcomatoid HCC, which contains poorly differentiated carcinomatous and sarcomatous components, is a rare histological subtype of HCC that differs from conventional HCC. It is highly aggressive and has a poor prognosis. Its clinicopathological characteristics, surgical outcomes and underlying mechanisms of its highly aggressive nature have not been fully elucidated.
Research motivation
A few studies have reported that sarcomatoid HCC is associated with a higher recurrence rate, more frequent metastasis and poorer survival than conventional HCC. However, these studies did not further stratify conventional HCC into low- [Edmondson-Steiner (ES) grade I and II] and high-grade (ES grade III and IV) HCC; in particular, high-grade HCC is considered similar to sarcomatoid HCC in terms of histological differentiation, more aggressive nature and poor prognosis. In addition, although sarcomatoid HCC has a high incidence of adjacent organ invasion and metastasis, the underlying mechanisms remain unknown. One previous study reported that most portal venous invasions and metastases had sarcomatous components, indicating that the sarcomatous component is responsible for metastasis. However, in the study, five (38%) patients underwent preoperative treatment, such as TACE, and their analysis included an autopsied case with extensive postoperative metastases comprising sarcomatoid components. Therefore, the results might be biased. In view of the deficiencies of previous studies, we will conduct further studies on sarcomatoid HCC.
Research objectives
To examine the clinicopathological characteristics and surgical outcomes of sarcomatoid HCC and explore the histogenesis of sarcomatoid HCC.
Research methods
In total, 196 patients [41 sarcomatoid HCC and 155 high-grade (ES grade III or IV) HCC] who underwent surgical resection between 2007 and 2017 were retrospectively reviewed. The characteristics and surgical outcomes of sarcomatoid HCC were compared with those of patients with high-grade HCC. The histological composition of invasive and metastatic sarcomatoid HCCs was evaluated.
Research results
Sarcomatoid HCC was more frequently diagnosed at an advanced stage with a larger tumor and higher rates of nonspecific symptom, adjacent organ invasion and lymph node metastasis than high-grade HCC (all P < 0.05). Compared with high-grade HCC patients, sarcomatoid HCC patients are less likely to have typical dynamic imaging features of HCC (44.4% vs 72.7%, P = 0.001) and elevated serum alpha-fetoprotein levels (> 20 ng/mL; 36.6% vs 78.7%, P < 0.001). The sarcomatoid group had a significantly shorter median recurrence-free survival (5.6 mo vs 16.4 mo, log-rank P < 0.0001) and overall survival (10.5 mo vs 48.1 mo, log-rank P < 0.0001) than the high-grade group. After controlling for confounding factors, the sarcomatoid subtype was identified as an independent predictor of poor prognosis. Pathological analyses indicated that invasive and metastatic lesions were mainly composed of carcinomatous components.
Research conclusions
Sarcomatoid HCC was associated with a more advanced stage, atypical dynamic imaging, lower serum alpha-fetoprotein levels and a worse prognosis. The highly aggressive nature of sarcomatoid HCC is perhaps mediated by carcinomatous components.
Research perspectives
Studies focusing on the underlying molecular pathogenesis of sarcomatoid HCC are urgently needed to understand better its highly aggressive biological features.
