Vascular neoplasms with NFATC1/C2 gene alterations: Expanding the clinicopathologic and molecular characteristics of a distinct entity Journal Article
| Authors: | Dashti, N. K.; Perret, R.; Balzer, B.; Naous, R.; Michal, M.; Dermawan, J. K.; Antonescu, C. R. |
| Article Title: | Vascular neoplasms with NFATC1/C2 gene alterations: Expanding the clinicopathologic and molecular characteristics of a distinct entity |
| Abstract: | Despite significant advances in their molecular pathogenesis, skeletal vascular tumors remain diagnostically challenging due to their aggressive radiologic appearance and significant morphologic overlap. Within the epithelioid category and at the benign end of the spectrum, recurrent FOS/FOSB fusions have defined most epithelioid hemangiomas, distinguishing them from epithelioid hemangioendothelioma and angiosarcoma. More recently, the presence of EWSR1/FUS::NFATC1/2 fusions emerged as the genetic hallmark of a novel group of unusual vascular proliferations, often displaying epithelioid morphology, with alternating vasoformative and solid growth, variable atypia, reminiscent of composite hemangioendothelioma. In this study, we further our understanding and morphologic spectrum of NFATC-fusion positive vascular neoplasms by describing 9 new cases, including soft tissue locations and novel fusion partners. Combining with the initial cohort of 5 cases, a total of 14 patients were analyzed, showing slight female predilection and an age range of 10 to 66 (mean 42 y). Twelve patients had solitary lesions, while 2 had multifocal polyostotic (pelvic bones) disease. Overall, 12 lesions were intra-osseous and 2 in soft tissue. By targeted RNA Fusion panels or FISH, there were 6 cases of EWSR1::NFATC1, 4 EWSR1::NFATC2, 2 FUS::NFATC2, 1 EWSR1 rearrangement, and 1 with a novel FABP4::NFATC2 fusion. Follow-up was available in 4 patients. One patient experienced 2 local recurrences, 11 and 15 years postdiagnosis, and one patient experienced progressive disease despite multimodality treatment (curettings, embolization, radiation) over 3 years. In summary, our extended investigation confirms that NFATC-related fusions define a distinct group of vascular neoplasms with variable architecture, epithelioid phenotype, and cytologic atypia, commonly located in the bone, occasionally multifocal and with potential for local recurrence and aggressive behavior but no metastatic potential. Molecular analysis is recommended in diagnostically challenging cases with atypical histology to exclude malignancy. © 2024 Wolters Kluwer Health. All rights reserved. |
| Keywords: | immunohistochemistry; adolescent; adult; child; clinical article; controlled study; human tissue; school child; aged; middle aged; young adult; unclassified drug; gene mutation; human cell; genetics; clinical feature; histopathology; cancer recurrence; multimodality cancer therapy; cancer radiotherapy; nuclear magnetic resonance imaging; follow up; vascular neoplasms; phenotype; cd34 antigen; protein; cohort analysis; transcription factor; pathology; transcription factors; soft tissue; fluorescence in situ hybridization; gene rearrangement; spine; transcription factor erg; vascular tumor; recurrent disease; protein s 100; metastasis potential; chromogranin; femur; maxilla; transcription factor nfat; soft tissue tumor; hemangioma; bone destruction; rna extraction; mandible; glucose transporter 1; cytokeratin ae1; synaptophysin; hemangioendothelioma; hemangioendothelioma, epithelioid; paraffin embedding; fusion protein; molecular pathology; epithelioid; aneurysmal bone cyst; epithelioid hemangioendothelioma; nfatc transcription factors; acetabulum; ewsr1; humans; human; male; female; article; fus; tfe3 protein; rna sequencing; ewsr1 protein; artificial embolization; platelet endothelial cell adhesion molecule 1; nfatc2; nfatc1; fabp4; vascular neoplasm; ewsr1 nfatc1 fusion protein; ewsr1 nfatc2 fusion protein; fabp4 nfatc2 fusion protein; fus fatc2 fusion protein; transcription factor delta fosb; transcription factor nfatc1; transcription factor nfatc2; nfatc1 protein, human |
| Journal Title: | American Journal of Surgical Pathology |
| Volume: | 48 |
| Issue: | 4 |
| ISSN: | 0147-5185 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2024-04-01 |
| Start Page: | 487 |
| End Page: | 496 |
| Language: | English |
| DOI: | 10.1097/pas.0000000000002175 |
| PUBMED: | 38189436 |
| PROVIDER: | scopus |
| PMCID: | PMC11591551 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK authors: Cristina R. Antonescu -- Source: Scopus |
