Retrospective Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jun 16, 2022; 10(17): 5606-5619
Published online Jun 16, 2022. doi: 10.12998/wjcc.v10.i17.5606
Hepatic epithelioid hemangioendothelioma: Clinical characteristics, diagnosis, treatment, and prognosis
Man Zhao, Fei Yin
Man Zhao, Fei Yin, Department of Gastroenterology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
Author contributions: Yin F designed the research study; Zhao M and Yin F performed the research, analyzed the data, and wrote the manuscript; all authors have read and approved the final manuscript.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee and Institutional Review Board of The Fourth Hospital of Hebei Medical University.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: The data that support the findings of this study are available from the corresponding author, upon reasonable request.
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: Fei Yin, PhD, Chief Physician, Department of Gastroenterology, The Fourth Hospital of Hebei Medical University, No. 12 Jiankang Road, Shijiazhuang 050000, Hebei Province. China. yinfei_4y@sina.com
Received: December 1, 2021
Peer-review started: December 1, 2021
First decision: January 12, 2022
Revised: January 23, 2022
Accepted: April 15, 2022
Article in press: April 15, 2022
Published online: June 16, 2022
Processing time: 189 Days and 23.1 Hours
Abstract
BACKGROUND

Hepatic epithelioid hemangioendothelioma (HEHE) is a rare hepatic vascular tumor with unpredictable malignant potential. The etiology, characteristics, diagnosis, treatment, and prognosis of HEHE are not well-understood, and large-scale retrospective studies are required to understand better this disease.

AIM

To determine the characteristics of HEHE and identify its optimal treatments and prognostic factors.

METHODS

The clinical data of two patients diagnosed with HEHE at the Fourth Hospital of Hebei Medical University and 258 previously reported cases retrieved from the China National Knowledge Infrastructure and PubMed databases between 1996 and 2021 were combined and summarized. All cases were pathologically identified as HEHE. Information such as clinical features, laboratory examination findings, imaging findings, pathological characteristics, treatment, and survival periods was reviewed. Kaplan-Meir curves were used for survival analysis. Prognostic factors were identified by Cox regression analysis.

RESULTS

HEHE primarily affected middle-aged women. The typical manifestations included epigastric pain, hepatosplenomegaly, inappetence, distension, weight loss, and fatigue. Tumor markers were expressed normally. The incidence of extrahepatic metastasis was 34.5% at the time of diagnosis. The most common sites of extrahepatic involvement were the lungs (22.3%), lymph nodes (5.6%), peritoneum (3.6%), bones (6.6%), and spleen (5.1%). Furthermore, “capsular retraction”, “target sign”, and “lollipop sign” were the characteristic features of HEHE on imaging. The immunohistochemical profile for HEHE (expression of vascular markers, such as factor VIII-related antigen, CD31, and CD34; expression levels of D2-40) can facilitate and ensure an accurate diagnosis. The management options for patients with HEHE include liver resection (29.7%), liver transplantation (16.1%), palliative treatments (12.7%), transhepatic arterial chemotherapy and embolization (TACE, 10.2%), chemotherapy (11.0%), antiangiogenic therapy (15.3%), and other treatments (5.1%); the mean survival time was 158.6, 147.3, 4.2, 90.8, 71.4, 83.1, and 55.0 mo, respectively. The survival time of patients who underwent surgical treatment was longer than that of patients who did not. TACE and antiangiogenic therapy tended to prolong survival compared with other nonsurgical treatments. The 1-, 5-, and 10-year survival rates were 82%, 71%, and 64%, respectively. Multivariate analysis showed that liver function (P = 0.045), intrahepatic metastasis (P = 0.029), and treatment (P = 0.045) were independent prognostic factors. The presence of extrahepatic metastases was not an independent risk factor for poor prognosis (P = 0.558).

CONCLUSION

The clinical course of HEHE is rare and variable, and patients with intrahepatic metastases and liver dysfunction may have a poorer prognosis than those without. Surgical intervention, whether liver resection or transplantation, might be warranted regardless of extrahepatic metastasis. For patients without the option for surgery, clinicians should consider the use of TACE with antiangiogenic drugs in the treatment of HEHE.

Keywords: Hepatic epithelioid hemangioendothelioma; Clinical characteristics; Diagnosis; Treatment; Prognosis

Core Tip: Hepatic epithelioid hemangioendothelioma (HEHE) is a rare hepatic vascular tumor with unpredictable malignant potential. Patients with intrahepatic metastases and liver dysfunction may have a poorer prognosis than those without. Surgical intervention, whether liver resection or transplantation, might be warranted regardless of extrahepatic metastasis. However, the therapeutic strategy for patients without the option for surgery is particularly controversial. Our experience highlights the efficacy of transhepatic arterial chemotherapy and embolization and antiangiogenic therapy in the management of HEHE.