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Background: Hepatic epithelioid hemangioendothelioma (EHE) is an extremely rare tumour. The aim of this study was to investigate the long-term prognosis and its relationship with treatment modalities., Methods: From March 2014 to June 2024, a total of 234 patients with histologically confirmed hepatic EHE were treated or followed up regularly by our team. The patients' clinical data at the time of diagnosis and initial treatment modalities were retrospectively collected. Kaplan-Meier curves were constructed to determine overall survival (OS). To explore prognostic factors and treatment outcomes, univariable and multivariable Cox proportional hazard models were developed., Results: A total of 228 patients were ultimately included. The median age of the cohort was 41 years. For all patients, the OS of 1-, 3- and 5-year were 96.2%, 87.9% and 84.9%, respectively. For patients who underwent liver transplantation (LT), the OS of 1- and 3-year were 62.5% and 25%, respectively. No difference was found in the OS between patients who received surgical therapy and those who did not (1-year: 100% vs. 96.9%; 3-year: 90.1% vs. 91.5%; 5-year: 87.2% vs. 88.2%; P = 0.891). In the multivariable analysis, age ≥ 60 years [HR (95% CI): 4.207 (1.266-13.973), P = 0.019], the size of the largest lesion > 10 cm [HR (95% CI): 12.140 (1.419-103.872), P = 0.023] and LT [HR (95% CI): 5.502 (1.343-22.536), P = 0.018] were poor prognostic factors., Conclusions: Compared with nonsurgical therapy, surgical therapy has no advantage in terms of long-term survival. The role of LT in the management of hepatic EHE should be reevaluated. Age ≥ 60 years and the size of the largest lesion > 10 cm are poor prognostic factors., (© 2024. The Author(s).)

