Matrix-Forming Tumors of Soft Tissue

Clinical Features

MO and FOPD typically occur in young adults. While MO seems to have a slight male predominance, FOPD is relatively common in females. Patients present with a short history (usually less than 3 months) of pain and/or swelling in the affected area. The lesion starts to mineralize weeks after the onset of symptoms and eventually becomes a hard and well-demarcated mass as the pain diminishes. Greater than 75% of cases of MO occur in the large skeletal muscles of proximal extremities (the quadriceps and the brachialis muscles are the most common sites). FOPD usually occurs in the subcutis of the proximal phalanges and predominates in the fingers and toes. Occasionally there may be localized erythema of the overlying skin. Not all patients recount a history of trauma to the site.

Radiologic Images

The radiologic appearance of MO varies depending on its degree of “maturity.” Early lesions exhibit a nonspecific soft tissue mass, where MRI typically reveals hyperintense signals on T2-weighted images. Intralesional hemorrhage and cystic formation, sometimes with fluid-fluid levels, may also be found, hence imparting an ABCST-like appearance. Later lesions appear as ossified soft tissue tumors, with the ossification typically starting from the periphery, thus assuming an egg shell-like picture ( Fig. 12.1A ). By contrast, the mineralization and ossification in FOPD is randomly distributed.

Pathologic Features

Gross Findings

MO typically measures less than 5.0 cm, but lesions larger than 10 cm have been reported. Lesions examined early in their evolution are solid grey and may exhibit gritty tan regions of mineralized bone. More mature MO has the appearance of a solid bone that requires cutting with a saw ( Fig. 12.1B ). FOPDs are firm, rubbery, tan nodules that typically measure less than 3.0 cm in maximum size ( Fig. 12.2 ) and may be less well demarcated. Centrally the cut surface of ABCST demonstrates blood-filled spaces separated by thin strands of red-grey soft tissues ( Fig. 12.3 ).

Microscopic Findings

In the early phase, MO demonstrates increased cellularity composed of sheets and fascicles of plump, spindled myofibroblastic cells that assume a fasciitis-like picture ( Fig. 12.4A ). These cells, embedded within a myxoid to collagenous matrix, have oval nuclei with vesicular chromatin and eosinophilic nucleoli. Morphologically typical mitotic figures are usually readily found. Necrosis is usually not seen. Intersecting trabeculae of fibrillary eosinophilic osteoid appear to arise from the spindle cells ( Fig. 12.4B ). These immature foci of woven osteoid transition to thicker, more obvious, mineralized woven bone that shows prominent osteoblastic rimming. These, in turn, become continuous with more mature lamellar bone peripherally ( Fig. 12.4C ). Entrapped skeletal muscle is often found ( Fig. 12.4D ). This gradual transition in the histologic appearance from plump spindle cells through immature woven bone to mature lamellar bone is referred to as a zoning phenomenon. This is one of the key histologic hallmarks of MO ( Fig. 12.4E ). The degree to which this is identifiable will depend on the type of specimen. Although it is one of the most characteristic features of MO, it is not always represented on histologic materials. When prominent cystic spaces are present, which are surrounded by (myo)fibroblasts with interspersed osteoclast-like multinucleated giant cells, hemorrhage, and hemosiderin- laden macrophages, the diagnosis of ABCST might be rendered ( Fig. 12.4F ). FOPD is morphologically similar to MO, except that the distribution of osteocartilaginous matrix is haphazard and cartilage is more prominent ( Fig. 12.5A–D ).

Ancillary Studies

Differential Diagnosis

The most important differential diagnostic consideration is soft tissue osteosarcoma (STO). Like MO, STO also occurs in the deep soft tissues, but it most commonly arises in patients in the fifth and sixth decades of life. STO is usually larger than 5.0 cm, grossly heterogeneous with hemorrhagic and necrotic regions, and histologically demonstrates nuclear pleomorphism and cytologic atypia (see later). STO generally lacks the zoning phenomenon as observed in MO, and the osteoid deposition quite often appears in the central areas of the tumor rather than at the periphery (so-called reverse zoning phenomenon). Soft tissue chondromas are better circumscribed, consist chiefly of cartilage, and often show dystrophic calcification and an osteoclastic giant cell reaction.

