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YAP1-TFE3-fused hemangioendothelioma: a multi-institutional clinicopathologic study of 24 genetically-confirmed cases

Authors :
Dermawan, Josephine K.
Azzato, Elizabeth M.
Billings, Steven D.
Fritchie, Karen J.
Aubert, Sebastien
Bahrami, Armita
Barisella, Marta
Baumhoer, Daniel
Blum, Veronika
Bode, Beata
Aesif, Scott W.
Bovée, Judith V. M. G.
Dickson, Brendan C.
van den Hout, Mari
Lucas, David R.
Moch, Holger
Oaxaca, Gabriel
Righi, Alberto
Sciot, Raf
Sumathi, Vaiyapuri
Yoshida, Akihiko
Rubin, Brian P.
Source :
Modern Pathology; December 2021, Vol. 34 Issue: 12 p2211-2221, 11p
Publication Year :
2021

Abstract

YAP1-TFE3-fused hemangioendothelioma is an extremely rare malignant vascular tumor. We present the largest multi-institutional clinicopathologic study of YAP1-TFE3-fused hemangioendothelioma to date. The 24 cases of YAP1-TFE3-fused hemangioendothelioma showed a female predominance (17 female, 7 male) across a wide age range (20–78 years old, median 44). Tumors were most commonly located in soft tissue (50%), followed by bone (29%), lung (13%), and liver (8%), ranging from 3 to 115 mm in size (median 40 mm). About two-thirds presented with multifocal disease, including 7 cases with distant organ metastasis. Histopathologically, we describe three dominant architectural patterns: solid sheets of coalescing nests, pseudoalveolar and (pseudo)vasoformative pattern, and discohesive strands and clusters of cells set in a myxoid to myxohyaline stroma. These patterns were present in variable proportions across different tumors and often coexisted within the same tumor. The dominant cytomorphology (88%) was large epithelioid cells with abundant, glassy eosinophilic to vacuolated cytoplasm, prominent nucleoli and well-demarcated cell borders. Multinucleated or binucleated cells, prominent admixed erythrocytic and lymphocytic infiltrates, and intratumoral fat were frequently present. Immunohistochemically, ERG, CD31, and TFE3 were consistently expressed, while expression of CD34 (83%) and cytokeratin AE1/AE3 (20%) was variable. CAMTA1 was negative in all but one case. All cases were confirmed by molecular testing to harbor YAP1-TFE3gene fusions: majority with YAP1exon 1 fused to TFE3exon 4 (88%), or less commonly, TFE3exon 6 (12%). Most patients (88%) were treated with primary surgical resection. Over a follow-up period of 4–360 months (median 36 months) in 17 cases, 35% of patients remained alive without disease, and 47% survived many years with stable, albeit multifocal and/or metastatic disease. Five-year progression-free survival probability was 88%. We propose categorizing YAP1-TFE3-fused hemangioendothelioma as a distinct disease entity given its unique clinical and histopathologic characteristics in comparison to conventional epithelioid hemangioendothelioma.

Details

Language :
English
ISSN :
08933952 and 15300285
Volume :
34
Issue :
12
Database :
Supplemental Index
Journal :
Modern Pathology
Publication Type :
Periodical
Accession number :
ejs57415808
Full Text :
https://doi.org/10.1038/s41379-021-00879-7