LGFMS is a variant of fibrosarcoma that affects mainly young adults in the second to fourth decade. The tumor affects the deep soft tissue of lower extremity and trunk, followed by upper extremity and head and neck region. The tumor is usually multinodular and is composed of fibromyxoid areas containing prominent curvilinear vessels separated by collagenized bands. The tumor is moderately cellular and composed of mildly atypical spindle cells that may show perivascular crowding in the myxoid area and fascicular arrangement in the fibrous regions. Some cases are characterized by the formation of pseudo-rosettes, which are characterized by a peripheral halo of epithelioid tumor cells that surrounds a core of acellular dense connective tissue. LGFMS stains consistently only for vimentin. EMA and CD34 may be focally positive. Desmin, S100 protein, pancytokeratin are negative. A recurrent t(7; 16) (q34; p11) translocation has been described. LGFMS is a low grade sarcoma that may recur in 10% of the cases with a low risk for metastasis.
MLS originates in the deep soft tissue of the extremities; however, it is more cellular than intramuscular myxoma (IM) and is associated with a prominent delicate and regular vascular network (“chicken-wire” pattern). Although the majority of the tumor cells in MLS are small primitive spindle cells, the tumor shows definite adipocytic differentiation with small univacuolated to multivacuolated lipoblasts. MLS is generally positive for S100 protein and has a recurrent t(12; 16) (q13; p11) translocation.
IM is a slow-growing benign neoplasm characterized by bland spindle cells embedded in abundant mucin with sparse vessels. It affects adults between the fourth and seventh decade of life and shows a distinct female predilection (2:1). It involves the musculature of the proximal extremities; the thigh is most commonly affected (more than 50% of cases), followed by shoulder and upper extremity, and buttocks. The majority of cases are solitary, but multiple lesions are seen in 5% to 10% of the cases, usually as part of a syndrome. The association of multiple myxomas with fibrous dysplasia is known as Mazabraud’s syndrome and as McCune-Albright syndrome when associated with cutaneous hyperpigmentation and endocrine abnormalities. Individual lesions are circumscribed but unencapsulated and some degree of muscle infiltration is usually present. IM is composed of myxoid matrix with sparse vascularity in the form of delicate capillaries. The tumor cells are widely spaced and are spindle to stellate is shape. The cytoplasm is scant and the nuclei small, ovoid, and hyperchromatic. Mitoses are generally absent. A small subset of IM shows increased cellularity and vascularity (cellular IM) that is associated with minimal risk of local recurrence but has no metastatic potential. IM is positive for vimentin and may be focally positive for smooth muscle actin (SMA) and CD34. Desmin and S100 protein are negative. Complete conservative excision is curative. IM, solitary or multiple, is associated with a point mutation of the GNAS1 gene, the same point mutation seen in fibrous dysplasia of bone.
NF is a rapidly growing, painless subcutaneous mass that is most common in young adults. Only rare cases may also involve skeletal muscle. Microscopically NF is more cellular than IM and is composed of myofibroblasts arranged in storiform or fascicular architecture that are embedded in myxoid to fibrous matrix. The myxoid matrix predominates in the center of the lesion and the fibrosis at the periphery. Younger lesions are predominantly myxoid, whereas older lesions are characterized by prominent fibrosis.
ESMC is a sarcoma that affects the deep soft tissue of the extremities, with the thigh being the most common site. Most patients are adults between the fourth and sixth decades of life. The lesion is slow growing and, depending on the location, may be associated with pain and tenderness. When discovered, ESMC is large, usually more than 10 cm in diameter, and appears well-circumscribed, myxoid, and often surrounded by a fibrous pseudocapsule. Areas of hemorrhage may be prominent. Microscopically the lesion is multinodular with abundant myxoid matrix. Differently formed IM, ESMC is more cellular with the tumor cells arranged in cords and clusters, frequently radially oriented. The tumor cells are round to stellate with eosinophilic cytoplasm, round and hyperchromatic nuclei, and sparse mitotic activity. ESMC is focally and weakly positive for S100 proteins. EMA and CD57 (leu7) are generally positive, and glial fibrillary acidic protein (GFAP) is negative. Keratin may be focally positive. ESMC is characterized by recurrent translocations. The most common is t(9; 22) (q22; q12), identified in up to 90% of cases and t(9; 17) (q22; q11) in the remaining cases. ESMC shows a high rate of local recurrence and is characterized by late metastases, requiring prolonged clinical follow-up.
