Fibroblastic and Fibrohistiocytic Tumors

Clinical Features

Non-ossifying fibromas most commonly involve the distal femur and the proximal tibia, sites that account for 80% of lesions. The distal tibia, both ends of the fibula, and the distal radius may also be involved. The flat bones, the small bones of the hands and feet, the spine, and the craniofacial skeleton are generally not affected. Most non-ossifying fibromas are asymptomatic and discovered incidentally on radiographs taken for other reasons. Undoubtedly, many are never diagnosed, and the WHO estimates that 30%–40% of children develop one or even multiple lesions during skeletal maturation. Large non-ossifying fibromas may cause pain, and some patients present with pathologic fracture. Symptoms, when present, usually develop in patients in their mid-teens.

Radiologic Features

Non-ossifying fibromas are lobulated and lytic metaphyseal lesions. Characteristically, they are eccentric in the medullary cavity and juxtaposed to one cortex. In addition, the margins are scalloped, often grape-shaped, and well corticated ( Fig. 18.1 ). Non-ossifying fibromas in older patients often show intralesional radiodensities, a manifestation of remodeling ( Fig. 18.2 ). Small intracortical lesions (1–2 cm) have traditionally been termed fibrous cortical defects , a term that is no longer recommended by the current WHO classification ( Fig. 18.3 ). Some non-ossifying fibromas can reach >5 cm in maximum diameter and cause cortical expansion and, eventually, pathologic fracture ( Fig. 18.4 ).

Pathologic Features

Microscopic Findings

Non-ossifying fibromas consist of a monomorphic spindle cell proliferation with scattered small multinucleated giant cells, although the giant cells may be scarce. Characteristically, the spindle cells are arranged in a whorled or storiform pattern ( Fig. 18.5 ). Occasionally, the stroma is cellular, and the spindle cells often have plump uniform nuclei. In some larger lesions, a moderate number of typical mitotic figures are present. In addition to the giant and stromal cells, foam cells and occasional hemosiderin-laden macrophages are seen ( Figs. 18.6 and 18.7 ). Reactive bone formation is common, especially in older lesions. In the presence of a pathologic fracture, the tumor may show extensive areas of necrosis. Non-ossifying fibroma has no specific immunohistochemical profile.

Differential Diagnosis

Because non-ossifying fibromas consist of spindle cells admixed with multinucleated giant cells, giant cell tumor of bone may be considered in the differential diagnosis. However, giant cell tumors typically involve the epiphyseal portions of a bone. In contrast, non-ossifying fibromas are confined to the metaphases and shift towards the diaphysis during skeletal growth. Genetically, giant cell tumors harbor pathogenic H3-3A ( H3F3A ) mutations, of which the most common variant (p.G34W) can be detected immunohistochemically. This mutation is not present in non-ossifying fibroma.

The fibrous stroma of a non-ossifying fibroma frequently contains reactive woven bone formation. This combination of new bone and a fibrous stroma may lead to the misdiagnosis of fibrous dysplasia . However, the radiographic presentation of non-ossifying fibroma and fibrous dysplasia are very characteristic and distinct; fibrous dysplasia furthermore does not typically show storiform spindle cell proliferation or multinucleated giant cells.

Some non-ossifying fibromas may show increased cellularity and contain numerous mitotic figures. These features, in addition to tumors demonstrating areas of necrosis, may lead to the misdiagnosis of a malignant tumor . However, nuclear pleomorphism and atypical mitotic figures are never present in a non-ossifying fibroma. Moreover, the radiographic features are those of a benign, well-circumscribed lesion with a sclerotic rim, features not seen in malignant neoplasms.

Prognosis and Treatment

Non-ossifying fibroma is a self-limited lesion. Although rarely it may reach >5 cm in maximum diameter, tumors usually measure between 2 and 4 cm. Small, asymptomatic, non-ossifying fibromas require no treatment; most regress spontaneously during skeletal maturation, which is why non-ossifying fibromas are rarely discovered in adults. Larger lesions, particularly those that expand the cortex or those that present with pathologic fracture, are treated with curettage and bone grafting. Recurrence after treatment is rare.

Clinical Features

Desmoplastic fibroma has been reported in patients between the ages of 20 months and 60 years. However, most lesions occur in adolescents and young adults with peak incidence being between the ages of 15 years and 25 years. Patients complain of pain, often for several years, which suggests slow growth. On rare occasions, a desmoplastic fibroma may be an incidental finding. Any bone may be affected, but most lesions occur in the long bones (particularly the distal femur and proximal tibia), mandible and the pelvis.

Radiologic Features

Desmoplastic fibromas present as purely lytic lesions that characteristically show a multilobulated, expansile pattern ( Fig. 18.8 ). They are usually well defined and often have a bubbly appearance ( Fig. 18.9 ). When they occur in a long bone, they are centered in the metaphysis ( Fig. 18.10 ), occasionally extending into the epiphysis. The cortex is often focally eroded or disrupted, and a soft tissue mass, best visualized on magnetic resonance imaging (MRI), may be present. Approximately 10% of patients present with pathologic fracture. A helpful clue to the diagnosis of desmoplastic fibroma on MRI is that most lesions have a low to intermediate signal on T2-weighted images.

Pathologic Features

Microscopic Findings

Desmoplastic fibromas show a patternless growth pattern and are composed of benign-appearing spindle cells embedded within a densely collagenized stroma ( Fig. 18.11 ). If infiltration is seen, it is usually limited and at the periphery of the tumor. The lesional cells show bland, oval, or elongated nuclei, usually without nucleoli and resemble fibroblasts or myofibroblasts ( Fig. 18.12 ). Mitotic figures are rare; necrosis is typically absent. There can be morphologic overlap with desmoid type fibromatosis. Lesional bone formation is not a feature of desmoplastic fibroma.

Ancillary Studies

Differential Diagnosis

Fibrous dysplasia and central low-grade osteosarcoma can both present with only little matrix formation and may be confused with desmoplastic fibroma. However, careful attention to imaging studies can be helpful since desmoplastic fibroma is generally purely lytic as opposed to the mixed lytic/sclerotic or ground glass patterns of both differential diagnoses. The background of fibrous dysplasia appears less dense in collagen fibers; in equivocal cases, testing for GNAS mutations usually allows a definitive diagnosis. FISH analysis can identify MDM2 amplification in central low-grade osteosarcoma, but since only one-third of cases are positive, the differential diagnosis can remain challenging in selected cases.