Superficial neurocristic FET::ETS fusion tumor: Expanding the clinicopathological and molecular genetic spectrum of a recently described entity Journal Article
| Authors: | Dehner, C. A.; Warmke, L. M.; Umphress, B.; Malik, F.; Cloutier, J. M.; Dermawan, J. K.; Fritz, M.; Que, S. K. T.; Ameline, B.; Fritchie, K. J.; Kerr, D. A.; Linos, K.; Baumhoer, D.; Billings, S. D.; Folpe, A. L. |
| Article Title: | Superficial neurocristic FET::ETS fusion tumor: Expanding the clinicopathological and molecular genetic spectrum of a recently described entity |
| Abstract: | Superficial neurocristic EWSR1::FLI1 fusion tumor is a very recently described, clinically indolent tumor of the skin and superficial soft tissues, which differs in essentially all ways from Ewing sarcoma, despite harboring an identical fusion event. The EWSR1 and FLI1 genes are members of the FET and ETS gene family, respectively, and very rare examples of Ewing sarcoma harbor alternative FET::ETS fusion events, such as EWSR1::ERG, FUS::FLI1, FUS::ERG, EWSR1::ETV4, and others. We report 5 new cases of this very rare entity, harboring in 3 cases alternative FET::ETS fusion events. The tumors occurred in 2 males and 3 females (median age, 14 years, range, 8-69 years) and presented as solitary dermal/subcutaneous masses of the thigh, foot, shoulder, arm, and back (median size, 1.8 cm; range, 1-2 cm). All patients underwent wide excisions; one received adjuvant chemotherapy. Clinical follow-up on 3 patients (median, 24 months; range, 18-31 months) showed all to be without disease. Morphologically, all tumors displayed typical features of this entity as described, with nests of cytologically bland, diffusely S100 protein/SOX10-positive round cells without mitotic activity, surrounded by fibrous bands containing spindled cells with similar nuclear features. The tumors also showed membranous CD99 (4/5) and nuclear NKX2.2 (3/3) expression. RNA sequencing (5 cases) demonstrated FUS::FLI1, FUS::ERG, EWSR1::FLI1, EWSR1::ERG, and a novel FUS::ETV5. Methylation profiling (4 cases) showed all to cluster with previously reported superficial neurocristic EWSR1::FLI1 fusion tumors and apart from conventional and “adamantinoma-like” Ewing sarcoma. Our findings confirm the distinctive clinicopathological features of this very rare, recently described entity and expand its molecular genetic spectrum. Reflecting on these findings, we propose modifying the name of this entity to “superficial neurocristic FET::ETS fusion tumor.” © 2024 United States & Canadian Academy of Pathology |
| Keywords: | immunohistochemistry; adolescent; adult; child; clinical article; human tissue; school child; aged; middle aged; young adult; gene cluster; human cell; methylation; exon; clinical feature; histopathology; cancer recurrence; doxorubicin; cancer combination chemotherapy; adjuvant therapy; molecular genetics; follow up; antineoplastic agent; cytology; cell infiltration; cyclophosphamide; vincristine; tumor biopsy; distant metastasis; ewing sarcoma; fluorescence in situ hybridization; fibrosarcoma; adjuvant chemotherapy; fusion gene; collagen; spindle cell; protein s 100; mitosis rate; melan a; wt1 protein; rhabdomyosarcoma; malignant peripheral nerve sheath tumor; extraskeletal myxoid chondrosarcoma; neurofibroma; mohs micrographic surgery; clear cell sarcoma; myogenin; cd99 antigen; alveolar soft part sarcoma; desmoplastic small round cell tumor; myxosarcoma; cytokeratin ae1; cytokeratin ae3; neurilemoma; synaptophysin; dermatofibrosarcoma protuberans; surgical margin; copy number variation; adipocyte; wide excision; angiomatoid fibrous histiocytoma; monoclonal antibody hmb 45; superficial cancer; high throughput sequencing; transcription factor sox10; low grade fibromyxoid sarcoma; human; male; female; article; sclerosing epithelioid fibrosarcoma; rna sequencing; myod1 protein; shave biopsy; adamantinoma; desmin (protein); homeobox protein nkx-2.2; fet::ets fusion; superficial neurocristic ewsr1::fli1 fusion tumor; adamantinoma like ewing sarcoma; ewsr1 erg fusion gene; ewsr1 etv4 fusion gene; ewsr1 fli1 fusion gene; fus erg fusion gene; fus fli1 fusion gene; intracranial mesenchymal tumor; superficial neurocristic tumor |
| Journal Title: | Modern Pathology |
| Volume: | 38 |
| Issue: | 2 |
| ISSN: | 0893-3952 |
| Publisher: | Nature Research |
| Date Published: | 2025-02-01 |
| Start Page: | 100656 |
| Language: | English |
| DOI: | 10.1016/j.modpat.2024.100656 |
| PUBMED: | 39522640 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
