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.

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.

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.

Effective combined therapy for pulmonary epithelioid hemangioendothelioma: A case report

BACKGROUND Pulmonary epithelioid hemangioendothelioma(P-EHE)is a rare disease.Thus far,consensus on a standard treatment for P-EHE has not been established given its low incidence worldwide.Apatinib combined with chemotherapy with doxorubicin/cyclophosphamide has been used as an effective combination treatment for human malignancies.However,the efficacy of this combination has not been reported in P-EHE cases.CASE SUMMARY We present the case of a 64-year-old woman with chest tightness,cough,and chest pain.Computed tomography showed multiple unresectable pulmonary nodules.She had been misdiagnosed with lung carcinoma and underwent gefitinib treatment at a hospital.Subsequently,the patient underwent a cardiothoracic surgery for further disease investigation.CD31,CD34,and Vimentin expression were detected in the resected nodule specimens by immunohistochemical analyses,and pathological analyses confirmed the diagnosis of P-EHE.Following this,four cycles of apatinib combined with chemotherapy with doxorubicin/cyclophosphamide were initiated.The patient demonstrated stabilization of multiple bilateral nodules and showed a dramatic improvement in the clinical presentation after combination treatment.The patient could not tolerate the side effects of chemotherapy.Therefore,she then continued apatinib monotherapy,which is ongoing to date.The patient was stable at the last follow-up after 24 mo.CONCLUSION Apatinib combined with chemotherapy with doxorubicin/cyclophosphamide may be an effective therapeutic option for P-EHE treatment.

CT and MRI diagnosis of hepatic epithelioid hemangioendothelioma

BACKGROUND: Hepatic epithelioid hemangioendothelioma (EHE) is a rare, low-grade malignant vascular tumor. Although its unusual imaging and pathologic findings are being recognized with increasing frequency, diagnosis is still difficult. This study aimed to analyze the CT and MRI features of hepatic EHE with a pathological study in order to improve the diagnostic accuracy and knowledge of this disease in daily practice. METHODS: Nine patients with hepatic EHE confirmed pathologically underwent plain and dynamic contrast-enhanced multi-detector row CT examination. Of these patients, four underwent additional MRI (plain Ti-weighted imaging (T1WI), T2-weighted imaging (T2WI), and dynamic contrast-enhanced scanning) and one had selective hepatic arteriography. The imaging findings were reviewed retrospectively together with the pathological results. RESULTS: A total of 79 lesions, ranging from 3.0 to 44.6 mm in maximum diameter, with an average of 16.8 +/- 7.1 mm, were found in various segments of the liver. Thirty of the 79 lesions grew adjacent to the hepatic capsule. In the 4 patients receiving MRI, 39 lesions were found with low signal intensity on unenhanced T1WI and intermediate to high signal intensity on T2WI. The 'capsular retraction' sign was found in all the 4 patients. Nine of the 39 lesions showed the 'halo' sign after contrast enhancement on MRI. Of the 79 lesions (hypodense nodules) in the 9 patients shown by unenhanced plain CT, 26 were confluent. Calcification was found in 2 patients and the 'capsular retraction' sign in 7. Thirty-eight of the 79 lesions demonstrated the 'halo' sign after contrast enhancement on CT, and this sign was more clearly demonstrated in the portal venous phase. In one patient, selective hepatic arteriography showed patchy stain in the peripheral liver parenchyma with small vessels around them. Histology in all patients revealed proliferation of abnormal fibrous tissue and vessel-like structures scattered with irregular epithelioid cells having a signet ring-like structure. Immunohistochemically, all patients were positive for CD34, 4 were positive for CD31, and 3 were positive for factor VIII-related antigen. CONCLUSIONS: Hepatic EHE may manifest as solitary or diffuse nodular lesions with a predilection for peripheral subcapsular growth and nodular confluence, together with the 'halo' and 'capsular retraction' signs. These imaging findings can help to improve the diagnostic accuracy of this rare hepatic tumor. (Hepatobiliary Pancreat Dis Int 2010; 9: 154-158)

Treatment and prognosis of hepatic epithelioid hemangioendothelioma based on SEER data analysis from 1973 to 2014

