International Multicenter Retrospective Study From the Ultra-rare Sarcoma Working Group on Low-grade Fibromyxoid Sarcoma, Sclerosing Epithelioid Fibrosarcoma, and Hybrid Forms: Outcome of Primary Localized Disease

Abstract

The aim of the study was to report the outcome of primary localized low-grade fibromyxoid sarcoma (LGFMS), sclerosing epithelioid fibrosarcoma (SEF), and hybrid LGFMS/SEF (H-LGFMS/SEF). Patients with primary localized LGFMS, SEF, or H-LGFMS/SEF, surgically treated with curative intent from January 2000 to September 2022, were enrolled from 14 countries and 27 institutions. Pathologic inclusion criteria were predefined by expert pathologists. The primary endpoint was overall survival (OS). Secondary endpoints were crude cumulative incidence (CCI) of local recurrence (LR), CCI of distant metastases (DM), and post-metastases OS (p-OS). Two hundred ninety-four patients (239 LGFMS, 32 SEF, and 23 H-LGFMS/SEF) were identified. At a median(m-) follow-up (FU) of 57.1 months, 12/294 patients died. The 5- and 10-year OS were 99.0% and 95.9% in LGFMS, 86.2% and 67.0% in SEF, and 84.8% and 84.8% in H-LGFMS/SEF, respectively. Predictors of worse OS included pathology, age at surgery, systemic therapy, and radiotherapy. LR developed in 13/294 (4.4%) patients. The observed m-time to LR was 10.7 months. The 5- and 10-yr CCI-LR were 4.7% in LGFMS and 6.6% in SEF, respectively. There were no LR events in H-LGFMS/SEF. The sole predictor of higher risk of LR was histology. DM developed in 23/294 (7.8%) patients. The observed m-time to DM was 28.2 months. The 5- and 10-yr CCI-DM were 1.3% and 2.7% in LGMFS, 29.9% and 57.7% in SEF, 48.9% and 48.9% in H-LGFMS/SEF, respectively. Predictors of higher risk of DM were histology, systemic therapy, and radiotherapy. Primary localized LGFMS treated with complete surgical resection has an excellent prognosis, while about 50% of H-LGFMS/SEF and SEF develop DM within 5 to 10 years. Very long-term FU is needed to understand absolute cure rates.

FIGURE 1

Low-grade fibromyxoid sarcoma: morphology and immunohistochemical features. At low power, the typical alternating multinodular myxoid and collagenous stroma can be appreciated (A). The tumor is characterized by bland spindle cells organized in short fascicles set in a fibromyxoid background (B). Strong and diffuse immunopositivity for MUC4 is observed in almost all cases (C).

FIGURE 2

Morphologic features of low-grade fibromyxoid sarcoma, sclerosing epithelioid fibrosarcoma, and hybrid forms. An example of LGFMS showing distinctive large collagenous pseudorosettes composed of a central hyalinized collagenous area surrounded by a collarette of neoplastic cells (A). SEF is composed of epithelioid cells organized in cords and nests set in a collagenous stroma (B). The hybrid form is composed of a combination of SEF and LGFMS areas (C).

FIGURE 3

Overall survival according to histologic subtype. LGFMS indicates low-grade fibromyxoid sarcoma; SEF, sclerosing epithelioid fibrosarcoma.

FIGURE 4

Local recurrence and distant metastases according to histologic subtype. SEF indicates sclerosing epithelioid fibrosarcoma; LR, local recurrence; DM, distant metastases.

FIGURE 5

Post-metastases overall survival according to histologic subtype. The graph represents the overall survival in patients who had a distant metastasis. Patients in the LGFMS subgroup who had an event (Fig. 3) are not represented in this curve because they did not have DM. LGFMS indicates low-grade fibromyxoid sarcoma; SEF; sclerosing epithelioid fibrosarcoma.