Expanding the spectrum of intraosseous rhabdomyosarcoma: Correlation between 2 distinct gene fusions and phenotype Journal Article
| Authors: | Agaram, N. P.; Zhang, L.; Sung, Y. S.; Cavalcanti, M. S.; Torrence, D.; Wexler, L.; Francis, G.; Sommerville, S.; Swanson, D.; Dickson, B. C.; Suurmeijer, A. J. H.; Williamson, R.; Antonescu, C. R. |
| Article Title: | Expanding the spectrum of intraosseous rhabdomyosarcoma: Correlation between 2 distinct gene fusions and phenotype |
| Abstract: | Primary intraosseous rhabdomyosarcomas (RMSs) are extremely rare. Recently 2 studies reported 4 cases of primary intraosseous RMS with EWSR1/FUS-TFCP2 gene fusions, associated with somewhat conflicting histologic features, ranging from spindle to epithelioid. In this study we sought to further investigate the pathologic and molecular abnormalities of a larger group of intraosseous RMSs by a combined approach using targeted RNA sequencing analysis and fluorescence in situ hybridization (FISH). We identified 7 cases, 3 males and 4 females, all in young adults, age range 20 to 39 years (median, 27 y). Three cases involved the pelvis, 2 involved the femur and 1 each involved the maxilla and the skull. Molecular studies identified recurrent gene fusions in all 7 cases tested, including: a novel MEIS1-NCOA2 fusion in 2 cases, EWSR1-TFCP2 in 3 cases, and FUS-TFCP2 gene fusions in 1 case. One case showed a FUS gene rearrangement, without a TFCP2 gene abnormality by FISH. The MEIS1-NCOA2-positive cases were characterized by a more primitive and fascicular spindle cell appearance, while the EWSR1/FUS rearranged tumors had a hybrid spindle and epithelioid phenotype, with more abundant eosinophilic cytoplasm and mild nuclear pleomorphism. Immunohistochemically, all tumors were positive for desmin and myogenin (focal). In addition, 4 tumors with TFCP2-associated gene fusions also coexpressed ALK and cytokeratin. In conclusion, our results suggest a high incidence of gene fusions in primary RMSs of bone, with 2 molecular subsets emerging, defined by either MEIS1-NCOA2 or EWSR1/FUS-TFCP2 fusions, showing distinct morphology and immunophenotype. Additional studies with larger numbers of cases and longer follow-up data are required to definitively evaluate the biological behavior of these tumors and to establish their relationship to other spindle cell RMS genetic groups. © 2019 Wolters Kluwer Health, Inc. All rights reserved. |
| Keywords: | rhabdomyosarcoma; intraosseous; meis1; ewsr1; fus; ncoa2; tfcp2 |
| Journal Title: | American Journal of Surgical Pathology |
| Volume: | 43 |
| Issue: | 5 |
| ISSN: | 0147-5185 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2019-05-01 |
| Start Page: | 695 |
| End Page: | 702 |
| Language: | English |
| DOI: | 10.1097/pas.0000000000001227 |
| PUBMED: | 30720533 |
| PROVIDER: | scopus |
| PMCID: | PMC6613942 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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