| Domain | Key facts | Ontology / coding suggestions |
|---|---|---|
| Identity / classification | Epithelioid hemangioendothelioma (EHE) is an ultra-rare malignant vascular sarcoma / soft-tissue tumor of endothelial lineage; often described as a translocation-associated, YAP/TAZ-driven cancer with highly variable clinical behavior (pqac-00000011, pqac-00000013, pqac-00000015) | MONDO: epithelioid hemangioendothelioma = MONDO:0015523 (from available disease-target context; verify locally). MeSH / ICD / OMIM / Orphanet: verify locally. NCIT: verify locally. |
| Epidemiology | Estimated prevalence is less than 1 per 1,000,000; EHE accounts for <1% of vascular tumors. Median/typical age at presentation is around 35-40 years, with broad reported range from 8-90 years. Female predominance has been reported (~1.5:1) (pqac-00000013, pqac-00000015) | Rare cancer category; disease-level aggregated literature and registry data, not individual EHR-derived. |
| Main sites | Most frequent sites include liver, lung, bone, and soft tissue; one review summarized liver 21%, bone 14%, lung 12%. Multifocal liver disease is a common presentation; tumors can arise in many organs/tissues (pqac-00000012, pqac-00000015) | UBERON suggestions: liver (UBERON:0002107), lung (UBERON:0002048), bone tissue (UBERON:0002481), soft tissue = verify locally. Cell type: endothelial cell (CL:0000115). |
| Defining alterations | Approx. 90% harbor WWTR1(TAZ)::CAMTA1 fusion; the remaining ~10% harbor YAP1::TFE3 fusion. In one synthesis, >90% carried WWTR1::CAMTA1 and ~45% of WWTR1::CAMTA1-positive tumors had no other genetic alterations. Secondary alterations reported in ~50% include CDKN2A/B, RB, APC, ATRX, XRCC2, FANCA (pqac-00000011, pqac-00000013) | HGNC genes: WWTR1, CAMTA1, YAP1, TFE3, CDKN2A, CDKN2B, RB1, APC, ATRX, XRCC2, FANCA. Structural variant class: gene fusion / chromosomal translocation. |
| Mechanism | Fusion oncoproteins preserve TEAD-binding function and drive constitutive Hippo-pathway effector activity, producing TEAD-dependent transcription, altered chromatin regulation via the ATAC histone acetyltransferase complex, and oncogenic programs promoting proliferation, survival, migration, anchorage-independent growth, and metastasis. TAZ-CAMTA1 also signals through CTGF, integrin αIIbβ3, and Ras-MAPK; MEK inhibition suppresses fusion-driven growth. CAMTA1 contributes a nuclear-localization function that helps evade normal Hippo cytoplasmic restraint (pqac-00000009, pqac-00000010, pqac-00000011) | GO suggestions: Hippo signaling (verify locally), regulation of transcription by RNA polymerase II (GO:0006357), chromatin organization (GO:0006325), cell proliferation (GO:0008283), cell migration (GO:0016477), anoikis / apoptotic process = verify locally. CL: endothelial cell (CL:0000115). |
| Diagnostic hallmarks | Diagnosis integrates morphology, endothelial differentiation, and molecular testing. WWTR1::CAMTA1 is pathognomonic/standard molecular marker; CAMTA1 immunohistochemistry can be a useful surrogate marker. YAP1::TFE3 defines a distinct subset, but TFE3 immunohistochemistry is not fully specific. Histology typically shows epithelioid endothelial cells in a prominent fibrous/myxohyaline stroma (pqac-00000007, pqac-00000012, pqac-00000013) | Diagnostic workflow: histopathology + endothelial immunophenotype + fusion confirmation by RNA sequencing/FISH/targeted molecular assay (verify locally for assay standards). HPO / SNOMED / LOINC coding: verify locally. |
| Prognosis | Clinical course is markedly heterogeneous, from indolent disease lasting years to rapidly fatal progression within months. Review-level survival figures include median overall survival ~75 months and 1-, 3-, 5-year survival of 83.4%, 55.7%, and 41.1%, respectively. Worse outcomes are associated with pleural/peritoneal disease; isolated soft-tissue disease has more favorable 5-year survival (~87%), compared with liver (~65%) and lung (~45%). Tumor size >3 cm and >3 mitoses/HPF were associated with worse 5-year survival (59% vs 100% in one review synthesis) (pqac-00000009, pqac-00000013, pqac-00000015) | Prognostic factor concepts: pleural effusion / serosal involvement, tumor size, mitotic activity. HPO suggestions: pleural effusion (HP:0002202), ascites (HP:0001541), pain (HP:0012531), weight loss (HP:0001824). |
| Treatment | For localized disease, surgery is the mainstay and can be curative for solitary lesions. Conventional chemotherapy is generally considered less effective in EHE than in angiosarcoma. Targeted/systemic approaches under study or use include sirolimus, trametinib, pazopanib, sorafenib, eribulin, and local ablative/interventional strategies in selected hepatic disease. In preclinical comparison, sirolimus showed greater antitumor activity than doxorubicin; in older case-series summaries, sirolimus showed prolonged benefit in a subset of patients (pqac-00000001, pqac-00000002, pqac-00000012, pqac-00000014) | NCIT intervention suggestions: Surgical Resection, Sirolimus, Trametinib, Pazopanib, Sorafenib, Eribulin, Doxorubicin, Liver Transplantation, Ablation (verify locally for exact NCIT IDs). Clinical trials: trametinib NCT03148275; eribulin NCT03331250; nab-sirolimus NCT07104331; albumin-bound sirolimus NCT07684287 (pqac-00000004). |
| Emerging biomarker | Circulating GDF-15 is a 2024 candidate biomarker of aggressiveness and treatment monitoring. In two cohorts, GDF-15 was significantly higher in EHE than controls (P<0.001 in both), highest in higher-risk disease (P=0.006 retrospective; P=0.002 prospective), and correlated with aggressiveness. Example longitudinal values rose from 6,792 to 11,475 pg/mL with progression and fell to 4,064 pg/mL with sirolimus-induced stability (pqac-00000003) | CHEBI / protein identifier coding: GDF-15 verify locally. Biomarker type: circulating protein biomarker. |
| Models | Strong model evidence now exists: (1) genetically engineered conditional Wwtr1-Camta1 mouse models showing that the fusion is sufficient to drive bona fide EHE; (2) Tet-Off overexpression mouse systems generating postnatal lesions; (3) NIH3T3 transformed-cell and xenograft models for mechanistic work; (4) 2024 patient-derived xenograft and matched cell line retaining WWTR1::CAMTA1 and tumor genomic/transcriptomic features (pqac-00000010, pqac-00000011) | Evidence types: in vitro, xenograft, genetically engineered mouse, patient-derived xenograft. Model organism: mouse (NCBI Taxon:10090). |
| Prevention | No established primary prevention, population screening, or protective-factor evidence is currently supported. EHE is largely fusion-driven, usually somatic, with no validated inherited predisposition pattern or confirmed environmental cause in the cited evidence. Prevention emphasis is therefore tertiary: expert pathology review, accurate fusion testing, surveillance of known disease, and management of complications (pqac-00000011, pqac-00000015) | Prevention coding: verify locally. Genetic counseling may be considered case-by-case, but routine hereditary screening is not evidence-based from available sources. |


*Table: This table condenses the highest-yield disease characteristics of epithelioid hemangioendothelioma for knowledge-base use, including defining fusions, mechanism, prognosis, treatment, and emerging biomarker evidence. It highlights exact reported percentages and flags ontology or coding elements that should be verified locally before database ingestion.*