# Low-Grade Fibromyxoid Sarcoma and Related Subtypes: A Systematic Review and Pooled Analysis of 773 Cases

## TL;DR

This study reviews 773 cases of low-grade fibromyxoid sarcoma, finding that complete surgical removal is most effective and that the cancer can recur or spread years later.

## Contribution

The study provides the largest pooled analysis of LGFMS cases, emphasizing the importance of complete resection and long-term monitoring.

## Key findings

- Complete (R0) surgical resection significantly improves recurrence-free survival compared to incomplete resection.
- Nearly 40% of patients experienced either local recurrence or metastasis, highlighting the tumor's potential for late progression.
- MUC4 positivity and FUS-CREB3L2 gene fusion are key diagnostic markers for LGFMS.

## Abstract

Low-grade fibromyxoid sarcoma (LGFMS) is a rare soft-tissue sarcoma that often appears harmless under the microscope, yet can recur or metastasize many years after surgery. Because of its subtle histological appearance, diagnosis can be difficult and is often confirmed by the presence of MUC4 protein and FUS-CREB3L2 gene fusion. We systematically reviewed all published cases of LGFMS and included four additional patients treated at our institution. Among 773 patients, wide (R0) surgical resection offered the best local control, while chemotherapy and radiotherapy provided little benefit. Nearly one in five patients developed local recurrence or metastasis, sometimes after a long disease-free interval. These findings highlight the need for careful diagnosis, complete resection, and long-term radiological follow-up in all patients with LGFMS.

Background: Low-grade fibromyxoid sarcoma (LGFMS) is a rare malignant fibroblastic tumor that often appears deceptively benign. Accurate diagnosis is challenging due to its variable morphology and low mitotic activity. This systematic review provides a comprehensive overview of LGFMS and its subtypes. Methods: A systematic search of PubMed and Embase up to September 2025 identified 273 studies, complemented by four institutional cases from Amsterdam UMC. Individual patient data were pooled to analyze clinical presentation, diagnostic approaches, treatment modalities, and outcomes. Results: In total, 773 patients were included, with a median age of 35 years and equal gender distribution. Tumors were predominantly deep-seated (80%), most commonly located in the thigh or pelvis. MUC4 positivity (96%) and FUS-CREB3L2 fusion (47%) were the most consistent diagnostic markers. Surgery was the mainstay of treatment (98%), with R0 resection achieved in 36% of cases and R1 in 15%. Adjuvant therapies, including chemotherapy and radiotherapy, were rarely used and showed limited efficacy. After a median follow-up of 3.0 years, 19% developed local recurrence and 21% developed metastases. R0 resections were associated with significantly better recurrence-free survival than R1 resection (p < 0.05). Conclusions: LGFMS exhibits indolent histology but potential for late recurrence and metastasis, warranting prolonged radiological follow-up and multicenter studies to evaluate adjuvant strategies.