Introduction: Epithelioid hemangioendothelioma (EHE) is an ultra-rare sarcoma, marked by distinctive molecular and pathological features and with a variable clinical behavior. Its natural history is still partially understood, reliable prognostic and predictive factors are lacking and many questions are still open on the optimal management. In the context of EURACAN, a prospective registry specifically dedicated to EHE was developed and launched with the aim of providing, through high-quality prospective data collection, a better understanding of this disease., Study Design: Registry-based cohort study including only new cases of patients with a pathological and molecularly confirmed diagnosis of EHE., Objectives: To improve the understanding of EHE natural history, validate and identify new prognostic and predictive factors, clarify the activity and efficacy of currently available treatment options, describe treatment pattern., Methods: Settings and participantsIt is an hospital-based registry established in centers with expertise in EHE including adult patients with a new pathological and molecularly confirmed diagnosis of EHE starting from the 1st December 2023. The characteristics of each patient in the facility who meets the above-mentioned inclusion criteria will be collected prospectively and longitudinally with follow-up at cancer progression and / or cancer relapse or patient death. It is a secondary use of data which will be collected from the clinical records. The data collected for the registry will not entail further examinations or admissions to the facility and/or additional appointments to those normally provided for routine patient follow-up. VariablesFull details on patients and disease features, treatment and outcome will be collected, according to common clinical practice guidelines developed and shared with all the contributing centers. In addition, data on potential confounders (e.g. comorbidity; functional status etc.) will also be collected. Statistical methodsThe data analyses will include descriptive statistics and analytical analyses. Multivariable Cox's proportional hazards model and Hazard ratios (HR) for all-cause or cause-specific mortality will be used to determine independent predictors of overall survival, recurrence and progression., Results: The registry has been joined by 21 sarcoma reference centers across EU and UK, covering 10 countries. Patients' recruitment started in December 2023. The estimated completion date is December 2033 upon agreement on the achievement of all the registry objectives. The already established collaboration and participation of EHE patient's associations involved in the project will help in promoting the registry and fostering accrual., Competing Interests: Anna Maria Frezza declares institutional research funding from Advenchen Laboratories, Amgen Dompé, AROG Pharmaceuticals, Ayala Pharmaceuticals, Bayer, Blueprint Medicines, Boehriger Ingelheim, Daiichi Sankyo, Deciphera, Eisai, Eli Lilly, Epizyme Inc, Foghorn Therapeutics Inc., Glaxo, Hutchison MediPharma Limited, Inhibrx, Inc., Karyopharm Pharmaceuticals, Novartis, Pfizer, PharmaMar, PTC Therapeutics, Rain Oncology, SpringWorks Therapeutics. Alexia Bertuzzi declares support for attending meeting and/or travels from Pharmamar and Istituto Gentili; support for scientific activities from Istituto Gentili. Antonella Brunello declares consulting fees or serving on advisory boards for Eli Lilly, Roche, GSK, Eisai, Pharmamar, Boehringer Ingelheim, Deciphera; payment or honoraria for educational events by GSK and Pharmamar; travel grants by Pharmamar, Istituto Gentili. Giacomo G. Baldi declares consulting fees from Eli Lilly, Pharmamar, AboutEvents; honoraria from Pharmamar, Eli Lilly, Glaxo Smith Kline, Merck Sharp & Dome, Eisai, IstitutoGentili; support for attending meetings and/or travels from Novartis, Pharmamar, Eli Lilly; participation on the advisory board from Pharmamar, Eli Lilly, Glaxo Smith Kline, Merck Sharp & Dome, Eisai. Paolo G. Casali declares institutional research funding from Advenchen Laboratories, Amgen Dompé, AROG Pharmaceuticals, Ayala Pharmaceuticals, Bayer, Blueprint Medicines, Boehriger Ingelheim, Daiichi Sankyo, Deciphera, Eisai, Eli Lilly, Epizyme Inc, Foghorn Therapeutics Inc., Glaxo, Hutchison MediPharma Limited, Inhibrx, Inc., Karyopharm Pharmaceuticals, Novartis, Pfizer, PharmaMar, PTC Therapeutics, Rain Oncology, SpringWorks Therapeutics. Virginia Ferraresi declares consultancy fees or honoraria from PharmaMar, Boehringer Ingelheim, Gentili e Serb Pharmaceuticals. Matilde Ingrosso reports institutional research funding from Advenchen Laboratories, Amgen Dompé, AROG Pharmaceuticals, Ayala Pharmaceuticals, Bayer, Blueprint Medicines, Boehriger Ingelheim, Daiichi Sankyo, Deciphera, Eisai, Eli Lilly, Epizyme Inc, Foghorn Therapeutics Inc., Glaxo, Hutchison MediPharma Limited, Inhibrx, Inc., Karyopharm Pharmaceuticals, Novartis, Pfizer, PharmaMar, PTC Therapeutics, Rain Oncology, SpringWorks Therapeutics. Laura Monteleone reports institutional research funding from Advenchen Laboratories, Amgen Dompé, AROG Pharmaceuticals, Ayala Pharmaceuticals, Bayer, Blueprint Medicines, Boehriger Ingelheim, Daiichi Sankyo, Deciphera, Eisai, Eli Lilly, Epizyme Inc, Foghorn Therapeutics Inc., Glaxo, Hutchison MediPharma Limited, Inhibrx, Inc., Karyopharm Pharmaceuticals, Novartis, Pfizer, PharmaMar, PTC Therapeutics, Rain Oncology, SpringWorks Therapeutics. Johanna Szkandera reports participation in advisory boards or invited speaker fees for PharmaMar, Bayer, Roche, Lilly, Amgen; travel expenses coverage from PharmaMar, Roche, Lilly, Amgen, Bristol Myers Squibb; research funding from PharmaMar, Roche, Eisai. Bruno Vincenzi reports consulting fees from Eisai, Lilly, Bayer, Deciphera, PharmaMar, Blueprint, Pfizer, GSK, Accord, Abbott and research support from PharmaMar, Novartis, Lilly Silvia Stacchiotti declares advisory board roles with Bayer, Boehringer, Daiichi, Ikena, Nec Oncology, Pharma Essentia, Regeneron, Servier; invited speaker roles for Bayer, Boehringer, Gentili, Pharmamar; institutional research funding from Advenchen Laboratories, Amgen Dompé, AROG Pharmaceuticals, Ayala Pharmaceuticals, Bayer, Blueprint Medicines, Boehriger Ingelheim, Daiichi Sankyo, Deciphera, Eisai, Eli Lilly, Epizyme Inc, Foghorn Therapeutics Inc., Glaxo, Hutchison MediPharma Limited, Inhibrx, Inc., Karyopharm Pharmaceuticals, Novartis, Pfizer, PharmaMar, PTC Therapeutics, Rain Oncology, SpringWorks Therapeutics. Carlo Cicala, Lorenzo D’Ambrosio, Angelo Paolo Dei Tos, Alessandro Gronchi, Nadia Hindi, Robin Jones, Iwona Lugowska, Julia Ketzer, Anna Mariuk-Jarema, Andrea Napolitano, Andri Papakonstantinou, Sandro Pasquali, Marta Sbaraglia, Federico Scolari, Elisa Crotti, Irene Benzonelli, Jean-Yves Blay, Christophe Bouvier, Javier Martin Broto, Hugh Leonard, Ninna Aggerholm-Pedersen, Andri Papakonstantinou, Giuseppe Bianchi, Federica Zuccheri, Paolo Baili, Simone Bonfarnuzzo, Domenico Campanacci, Armelle Dufresne, Sebastian Bauer, Serena Bazzurri, Stefano Gabellini, Claudia Giani, Vincenzo Giannusa, Melissa Gil-Sanjines, Teresa Grassani, Paolo Lasalvia, Stefan Lindskog, Salvatore Vizzaccaro, Nils Dieckmann, Alessandro Mazzocca, Andrei Ivanescu, Giuseppe Badalamenti, Carlo Morosi, Stephanie Elston, Kyetil Boye, Francesca Nardozza, Elisabetta Neri, Maria Nilsson and Annalisa Trama declares no conflict of interest., (Copyright: © 2024 Frezza et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Epithelioid hemangioendothelioma is a rare vascular malignancy, and currently, there is no standard treatment regimen for this disease and existing treatment options have limited efficacy. In this case report, we present a patient with lung and lymph node metastases from prostate epithelioid hemangioendothelioma who achieved a significant partial response. This was accomplished through alternating nivolumab therapy with ipilimumab and liposomal doxorubicin, resulting in a progression-free-survival more than 6 months to date. The treatment was well-tolerated throughout. Our report suggests that dual immunotherapy alternating with anti-PD-1antibody plus doxorubicin may be a potential treatment modality for epithelioid hemangioendothelioma. However, larger sample studies are necessary to ascertain the effectiveness of this treatment strategy and it is essential to continue monitoring this patient to sustain progression-free survival and overall survival., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Ye, Yang, Li, Huang, Zhou, Feng, Liu and Xie.)