Prognosis and Treatment

MO, FOPD, and ABCST are benign tumors that are treated by simple excision. Recurrence is extremely uncommon, even when resection margins are positive.

Clinical Features

STO occurs in adults with a peak incidence in the fifth and sixth decades of life. This is in contrast with skeletal osteosarcoma that most commonly occurs in younger patients. The tumors typically arise in the deep soft tissues of the proximal extremities, most commonly the thigh and buttocks, where they present as a painless mass. Rarely, patients may have a history of prior therapeutic irradiation at the site of the tumor. Males are affected approximately twice as frequently as females.

Radiologic Features

Usually, the tumors present nonspecific imaging characteristics that appear only as soft tissue masses. Radiographically detectable mineralization is uncommon.

Pathologic Features

Gross Findings

STOs are usually large (often >10 cm), grossly heterogeneous tumors that exhibit regions of hemorrhage, necrosis or both ( Fig. 12.6 ). Like most soft tissue sarcomas, they may appear grossly circumscribed; however, they are microscopically infiltrative. Grossly detectable mineralized bone is not usually present.

Microscopic Findings

STOs are highly cellular, cytologically pleomorphic sarcomas ( Fig. 12.7A ). Most tumor cells are spindled to epithelioid in shape. The defining feature is the presence of neoplastic bone production. The bone usually outlines individual cells or clusters of cells in a “lace-like” manner; however, solid sheets of amorphous bone, with or without mineralization, may also be found ( Fig. 12.7B ). Bone production may only be focally present, and frequently the neoplasm has the appearance of an undifferentiated, spindle cell sarcoma. Lobules of highly cellular atypical cartilage may also be present ( Fig. 12.7C ). Any of the microscopic patterns seen in high-grade intraosseous osteosarcoma may be present in STO. Usually, the tumors demonstrate a high mitotic rate, including atypical mitotic figures. Necrosis may be prominent.

Differential Diagnosis

Most STOs are high-grade tumors, and because the bone production may be a focal finding, the differential diagnosis includes other high-grade spindle cell sarcomas. Particularly in its early cellular phase with relatively scant bone production, MO is usually readily distinguished from STO by the uniform reactive appearance of the proliferating myofibroblastic and osteoblastic cells. High-grade nuclear atypia and atypical mitoses are characteristic of STOs but absent in MO. Clinical features (see earlier) also are usually of help in the distinction between the two entities. Soft tissue recurrence or metastasis of skeletal osteosarcoma will appear histologically identical to STO and can be recognized only by the history. The diagnosis of STO also requires the exclusion of other distinct sarcoma types with heterologous osteosarcomatous differentiation, particularly dedifferentiated liposarcoma (DDLPS) and malignant peripheral nerve sheath tumor (MPNST). For the most part, the diagnosis of DDLPS depends on the identification of a pre-existing well-differentiated component, although there may occasionally be a role for immunohistochemistry or FISH to demonstrate MDM2 amplification. Similarly, identification of areas of more conventional spindle cell MPNST, as well as origin from pre-existing neurofibroma, is typically key to the diagnosis of MPNST with heterologous osteosarcomatous differentiation. Mesenchymal chondrosarcomas may show foci of bone production, but consist of monotonous round to spindled cells arrayed about a prominent branching vasculature. Demonstration of the HEY1-NCOA2 fusion is diagnostic of mesenchymal chondrosarcoma.

Prognosis and Treatment

STOs are high-grade tumors. Patients commonly present with metastatic disease, which accounts for the high mortality rate with these tumors. Treatment involves wide surgical resection and systemic chemotherapy.