Cartilaginous and Osseous Soft Tissue Lesions

Clinical Features

Myositis ossificans, also known as myositis ossificans circumscripta , is an apparently nonneoplastic soft tissue lesion that occurs more commonly during the second and third decades of life, usually in physically active individuals. These lesions show a male predilection and most commonly occur within the skeletal muscles of the lower extremities, especially the thighs and buttocks ( Fig. 14.1 ). However, similar processes can also occur in adipose tissue (panniculitis ossificans) or fascia (fasciitis ossificans). In more than 50% of cases, a history of trauma is elicited; pain is a common and early complaint. A lesion indistinguishable from myositis ossificans has also been reported in the mesentery.

Heterotopic ossification is considered by some a synonym for myositis ossificans, perhaps a more mature, later phase of the latter process. Others consider heterotopic ossification an aberrant chondro-ossification of soft tissues caused by a variety of distinct disorders. McCarthy and Sundaram have provided a comprehensive review of the subject.

Pathologic Features

Histologically, myositis ossificans is a generally well-circumscribed lesion characterized by a central cellular spindle cell area, composed of (myo)fibroblasts with nodular fasciitis–like features associated with immature woven bone formation ( Fig. 14.2 ). Toward the periphery, the lesion displays more organized and mature lamellar bone formation ( Fig. 14.3 ). This progressive maturation from the center to the periphery is classically known as a “zoning” phenomenon and is essentially diagnostic of myositis ossificans. Foci of cartilage undergoing endochondral ossification are also commonly seen. Other findings include cystic degeneration, hemorrhage, and the presence of multinucleated osteoclast-like giant cells as well as other chronic inflammatory cells. The histologic features are nicely mirrored by the radiologic findings, which show a characteristic shell of bone with ring-like features and central lucency ( Fig. 14.4 ), usually after 3 to 4 weeks of evolution . As such, myositis ossificans is usually diagnosed at the radiologic level. Histologic analysis is typically required for sizable lesions or lesions with unusual radiologic features or clinical evolution.

Immunohistochemistry and Molecular Genetics

Currently there is no role for immunohistochemistry or genetic analysis for the diagnosis of myositis ossificans. By immunohistochemistry, the spindle cell component can express muscle-specific actin or smooth muscle actin.

Differential Diagnosis

The most important differential diagnosis for myositis ossificans is extraskeletal osteosarcoma. In contrast to myositis ossificans, extraskeletal osteosarcoma tends to occur in older patients and does not exhibit a “zoning” phenomenon; bone formation in extraskeletal osteosarcoma is more randomly distributed. Furthermore, marked nuclear pleomorphism and hyperchromasia are typical of extraskeletal osteosarcoma and should not be seen in myositis ossificans. Cystic degeneration and hemorrhage in myositis ossificans simulate the histologic features of soft tissue aneurysmal bone cyst. Fracture callus can occasionally be mistaken for myositis ossificans. This problem can easily be solved by good radiologic correlation (see earlier discussion).

Prognosis and Treatment

Myositis ossificans is a benign and self-limited condition. Surgery is usually not necessary except when secondary complications arise. Malignant transformation in myositis ossificans has been reported but remains a debatable subject.

Clinical Features

Fibro-osseous pseudotumor of the digits (FOPD), also known as florid reactive periostitis or a form of bone surface heterotopic ossification, is a poorly understood condition that closely simulates myositis ossificans. FOPD more commonly occurs around the proximal phalanx of the fingers of young women. Toes can sometimes be affected. Whether FOPD is reactive or neoplastic in nature remains controversial. Clinically, FOPD presents as a painful swelling of the subcutaneous tissues of the involved digit that simulates a neoplasm.

Pathologic Features

Histologically, FOPD is composed of a cytologically bland spindle cell proliferation with nodular fasciitis–like features associated with immature woven bone formation in a somewhat disorganized fashion ( Fig. 14.5 ). No zoning pattern is seen. Some authorities believe that the lesion is related to bizarre parosteal osteochondromatous proliferation (BPOP), which is among the most important differential diagnoses (see section “ Differential Diagnosis ”).

Immunohistochemistry and Molecular Genetics

FOPD has no distinctive immunohistochemical or molecular genetic signature.

Differential Diagnosis

The most important differential diagnosis for FOPD is BPOP, which is also attached to the bone surface and has recently been shown to be neoplastic in nature. In contrast to FOPD, BPOP is characterized by a hypercellular cartilaginous cap that matures into trabecular bone. The chondrocytes are enlarged and can be atypical, closely simulating the atypical chondrocytes in chondrosarcoma. However, a typical feature of BPOP is the presence of a peculiar basophilic calcification similar to that seen in aneurysmal bone cyst (“blue bone”) at the junction between the cartilaginous cap and the trabecular bone. Osteosarcoma (skeletal and extraskeletal) is another important diagnostic consideration but shows a much higher degree of cytologic atypia and pleomorphism. In addition, osteosarcoma is rare in the distal extremities. Subungual exostosis shows characteristic radiologic features and often displays a cartilaginous component that matures into trabecular-like bone.

Prognosis and Treatment

FOPD follows a benign clinical course but can recur locally. Surgical excision is the primary treatment.

Clinical Features

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder characterized by several skeletal malformations and progressive extraskeletal aberrant chondro-ossification. The clinical onset of FOP commonly occurs before the fifth year of life. The progressive soft tissue chondro-ossification develops initially around the upper paraspinal muscles and progresses distally and centripetally to the extremities.

Pathologic Features

The histologic features of FOP are relatively nonspecific and characterized by an initial fibroblastic proliferative phase that evolves over time to an aberrant ossification of muscles, adipose tissue, fascia, tendons, and other structures.

Molecular Genetics

FOP has recently been found to be caused by a constitutive activating mutation of the activin A receptor gene ( ACVR1 ; R206H), which encodes for bone morphogenetic protein type I receptor. This leads to aberrant signaling of this pathway and resultant progressive ectopic soft tissue osteochondrogenesis. Recently, hypoxic signaling via HIF-1α has been implicated in the development of both FOP and nonsyndromic heterotopic ossification.

Differential Diagnosis

The differential diagnosis of FOP is varied and includes any benign soft tissue osteocartilaginous lesion. A high degree of suspicion and a detailed clinical history are among the most important tools for reaching the correct diagnosis of FOP.

Prognosis and Treatment

Currently there is no specific treatment for FOP, and various attempts at pharmacologic approaches have shown limited success. The disease is progressive and ultimately leads to respiratory insufficiency and death due to involvement of the thoracic cage.

Clinical Features

Tumoral calcinosis is a nonneoplastic condition characterized by periarticular tumor-like calcium deposits most commonly surrounding the major joints, especially the hips, shoulders, and elbows. Unfortunately the nomenclature regarding tumoral calcinosis is confusing, and different authors adopt different classification schemes. Overall, tumoral calcinosis can be familial or sporadic, or it may occur as a secondary manifestation of a number of diseases or conditions (discussed further on). In the latter situation, the deposits can be referred to as tumoral calcinosis–like lesions to differentiate them from primary or familial tumoral calcinosis. Patients typically present during the first two decades of life and the lesions are often multicentric and bilateral. Tumor calcinosis is more common in black males.