New Molecular Insights, and the Role of Systemic Therapies and Collaboration for Treatment of Epithelioid Hemangioendothelioma (EHE).

OPINION STATEMENT: Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated vascular sarcoma. EHE can have different clinical presentations from indolent to rapidly evolving cases, behaving as a high-grade sarcoma. Serosal effusion and systemic symptoms such as fever and severe pain are known as adverse prognostic factors; however, outcome prediction at disease onset remains a major challenge. In spite of its rarity, an international collaborative effort is in place with the support of patient advocates to increase the knowledge of EHE biology, develop new treatment options, and improve patient access to new active medications. Currently, systemic therapies are indicated only for patients suffering from progressive and/or symptomatic disease and in patients with a high risk of organ dysfunction. Standard systemic agents available so far for treatment of sarcomas, and in particular anthracycline-based chemotherapy, have marginal activity in EHE. On this background, EHE patients should be always considered for clinical study when available. The MEK inhibitor trametinib has been recently investigated prospectively in advanced EHE showing some activity, but the publication of the full dataset is still awaited to better interpret the results. Besides, there are data on response to antiangiogenics such as sorafenib and bevacizumab and, from retrospective studies, interferon, thalidomide, and sirolimus. Unfortunately, none of these agents is formally approved for EHE patients and access to treatments varies greatly between countries causing a huge disparity in patient care from one country to another.

Hemangioendotelioma epitelioide como causa infrecuente de tumor hepático / No disponible

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Case of epithelioid hemangioendothelioma occurring in the postradiation setting for breast cancer.

Epithelioid hemangioendothelioma (EHE) is a rare malignant vascular tumor, which is typically characterized by recurrent fusion genes. EHEs most commonly occur in the lung, liver, bone, and internal organs. EHE has rarely been reported to occur in the post-radiotherapeutic setting, the breast site or in association with breast cancer. The differential diagnosis for radiation-associated vascular lesions of the breast is classically limited to atypical vascular lesion and angiosarcoma and does not include EHE. We present the case of a woman with a history of breast cancer and post-surgical radiotherapy who went on to develop an EHE of the chest wall skin within 3 years of the completion of radiotherapy. Microscopically, the lesion was infiltrative and composed of anastomosing nests of epithelioid-to-spindled cells with eosinophilic and vacuolated cytoplasm. By immunohistochemistry, the cells were positive for ERG, D2-40, and CD31. The diagnosis was confirmed by identification of a characteristic WWTR1-CAMTA1 fusion gene using RNA sequencing. This case expands our understanding of radiation-associated tumors.

[Research Progress of Pulmonary Epithelioid Hemangioendothelioma].

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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A case of intravascular epithelioid hemangioendothelioma occurring 14 years after coil embolization for an extracranial internal carotid artery aneurysm.

Epithelioid hemangioendothelioma (EHE) is a rare neoplasm originating from various organs. The clinical outcome mostly depends on surgical resectability. The authors report an EHE of the extracranial internal carotid artery developed in a 59-year-old male patient 14 years after the intravascular coil embolization for a carotid aneurysm at the same site. Because the lesion was initially diagnosed as regrowth of the thrombosed aneurysm, decision for radical resection was delayed, and the patient died from rapid tumor progression. Differential diagnosis of atypical vascular mass lesions should include neoplasm, because initial radical resection may be the key to achieve a better prognosis.

Primary pleural epithelioid hemangioendothelioma.

Epithelioid hemangioendothelioma is a rare neoplasm of vascular endothelial origin. It can develop in any tissue, but it occurs primarily in the soft tissue, liver, and rarely in the lung. Pulmonary epithelioid hemangioendothelioma can present in the thorax in various manifestations. In the typical pulmonary forms, epithelioid hemangioendothelioma presents as either a solitary nodule, or more often as multiple, small nodules. Pulmonary epithelioid hemangioendothelioma involving the pleural space occurs in patients with disseminated disease [1, 2]. We present a case of primary pleural epithelioid hemangioendothelioma.

Epithelioid hemangioendothelioma after radiotherapy for congenital hemangioma: a case report.

A rare case of post-radiation epithelioid hemangioendothelioma arising in a congenital hemangioma of the lower leg 18 years after radiotherapy is reported. At 7 years of age, the patient underwent partial resection of a subcutaneous congenital hemangioma with intramuscular extension of the left lower leg, and at 10 years of age, the patient was given radiotherapy with a total dose of 30 Gy for recurrence. At 28 years of age, the patient noticed a large tumor mass with intractable pain at the antero-lateral aspect of the proximal lower leg, and she presented to our hospital. Since microscopic examination of a biopsy specimen showed epithelioid hemangioendothelioma, disarticulation at the knee joint was performed. Although malignant change in a benign vascular tumor is extremely rare, irradiation can induce malignant transformation of a hemangioma.

