Definition

Low-grade fibromyxoid sarcoma (LGFMS) is a malignant soft tissue tumor classified among fibroblastic-myofibroblastic neoplasms. It is also known as Evans tumor.

Epidemiology and Presentation

LGFMS is a very rare tumor with a misleadingly bland histological appearance that typically arises in the deep soft tissues of the proximal extremities (thigh is the most common site) or trunk of young adults (median age, 34 years; range, 3–78 years) with a slight male predominance. It has been rarely described in the retroperitoneum, mediastinum, and superficial acral sites.

The lesion usually presents as a painless mass (2–20 cm in diameter) which can remain undiagnosed for years.

Pathology

The tumor is characterized by an admixture of heavily collagenized hypocellular zones and more cellular myxoid nodules. Short fascicular and characteristic whorling growth patterns are observed. Tumor vasculature is made of arcades of small vessels with perivascular sclerosis. Mitotic figures are rare.

Rarely the lesion is hardly distinguishable from sclerosing epithelioid fibrosarcoma (→ see dedicated section), a likely related neoplasm. Hybrid tumors displaying composite histologic features of LGFMS and sclerosing epithelioid fibrosarcoma have been recently described.

The hyalinizing spindle cell tumor with giant rosettes (HSCTGR), which is now accepted as a subtype of LGFMS, is much more rarely described: the immunohistochemical features and biological behavior of the two neoplasms are identical.

Differential diagnosis may be needed with the following: fibromatosis (usually it lacks myxoid areas; fibrous cells are aligned in broad sweeping fascicles; cells appear more like reactive fibroblasts; distinct ectatic vessels are present; diffuse or occasionally focal nuclear beta-catenin staining); fibrosarcoma (no myxoid component; “herringbone” fascicular pattern, a diagnosis of exclusion); myxofibrosarcoma (more myxoid and less fibrous, more nuclear pleomorphism and hyperchromatism in contrast to LGFMS which is almost always bland and monomorphic with little to no pleomorphism; more developed vascular network, tumor cells aggregate around vessels); myxoid neurofibroma (wavy nuclei, background of thick collagen bundles, S100 positive); nodular fasciitis (tissue culture histology, extravasated erythrocytes, myxoid cystic degeneration); and sclerosing epithelioid fibrosarcoma (MUC4 positive like LGFMS but characterized by EWSR1 rearrangements and not by FUS rearrangements).

Biomarkers

MUC4, an epithelial glycoprotein, is constantly expressed by LGFMS. CD99 is frequently expressed (90% of cases). LGFMS stains negative for S100, desmin, cytokeratins, CD34, MDM2, SMA,Footnote 1 h-caldesmon, CD117, and nuclear beta-catenin.

The majority of LGFMS cases harbor the chromosomal translocation t(7;16)(q34;p11), which results in the formation of the FUS-CREB3L2 fusion gene.Footnote 2 A minority of cases have been shown to carry the FUS-CREB3L1 fusion gene resulting from chromosomal translocation t(11;16)(p11;p11).

Though less frequently, the FUS-CREB3L2 fusion gene has been reported also in sclerosing epithelioid fibrosarcoma (→ see dedicated section), which has led to the hypothesis that the two entities are related.

Prognosis

Despite the low-grade histological appearance, LGFMS is a malignant, often late-metastasizing tumor. Disease relapse and metastasis rates are low during the first years of follow-up, but they increase over time (up to >60% and >40%, respectively). No histological feature is known to correlate with prognosis.

Therapy

Surgery is the mainstay of treatment.