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.

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)

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.

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.

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.

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.

Epithelioid haemangioendothelioma of the lung:one case report with positive pulmonary hilar lymph nodes

Pulmonary epithelioid hemangioendothelioma (PEH) is a rare tumor that occurs among young women and typically presents as bilateral multiple nodules. In this report, we described an unusual case of PEH presented as a single mass in a 46-year-old man, with 6 positive pulmonary hilar lymph nodes. Histologic findings were compared with conventional PEH, except those features such as round to oval-shaped nodules, hypocellular/cellular peripheral zone, hyaline, myxomatous intercellular stroma and intracellular vacuoles, and we found the patient's pulmonary hilar lymph nodes were metastasis and cholesterol crystal were discovered in the focal infarction areas. Immunohistochemically, the tumor cells were strong positive for CD34, CD31, factor VIII related endothelial antigen and vimentin. The patient died 3 and half months after the surgery without receiving any radiotherapy or chemotherapy. This report may contribute to the data on clinical and histological finding of this rare tumour.

Epithelioid hemangioendothelioma adjacent to the axilla:a case report

We described a case of a 71-year-old woman with an epithelioid hemangioendothelioma (EHE) in her left axilla,a rare location which hasn’t been reported yet.The patient suffered from numbness,pain and decreased muscle strength of her left upper extremity. Sonography revealed a hypoechoic mass surrounded the axillary artery and brachial artery. No obvious capsule was demonstrated.CT showed a soft-tissue mass with some calcifications and peripheral ring-like enhancement. The MRI indicated a mass with mainly intermediate signal intensity on T1-weighted imagine and intermediate signal intensity on T2-weighted imagine. The diagnosis was confirmed by histopathologic examination after surgery. There are some correlations of these imaging features with its histopathologic characters.

Epithelioid Hemangioendothelioma of the Liver:Etiology,Natural History and Treatment

Epithelioid hemangioendothelioma （EHE） is an uncommon vascular tumor, which also has been called histiocytoid haemangioma. This low-grade malignant tumor was first described as a distinctive entity in 1982 by Weiss and Enzinger Histopathologically, EHE is characterized by round or spindle-shaped endothelial cells with cytoplasmic vacuolation121. The tumor may occur in numerous organs, including liver, lung, parotid grand, skin, pleura, thyroid, spleen, cardiac valve, radial artery, oral cavity and parapharyngeal space. Many cases have been reported, but its etiology and natural history remain unclear.

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.

Hepatic Hemangioendothelioma: An update

Primary epithelioid hemangioendotheliomas of the liver(EHL)are rare tumors with a low incidence.The molecular background of EHL is still under investigation,with WWTR1-CAMPTA1 mutation may function as a tumor marker.Commonly,this tumor is misdiagnosed with angiosarcoma,cholangiocarcinomas,metastatic carcinoma,and hepatocellular carcinoma(sclerosing variant).Characteristic features on imaging modalities such as ultrasound,computed tomography,magnetic resonance imaging and positron emission tomography/computed tomography guide in diagnosis and staging.The“halo sign”and the“lollipop sign”on computed tomography and magnetic resonance imaging are described in the literature.Currently,there are no standardized guidelines for treating EHL with treatment options are broad including:chemotherapy,ablation,surgery and liver transplantation with inconsistent results.

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.

Primary peritoneal hemangioendothelioma simulating an ovarian cyst:A case report and review of literature

BACKGROUND Epithelioid hemangioendothelioma(EHE)is an extremely rare tumor with a prevalence of one in a million and a very heterogenous spectrum of disease that varies from an indolent to a metastasizing aggressive disease,with the liver,lung and bone being the primarily involved organs.Peritoneal forms of EHE are even rare,and only 12 cases have been reported to date in the literature.CASE SUMMARY A 66-year-old female came to our attention complaining low abdominal and perineal pain.Magnetic resonance imaging examination showed a 52 mm×58 mm×32 mm cystic mass with some smooth septa,simulating an ovarian cyst.Explorative laparoscopy demonstrated the presence of a peritoneal mass of augmented consistency connected with a sigmoid epiploic appendix in the right side of the Pouch of Douglas,that was surgically removed.Histological examination revealed a primitive peritoneafl hemangioendothelioma.The patient easily recovered from surgery with no residual pain or discomfort.She is regularly attending a 3-years follow-up that is negative for local recurrence of disease or distant metastases.CONCLUSION Peritoneal form of EHE often simulates masses of other nature,as in our case.Given its unspecific clinical and radiological presentation,patients are often forced to a large series of tests and examinations before reaching a definitive diagnosis,that can only histologically made.The possibility of EHE should always be considered in case of unexplained chronic abdominal pain associated to a non-specific mass.