Background: Hepatic epithelioid hemangioendothelioma (HEH) is a rare tumor of vascular origin with an unknown etiology, a low incidence, and a variable natural course. We evaluated the management and prognosis of HEH from the Surveillance, Epidemiology and End Results (SEER) program and changes in treatment modalities of HEH over 30 years. Methods: From 1973 to 2014 in the SEER database, we selected patients diagnosed with HEH. We analyzed the clinical characteristics, patterns of management, and clinical outcomes of patients with HEH. Results: We identi ed 79 patients with HEH (median age: 54.0 years;male to female ratio: 1:2.6). The initial extent of disease was local in 22 (27.8%) patients, regional metastasis in 22 (27.8%), distant metas-tasis in 31 (39.2%) and unknown in 4 (5.1%). The median size of primary tumor was 3.85 cm (interquartile range, 2.50 7.93 cm). Among 74 patients with available management data, the most common manage-ment was no treatment (29/74, 39.2%), followed by chemotherapy only (22/74, 29.7%), liver resection-based (13/74, 17.6%), and transplantation-based therapy (6/74, 8.1%). The 5-year cancer-speci c survival rate was 57.8%. Patients who underwent surgical treatment had signi cantly higher survival than those who underwent non-surgical treatment (5-year survival;88% vs. 49%, P=0.019). Multivariate analysis revealed that surgical therapy was the only independent prognostic factor for survival (hazard ratio: 0.20, P=0.040). Conclusions: Resection or liver transplantation is worth considering for treatment of patients with HEH.

Aggressive primary hepatic epithelioid hemangioendothelioma:a case report and literature review

A new case of epithelioid hemangioendothelioma is reported to have occurred to a 67-year-old patient who consulted for rightsided chest pain. The work-up showed multiple right pulmonary lesions associated with bilateral moderate pleural effusion and left-sided pleural thickening and three hypodense nodules in the right lobe of the liver, peritoneal thickening, ascites, and multiple vertebral lytic lesions. The diagnosis of an epithelioid hemangioendothelioma was concluded through a histological examination of a computed tomography scan guided biopsy of the liver. The patient received a primary mono-chemotherapy with Adriamycin(75 mg/m^2 every three weeks) and intravenous bisphosphonates without response and general status impairment. The patient died after 16 months of follow-up.

Femoral epithelioid hemangioendothelioma detected with magnetic resonance imaging and positron emission tomography/computed tomography:A case report

BACKGROUND Epithelioid hemangioendothelioma(EHE)is an uncommon low-grade aggressive vascular tumor.It can occur in almost all locations,but is rarely encountered in bone.CASE SUMMARY We report a 23-year-old man who presented with left hip pain with no obvious cause.X-ray revealed bone destruction in the left femoral neck with sclerosis at the edges of the lesions.Magnetic resonance imaging(MRI)showed bone destruction in the medullary cavity of the left femoral head and neck.18Fdeoxyglucose-positron emission tomography/computed tomography(PET/CT)imaging showed bone destruction in the left ischium,acetabulum,and left femoral head neck,accompanied by increased radioactive uptake;the maximum standard uptake value was 4.2.Histopathologic examination revealed spindleshaped mesenchymal tissue hyperplasia with scattered epithelioid cells.The patient underwent left femoral head replacement surgery.No signs of recurrence were observed as of the 18-mo follow-up.CONCLUSION The definitive diagnosis of femoral EHE can be established aided by the MRI and PET/CT findings.

Activity of Angiogenesis Inhibitors in Metastatic Epithelioid Hemangioendothelioma:A Case Report

This report describes a patient with metastatic epithelioid hemangioendothelioma treated with bevacizumab and nanoparticle albumin-bound paclitaxel.The treatment was well tolerated and led to the stabilization of an aggressive variant of the disease. This case report is the first one that describes the activity of the combination of chemotherapy and bevacizumab in epithelioid hemangioendothelioma.Literature describing the activity of bevacizumab and other agents(thalidomide,lenalidomide,and interferon) believed to possess anti-angiogenic activities is also reviewed.

