Low-Grade Central Osteosarcoma (LGCOS)

Staging is according to bone sarcoma protocols (see TNM staging of tumors of bone). See also the information on staging in section Bone tumors: Introduction.

Amplification of 12q13-q15 involving MDM2 and CDK4 is common. MDM2 amplification is maintained in high-grade progression. A subset of LGCOSs lacks MDM2 amplification.

LGCOS is a large, relatively well-circumscribed, white rubbery fibrous tissue mass with gritty calcification, located in the medullary cavity.

LGCOS is composed of mildly to moderately cellular fascicles of spindle cells with mild nuclear atypia in a fibrosclerotic stroma. These are admixed with a neoplastic bone component, which typically consists of long and thick bony trabeculae, often with parallel arrangement, resembling parosteal osteosarcoma. Bone can be thinner and more irregular. Bone is typically woven, but it may be lamellar. Pagetoid bone with irregular cement lines may be present. Permeation of host bone is invariably present. Cortical destruction with soft tissue infiltration may also be present. Mitotic activity is low. Cartilage formation may be focally present. Some tumors focally lack bone matrix. In 10–36% of cases, LGCOS progresses to high-grade sarcoma. This phenomenon, known as dedifferentiation, may occur at presentation or in a recurrence. High-grade areas often show high-grade osteosarcoma histology indistinguishable from that of COS, with lace-like immature osteoid formation and higher cellularity, nuclear grade, and mitotic activity. High-grade areas may lack osteoid formation and resemble undifferentiated pleomorphic sarcoma or fibrosarcoma.

Not clinically relevant

LGCOS has a good prognosis when widely resected, with a metastatic rate of < 5% and 5-year and 10-year overall survival rates of 90% and > 80%, respectively. The tumor invariably recurs after curettage and incomplete excision. The presence of dedifferentiation confers a worse prognosis, and detecting such areas is therefore critical. It remains to be determined whether the volume of the dedifferentiated component may be prognostically significant. Chemotherapy is reserved for dedifferentiated tumors.

Testing for MDM2 amplification is helpful to differentiate LGCOS from benign mimics. Because MDM2 amplification is rare in COS, it may help separate dedifferentiated LGCOS from COS in the appropriate histological context. Unlike fibrous dysplasia, LGCOS lacks GNAS mutation. The lack of MDM2 amplification cannot exclude the diagnosis of LGCOS.

Essential: bone tumor with compatible imaging; intramedullary location; predominantly fibroblastic osteosarcoma with mild nuclear atypia and well-formed neoplastic bony trabeculae.

Desirable: MDM2 amplification.