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Orphanet Journal of Rare Diseases Feb 2020Kaposiform hemangioendothelioma (KHE) is a rare vascular neoplasm with high morbidity and mortality. The initiating mechanism during the pathogenesis of KHE has yet to... (Review)
Review
Kaposiform hemangioendothelioma (KHE) is a rare vascular neoplasm with high morbidity and mortality. The initiating mechanism during the pathogenesis of KHE has yet to be discovered. The main pathological features of KHE are abnormal angiogenesis and lymphangiogenesis. KHEs are clinically heterogeneous and may develop into a life-threatening thrombocytopenia and consumptive coagulopathy, known as the Kasabach-Merritt phenomenon (KMP). The heterogeneity and the highly frequent occurrence of disease-related comorbidities make the management of KHE challenging. Currently, there are no medications approved by the FDA for the treatment of KHE. Multiple treatment regimens have been used with varying success, and new clinical trials are in progress. In severe patients, multiple agents with variable adjuvant therapies are given in sequence or in combination. Recent studies have demonstrated a satisfactory efficacy of sirolimus, an inhibitor of mammalian target of rapamycin, in the treatment of KHE. Novel targeted treatments based on a better understanding of the pathogenesis of KHE are needed to maximize patient outcomes and quality of life. This review summarizes the epidemiology, etiology, pathophysiology, clinical features, diagnosis and treatments of KHE. Recent new concepts and future perspectives for KHE will also be discussed.
Topics: Hemangioendothelioma; Humans; Infant; Kasabach-Merritt Syndrome; Quality of Life; Retrospective Studies; Sarcoma, Kaposi
PubMed: 32014025
DOI: 10.1186/s13023-020-1320-1 -
ESMO Open Jun 2021Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clinical behavior is variable, ranging from that of a low-grade malignancy... (Review)
Review
Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clinical behavior is variable, ranging from that of a low-grade malignancy to that of a high-grade sarcoma and it is marked by a high propensity for systemic involvement. No active systemic agents are currently approved specifically for EHE, which is typically refractory to the antitumor drugs used in sarcomas. The degree of uncertainty in selecting the most appropriate therapy for EHE patients and the lack of guidelines on the clinical management of the disease make the adoption of new treatments inconsistent across the world, resulting in suboptimal outcomes for many EHE patients. To address the shortcoming, a global consensus meeting was organized in December 2020 under the umbrella of the European Society for Medical Oncology (ESMO) involving >80 experts from several disciplines from Europe, North America and Asia, together with a patient representative from the EHE Group, a global, disease-specific patient advocacy group, and Sarcoma Patient EuroNet (SPAEN). The meeting was aimed at defining, by consensus, evidence-based best practices for the optimal approach to primary and metastatic EHE. The consensus achieved during that meeting is the subject of the present publication.
Topics: Adult; Child; Consensus; Hemangioendothelioma, Epithelioid; Humans; Medical Oncology; Patient Advocacy; Sarcoma
PubMed: 34090171
DOI: 10.1016/j.esmoop.2021.100170 -
Histopathology Jan 2022Recent molecular advances have shed significant light on the classification of vascular tumours. Except for haemangiomas, vascular lesions remain difficult to diagnose,... (Review)
Review
Recent molecular advances have shed significant light on the classification of vascular tumours. Except for haemangiomas, vascular lesions remain difficult to diagnose, owing to their rarity and overlapping clinical, radiographic and histological features across malignancies. In particular, challenges still remain in the differential diagnosis of epithelioid vascular tumours, including epithelioid haemangioma and epithelioid haemangioendothelioma at the benign/low-grade end of the spectrum, and epithelioid angiosarcoma at the high-grade end. Historically, the classification of vascular tumours has been heavily dependent on the clinical setting and histological features, as traditional immunohistochemical markers across the group have often been non-discriminatory. The increased application of next-generation sequencing in clinical practice, in particular targeted RNA sequencing (such as Archer, Illumina), has led to numerous novel discoveries, mainly recurrent gene fusions (e.g. those involving FOS, FOSB, YAP1, and WWTR1), which have resulted in refined tumour classification and improved diagnostic reproducibility for vascular tumours. However, other molecular alterations besides fusions have been discovered in vascular tumours, including somatic mutations (e.g. involving GNA family and IDH genes) in a variety of haemangiomas, as well as copy number alterations in high-grade angiosarcomas (e.g. MYC amplifications). Moreover, the translation of these novel molecular abnormalities into diagnostic ancillary markers, either fluorescence in-situ hybridisation probes or surrogate immunohistochemical markers (FOSB, CAMTA1, YAP1, and MYC), has been remarkable. This review will focus on the latest molecular discoveries covering both benign and malignant vascular tumours, and will provide practical diagnostic algorithms, highlighting frequently encountered pitfalls and challenges in the diagnosis of vascular lesions.