Epithelioid hemangioendothelioma is a low-grade malignant vascular tumor with an intermediate clinical behavior between benign hemangiomas and high-grade angiosarcomas. Pathologic or molecular factors to predict this clinical heterogeneity are not well defined. A WWTR1-CAMTA1 fusion is present in most classic epithelioid hemangioendothelioma, regardless of their clinical behavior, suggesting that additional genetic abnormalities might be responsible in driving a more aggressive biology. A small subset of cases show distinct morphology and are characterized genetically by a YAP1-TFE3 fusion. Two histologic grades have been described in classic epithelioid hemangioendothelioma of the soft tissue. However, proposed criteria do not apply to other clinical presentations and have not been assessed in the YAP1-TFE3 positive tumors. Furthermore, no previous studies have compared the survival of these two molecular subsets. In this study we investigate the clinicopathologic and molecular findings of a large cohort of 93 translocation-positive epithelioid hemangioendothelioma managed at our institution. Patient characteristics, histologic features, treatment outcomes, and genetic abnormalities were investigated and these factors were correlated with overall survival. In 18 patients (15 with WWTR1-CAMTA1 and 3 with YAP1-TFE3) Memorial Sloan Kettering-IMPACT targeted DNA sequencing was performed to identify secondary genetic alterations showing more than half of tumors had a genetic alteration beyond the disease-defining gene fusion. Patients with conventional epithelioid hemangioendothelioma with WWTR1-CAMTA1 fusion had a less favorable outcome compared with the YAP1-TFE3 subset, the 5-year overall survival being 59% versus 86%, respectively. Soft tissue epithelioid hemangioendothelioma were frequently solitary, followed an uneventful clinical course being often managed with curative surgery. Multifocality, pleural involvement, lymph node or distant metastases had a significantly worse outcome. Patients with pleural disease or lymph node metastases had an aggressive clinical course akin to high-grade sarcomas, with 22% and 30%, respectively, alive at 5 years, compared with >70% survival rate in patients lacking these two adverse factors.

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 identified 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 metastasis 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 management 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-specific survival rate was 57.8%. Patients who underwent surgical treatment had significantly 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., Competing Interests: Competing interest No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article., (Copyright © 2019. Published by Elsevier B.V.)