A Case of Epithelioid Hemangioendothelioma in the Liver

A 15-year-old girl was admitted to our hospital with a 9-month history of upper abdominal pain and loss of appetite. Her history showed no indication of hepatitis. Her abdomen appeared to be even and soft, and the liver and spleen could not be felt below the costal margin. Percussion pain in hepatic region was negative. Gastroscopy showed no abnormalities. An abdominal ultrasound examination revealed the presence of hepatic hypoechoic areas and an abdominal CT scan showed multiple roundlike low-density masses in both hepatic lobes. The edges of the focal lesions were smooth and continuous, with a heterogeneous center, the round-like edges were enhanced, but the enhancement in the focal lesions was not obvious.

Primary malignant vascular tumors of the liver in children:Angiosarcoma and epithelioid hemangioendothelioma

Primary malignant vascular neoplasms of the liver,angiosarcoma and epithelioid hemangioendothelioma,are extremely rare entities in the pediatric population.International Society for the Study of Vascular Anomalies classification system is recommended for the pathologic diagnosis of hepatic vascular lesions in this age group.In this article,we highlight the clinicopathologic characteristics of hepatic angiosarcoma and epithelioid hemangioendothelioma in the pediatric population.Hepatic angiosarcoma in children shows a slight female predominance with an average age of 40 mo at diagnosis.The distinct histologic features include whorls of atypical spindled cells and eosinophilic globules,in addition to the general findings of angiosarcoma.Histologic diagnosis of pediatric hepatic angiosarcoma is not always straightforward,and the diagnostic challenges are discussed in the article.Hepatic epithelioid hemangioendothelioma also demonstrates a female predominance,but is more commonly identified in adolescents(median age at diagnosis:12 years).Histologically,the lesion is characterized by epithelioid cells and occasional intracytoplasmic lumina with a background of fibromyxoid stroma.While WWTR1-CAMTA1 and YAP1-TFE3 fusions have been associated with epithelioid hemangioendothelioma,there are currently no known signature genetic alterations seen in pediatric hepatic angiosarcoma.Advancement in molecular pathology,particularly for pediatric hepatic angiosarcoma,is necessary for a better understanding of the disease biology,diagnosis,and development of targeted therapies.

Hepatic epithelioid hemangioendothelioma after thirteen years'follow-up:A case report and review of literature

BACKGROUND Hepatic epithelioid hemangioendothelioma(EHE)is a rare vascular endothelial cell tumor of the liver,consisting of epithelioid and histiocyte-like vascular endothelial cells in mucus or a fibrotic matrix.Immunohistochemistry is usually positive for vascular markers,such as factor VIII-related antigen,CD31,and CD34.Hepatic EHE can have a varied clinical course;treatment includes liver transplantation,liver resection,chemotherapy,and radiation therapy.CASE SUMMARY A 46-year-old woman with abdominal discomfort and elevated serum carcinoembryonic antigen was found to have multiple low-density lesions in the liver and lung on computed tomography(CT)evaluation.An ultrasound-guided fine needle aspiration biopsy revealed a fibrous stroma with dendritic cells,containing intracellular vacuoles.Immunohistochemical staining found that the tumor cells were positive for CD34,CD31,and factor VIII-related antigen.The patient received four courses of combined chemotherapy and was followed-up for 13 years,at which time the patient was in stable condition without disease progression and a confined neoplasm,as evidenced by CT scans.CONCLUSION The histology and immunohistochemical characteristics of hepatic EHE are well described.Chemotherapy may be effective in patients with extrahepatic lesions.

Open surgical treatment for rare epithelioid hemangioendothelioma of the common femoral vein

Epithelioid hemangioendothelioma is a very rare disease affecting big blood vessels,especially veins.There have been very few articles describing the disease.We hereby present the case of a 56-year-old woman presenting with lower limb edema,who was initially being treated for residual thrombus in the common femoral vein but was eventually diagnosed with epithelioid hemangioendothelioma(EHE).The common femoral vein was resected and reconstructed using the external jugular vein.No additional therapy was administered.In this article,previous literature about EHE has been reviewed and oncologic principles have been discussed.

