Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 7, 2025; 31(5): 98928
Published online Feb 7, 2025. doi: 10.3748/wjg.v31.i5.98928
Histopathological diagnosis of microvascular invasion in hepatocellular carcinoma: Is it reliable?
Liu-Jun Li, Chao-Qun Wu, Fei-Le Ye, Zhou Xuan, Xiao-Li Zhang, Jian-Ping Li, Jia Zhou, Zhong-Zhen Su
Liu-Jun Li, Jia Zhou, Department of Ultrasound, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, Hunan Province, China
Liu-Jun Li, Chao-Qun Wu, Fei-Le Ye, Zhong-Zhen Su, Department of Ultrasound, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, Guangdong Province, China
Liu-Jun Li, Chao-Qun Wu, Fei-Le Ye, Zhong-Zhen Su, Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, Guangdong Province, China
Zhou Xuan, Department of Pathology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, Guangdong Province, China
Xiao-Li Zhang, Jian-Ping Li, Department of Pathology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, Hunan Province, China
Co-corresponding authors: Jia Zhou and Zhong-Zhen Su.
Author contributions: Li LJ, Zhou J, and Su ZZ designed and coordinated the study; Li LJ, Wu CQ, Ye FL, Xuan Z, Zhang XL, and Li JP performed the experiments, acquired and analyzed data; Li LJ, Wu CQ, Ye FL, Zhou J, and Su ZZ interpreted the data; Li LJ, Wu CQ, Zhou J, and Su ZZ wrote the manuscript; and all authors approved the final version of the article. The co-corresponding authors, Zhou J and Su ZZ made equal contributions in the conception, design, data analysis, paper writing, and review. Su ZZ acquired the research funding, oversaw the research, and guided and revised the research design and experimental protocol. Zhou J mainly focused on animal model construction, data analysis, and paper writing guidance. Their work complemented each other, ensuring the high-quality completion of the research.
Supported by the National Natural Science Foundation of China, No. 82072038 and No. 82371975.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Zhuhai BesTest Bio-Tech Co., Ltd., IACUC protocol number: No. IAC(L)202104001.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Zhong-Zhen Su, MD, PhD, Department of Ultrasound, The Fifth Affiliated Hospital of Sun Yat-sen University, No. 52 Meihua Road, Zhuhai 519000, Guangdong Province, China. suzhzh3@mail.sysu.edu.cn
Received: July 11, 2024
Revised: November 5, 2024
Accepted: December 12, 2024
Published online: February 7, 2025
Processing time: 172 Days and 5.5 Hours
Abstract
BACKGROUND

Microvascular invasion (MVI) is a critical prognostic factor for postoperative hepatocellular carcinoma recurrence, but the reliability of its current pathological diagnosis remains uncertain.

AIM

To evaluate the accuracy of current 7-point sampling methods and propose an optimal pathological protocol using whole-mount slide imaging (WSI) for better MVI detection.

METHODS

We utilized 40 New Zealand white rabbits to establish VX2 liver tumor models. The entire tumor-containing liver lobe was subsequently obtained, following which five different sampling protocols (A-E) were employed to evaluate the detection rate, accuracy, quantity, and distribution of MVI, with the aim of identifying the optimal sampling method.

RESULTS

VX2 liver tumor models were successfully established in 37 rabbits, with an incidence of MVI of 81.1% (30/37). The detection rates [27% (10/37), 43% (16/37), 62% (23/37), 68% (25/37), and 93% (14/15)] and quantity (15, 36, 107, 125, and 395) of MVI increased significantly from protocols A to E. The distribution of MVI showed fewer MVIs farther away from the tumor, but the percentage of MVI detected quantity gradually increased from 6.7% to 48.3% in the distant nonneoplastic liver tissue from protocols A to E. Protocol C was identified as the optimal sampling method by comparing them in sequence. The sampling protocol of three consecutive interval WSIs at the tumor center (WSI3) was further screened to determine the optimal number of WSIs. Protocol A (7-point sampling method) exhibited only 46% accuracy and a high false-negative rate of 67%. Notably, the WSI3 protocol improved the accuracy to 78% and decreased the false-negative rate to 27%.

CONCLUSION

The current 7-point sampling method has a high false-negative rate in MVI detection. In contrast, the WSI3 protocol provides a practical and effective approach to improve MVI diagnostic accuracy, which is crucial for hepatocellular carcinoma diagnosis and treatment planning.

Keywords: Hepatocellular carcinoma; Microvascular invasion; Histopathological diagnosis; Whole-mount slide imaging; Sampling protocol

Core Tip: This study investigated the effectiveness of various pathological sampling protocols for detecting microvascular invasion (MVI) in hepatocellular carcinoma. Conventional 7-point sampling methods have a high false-negative rate for MVI detection. However, the study revealed that whole-mount slide imaging, particularly when three consecutive interval whole-mount slide imaging from the tumor center are used, significantly improves diagnostic accuracy. This innovative approach improves the detection of MVI, especially in distant nonneoplastic liver tissue that have previously been ignored, offering a more reliable method for postoperative prognosis.