Hepatic epithelioid hemangioendothelioma: Clinical characteristics, diagnosis, treatment, and prognosis

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.