Background: Hepatic epithelioid hemangioendothelioma (HEHE) is a rare angiogenic tumor with no recognized effective treatment. Treatment options used worldwide include liver transplantation (LT), liver resection (LR), radiofrequency ablation (RFA), chemotherapy, and observation. The aim of this study was to describe the efficacy of different treatment options used for HEHE at our center., Methods: The medical charts of 12 patients with HEHE (9 women and 3 men) who were diagnosed and treated at the First Affiliated Hospital of Zhejiang University, China, between January 2011 and December 2017 were retrospectively reviewed., Results: The patients were diagnosed by postoperative histopathology or fine needle aspiration biopsy. Two patients with diffuse lesions received LT and were alive without recurrence at the last follow-up. Three patients received LR as the initial treatment, and all of them developed recurrence during the follow-up period. One patient received RFA and remained free of disease, while the remaining six patients opted for simple observation rather than treatment. One of the patients who received LR passed away because of tumor recurrence within 32 months after surgery; the other patients showed no significant disease activity after treatments for their recurrent lesions. As of April 2018, the mean follow-up duration was 39.6 ± 20.1 months (15-82 months)., Conclusions: There are multiple strategies for HEHE. Considering its indolent course, initial observation for assessment of the lesion behavior may aid in the selection of appropriate treatment. Surgery or LT is suitable for patients with disease progression during the observation period. However, our sample size was small, and further studies are required to gather more information that can aid in optimal treatment selection.

Rationale: Epithelioid hemangioma (EH) of bone is an intermediate vascular tumor that can be locally aggressive. The optimum management of multifocal EH of bone is not well delineated. We described our experience treating one patient with multifocal EH of bone in an effort to document the effect of bisphosphonates in bone EH., Patient Concerns: In this report, a 53-year old male patient presented with back pain which was initially been diagnosed of multiple bone metastatic carcinoma by 18F-FDG PET/CT scan and bone scintigraphy., Diagnosis: CT-guided bone biopsy of ilium indicated that puncture tissue had irregular hyperplasia of thick and thin-walled blood vessels, immunohistochemistry revealed positive staining for CD31 and CD34, negative for CAMTA-1, PCK and EMA, which confirmed the diagnosis of multiple EH., Interventions: The patient was treated with 4 times of intravenous Zometa (zoledronate, 4 mg each time) with average three-month interval. Bone metabolic markers including serum bone specific alkaline phosphatase (BALP) and type I collagen cross-linked C-terminal telopeptide (CTX) levels were closely monitored before and after use of bisphosphonates each time., Outcome: BALP and CTX were significantly lowered following intravenous Zometa and the back pain improved with integrated therapy including bone graft fusion internal fixation surgery and vertebroplasty., Conclusions: EH of multiple bones responded favorably to intravenous Zometa with improvement of bone metabolic markers. After 1 year on follow-up, the patient was doing well with no significant pain. We suggest that bisphosphonates should be considered in the treatment of multifocal osteolytic EH of bone.

