Extraskeletal Osteosarcoma

Union for International Cancer Control (UICC) and American Joint Committee on Cancer (AJCC) TNM staging can be applied.

Conventional karyotyping has shown clonal chromosomal and highly complex aberrations. Recurrent copy-number losses in tumor suppressor genes (CDKN2A, TP53, RB1, PTEN, NF1, LSAMP); gains and amplifications in oncogenes (RUNX2, CDC5L, COPS3, EGFR, MDM2, CDK4, PMP22); mutations involving tumor suppressor genes (TP53, PTEN, RB1, NF1, SMARCA4), chromatin-remodeling genes (ATRX, DAXX, BRCA1, DAXX2, CHEK2, ARID5B), histone methylation and demethylation genes (BCOR, DNMT3A, MKK3 [MAP2K3]), and WNT/β-catenin and sonic hedgehog pathway genes (AMER1, AXIN2, GSK3B, GLI1, NOTCH3); and in some cases TERT promoter mutation and PIK3CA mutations have been reported. The genomic signature of this tumor shows features overlapping those of conventional skeletal osteosarcoma.

These tumors range in size from 1 to 50 cm (mean: 8–10 cm) and vary considerably in gross appearance; many tumors are circumscribed, tan-white, hemorrhagic, and focally necrotic gritty masses. Extensive hemorrhagic cystic change is present in a minority of cases.

Extraskeletal osteosarcoma shows an extremely broad spectrum of morphology, and all the major histological patterns of osteosarcoma in bone can be seen. The osteoblastic type is the most common. In general, the tumors are composed of spindle or polygonal cells that are variously pleomorphic, cytologically atypical, and mitotically active and frequently demonstrate atypical mitotic figures. Tumor necrosis is also a common feature.

Identification of the neoplastic bone intimately associated with tumor cells, which may be deposited in lace-like, trabecular, or sheet-like patterns, is necessary for diagnosis. SATB2 immunoreactivity could be useful to detect osteoblastic differentiation when immature osteoid is difficult to distinguish from collagenous stroma. The amount and distribution of the neoplastic bone vary from tumor to tumor and even between different portions of the same tumor. The bone is sometimes more prominent in the center of the tumor, with the more densely cellular areas located in the periphery, a pattern that is the reverse of myositis ossificans.

The rare well-differentiated subtype contains abundant bone deposited in well-formed trabeculae, surrounded by a minimally atypical spindle cell component similar to parosteal osteosarcoma; high-grade transformation or dedifferentiation has been reported in several cases.

Cytologically, a hypercellular smear consists of mostly individually dispersed and small clusters of atypical cells. Most cases could be recognized as malignant, and fragments of osteoid-like matrix material might be observed in association with the individual cells and cell clusters.

The prognosis is usually poor, and recent large series reported the 5-year overall survival rate to be 37–52%. Distant metastasis, old age (> 60 years), large tumor size (> 10 cm), and positive margin status were associated with poor prognosis in more than one study.

Not clinically relevant

Essential: no connection to the skeletal system; identification of neoplastic bone/osteoid in association with malignant cells in otherwise unclassified soft tissue sarcoma.