Low-grade intraosseous osteosarcoma

Abstract

A study of 80 well-differentiated osteosarcomas, 16 from the Mayo Clinic files and 64 from our consultation files, revealed that males and females were about equally affected, most of the patients were young adults, and skeletal distribution was similar to the distribution seen in conventional osteosarcoma. Radiographs generally showed poor margination, suggestive of malignancy. Histologically, the tumors were composed of spindle cells with only minimal atypia. Some tumors had bone spicules similar to those seen in fibrous dysplasia. An invasive growth pattern was the most helpful feature in differentiating low-grade osteosarcoma from fibrous dysplasia. Initial treatment was highly variable. Local excision was almost always associated with recurrence. Wide excision was almost never followed by recurrence. The recurrent tumor was a high-grade, conventional osteosarcoma in 15% of the patients, and this was associated with a poor prognosis. Wide excision seems to be the treatment of choice for this very rare variant of osteosarcoma.

MDM2 and CDK4 immunohistochemistry is a valuable tool in the differential diagnosis of low-grade osteosarcomas and other primary fibro-osseous lesions of the bone

“…Approximately 80% of these tumors are located in the long bones, with a distinct predilection for the distal femur and proximal tibia. 1,3 The radiographic appearance of low-grade central osteosarcoma is highly variable at presentation, but the majority of these tumors will show some degree of cortical disruption, with or without extension to soft tissue. 1 Nevertheless, a significant number of these lesions may initially present a misleading radiographic appearance, suggestive of a benign lesion.…”

“…1 Eighteen percent of low-grade central osteosarcomas also have cartilage differentiation, seen as small scattered foci of atypical cartilage. 3 The clinical behavior of both parosteal osteosarcoma and low-grade central osteosarcoma is favorable and indistinguishable, with identical rates of local recurrence (7%) and 5-year survival above 80%. 2,5,6 The prognosis is mainly conditional on the risk of local recurrence after inadequate resection and dedifferentiation.…”

“…2 About 15-29% of low-grade osteosarcomas will show dedifferentiation. 1,3,7,10 Dedifferentiated low-grade osteosarcomas are defined by the presence of areas of undifferentiated spindle cells and/or pleomorphic sarcoma (ie, fibrosarcoma or malignant fibrous histiocytoma) or high-grade osteosarcoma. 3,7,10,11 Wide surgical excision is recommended for primary lesions, and adjuvant chemotherapy is reserved for dedifferentiated lesions.…”

“…5 Several studies have documented difficulties in the diagnosis of low-grade osteosarcoma. 2,3,8,9,12 Inability to diagnose the lesion correctly often leads to inadequate initial operative procedures. In two reviews of the literature, low-grade osteosarcomas were initially misdiagnosed as benign tumors in 32-60% of cases.…”

“…14 The differential diagnosis may include diverse entities such as fibrous dysplasia, non-ossifying fibroma, myositis ossificans, fracture callus, ossifying hematoma, osteochondroma, desmoplastic fibroma, osteoma and giant bone island. [2][3][4]6,12,15 Little information on low-grade osteosarcoma genetics is available in the literature. These tumors seem to share similarities in changes in cytogenetics and molecular genetics involving ring or giant marker chromosomes, which contain amplification of the 12q13-15 region, including murine doubleminute type 2 (MDM2) and cyclin-dependent kinase 4 (CDK4).…”