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Prognostic stratification of clinical and molecular epithelioid hemangioendothelioma subsets.
- Source :
-
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc [Mod Pathol] 2020 Apr; Vol. 33 (4), pp. 591-602. Date of Electronic Publication: 2019 Sep 19. - Publication Year :
- 2020
-
Abstract
- 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.
- Subjects :
- Adaptor Proteins, Signal Transducing genetics
Adolescent
Adult
Aged
Aged, 80 and over
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors genetics
Calcium-Binding Proteins genetics
Female
Genetic Predisposition to Disease
Hemangioendothelioma, Epithelioid mortality
Hemangioendothelioma, Epithelioid therapy
Humans
Male
Middle Aged
Neoplasm Grading
Phenotype
Retrospective Studies
Time Factors
Trans-Activators genetics
Transcription Factors genetics
Transcriptional Coactivator with PDZ-Binding Motif Proteins
YAP-Signaling Proteins
Young Adult
Biomarkers, Tumor genetics
Gene Fusion
Hemangioendothelioma, Epithelioid genetics
Hemangioendothelioma, Epithelioid pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1530-0285
- Volume :
- 33
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
- Publication Type :
- Academic Journal
- Accession number :
- 31537895
- Full Text :
- https://doi.org/10.1038/s41379-019-0368-8