A Primary Epithelioid Hemangioendothelioma of the Right Atrium: Report of a Case and Literature Review

Primary cardiac epithelioid hemangioendothelioma (EHE) is extremely uncommon. To our knowledge, only fourteen cases have been reported. We report a case of a primary EHE of the right atrium which incidentally detected in 77-year-old woman. Echocardiograhpy revealed a 26 × 16 mm right atrial mass attached to the base of the interatrial septum and moderate regurgitation of the tricuspid valve. The tumor and stalk were completely resected from the interatrial septum with a partial resection of the septal leaflet of the tricuspid valve. The patient had an uneventful postoperative course and no signs of recurrence nor metastasis of EHE 4 years after operation. Because of malignant potential of EHE, a longer period of close follow up is necessary.

Application of Ultrahigh Doses of Morphine in Systemic Multiple Epithelioid Hemangioendothelioma without Addiction: A Case Report

Morphine is a potent opioid which is commonly used for relieving cancer pain with strong analgesic properties. Epithelioid hemangioendothelioma (EHE), a rare vascular tumor that can cause severe chronic pain, is usually diagnosed in a surgical biopsy. We describe ultrahigh doses of morphine used in a case of a 17-year-old male who suffered from severe chest pain with systemic multiple EHE. The total dosage of morphine was as high as 92,530 mg given within 164 days. However, we observed no indications that the patient was addicted.

Case analysis of epithelioid hemangioendothelioma of pancreas with liver and lung involvement

Objective:To summarize the clinical manifestation,diagnosis and treatment of a case of epithelioid hemangioendothelioma of the pancreas(epithelioid hemangioendothelioma,EHE)with liver and right lung involvement.Methods:The clinical,imaging,histomorphological and immunohistochemical features of a patient with pancreatic epithelioid hemangioendothelioma with liver and right lung involvement diagnosed in Laizhou traditional Chinese Medicine Hospital in 2021 were analyzed retrospectively,and the related literatures were reviewed.Results:After 8 cycles of chemotherapy combined with hyperthermia and traditional Chinese medicine treatment,the clinical discomfort symptoms were significantly improved,the quality of life was improved,and the condition was stable,which is still in the process of treatment.Conclusion:Pancreatic EHE is rare in clinic.Imaging plays an important role in the diagnosis of pancreatic EHE,but the final diagnosis should be confirmed by pathological examination.The histological features of this case of EHE should be distinguished from metastatic carcinoma,epithelioid sarcoma,mesothelioma and other common tumors in the abdominal cavity,and its diagnosis is challenging.Surgical resection is the first choice for EHE,but its sensitivity to radiotherapy and chemotherapy is not accurate.The prognosis of EHE needs to collect more case data for in-depth and systematic study and analysis.

Contrast-enhanced multiple-phase imaging features in hepatic epithelioid hemangioendothelioma

AIM： To investigate and review the contrast-enhanced multiple-phase computed tomography （CEMP CT） and magnetic resonance imaging （MRI） findings in patients with pathologically confirmed hepatic epithelioid hemangioendothelioma （HEHE）. METHODS： Findings from imaging examinations in 8 patients （5 women and 3 men） with pathologically confirmed HEHE were retrospectively reviewed （CT images obtained from 7 patients and MR images obtained from 6 patients）. The age of presentation varied from 27 years to 60 years （average age 39.8 years）. RESULTS： There were two types of HEHE： multifocal type （n = 7） and diffuse type （n = 1）. Tn the multifocal-type cases, there were 74 lesions on CT and 28 lesions on MRI with 7 lesions found with diffusion weighted imaging; 18 （24.3%） of 74 lesions on plain CT and 26 （92.9%） of 28 lesions on pre-contrast MRI showed the target sign. On CEMP CT, 28 （37.8%） of 74 lesions appeared with the target sign and a progressive-enhancement rim and 9 （12.2%） of 74 lesions displayed progressive enhancement, maintaining a state of persistent enhancement. On CEMP MRI, 27 （96.4%） of 28 lesions appeared with the target sign with a progressive-enhancement rim and 28 （100%） of 28 lesions displayed progressive-enhancement, maintaining a state of persistent enhancement. In the diffuse-type cases, an enlarged liver was observed with a large nodule appearing with persistent enhancement on CEMP CT and MRI. CONCLUSION： The most important imaging features of HEHE are the target sign and/or progressive en- hancement with persistent enhancement on CEMP CT and MRI. MRI is advantageous over CT in displaying these imaging features.