Myxofibrosarcoma Tumors and Key Factors Influencing Recurrence

Myxofibrosarcoma is a soft tissue sarcoma with a high potential for local recurrence. It primarily affects older adults and often arises in the extremities, making complete surgical removal difficult. Its aggressive nature and tendency to infiltrate surrounding tissues complicate achieving clear surgical margins.

Understanding the factors influencing recurrence is essential for improving patient outcomes.

Tumor Characteristics

Myxofibrosarcoma has a distinct histological profile. It features a myxoid extracellular matrix, giving it a gelatinous appearance on gross examination. This stroma contains spindle-shaped tumor cells with varying degrees of pleomorphism, ranging from low-grade lesions with minimal atypia to high-grade forms with significant nuclear irregularities and increased mitotic activity. Higher-grade variants are more prone to aggressive local invasion.

A key characteristic is its infiltrative growth pattern, which complicates surgical resection. Unlike well-circumscribed sarcomas, myxofibrosarcoma extends along fascial planes and infiltrates surrounding tissues in a finger-like manner. Microscopic spread often extends beyond what is visible on imaging or gross pathology, leading to high rates of positive surgical margins even after wide excision. Studies report recurrence rates as high as 50–60% (Fletcher et al., 2020, World Health Organization Classification of Tumours).

The tumor’s vascularity and stromal composition influence its behavior. It is often highly vascularized, with irregular blood vessels that predispose it to hemorrhage and necrosis, particularly in high-grade lesions. This vascular network supports tumor proliferation and contributes to recurrence. The myxoid matrix, rich in hyaluronic acid and proteoglycans, facilitates tumor cell migration and invasion while potentially influencing therapy resistance.

Common Clinical Presentations

Patients typically present with a slow-growing, painless mass in the extremities, particularly the lower limbs. The insidious onset and lack of early symptoms often delay diagnosis, allowing tumors to grow significantly before detection. Deep-seated lesions may go unnoticed until they interfere with surrounding structures.

The tumor’s infiltrative nature results in ill-defined, irregular borders on palpation, distinguishing it from more encapsulated soft tissue tumors. This spread can tether the mass to adjacent muscles or subcutaneous tissue, limiting mobility and creating a firm, non-mobile consistency. High-grade lesions may grow rapidly, sometimes causing thinning, erythema, or ulceration of the overlying skin, particularly in recurrent cases.

Neurological symptoms may occur if the tumor compresses or invades nearby nerves, leading to numbness, tingling, or hypoesthesia. Motor nerve involvement is less common but can cause weakness or functional impairment, especially when near joints or major nerve trunks. Vascular involvement is rare but may result in swelling due to venous compression or, in severe cases, ischemia from arterial obstruction. These symptoms often prompt further imaging studies to assess local invasion.

Diagnostic Techniques

Diagnosing myxofibrosarcoma requires imaging, histopathology, and molecular analysis. Magnetic resonance imaging (MRI) is the preferred modality for assessing soft tissue involvement, as it highlights the tumor’s myxoid matrix and characteristic tail-like extensions along fascial planes. These infiltrative projections, visible as hyperintense areas on T2-weighted sequences, help differentiate myxofibrosarcoma from more circumscribed tumors. Contrast-enhanced MRI aids in delineating tumor margins and identifying necrotic regions in high-grade lesions. Computed tomography (CT) is useful for evaluating potential bone involvement in advanced cases but lacks the necessary soft tissue contrast.

A core needle biopsy is typically performed for histopathological examination. Fine-needle aspiration is inadequate due to tumor heterogeneity, which may lead to misclassification. Histologically, myxofibrosarcoma is distinguished by a myxoid stroma interspersed with spindle and pleomorphic cells, often displaying a curvilinear vascular pattern. Immunohistochemical staining supports diagnosis, with tumors frequently expressing vimentin while lacking specific markers such as S-100 and desmin. Although myxofibrosarcoma lacks a defining genetic alteration, fluorescence in situ hybridization (FISH) or next-generation sequencing may be used to rule out other myxoid-rich sarcomas, such as myxoid liposarcoma.

Treatment Modalities

Managing myxofibrosarcoma requires a multimodal approach due to its high recurrence rate and infiltrative nature. Surgery is the primary treatment, with the goal of achieving wide negative margins. However, microscopic extensions into surrounding tissues make this challenging. Studies indicate that positive surgical margins significantly increase recurrence risk, emphasizing the importance of meticulous preoperative planning. MRI findings guide resection, and intraoperative frozen section analysis may assess margin status in real-time.

Radiation therapy is commonly used in both preoperative and postoperative settings, particularly for high-grade or deep tumors. Preoperative radiation can shrink tumors and limit microscopic spread, improving the likelihood of negative margins. Postoperative radiation is often administered when margins are close or positive, reducing recurrence risk. A study published in The Journal of Clinical Oncology found that patients who received adjuvant radiation had lower recurrence rates than those treated with surgery alone. However, radiation can lead to fibrosis, impaired wound healing, and increased susceptibility to secondary malignancies.

Chemotherapy is generally reserved for metastatic or unresectable cases, as myxofibrosarcoma shows limited sensitivity to conventional agents. Anthracycline-based regimens such as doxorubicin remain standard for advanced soft tissue sarcomas, though response rates in myxofibrosarcoma vary. Some studies suggest that combination therapy with ifosfamide may improve tumor control in select patients, but overall survival benefits remain uncertain. Targeted therapies are under investigation, with early research exploring tyrosine kinase inhibitors and agents targeting tumor-associated pathways.

Prognostic Factors

Several factors influence prognosis, particularly the likelihood of recurrence and overall survival. Tumor grade is a key determinant, with high-grade lesions exhibiting greater cellular atypia, increased mitotic activity, and a higher propensity for aggressive local invasion. Recurrence rates exceed 50% for high-grade tumors, whereas low-grade variants have a more indolent course.

Tumor size also affects outcomes, with lesions larger than 5 cm associated with worse prognoses due to the difficulty of achieving negative margins. Larger tumors often require more extensive resections, which may not always be feasible in anatomically constrained locations such as the hands or feet.

Depth of invasion further impacts prognosis, as deeply seated tumors have a higher risk of microscopic extension beyond what is detectable on imaging. Superficial tumors are more amenable to wide excision with clear margins, reducing recurrence risk. Margin status is one of the strongest predictors of local relapse, with positive margins nearly doubling recurrence rates. Even with adjuvant radiation, residual microscopic disease remains a concern, underscoring the need for complete resection.

Recurrent tumors tend to behave more aggressively than primary lesions, with each recurrence increasing the likelihood of distant metastasis, particularly to the lungs.