Background/aim: Epithelioid hemangio-endothelioma (EHE) of the liver is an uncommon vascular tumor with variable clinical courses ranging from stable disease to fatal outcome. EHE can mimic epithelioid angiosarcoma, which has a more aggressive behavior, especially in a small biopsy sample. EHEs are known to have the WWTR1-CAMTA1 fusion gene, and nuclear expression of CAMTA1 by immunohistochemistry (IHC) has been reported in about 90% of EHEs in multiple organs. Our study aimed to validate the diagnostic utility of CAMTA1 expression in EHEs, especially in the liver., Patients and Methods: IHC was performed using anti-CAMTA1 antibody in 34 tumors (24 hepatic EHEs and 10 angiosarcomas). In CAMTA1-negative EHEs, TFE3 IHC was performed., Results: Of the 24 hepatic EHEs, 22 (91.6%) showed nuclear staining for CAMTA1. One of two CAMTA1-negative cases showed TFE3 positivity. The other case was negative for TFE3. Meanwhile, all 10 angiosarcoma cases had no CAMTA1 expression., Conclusion: CAMTA1 is a highly sensitive and specific marker for diagnosis of hepatic EHE. It is helpful for differentiation of hepatic EHE and angiosarcoma, especially in small biopsy samples., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Epithelioid haemangioendothelioma (EHE) is a rare tumor with a wide spectrum of clinical behavior. There is no consensus on the role of local therapy in symptomatic, multi-focal disease., Patients and Methods: A retrospective review of patients presenting to the Royal Marsden Hospital between January 2000 and December 2017 was conducted., Results: Fifty-three patients with EHE were identified, of which 18 patients (34.0%) received local therapy, and 11 patients (20.8%) underwent active surveillance. A variety of local treatment modalities were used with few toxicities, and local recurrence was managed with other local treatments or systemic therapy. Distal disease progression was infrequent (n=4, 7.5%). Patients who developed pleural effusion (n=5, 9.4%) had poor outcome irrespective of treatment., Conclusion: Local therapy has a role in a selected patient group managed in a multidisciplinary setting, including patients with indolent disease, and patients with a solitary area of progression/symptomatic disease., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Epithelioid hemangioendothelioma (EHE) is a rare vascular neoplasm that develops from vascular endothelial cells. It has been reported to occur many sites of body, but the most common EHE presentations are soft tissue (limbs), bone, liver and lung. Compared with other pulmonary tumors, pulmonary epithelioid hemangioendothelioma (P-EHE) is relatively rare. According to a literature review, more than 100 cases have been described all over the world. Due to the low incidence of P-EHE, lack of specificity in clinical symptoms and radiological findings, it is often misdiagnosed. Meanwhile, many patients do not receive appropriate treatment, resulting in poor prognosis in some cases. Histology and immunohistochemical methods are essential for diagnosis. However, there is no established standard treatment for P-EHE, because of the rarity of the disease. When the lesions are small and limited in number, surgical is the best treatment, achieving the purpose of diagnosis and treatment at the same time. This article tries to present the etiopathogenesis, clinical manifestations, diagnosis, treatment and prognosis of P-EHE.
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BACKGROUND Epithelioid hemangioendothelioma (EHE) is a rare vascular malignancy that occurs in multiple organs and tissues with a predilection for the extremities, bone, liver, and lung. It is often characterized by a clinically indolent course, delayed diagnosis, and unestablished standardized treatment options. CASE REPORT A 46-year-old female presented with a 2-month history of right shoulder and arm pain. Imaging revealed involvement of the humerus, lung, liver; and brain and biopsies of both the lung and humerus were performed. A diagnosis of epithelioid hemangioendothelioma was confirmed and the patient received radiation therapy to the right humerus and brain stereotactic radiosurgery. She was scheduled to begin palliative chemotherapy with doxorubicin but developed complications and never received chemotherapeutic agents. She died 5.5 months from her first admission with widespread metastasis. CONCLUSIONS Epithelioid hemangioendothelioma (EHE) is typically a low-to-intermediate grade vascular malignancy, but, as seen in this case, can be aggressive. In the future, diagnosis, prognosis, and treatment may improve using genetic or immune therapy considering a structural chromosomal translocation has been identified.

Integration of morphological, immunohistochemical, and molecular methods is often necessary for the precise diagnosis and optimal clinical management of sarcomas. We have validated and implemented a clinical molecular diagnostic assay, MSK- Fusion Solid, for detection of gene fusions in solid tumors, including sarcomas. Starting with RNA extracted from formalin-fixed paraffin-embedded tumor material, this targeted RNA sequencing assay utilizes anchored multiplex PCR to detect oncogenic fusion transcripts involving 62 genes known to be recurrently rearranged in solid tumors including sarcomas without prior knowledge of fusion partners. From 1/2016 to 1/2018, 192 bone and soft tissue tumors were submitted for MSK- Fusion Solid analysis and 96% (184/192) successfully passed all the pre-sequencing quality control parameters and sequencing steps. These sarcomas encompass 24 major tumor types, including 175 soft tissue tumors and 9 osteosarcomas. Ewing and Ewing-like sarcomas, rhabdomyosarcoma, and sarcoma-not otherwise specified were the three most common tumor types. Diagnostic in-frame fusion transcripts were detected in 43% of cases, including 3% (6/184) with novel fusion partners, specifically TRPS1-PLAG1, VCP-TFE3, MYLK-BRAF, FUS-TFCP2, and ACTB-FOSB, the latter in two cases of pseudomyogenic hemangioendothelioma, representing a novel observation in this sarcoma. Our experience shows that this targeted RNA sequencing assay performs in a robust and sensitive fashion on RNA extracted from most routine clinical specimens of sarcomas thereby facilitating precise diagnosis and providing opportunities for novel fusion partner discovery.

Pulmonary epithelioid hemangioendothelioma is an uncommon neoplastic disease of endothelial origin, with an incidence inferior to one in a million. It usually behaves as a low-grade malignancy; nevertheless, a few cases have been described in which this tumour manifests a highly aggressive behavior, spreading throughout the organism. We report the case of a 77-year-old woman who was diagnosed with metastatic pulmonary epithelioid hemangioendothelioma with severe symptoms, requiring urgent treatment to palliate them. Key words. Epithelioid hemangioendothelioma. Lung.

