Hepatic epithelioid hemangioendothelioma:Update on diagnosis and therapy

With an estimated incidence of only 1-2 cases in every 1 million people,hepatic epithelioid hemangioendothelioma(HEHE)is a rare vascular endothelial cell tumor occurring in the liver and consisting of epithelioid and histiocyte-like vascular endothelial cells in mucus or a fibrotic matrix.HEHE is characterized as a low-to-moderate grade malignant tumor and is classified into three types:solitary,multiple,and diffuse.Both the etiology and characteristic clinical manifestations of HEHE are unclear.However,HEHE has a characteristic appearance on imaging including ultrasound,magnetic resonance imaging,and positron emission tomography/computerized tomography.Still,its diagnosis depends mainly on pathological findings,with immunohistochemical detection of endothelial markers cluster of differentiation 31(CD31),CD34,CD10,vimentin,and factor VIII antigen as the basis of diagnosis.Hepatectomy and/or liver transplantation are the first choice for treatment,but various chemotherapeutic drugs are reportedly effective,providing a promising treatment option.In this review,we summarize the literature related to the diagnosis and treatment of HEHE,which provides future perspectives for the clinical management of HEHE.

Long-term durable response to lenalidomide in a patient with hepatic epithelioid hemangioendothelioma

Epithelioid hemangioendothelioma(EH)is a rare tumor arising from the vascular endothelial cells of soft tissue or visceral organs.The most common visceral site is the liver,where it is often involved in a multifocal man-ner known as hepatic EH(HEH).Surgical resection with curative intent represents the gold standard therapy.When surgery is not feasible,or in cases of metastatic disease,no standard medical treatment is currently indicated.In small series,drugs with anti-angiogenic activity(such as bevacizumab,sorafenib,thalidomide,and lenalidomide)have been proposed with promising results.We describe a 73-year-old man with multifocal non-resectable HEH treated with lenalidomide.Disease status was evaluated by abdominal ultrasound and magnetic resonance every four months.The patient was treated for a total of 39 mo with prolonged disease stabilization and,at the time of writing,is still under treatment with a good tolerance profile.During a short period of treatment discontinuation,the disease showed slight progression that immediately resolved after the reintroduction of lenalidomide.Lenalidomide may represent a valid treatment option for HEH due to its anti-angiogenic and antineoplastic activities.This preliminary result merits further study in a large series.

Hepatic epithelioid hemangioendothelioma: Dilemma and challenges in the preoperative diagnosis

Hepatic epithelioid hemangioendothelioma(HEHE) is a rare category of vascular tumor with uncertain malignant potential. It commonly presents nonspecific and variable clinical manifestations, ranging from asymptomatic to hepatic failure. In addition, laboratory measurements and imaging features also lack specificity in the diagnosis of HEHE. The aim of the present study is to highlight the dilemma and challenges in the preoperative diagnosis of HEHE, and to enhance awareness of the range of hepatobiliary surgery available in patients with multiple hepatic nodular lesions on imaging. In these patients, HEHE should at least be considered in the differential diagnosis.

Spontaneous rupture of hepatic epithelioid hemangioendothelioma: A case report

Hepatic epithelioid hemangioendothelioma(HEH) is a rare tumor of vascular endothelial origin. Spontaneous rupture of HEH is a life-threatening complication and is extremely rare. HEH has variable malignant potential, and the clinical diagnosis remains challenging. Here we report a case of HEH with spontaneous rupture. A 44-year-old man presented with constant cutting pains over the right upper abdomen after eating. He had hemoptysis 11 d previously. Diagnostic abdominal puncture demonstrated active bleeding. Chest and abdominal computer tomography scan showed multiple ground-glass nodules over the lungs, multiple low-density intrahepatic nodules and massive hemorrhage. Transcatheter arterial embolization and exploratory laparotomy were performed and subsequent immunohistochemical examination confirmed a diagnosis of HEH.

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 largescale 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.

Two-stage treatment with hepatectomy and carbon-ion radiotherapy for multiple hepatic epithelioid hemangioendotheliomas

Hepatic epithelioid hemangioendothelioma(HEH)is a rare neoplasm of vascular origin with variable malignant potential.Because most patients with this condition have multiple bilobar lesions,liver transplantation is the standard treatment,and hepatectomy is much less frequently indicated.We describe a case of a 35-yearold woman with unresectable multiple bilobar HEH successfully treated by combination treatment with hepatectomy and carbon-ion radiotherapy.This case is very meaningful since it demonstrated the effectiveness of carbon-ion radiotherapy for HEH and the possibility of expanding the curative treatment options for multiple bilobar hepatic tumors.

Pediatric vascular tumors of the liver:Review from the pathologist’s point of view

Differential diagnosis of pediatric vascular liver tumors can be challenging due to inconsistent nomenclature,histologic overlap and the rarity of some entities.Here we give an up-to-date overview of the most important entities.We discuss the clinic,histology and pathophysiology of hepatic congenital and infantile heman-gioma,hepatic epithelioid hemangioendothelioma and hepatic angio-sarcoma.

Liver transplantation for benign liver tumors

Benign liver tumors are common lesions that are usually asymptomatic and are often found incidentally due to recent advances in imaging techniques and their widespread use.Although most of these tumors can be managed conservatively or treated by surgical resection,liver transplantation(LT)is the only treatment option in selected patients.LT is usually indicated in patients that present with life-threatening complications,when the lesions are diffuse in the hepatic parenchyma or when malignant transformation cannot be ruled out.However,due to the significant postoperative morbidity of the procedure,scarcity of available donor liver grafts,and the benign course of the disease,the indications for LT are still not standardized.Hepatic adenoma and adenomatosis,hepatic hemangioma,and hepatic epithelioid hemangioendothelioma are among the most common benign liver tumors treated by LT.This article reviews the role of LT in patients with benign liver tumors.The indications for LT and long-term outcomes of LT are presented.

Liver transplantation in malignant disease

Liver transplantation for malignant disease has gained increasing attention as part of transplant oncology.Following the implementation of the Milan criteria,hepatocellular carcinoma(HCC)was the first generally accepted indication for transplantation in patients with cancer.Subsequently,more liberal criteria for HCC have been developed,and research on this topic is still ongoing.The evident success of liver transplantation for HCC has led to the attempt to extend its indication to other malignancies.Regarding perihilar cholangiocarcinoma,more and more evidence supports the use of liver transplantation,especially after neoadjuvant therapy.In addition,some data also show a benefit for selected patients with very early stage intrahepatic cholangiocarcinoma.Hepatic epithelioid hemangioendothelioma is a very rare but nonetheless established indication for liver transplantation in primary liver cancer.In contrast,patients with hepatic angiosarcoma are currently not considered to be optimal candidates.In secondary liver tumors,neuroendocrine cancer liver metastases are an accepted but comparability rare indication for liver transplantation.Recently,some evidence has been published supporting the use of liver transplantation even for colorectal liver metastases.This review summarizes the current evidence for liver transplantation for primary and secondary liver cancer.