Untying the Gordian knot of composite hemangioendothelioma: Discovery of novel fusions

Linos K, Dermawan JK, Pulitzer M, Hameed M, Agaram NP, Agaimy A, Antonescu CR (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Genes Chromosomes & Cancer Wiley-Blackwell

DOI: 10.1002/gcc.23198

Abstract

Composite hemangioendothelioma is a rare, locally aggressive, and rarely metastasizing vascular neoplasm which affects both children and adults. Recently, a number of gene fusions including YAP1::MAML2, PTBP1::MAML2, and EPC1::PHC2 have been detected in a small subset of cases with or without neuroendocrine expression. Herein, we present four additional cases with novel in-frame fusions. The cohort comprises two females and two males with a wide age range at diagnosis (24–80 years). Two tumors were deep involving the right brachial plexus and mediastinum, while the remaining were superficial (right plantar foot and abdominal wall). The size ranged from 1.5 to 4.8 cm in greatest dimension. Morphologically, all tumors had an admixture of at least two architectural patterns including retiform hemangioendothelioma, hemangioma, epithelioid hemangioendothelioma, or angiosarcoma. The tumors were positive for endothelial markers CD31 (3/3), ERG (4/4), and D2-40 (1/4, focal), while SMA was expressed in 2/3 highlighting the surrounding pericytes. Synaptophysin showed immunoreactivity in 2/3 cases. One patient had a local recurrence after 40 months, while two patients had no evidence of disease 4 months post-resection. Targeted RNA sequencing detected novel in-frame fusions in each of the cases: HSPG2::FGFR1, YAP1::FOXR1, ACTB::MAML2, and ARID1B::MAML2. The two cases with neuroendocrine expression occurred as superficial lesions and harbored YAP1::FOXR1 and ARID1B::MAML2 fusions. Our study expands on the molecular spectrum of this enigmatic tumor, further enhancing our current understanding of the disease.

Authors with CRIS profile

Abbas Agaimy Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie

Involved external institutions

Memorial Sloan Kettering Cancer Center US United States (USA) (US)

How to cite

APA:

Linos, K., Dermawan, J.K., Pulitzer, M., Hameed, M., Agaram, N.P., Agaimy, A., & Antonescu, C.R. (2023). Untying the Gordian knot of composite hemangioendothelioma: Discovery of novel fusions. Genes Chromosomes & Cancer. https://doi.org/10.1002/gcc.23198

MLA:

Linos, Konstantinos, et al. "Untying the Gordian knot of composite hemangioendothelioma: Discovery of novel fusions." Genes Chromosomes & Cancer (2023).

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