Untying the Gordian knot of composite hemangioendothelioma: Discovery of novel fusions Journal Article
| Authors: | Linos, K.; Dermawan, J. K.; Pulitzer, M.; Hameed, M.; Agaram, N. P.; Agaimy, A.; Antonescu, C. R. |
| Article Title: | Untying the Gordian knot of composite hemangioendothelioma: Discovery of novel fusions |
| 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. © 2023 Wiley Periodicals LLC. |
| Keywords: | adult; child; clinical article; aged; aged, 80 and over; middle aged; cancer surgery; young adult; genetics; cancer recurrence; metabolism; tumor localization; diagnosis, differential; differential diagnosis; cohort analysis; pathology; angiosarcoma; immunoreactivity; tumor marker; carcinogenesis; nucleotide sequence; newborn; gene fusion; transcription factor erg; fusion gene; base sequence; mediastinum; yap1; hemangioma; abdominal wall; monoclonal antibody d2-40; synaptophysin; hemangioendothelioma; hemangioendothelioma, epithelioid; composite; brachial plexus; epithelioid hemangioendothelioma; heterogeneous nuclear ribonucleoprotein; heterogeneous-nuclear ribonucleoproteins; very elderly; humans; human; male; female; article; rna sequencing; fgfr1; biomarkers, tumor; retiform hemangioendothelioma; polypyrimidine tract-binding protein; arid1b; actb; platelet endothelial cell adhesion molecule 1; polypyrimidine tract binding protein; maml2; foxr1; hspg2; ptbp1 protein, human; actb maml2 gene; arid1b maml2 gene; hspg2 fgfr1 gene; yap1 foxr1 gene |
| Journal Title: | Genes Chromosomes and Cancer |
| Volume: | 63 |
| Issue: | 1 |
| ISSN: | 1045-2257 |
| Publisher: | Wiley Periodicals, Inc |
| Date Published: | 2024-01-01 |
| Start Page: | e23198 |
| Language: | English |
| DOI: | 10.1002/gcc.23198 |
| PUBMED: | 37658696 |
| PROVIDER: | scopus |
| PMCID: | PMC10842102 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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