Topics: Hemangioendothelioma; Hemangioma; Hemangiosarcoma; Humans; Isocitrate Dehydrogenase; Mutation; Vascular Neoplasms
PubMed: 34958509
DOI: 10.1111/his.14458 -
Archives of Pathology & Laboratory... Jun 2019First described in 2003 as and later in 2011 as , this rare vascular tumor is of intermediate malignant potential. It was officially included for the first time in the... (Review)
Review
First described in 2003 as and later in 2011 as , this rare vascular tumor is of intermediate malignant potential. It was officially included for the first time in the most recent World Health Organization's . It typically affects young adults with a predilection for the distal lower extremity. This tumor lacks morphologic features of vascular differentiation but shows unequivocal evidence of such differentiation with the use of relevant immunohistochemical stains such as FLI1, ERG, and CD31. Pseudomyogenic hemangioendothelioma can be diagnostically challenging and might be confused with other tumors, such as epithelioid sarcoma. In this review we discuss the clinical, morphologic, and immunohistochemical features of this tumor with particular emphasis on the differential diagnosis. Salient molecular and prognostic features are also reviewed.
Topics: Hemangioendothelioma, Epithelioid; Humans
PubMed: 30576238
DOI: 10.5858/arpa.2017-0430-RS -
Journal of Nippon Medical School =... 2019Pseudomyogenic hemangioendothelioma (PMHE) is a new entity. It is an intermediate soft tissue tumor clinically and/or histopathologically mimicking some other high-grade...
Pseudomyogenic hemangioendothelioma (PMHE) is a new entity. It is an intermediate soft tissue tumor clinically and/or histopathologically mimicking some other high-grade malignant tumors and some inflammatory diseases. We report a case of PMHE on the left plantar surface of a 28-year-old woman. Histopathological examination of the resected specimen revealed spindle and epithelioid cells with plump and atypical nuclei proliferated in the dermis and subcutaneous fat tissue with marked fibroplasia. Both spindle and epithelioid cells had abundant eosinophilic cytoplasm. Neoplastic cells were diffusely positive for AE1/AE3, CK7, vimentin, CD31, FLI-1, ERG, and INI-1. From those findings, we made the diagnosis of PMHE. We describe the main points of differentiation between PMHE and diseases that have similar clinical and/or histopathological findings, including cellular dermatofibroma, spindle cell squamous cell carcinoma, epithelioid sarcoma, epithelioid hemangioendothelioma, epithelioid angiosarcoma, nodular or proliferative fasciitis, and granulomatous fibrosing granulation tissue due to a ruptured epidermal cyst.
Topics: Adult; Antiporters; Diagnosis, Differential; Female; Hemangioendothelioma, Epithelioid; Humans; Keratins; Platelet Endothelial Cell Adhesion Molecule-1; Proto-Oncogene Protein c-fli-1; SMARCB1 Protein; Soft Tissue Neoplasms; Transcriptional Regulator ERG; Vimentin
PubMed: 31130564
DOI: 10.1272/jnms.JNMS.2019_86-209 -
Archives of Pathology & Laboratory... Feb 2018Epithelioid hemangioendothelioma is a rare vascular tumor, composed of epithelioid and histiocytoid vascular endothelial cells in myxoid or fibrotic stroma, which can... (Review)
Review
Epithelioid hemangioendothelioma is a rare vascular tumor, composed of epithelioid and histiocytoid vascular endothelial cells in myxoid or fibrotic stroma, which can arise in multiple locations throughout the body. In the liver, this neoplasm usually presents on imaging as an incidental finding of multifocal, heterogeneously enhancing nodules in both lobes or presents clinically with nonspecific abdominal symptoms. Histologically, the tumor has been mistaken for metastatic carcinoma, angiosarcoma, hepatocellular carcinoma, and cholangiocarcinoma. The neoplasm usually stains positive for vascular markers, such as factor VIII-related antigen, CD31, and CD34, and negative for cytokeratins. The translocation t(1;3)(p36.3;q25), resulting in the CAMTA1- WWTR1 fusion product, is the most commonly identified genetic abnormality with this tumor. Although hepatic epithelioid hemangioendothelioma can have a varied clinical course, it is generally considered less aggressive than angiosarcoma. There is no consensus treatment protocol and techniques including liver transplantation, liver resection, chemotherapy and/or radiation therapy, and surveillance have all been used with varying outcomes.
