Parosteal Osteosarcoma

The Union for International Cancer Control (UICC) TNM classification of malignant tumors does not recommend that the TNM staging system for bone tumors be applied to surface/juxtacortical osteosarcoma or juxtacortical chondrosarcoma. However, other staging systems, such as the American Joint Committee on Cancer (AJCC) TNM system, do include these tumors in the bone staging system. See also the information on staging in section Bone tumors: Introduction.

Parosteal osteosarcomas are cytogenetically characterized by one or more supernumerary ring chromosomes, often as the sole aberration. The chromosome number is typically near-diploid, and the tumors do not show the massive chromosomal rearrangements associated with high-grade osteosarcomas. The ring chromosomes contain amplified material from chromosomal region 12q13-q15. Potential target genes in these amplicons include MDM2 and CDK4, which are amplified in > 85% of the cases. The same genes may be amplified in high-grade osteosarcoma with ring chromosomes, but the overall frequency of amplification is about 10% in conventional high-grade osteosarcomas, some of which may represent unrecognized dedifferentiated low-grade osteosarcomas. Gene amplification is usually accompanied by increased expression of MDM2 and CDK4 at the RNA and protein levels.

Parosteal osteosarcoma presents as an exophytic, lobulated mass, typically attached to the underlying cortex by a broad base. Large tumors may encircle the involved bone. Satellite nodules may be noted, particularly in recurrent lesions. The cut surface shows a tan-white tumor with a hard gritty texture. Nodules of cartilage may be present. Occasionally, the cartilage may form an incomplete cartilage cap on the outer surface, simulating an osteochondroma. Penetration of the underlying cortex with or without invasion into the medullary cavity may be seen. Soft and fleshy areas, if present, suggest dedifferentiation of the tumor. Focal necrosis, hemorrhage, and fluid cavities may be present.

Parosteal osteosarcoma is composed of well-formed bone trabeculae with intervening fascicles of spindle cells. Typically, the tumor is hypocellular with minimal atypia and low mitotic activity. At the periphery of the tumor, the spindle cell component may show invasion into the adjacent skeletal muscle. Some tumors may resemble desmoplastic fibroma because of focal lack of bone formation. In about 20% of the cases, the tumor is more cellular and the spindle cells show moderate atypia. The bone trabeculae are arranged mostly in a parallel fashion and may or may not show osteoblastic rimming. Some tumors contain irregular anastomosing and curved bone trabeculae, simulating woven bone in fibrous dysplasia. Approximately 50% of cases display cartilaginous differentiation, in the form of small scattered nodules or a cartilaginous cap. Progression to high-grade sarcoma, which can also be referred to as dedifferentiation, occurs in 15–43% of cases, either at presentation or (more often) at the time of recurrence. The high-grade component can be osteosarcoma or undifferentiated spindle cell sarcoma, or very rarely rhabdomyosarcoma.

Not clinically relevant

The prognosis is excellent, with a 90% overall survival rate at 5 years. For pure low-grade tumors, wide surgical excision is curative. Incomplete resection results in local recurrence. Metastasis, usually a late phenomenon, occurs rarely in low-grade tumors, whereas dedifferentiated tumors metastasize at a high rate, leading to a poor prognosis. Chemotherapy is reserved for dedifferentiated tumors.

FISH for MDM2 amplification is more sensitive and specific than immunohistochemistry.

Essential: bone tumor with compatible imaging; parosteal location; low-grade spindle cell tumor with woven bone formation.

Desirable: MDM2 amplification.