ZFP64::NCOA3 gene fusion defines a novel subset of spindle cell rhabdomyosarcoma Journal Article
| Authors: | Han, R.; Dermawan, J. K.; Demicco, E. G.; Ferguson, P. C.; Griffin, A. M.; Swanson, D.; Antonescu, C. R.; Dickson, B. C. |
| Article Title: | ZFP64::NCOA3 gene fusion defines a novel subset of spindle cell rhabdomyosarcoma |
| Abstract: | Spindle cell rhabdomyosarcoma represents a rare neoplasm characterized by monomorphic spindle cells with a fascicular architecture and variable skeletal muscle differentiation. Following incidental identification of a ZFP64::NCOA3 gene fusion in an unclassified spindle cell sarcoma resembling adult-type fibrosarcoma, we performed a retrospective archival review and identified four additional cases with a similar histology and identical gene fusion. All tumors arose in adult males (28–71 years). The neoplasms were found in the deep soft tissues, two were gluteal, and one each arose in the thigh, abdominal wall, and chest wall. Morphologically, the tumors were characterized by spindle cells with a distinctive herringbone pattern and variable collagenous to myxoid stroma. The nuclei were relatively monomorphic with variable mitotic activity. Three tumors had immunoreactivity for MyoD1, and four contained variable expression of desmin and smooth muscle actin. All cases tested for myogenin, CD34, S100, pankeratin, and epithelial membrane antigen were negative. Targeted RNA sequencing revealed a ZFP64::NCOA3 fusion product in all five tumors. Three patients developed distant metastases, and two ultimately succumbed to their disease within 2 years of initial diagnosis. This study suggests ZFP64::NCOA3 fusions define a novel subtype of rhabdomyosarcoma with a spindle cell morphology and aggressive clinical behavior. The potential for morphologic and immunohistochemical overlap with several other sarcoma types underscores the value of molecular testing as a diagnostic adjunct to ensure accurate classification and management of these neoplasms. © 2022 Wiley Periodicals LLC. |
| Keywords: | immunohistochemistry; adult; clinical article; controlled study; human tissue; aged; unclassified drug; human cell; cancer patient; gene; cd34 antigen; cohort analysis; immunoreactivity; retrospective study; histology; distant metastasis; soft tissue; fibrosarcoma; thigh; gene fusion; stroma; spindle cell; protein s 100; mitosis rate; rhabdomyosarcoma; thorax wall; cancer morphology; abdominal wall; myogenin; fusion; epithelial membrane antigen; smooth muscle actin; keratin; pankeratin; human; male; article; rna sequencing; myod1 protein; gluteus muscle; ncoa3; desmin (protein); zfp64; ncoa3 gene; zfp64 gene |
| Journal Title: | Genes Chromosomes and Cancer |
| Volume: | 61 |
| Issue: | 11 |
| ISSN: | 1045-2257 |
| Publisher: | Wiley Periodicals, Inc |
| Date Published: | 2022-11-01 |
| Start Page: | 645 |
| End Page: | 652 |
| Language: | English |
| DOI: | 10.1002/gcc.23052 |
| PUBMED: | 35521817 |
| PROVIDER: | scopus |
| PMCID: | PMC9811222 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 November 2022 -- Source: Scopus |
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