Topics: Hemangioendothelioma, Epithelioid; Humans; Liver Neoplasms
PubMed: 29372848
DOI: 10.5858/arpa.2016-0171-RS -
Modern Pathology : An Official Journal... Jan 2014Although benign hemangiomas are among the most common diagnoses amid connective tissue tumors, sarcomas showing endothelial differentiation (ie, angiosarcoma and... (Review)
Review
Although benign hemangiomas are among the most common diagnoses amid connective tissue tumors, sarcomas showing endothelial differentiation (ie, angiosarcoma and epithelioid hemangioendothelioma) represent under 1% of all sarcoma diagnoses, and thus it is likely that fewer than 500 people in the United States are affected each year. Differential diagnosis of malignant vascular tumors can be often quite challenging, either at the low end of the spectrum, distinguishing an epithelioid hemangioendothelioma from an epithelioid hemangioma, or at the high-grade end of the spectrum, between an angiosarcoma and a malignant epithelioid hemangioendothelioma. Within this differential diagnosis both clinico-radiological features (ie, size and multifocality) and immunohistochemical markers (ie, expression of endothelial markers) are often similar and cannot distinguish between benign and malignant vascular lesions. Molecular ancillary tests have long been needed for a more objective diagnosis and classification of malignant vascular tumors, particularly within the epithelioid phenotype. As significant advances have been recently made in understanding the genetic signatures of vascular tumors, this review will take the opportunity to provide a detailed update on these findings. Specifically, this article will focus on the following aspects: (1) pathological and molecular features of epithelioid hemangioendothelioma, including the more common WWTR1-CAMTA1 fusion, as well as the recently described YAP1-TFE3 fusion, identified in a morphological variant of epithelioid hemangioendothelioma; (2) discuss the heterogeneity of angiosarcoma clinical, morphological and genetic spectrum, with particular emphasis of MYC and FLT4 gene amplification in radiation-induced angiosarcoma; and (3) provide a practical guide in the differential diagnosis of epithelioid vascular tumors using molecular testing.
Topics: Biomarkers, Tumor; Diagnosis, Differential; Genetic Predisposition to Disease; Hemangioendothelioma, Epithelioid; Hemangiosarcoma; Humans; Phenotype; Predictive Value of Tests; Prognosis
PubMed: 24384851
DOI: 10.1038/modpathol.2013.176 -
Cancer Medicine Jul 2023Malignant hemangioendothelioma is an endothelial cancer with heterogeneous clinical behavior that can range from indolent to aggressive, of which the majority are...
BACKGROUND
Malignant hemangioendothelioma is an endothelial cancer with heterogeneous clinical behavior that can range from indolent to aggressive, of which the majority are epithelioid (EHE). Its incidence and demographics have not been previously well defined in a large cohort.
METHODS
This retrospective analysis used the US Cancer Statistics National Program of Cancer Registries - Surveillance Epidemiology End Results (SEER) combined database to identify patients in the US newly diagnosed with hemangioendothelioma between the years of 2001 and 2017 (n = 1986). Survival analyses were performed on a subset of patients within the SEER-18 database with survival information available (n = 417). Outcomes included incidence, demographics of patients newly diagnosed with hemangioendothelioma, extent of disease at presentation, and overall survival.
RESULTS
The incidence of hemangioendothelioma in the US is 0.4 cases per million person-years. Although cases rose to 122 newly diagnosed in the year 2017 (90 EHE, 32 other hemangioendothelioma), incidence rates were stable. Skin and connective tissues were the most common presenting sites (33.4%), followed by liver (24.5%), lung (17.6%), and bone (12.5%). Median age at diagnosis was 55 years; 27.2% of patients were pediatric, adolescent, or young adult (<40 years). At presentation, 36.4% of patients had localized disease; 21.6% presented with regional and 41.7% with distant metastases. Observed survival at 3 years was 79.7%, 70.7%, and 46.0% for patients presenting with local, regional, and distant disease and most deaths occurred within the first 2 years.
CONCLUSIONS
Malignant hemangioendothelioma is ultra-rare but meaningfully impacts affected patients. These data may provide benchmarks for comparison of new approaches to hemangioendothelioma therapy and highlight poor survival outcomes.
Topics: Adolescent; Young Adult; Humans; Child; United States; Middle Aged; Incidence; Hemangioendothelioma, Epithelioid; Retrospective Studies; Hemangiosarcoma; Hemangioendothelioma
PubMed: 37260142
DOI: 10.1002/cam4.6181 -
RoFo : Fortschritte Auf Dem Gebiete Der... Sep 2019
Topics: Arteriovenous Malformations; Child, Preschool; Embolization, Therapeutic; Hemangioendothelioma; Hemangioma, Cavernous; Humans; Infant; Infant, Newborn; Lymphatic Abnormalities; Prognosis; Vascular Malformations
PubMed: 31430780
DOI: 10.1055/a-0943-1330 -
Archives of Pathology & Laboratory... Apr 2020Pseudomyogenic hemangioendothelioma (PMH) is a rare vascular tumor that presents more frequently in young adults and has a male predominance. It is usually located in... (Review)
Review
Pseudomyogenic hemangioendothelioma (PMH) is a rare vascular tumor that presents more frequently in young adults and has a male predominance. It is usually located in the superficial or deep soft tissues of the extremities, but concurrent bone involvement can be present. In approximately two-thirds of patients this disease is multifocal, often involving multiple tissue planes. It is a relapsing lesion with low metastatic potential. Given its clinical and morphologic characteristics (multifocality, epithelioid morphology, absence of clearly evident vascular differentiation on hematoxylin-eosin slides), PMH can be easily misinterpreted as other lesions, often with radically different treatment and prognosis. For this reason, we think it is important to recognize this entity, which has some unique features. Here, we will briefly describe the clinical and pathologic features of PMH, detailing its more relevant differential diagnoses.
Topics: Adult; Diagnosis, Differential; Female; Hemangioendothelioma, Epithelioid; Humans; Male; Young Adult
PubMed: 31017450
DOI: 10.5858/arpa.2018-0395-RS