| Objective:Hepatic epithelioid hemangioendothelioma(HEHE) is a rare hepatic vascular tumor with a clinical course between benign hemangioma and angiosarcoma. It usually affects adult women and its clinical course is nonspecific, ranging from complete remission to hepatic failure and death. The aim of the study was to recognize the characteristics of HEHE and identify its prognostic factors. In addition, a comparative study were made to explore the difference between Chinese and foreign patients.Methods:Two cases diagnosed with HEHE in the Fourth Hospital of Hebei Medical University between 2004 and 2014 combined with 184 previously reported cases retrieved from the literature between 1996 and 2014 were summarized. Parameters such as demographic statistics, clinical manifestations, diagnostic methods, therapeutic methods and clinical outcome were reviewed. All data were analysed with the SPSS 21.0 computer software. P<0.05 represented the difference possessing statistical significance.Results:1 General information: The male to female ratio of patients was 2:4.9 with the mean age of 42.6±14 years(range, 3-80 years).2 Clinical features: Its clinical manifestations were variable. The typical manifestations of HEHE included epigastric pain(40%), hepatosplenomegaly(13.9%), inappetence(13.3%), distension(12.2%) and weight loss(10.6%),followed by fatigue, epigastric discomfort, hydrothorax and ascite. However, HEHE also had been discovered incidentally in asymptomatic patients(30%). Most of the patients presented with multiple lesions involving both lobes of the hepatic(65.9%),only 15.4% of the patients were single lesion. Whether single lesion or multiple lesions, the right lobe was affected more than the left lobe. 31.7% of the patients had extrahepatic metastases. The lungs(20.3%), lymph nodes(6.5%), bone(4.1%), peritoneum(3.3%) and spleen(3.3%) were the most frequent sites of extrahepatic metastases at the time of diagnosis.3 Diagnosis: The combined use of laboratory tests, imaging and pathological examinations could help make a diagnosis. 40.2% of the patients had abnormal liver function, most common changes were elevated alanine transaminase(ALT, 24.7%), aspartate transaminase(AST, 23.7%), total bilirubin(TBIL, 10.3%), γ glutamyl transpeptidase(GGT, 16.5%) and alkaline phosphatase(ALP, 24.7%). Alpha fetoprotein(AFP), carcinoembryonic antigen(CEA) and carbohydrate antigen19-9(CA-199) were always in the normal level. On imaging study, most tumors were found in subcapsular locations, they presented as multiple hepatic nodules and formed large, confluent masses over time. Abdominal computed tomography(CT) demonstrated round or oval areas of low density(98.6%). Contrast-enhanced CT showed the peripheral rim of the tumors were enhanced(86.4%). “Capsular retraction”(18.1%), “target sign”(26.2%) and “lollipop sign”(11.7%) could highly suggest the diagnosis of HEHE. However, its definitive diagnosis was completely dependent on pathological examination. In immunohistochemical staining, the neoplastic cells were positive for factor FⅧ-RAg, CD31 and CD34. Among liver tumors, D2-40 was specifically expressed in epithelioid hemangioendothelioma but not in other hepatic tumors, D2-40 would be a useful tumor marker in the diagnoses of HEHE.4 Treatment and survival rate: Management for the HEHE patients included liver resection(LRx, 27.9%), liver transplantation(LTx, 17.6%), palliative treatment(14.7%), transhepatic arterial chemotherapy and embolization(TACE, 11.8%), chemotherapy or radiotherapy(10.3%), interferon(4.4%) and other treatments(such as antiangiogenic drugs, chinese traditional medicine and so on)(13.2%). No matter what kind of treatments, the 1-year,5-year and 10-year patient survival rates were 79%, 74% and 66%.5 Prognostic analysis: On univariate analysis: gender, age, tumor markers, hepatitis, tumor type(multinodular/mononodular), extrahepatic metastasis and tumor resection had no significantly(P>0.05); but symptoms and liver function influenced the prognosis significantly(P<0.05). On multiplicity analysis: symptoms and liver function were independent prognostic factors.6 Chinese and foreigner contrast:The demographic statistics and most of the clinical manifestations in chinese patients were similar to those found in abroad country. The incidences of thoracalgia, humeral back pain and liver dysfunction were significantly higher in foreign patients(15% vs 1.4%, P=0.002; 54.5% vs 32.8%, P=0.039). The percentage of extrahepatic metastasis(21% vs 52.4%,P = 0.000) was lower in Chinese patients at diagnosis, especially pulmonary metastasis rate(12.3% vs 35.7%, P = 0.002). TACE was a more common treatment in china.Conclusion:1 Hepatic epithelioid hemangioendothelioma was a rare vascular tumor. For its nonspecific manifestations and variable imaging findings,definite diagnosis was depended on pathologic study. Pathological characteristics of tumor cells were expressions of endothelial markers(FⅧ-RAg, CD34 and CD31). D2-40 would be useful as a diagnostic marker for HEHE.2 For patients with resectable HEHE, LRx was preferred. LTx had been proposed as the treatment of choice in patients with unresectable and diffuse HEHE. Interferon treatment might benefit the patients. Standardized treatment remained undefined and individualized treatment might exhibit an improved clinical outcome.3 Its prognosis was further better than that of other hepatic malignant tumors. Patients with obvious symptoms and liver dysfunction might encounter a poorer prognosis.4 Notably, unlike foreign cases, a number of HEHE patients in China were asymptomatic with normal liver function and exhibit less extrahepatic metastasis for a considerable part of the disease course. Furthermore, TACE was a more common treatment option in China. |
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