Low-grade fibromyxoid and sclerosing epithelioid fibrosarcoma: distinct behaviour in the same spectrum of ultra-rare sarcomas
6 affiliations
- 1Medical Oncology Department, Hospital Garcia de Orta
- 2Medical Oncology Department, Instituto Português de Oncologia do Porto Francisco Gentil
- 3Genetics Department, Instituto Português de Oncologia do Porto Francisco Gentil
- 4Pathology Department, Instituto Português de Oncologia do Porto Francisco Gentil
- 5Radiation Oncology Department, Instituto Português de Oncologia do Porto Francisco Gentil
- 6Surgery Department, Instituto Português de Oncologia do Porto Francisco Gentil
Abstract
Introduction: Low-grade fibromyxoid sarcoma (LGFMS) and sclerosing epithelioid fibrosarcoma (SEF) represent a molecularly related spectrum of ultra-rare soft-tissue sarcomas characterised by recurrent FUS or EWSR1 rearrangements and frequent MUC4 expression. Despite sharing recurrent molecular alterations, their clinical behaviour differs markedly, positioning them at opposite ends of a biologically related spectrum with distinct clinical trajectories. This study aimed to characterise the clinicopathological features, molecular profiles, treatment approaches, and outcomes across this spectrum.
Methods: We retrospectively reviewed consecutive patients with LGFMS or SEF at a national EURACAN-designated sarcoma reference centre between 2013 and 2024. Clinicopathological characteristics, molecular findings, treatments, and outcomes were collected and analysed descriptively.
Results: Twenty patients were included: 11 (55%) LGFMS, six (30%) SEF and three (15%) hybrid tumours. MUC4 was positive in 13 cases (65%). Molecular analysis was informative in 19 patients (95%), with FUS or EWSR1 rearrangements in 16 (84%). FUS predominated (63%); EWSR1 rearrangements were confined to SEF (21%). Nineteen patients (95%) underwent curative-intent surgery. Local recurrence occurred in two (10%). Distant metastases developed in three (15%), all with SEF or hybrid histology. Metastatic progression was early (median 6 months), associated with high-risk histological features and EWSR1 rearrangement. SEF accounted for the only disease-related death; median overall survival was not reached, with 95% of patients alive at last follow-up.
Discussion: These findings highlight the divergent clinical behaviour across the LGFMS–SEF spectrum and support closer surveillance of high-risk tumours.
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BibTeX
@article{castanheira2026lowgrade,
title = {{Low-grade fibromyxoid and sclerosing epithelioid fibrosarcoma: distinct behaviour in the same spectrum of ultra-rare sarcomas}},
author = {Beatriz Castanheira and Inês Soldin and Joana Vieira and Mariana Afonso and Sofia Conde and Augusto Moreira and Miguel Henriques Abreu},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1943496},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1943496/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Low-grade fibromyxoid and sclerosing epithelioid fibrosarcoma: distinct behaviour in the same spectrum of ultra-rare sarcomas
AU - Beatriz Castanheira
AU - Inês Soldin
AU - Joana Vieira
AU - Mariana Afonso
AU - Sofia Conde
AU - Augusto Moreira
AU - Miguel Henriques Abreu
PY - 2026
DA - 2026/10/15
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1943496
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1943496/full
AB - Introduction: Low-grade fibromyxoid sarcoma (LGFMS) and sclerosing epithelioid fibrosarcoma (SEF) represent a molecularly related spectrum of ultra-rare soft-tissue sarcomas characterised by recurrent FUS or EWSR1 rearrangements and frequent MUC4 expression. Despite sharing recurrent molecular alterations, their clinical behaviour differs markedly, positioning them at opposite ends of a biologically related spectrum with distinct clinical trajectories. This study aimed to characterise the clinicopathological features, molecular profiles, treatment approaches, and outcomes across this spectrum. Methods: We retrospectively reviewed consecutive patients with LGFMS or SEF at a national EURACAN-designated sarcoma reference centre between 2013 and 2024. Clinicopathological characteristics, molecular findings, treatments, and outcomes were collected and analysed descriptively. Results: Twenty patients were included: 11 (55%) LGFMS, six (30%) SEF and three (15%) hybrid tumours. MUC4 was positive in 13 cases (65%). Molecular analysis was informative in 19 patients (95%), with FUS or EWSR1 rearrangements in 16 (84%). FUS predominated (63%); EWSR1 rearrangements were confined to SEF (21%). Nineteen patients (95%) underwent curative-intent surgery. Local recurrence occurred in two (10%). Distant metastases developed in three (15%), all with SEF or hybrid histology. Metastatic progression was early (median 6 months), associated with high-risk histological features and EWSR1 rearrangement. SEF accounted for the only disease-related death; median overall survival was not reached, with 95% of patients alive at last follow-up. Discussion: These findings highlight the divergent clinical behaviour across the LGFMS–SEF spectrum and support closer surveillance of high-risk tumours.
SN - 2234-943X
ER -