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.

Medical and interventional therapy of Kasabach-Merritt phenomenon associated with Kaposiform hemangioendothelioma:A case report

An infant with Kasabach-Merritt Phenomenon(KMP)presented with a giant subcutaneous mass in the right lower limb,severe hypofibrinogenemia,and thrombocytopenia.Glucocorticoids,along with supportive treatments including transfusion of blood products and clotting factors,were administered to reverse fatal disseminated intravascular coagulation and acute hemolysis.The glucocorticoid dose was tapered slowly,and sirolimus was added to treat the hemangiomas.The patient subsequently underwent interventional therapy.After 6 months of medical and interventional therapy,the patient was doing well with a normal platelet count,the tumor volume was markedly reduced,and the primary cutaneous lesion became pale pink.Currently,the patient remains on sirolimus,and no recurrence of thrombocytopenia or further growth of the mass was observed after six months of follow-up.

Rotationplasty type BIIIb as an effective alternative to limb salvage procedure in adults:Two case reports

BACKGROUND Rotationplasty is often performed for malignant tumors,but type BIIIb rotationplasty is rarely reported,and there needs to be more evidence of the procedure and treatment.The purpose of this case study was to report a new direction in the use of type BIIIb rotationplasty in treating patients with limb salvage and longterm non-healing infections.CASE SUMMARY Case 1:A 47-year-old man underwent radiotherapy for hemangioendothelioma in his left thigh,resulting in a femoral fracture.Despite the use of plates,intramedullary nailing,and external fixators,the femoral bone failed to unite due to infectious nonunion.Multiple operations were unable to control the infection,leaving the patient immobile.We performed a modified tibia-pelvic-constrained hip rotationplasty,utilizing a constrained prosthetic hip between the tibia and pelvis following a femur resection.Two years post-surgery,the patient was able to walk with the prosthetic device without any signs of recurring infection.The corresponding functional scores were 72 points for the Musculoskeletal Tumor Society(MSTS),53 for the Functional Mobility Assessment(FMA),93 for the Toronto Extremity Salvage Score(TESS),and 56 for the MOS 36-item short form health survey(SF-36).Case 2:A 59-year-old woman presented with liposarcoma in her left thigh.Magnetic resonance imaging revealed tumors in the medial,anterior,and posterior femur muscles,encircling the femoral vessels and nerves.Fortunately,there were no symptoms of sciatic dysfunction,and the tumor had not invaded the sciatic nucleus.After one year of follow-up,the patient expressed satisfaction with limb preservation post-type BIIIb rotationplasty.The corresponding functional scores were 63 points for the MSTS,47 for the FMA,88 for the TESS,and 52 for the SF-36.CONCLUSION Our study suggests that type BIIIb rotationplasty may be an alternative to amputation in patients with incurable infections.For malignant tumors of the lower extremities without invasion of the sciatic nerve,type BIIIb rotationplasty remains an excellent alternative to amputation.This surgical method may prevent amputation,improve functional outcomes,and facilitate biological reconstruction.

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.

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)

Epithelioid hemangioendothelioma of the liver as a rare indication for liver transplantation

AIM: To investigate the indications and outcomes of liver transplantation for hepatic epithelioid hemangioendothelioma (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: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.

Liver transplantation for hepatic tumors:a systematic review

Improvements in the medical and pharmacological management of liver transplantation (LT) recipients have led to a better long-term outcome and extension of the indications for this procedure. Liver tumors are relevant to LT; however, the use of LT to treat malignancies remains a debated issue because the high risk of recurrence. In this review we considered LT for hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), liver metastases (LM) and other rare tumors. We reviewed the literature, focusing on the past 10 years. The highly selected Milan criteria of LT for HCC (single nodule < 5 cm or up to 3 nodules < 3 cm) have been recently extended by a group from the University of S. Francisco (1 lesion < 6.5 cm or up to 3 lesions < 4.5 cm) with satisfying results in terms of recurrence-free survival and the “up-to-seven criteria”. Moreover, using these criteria, other transplant groups have recently developed downstaging protocols, including surgical or loco-regional treatments of HCC, which have increased the post-operative survival of recipients. CCA may be treated by LT in patients who cannot undergo liver resection because of underlying liver disease or for anatomical technical challenges. A well-defined protocol of chemoirradiation and staging laparotomy before LT has been developed by the Mayo Clinic, which has resulted in long term disease-free survival comparable to other indications. LT for LM has also been investigated by multicenter studies. It offers a real benefit for metastases from neuroendocrine tumors that are well differentiated and when a major extrahepatic resection is not required. If LT is an option in these selected cases, liver metastases from colorectal cancer is still a borderline indication because data concerning the disease-free survival are still lacking. Hepatoblastoma and hemangioendothelioma represent rare primary tumors for which LT is often the only possible and effective cure because of the frequent multifocal, intrahepatic nature of the disease. LT is a very promising procedure for both primary and secondary liver malignancies; however, it needs an accurate evaluation of the costs and benefits for each indication to balance the chances of cure with actual organ availability.

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.

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.

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.

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.

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.

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.

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.

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.