Epithelioid hemangioendothelioma (EHE) is a rare indolent vascular tumor which occurs at liver, lung, bone, and so on. However, the etiology of EHE is evasive.These patients were enrolled at the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to December 2015. Retrospective analysis is done by demographic data of clinical manifestations, laboratory parameters, CT imaging, histological, and immunohistochemical features in 9 cases in Shaanxi.Of the patients, 8 were females (88.9%) and 1 were males (11.1%). The age ranged from 34 to 71 years (mean 49 years; median 49 years). Anatomical sites of primary lesions were as follows: liver (n = 6, 66.7%), upper extremities (n = 1, 11.1%), sublingual gland (n = 1, 11.1%), and spine (n = 1, 11.1%). Metastatic disease was diagnosed in 5 cases (55.6%) with occurrence in lung (n = 4, 44.4%), bone (n = 2, 22.2%), upper extremities (n = 1, 11.1%), pleura (n = 1, 11.1%), and spleen (n = 1, 11.1%). Tumor size ranged from 0.5 to 6.8 cm (mean 3 cm). The most tumors were composed of highly cellular areas with small and prominent nucleoli in vesicular nuclei, and ERG (100%) was the most frequently positive in these cases, followed by CD31 (88.9%) and CD34 (77.8%) via histology and immunohistochemistry techniques.EHE is a very rare in Shaanxi. It is significant to find its clinical, radiological, and pathological characters, helping for EHE early diagnosis and treatment, reducing misdiagnosis and improving life quality.

We aim to investigate the pathological characteristics of liver biopsies and their implications for the prognosis of hepatic epithelioid hemangioendothelioma (HEHE). Clinical data of eight patients (5 male, 3 female) with HEHE were analyzed retrospectively. Expression of CD34, FVIII, AE1/AE3, Hepa-par1, GPC3, CK19 and the proliferation index marker Ki-67 were determined by immunohistochemical staining. The clinical pathological features and effects of treatment on prognosis were investigated. Among the eight patients, four did not exhibit significant symptoms, while four showed symptoms such as abdominal distension, aversion to greasy food and mild fever. Two patients had single liver lesions, while multiple lesions were observed in six cases, in which the tumor cells exhibited spindle, irregular or epithelioid morphology, with scattered, streaked and nested distribution. Individual luminal cells were also visible, containing red cells and accompanied by mucoid or fibrous stroma. All cases were CD34 positive, one case was FVIII factor negative, two cases were AE1/AE3 positive, Ki-67 staining exceeded 15% in two cases, and nuclear fission was visible in two cases. Patients with nuclear fission and Ki-67 > 15% died within 2 years after artery embolization, liver transplantation without relapse was observed in two cases and one case survived with the tumor. The other patients without cellular atypia, without nuclear fission and with Ki-67 < 10% did not relapse during the 2-5 years of follow-up. HEHE can be diagnosed according to hematoxylin and eosin morphology and immunohistochemical characteristics in biopsies before treatment allowing the selection of different treatment protocols based on pathological characteristics.

We would like to report the first case in English literature, to the best of our knowledge, of a synchronous hepatic epithelioid hemangioendothelioma (HEHE) and hepatocellular carcinoma (HCC), as well as to address the current trends and challenges in the management of HEHE.An otherwise well 58-year-old man was referred to his local hepatology service with elevated serum γ-GT levels. Imaging revealed bilobar liver lesions consistent with HEHE, a discrete left lobe lesion suspected as HCC, and multiple pulmonary nodules. Biopsies confirmed HEHE with pulmonary metastases. After multidisciplinary team discussions, the patient was admitted under our team and underwent an uneventful laparoscopic left lateral hepatectomy for suspected HCC, which was confirmed histologically.As part of a watch-and-wait approach to metastatic HEHE, in the first follow-up (3 months postoperatively) the patient was clinically fine and the surveillance CT scan did not show recurrent disease.By presenting this case, we aim to raise awareness that this rare entity can coexist with others, potentially complicating their management.

