Myxofibrosarcoma

Myxofibrosarcoma is a soft tissue sarcoma that primarily affects adults over 50 years old. It is one of the most common soft tissue sarcoma of the extremities in adults. It typically presents as a slowly growing, painless mass in the limbs, often growing along fascial planes. Myxofibrosarcoma is treated with wide margin surgical resection, usually accompanied by radiation, but it nonetheless has an increased rate of local recurrence and a significant risk of metastasis depending on tumor size and grade.

Epidemiology

Myxofibrosarcoma is usually seen in patients in their sixth to eighth decades of life, with males being affected more often than females. Myxofibrosarcoma tends to develop in the extremities and proximal limb girdles, and it rarely occurs in the trunk, head, neck, or acral regions. Some cases are located in dermal or subcutaneous sites.

Clinical Features

Myxofibrosarcoma often presents as a painless, slow-growing mass. The clinical presentation can vary depending on the tumor’s location and depth. Deep-seated tumors, which account for 50% of cases, are located beneath the muscle fascia. These tumors can grow to substantial sizes before detection, often causing only vague discomfort or a feeling of fullness in the affected area. Such lesions are frequently discovered only when they become large enough to cause visible swelling, a palpable mass, or compression of nearby tissues leading to symptoms. Superficial tumors, located in the dermal or subcutaneous tissues, are generally smaller at presentation compared to deep-seated tumors. They may present as multinodular masses or cause skin discoloration or ulceration in advanced cases.

Myxofibrosarcomas can vary significantly in size, ranging from a few centimeters to well over 10 cm in diameter. On palpation, they often feel firm or rubbery. In the early stages, these tumors are usually mobile, but as they grow, they may become fixed to underlying structures. While these tumors are often asymptomatic, larger masses may compress nearby nerves, causing numbness or tingling, and they may restrict the range of motion in nearby joints. In rare cases, advanced tumors can lead to systemic symptoms such as fatigue or weight loss.

Radiologic Features

On magnetic resonance imaging, myxofibrosarcoma, as is the case with most soft tissue sarcomas, is typically isointense to muscle on T1-weighted sequences and hyperintense on fat-suppressed T2-weighted sequences. It frequently demonstrates a “tail sign” following gadolinium administration (Figure 1). The “tail sign” represents thickened fascia extending from the tumor margin and should be incorporated into the planned future resection. Although some consider the tail sign to be sensitive and specific for myxofibrosarcoma, others have detected a similarly high rate of positive tail signs in other sarcomas (e.g., undifferentiated pleomorphic sarcoma) as well as benign myxoma. The presence of the tail sign may be associated with a higher risk of local recurrence as this permeation of tumor cells makes it more difficult to obtain a margin-negative resection.

Figure 1A-C: Coronal (A) T1, (B) fat-suppressed T2, and (C) post-gadolinium, fat-suppressed T1 sequences demonstrating a myxofibrosarcoma. The ill-defined mass is isointense to muscle on T1, hyperintense on T2, and enhances along the fascial planes post-gadolinium administration (orange arrow).

For all soft-tissue sarcomas, a staging workup should be performed after biopsy confirmation of the diagnosis. A computed tomography (CT) scan of the chest, abdomen, and pelvis or a whole-body positron emission tomography (PET)-CT scan is recommended for detecting metastatic disease.

Pathology

Myxofibrosarcoma exhibits a spectrum of tumors ranging from low through intermediate and high grade lesions. These tumors are notoriously heterogeneous such that they demonstrate intervening areas of higher and lower grade histology throughout the tumor. As such, needle biopsies of these lesions may underestimate the grade of the lesion if a higher grade area is missed by the biopsy needle. These tumors show a multinodular growth pattern with incomplete fibrous septa and a myxoid stroma. Within this myxoid stroma are areas of increased cellularity among areas of decreased cellularity. They are also characterized by prominent curvilinear vessels, spindle and pleomorphic tumor cells, and scattered pseudo-lipoblasts (Figure 2). The tumor often has infiltrative tentacles that interdigitate with surrounding muscle fibers, contributing to the high rate of margin-positive resections. There are no specific immunohistochemical markers for myxofibrosarcoma; however, it typically stains positively for mesenchymal markers such as vimentin and CD34. Higher-grade tumors are distinguished by increased cellularity, nuclear atypia, mitotic figures, bizarre mitoses, hemorrhage, and necrosis.

Figure 2: H&E stain, myxofibrosarcoma: on high power, cytologically atypical pleomorphic cells can be seen in a myxoid stroma. Notice the infiltrative, atypical cells within the adipose tissue, which do not demonstrate any histologic or immunohistochemical differentiation. (Image courtesy of Drs. Amir Qorbani and Andrew Horvai)

Differential Diagnosis

Myxofibrosarcoma can be confused with a variety of benign and malignant conditions. It may be mistaken for benign conditions such as nodular fasciitis, myxoma, benign fibrous histiocytoma, or myxoid neurofibroma. Among malignant conditions, low-grade fibromyxoid sarcoma and myxoid liposarcoma are important considerations. Imaging characteristics, particularly the “tail sign” on MRI as previously described, may be suggestive, but histological examination remains crucial for a definitive diagnosis. Pathologists look for characteristic features such as curvilinear vessels and the infiltrative growth pattern typical of myxofibrosarcoma. In challenging cases, immunohistochemistry and molecular studies may be necessary to reach a conclusive diagnosis.

Disease Course: Treatment and Prognosis

The mainstay of treatment for myxofibrosarcoma is surgery, usually combined with neoadjuvant (pre-operative) or adjuvant (post-operative) radiation therapy. Regardless of the tumor grade, myxofibrosarcoma has a high rate of local recurrence, occurring in up to 60% of cases, with many patients experiencing multiple local recurrences. The tumor grade often increases with each recurrence, which progressively raises the risk of metastasis. Low-grade tumors are less likely to metastasize compared to intermediate and high-grade tumors. Chemotherapy is typically reserved for treating metastatic disease in younger patients but there is little evidence showing the effectiveness of chemotherapy in these cases. The overall 5- and 10-year survival rates are approximately 75% and 65%, respectively, with low-grade, superficial tumors generally having a better prognosis.

Key Test Topics

The tail sign may indicate tumor extension along the fascial planes and is probably a predictor for increased risk of local recurrence.
Myxofibrosarcoma has a high rate of local recurrence compared to other sarcomas.
Tumor grade does not predict local recurrence but does influence survival.