Hemangioendotelioma epiteloide pulmonar / Pulmonary Epithelioid Hemangioendothelioma

El hemangioendotelioma epitelioide es una enfermedad de difícil diagnóstico, descrita como un tumor multicéntrico y de escasa actividad metastásica, que aparece con mayor frecuencia en mujeres jóvenes asintomáticas y como un hallazgo casual. El patrón radiológico es heterogéneo. El dato más importante para su diagnóstico es la confirmación histológica de cuerpos de Weibel-Palade, o bien la inmunohistoquímica, con marcadores tumorales específicos como el factor VIII y CD34. Presentamos el caso de una mujer de 73 años en quien de forma casual se detectaron, en una imagen radiológica, nódulos pulmonares múltiples que posteriormente se diagnosticaron como esta entidad tumoral(AU)

Epithelioid hemangioendothelioma is a multifocal tumor that rarely metastasizes. It is difficult to diagnose and is most often an incidental finding in young asymptomatic women. It has a heterogeneous radiologic pattern. The most important diagnostic information is histologic confirmation of Weibel-Palade bodies or immunohistochemistry based on specific tumor markers such as factor VIII and CD34. We report the case of a 73-year-old woman in whom multiple pulmonary nodules detected by chance in a radiograph were subsequently diagnosed as epithelioid hemangioendothelioma(AU)

Breast implants as a possible etiology of epithelioid hemangioendothelioma and successful therapy with interferon-alpha2.

Epithelioid hemangioendothelioma is a rare vascular tumor with unpredictable behavior. It often presents as liver or lung nodules and is refractory to conventional chemotherapy. Surgical resection and/or liver transplantation have been the mainstay of therapy, but the results are mixed and unsatisfactory. Although the etiology of this malignancy is unknown, an increased incidence in women has been noted, and an association with exposure to vinyl chloride is emerging as a possible risk factor. This review proposes polyurethane/silicone breast implants as a potential cause of the condition and highlights the dramatic response to interferon (IFN)-alpha in a woman, so exposed, with widespread disease in the liver and lungs. The implications for other women who have had this type of implant could be significant, and the early use of IFN-alpha may be optimal.

Epithelioid hemangioendothelioma and multiple thoraco-lumbar lateral meningoceles: two rare pathological entities in a patient with NF-1.

Epithelioid hemangioendothelioma (EHE) is a rare vascular soft-tissue tumour of intermediate malignancy. Neurofibromatosis type I (NF-1) is a genetic syndrome associated with soft tissue sarcoma and higher risk of developing neoplasia. Lateral meningoceles are uncommon entities, being mostly associated with NF-1. We report a case of a 31-year-old woman, with NF-1 and past history of right thalamic/peduncular astrocytoma WHO grade II, admitted to the Neurosurgery Department in December 2003 due to severe low back pain, irradiating to the left leg without a radicular pattern. Thoraco-lumbar magnetic resonance imaging (MRI) showed a large left posterior paravertebral expansive lesion, bilateral and multiple thoraco-lumbar lateral meningoceles and dural ectasias with scalloping of the vertebral bodies. Biopsy of the paravertebral mass lesion disclosed EHE. We present this case because of the novel association between NF-1 and EHE, and the unusual aggressiveness of the neoplasia. Additionally, we highlight the co-existence of bilateral and multiple lateral meningoceles.

Hemangioendotelioma epitelióide de pleura / Epithelioid hemangioendothelioma of the pleura

Relata-se o caso de um paciente exposto profissionalmente a asbesto por dez anos e portador de um tumor pleural muito raro, o hemangioendotelioma epitelióde. O paciente apresentava derrame pleural serohemorrágico, sem evidência de células neoplásicas e com predomínio de linfócitos. A biópsia pleural por agulha revelou processo inflamatório crônico inespecífico, com áreas de tecido mixóide. A videotoracoscopia mostrou nódulos difusos nas pleuras parietal e visceral. A biópsia revelou neoplasia mesenquimal e eram semelhantes às áreas focais observadas na primeira biópsia. O estudo imunohistoquímico demonstrou a presença dos marcadores vasculares CD31, CD34 e Fator VIII, caracterizando a origem vascular do tumor. O paciente foi tratado com cisplatina e ectoposide, tendo o óbito ocorrido três meses após o diagnóstico.

Malignant vascular tumours of the pleura in "asbestos" workers and endothelial differentiation in malignant mesothelioma.

BACKGROUND: Three cases of diffuse malignant vascular tumours of the pleura are described which mimicked malignant mesothelioma clinically and pathologically (so called "pseudomesothelioma"). All had occupational histories of exposure to asbestos. The relationship of these tumours to mesothelioma and asbestos exposure is discussed. METHODS: To examine the histogenetic relationship between mesothelioma and these three tumours an immunohistochemical analysis of vascular marker (CD31, CD34, and Von Willebrand factor) expression was undertaken in 92 cases of pleural mesothelioma, in addition to these three tumours. Electron microscopic fibre analysis of lung tissue was performed on each of the three cases to assess asbestos fibre content. RESULTS: Diffuse pleural epithelioid haemangioendotheliomas may closely resemble malignant mesothelioma clinically and pathologically but, of the 92 pleural mesotheliomas tested, none showed expression of CD31, CD34, and Von Willebrand factor. Although all three cases had claimed exposure to asbestos, ferruginous bodies typical of asbestos were only seen by light microscopy in case 2, and only in this subject was the asbestos fibre content raised in comparison with the range seen in a non-exposed background population. The latent period in the pleural epithelioid haemangioendotheliomas ranged from 18 to 60 years. CONCLUSIONS: Endothelial differentiation does not appear to occur in mesothelioma and therefore should be clearly separated from it. No definite association between pleural epithelioid haemangioendothelioma and exposure to asbestos can be made from this small series but further investigation is warranted.