A 29-year-old man presented with a 2-week history of severe pain in the left foot with no preceding history of trauma. A left foot radiograph demonstrated a cortical lucency in the mid-distal shaft of the third metatarsal bone. MRI of the left foot showed an expansile lesion in the same location. A staging bone scan showed a focal uptake in the known lucency in the left third metatarsal and in the proximal left femur. A subsequent left hip radiograph demonstrated a lucency in the intertrochanteric region. CT scan of the chest, abdomen and pelvis was unremarkable. A biopsy of the left third metatarsal expansile lesion performed during an incision and curettage procedure revealed an epithelioid haemangioma (EHE) of the bone. MRI of the left hip performed in response to the findings on the bone scan showed metastatic disease in the left intertrochanteric region. A prophylactic left hip fixation surgery with an interlocking intramedullary femoral nail was therefore undertaken to avoid a pathological fracture of the left hip from the metastatic disease. Simultaneously, a left hip biopsy was performed, which also revealed an EHE. The patient underwent external beam radiation to the left femoral head and neck. This was followed by fractionated radiosurgery to the left third metatarsal. Once the left foot wound had healed, the patient subsequently received four cycles of doxorubicin and ifosfamide. A restaging positron emission tomography CT carried out after completion of therapy showed no metabolic evidence of residual primary tumour or metastasis. More than 2 years after completing his trimodality therapy, the patient remains fully functional and symptom free., (2015 BMJ Publishing Group Ltd.)

Epithelioid hemangioendothelioma (EHAE) is a malignant vascular tumor derived from endothelial cell often misdiagnosed as Hepatic carcinoma on the basis of radiological features. Till now etiology of this rare curiosity is unknown but it is related with use of oral contraceptives pills (OCP), liver trauma, exposure to vinyl chloride and hepatitis. We herein report on a case which failed to be diagnosed by cytopathology, computed tomography (CT) and magnetic resonance imaging (MRI). Patient was a 46 yr old man presented with abdominal distension for a month. Initial liver function test (LFT) was increased whereas renal function test (RFT) and alpha-fetoprotein (AFP) were normal. His abdominal ultrasound revealed multiple hypoechoic nodules and multiple liver calcifications. Subsequently laparoscopic omental biopsy and Ultrasound guided liver biopsy was done showing the neoplastic cells scattered in fibrous stroma. The immunohistochemistry for endothelial tumor cells stained positive for Vimentin (+++), CD10 (+++), CD34 (++), CD31 (+), Factor VIII antigen (focal) (+) and low proliferative activity for ki-67. Our case is very interesting in which patient admitted with nonspecific symptoms of abdominal pain and diagnosed to be a Malignant Hepatic EHAE metastasized to the peritoneum, omentum and mesentery. The patient was on thalidomide 50 mg/day and increased to 100 mg/day. 5-Flurouracil (FU) intraperitoneal chemotherapy and other symptomatic and supportive treatment was given to the patient. Our case highlights on the importance of immunohistopathological diagnosis, compare the radiological findings of this disease and discuss the treatment strategy with review of available literature.

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-year-old 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.

Background: The biology of hepatic epithelial haemangioendothelioma (HEHE) is variable, lying intermediate to haemangioma and angiosarcoma. Treatments vary owing to the rarity of the disease and frequent misdiagnosis., Methods: Between 1989 and 2013, patients retrospectively identified with HEHE from a single academic cancer centre were analysed to evaluate clinicopathological factors and initial treatment regimens associated with survival., Results: Fifty patients with confirmed HEHE had a median follow-up of 51 months (range 1-322). There was no difference in 5-year survival between patients presenting with unilateral compared with bilateral hepatic disease (51.4% versus 80.7%, respectively; P = 0.1), localized compared with metastatic disease (69% versus 78.3%, respectively; P = 0.7) or an initial treatment regimen of Surgery, Chemotherapy/Embolization or Observation alone (83.3% versus 71.3% versus 72.4%, respectively; P = 0.9). However, 5-year survival for patients treated with chemotherapy at any point during their disease course was decreased compared with those who did not receive any chemotherapy (43.6% versus 82.9%, respectively; P = 0.02) and was predictive of a decreased overall survival on univariate analysis [HR 3.1 (CI 0.9-10.7), P = 0.02]., Conclusions: HEHE frequently follows an indolent course, suggesting that immediate treatment may not be the optimal strategy. Initial observation to assess disease behaviour may better stratify treatment options, reserving surgery for those who remain resectable/transplantable. Prospective cooperative trials or registries may confirm this strategy., (© 2013 International Hepato-Pancreato-Biliary Association.)

Epithelioid hemangioendothelioma is a relatively uncommon lesion usually presenting in soft tissues. The occurrence in the mediastinum is exceptional rare. Histologically, this tumor is characterized by epithelioid cells with intracytoplasmic vacuoles in a hyalinized or mucinous stroma. Occasionally, spindle cells or osteoclast-like giant cells can be observed. Herein, we present a case of epithelioid hemangioendothelioma in a 38 year-old Chinese male. The tumor was predominantly composed of abundant spindle cells with marked atypia and scattered osteoclast-like giant cells reminiscent of malignant fibrous histiocytoma. The unusual histological appearance can pose a great diagnostic challenge. It may be easily misdiagnosed, especially if the specimen is limited or from fine-needle aspiration.

Epithelioid hemangioendothelioma (EHE) is a rare, well-differentiated endothelial tumor with intermediate malignancy which develops more frequently from the peripheral veins, generally in the lower limb. Bone EHE comprises less than 1% of the bone neoplasms. We present the case of a young man, 24-year-old, with EHE of the forearm with secondary involvement of the distal radius. The location and the extension of the tumor allowed a wide excision, without the reconstruction of radius, followed by adjuvant radiotherapy, with a subsequent favorable evolution. Based on the clinical, radiographic, and pathological features of the EHE review, we concluded that it is difficult to adopt a standardized therapeutic approach due to the extremely low incidence of the bone involvement in EHE and the variable tendencies towards malignancy of this tumor. To our knowledge this is the third case of EHE with the involvement of the radius.

Background/purpose: Hepatic epithelioid hemangioendothelioma (HEH) is a rare vascular tumor of the liver typically with a slow but progressive course. We report the clinical and immunohistochemical characteristics of six cases from our institution between 1993 and 2008., Methods: We searched the files of the Department of Pathology in National Taiwan University Hospital from January 1993 to December 2008 and found six cases of primary HEH. The clinical data were reviewed. The microscopic findings of each case were listed and analyzed. Confirmational immunoperoxidase stains were performed with antibodies against two endothelial markers (CD31 and CD34) and one epithelial marker (AE1/AE3 or cytokeratin)., Results: There were five female patients and one male patient with HEH, and the mean age was 45.3 years (range, 25-86 years). Most patients were asymptomatic and one third of cases presented as right costal or abdominal pain. Anemia was the most common laboratory abnormality. Liver failure developed at the advanced diffuse stage. Imaging studies revealed three different patterns as single nodular, multiple nodular, or diffuse types, reflecting different stages of disease and clinical symptoms. Microscopic findings included intracytoplasmic vascular lumen formation (100%), sinusoidal spreading (100%), vessel obliteration (66.7%), necrosis (66.7%), and cellular pleomorphism (16.7%). All cases expressed endothelial markers of CD31 and CD34, reflecting their vascular nature. Two patients received surgical treatment including partial liver resection and liver transplantation. Tumor recurrence developed 8 and 17 months later, respectively., Conclusion: HEH showed insidious growth and frequent multicentricity, making early diagnosis and tumor resection difficult. Definite diagnosis totally relies on pathologic study. Tumor progression to hepatic failure is slow. Liver transplantation is currently the most prevalent treatment modality for HEH, but experience in Taiwan is limited due to the rarity of this disease., (2010 Formosan Medical Association & Elsevier. Published by Elsevier B.V. All rights reserved.)

Epithelioid hemangioendothelioma is an uncommon vascular tumor of soft tissue and bone that may rarely occur in the liver, lung and the head and neck. We present five new cases of epithelioid hemangioendothelioma of the head and neck region diagnosed and managed in one institution in order to define the phenotypic characteristics, podoplanin immunohistochemical staining and the biological outcome. Podoplanin is a transmembrane mucoprotein selectively expressed in lymphatic endothelium and recently in some vascular neoplasms. The patients were comprised of two male and three female patients ranging in age from 4 to 71 years. The lesions were found in the gingiva, submandibular region soft tissue, nasal cavity and tongue, and ranged in size from 0.7 to 2.5 cm. All tumors manifested infiltrative cords and nests of epithelioid cells with occasional spindle morphology in a myxoid stroma. Immunohistochemical analysis of vascular and epithelial markers showed strong and uniform cytoplasmic reactivity for podoplanin and variable intensity and staining of CD31 and lack of cytokeratin staining in tumor cells. Surgical treatment included simple and wide local excisions. Of the three patients with follow-up, one developed lymph node metastasis and one had no evidence of disease 10 months after surgery. The patient with multiple recurrences and LN metastases was additionally treated with chemotherapy and is under consideration for radiation therapy. Hemangioendothelioma of the head and neck is: (1) a low-grade malignancy with a tendency for local recurrence and regional lymph node metastasis, (2) complete excision with negative margins is the treatment of choice for localized disease and (3) podoplanin may be useful in differentiating epithelioid hemangioendothelioma from non-vascular tumors.