Besides conventional chondrosarcoma, several rare chondrosarcoma subtypes are described, comprising about 15% of all chondrosarcomas. Clear cell chondrosarcoma (CCS) is a low-grade malignant tumour, often recurring after curettage, and showing overall survival of about 85%. Mesenchymal chondrosarcoma (MCS) is a highly malignant tumour occurring in bone and soft tissue of relatively young patients. The tumour shows differentiated cartilage mixed with undifferentiated small round cells. It often metastasises and shows a 5-year overall survival of 55%. Dedifferentiated chondrosarcoma (DDCS) is a tumour containing a high-grade non-cartilaginous sarcoma (DD), and a usually low-grade malignant cartilage-forming tumour (WD). The prognosis is poor. The lack of efficacious treatment of these rare tumours emphasises the need to learn more about their characteristics and to unravel potential targets for therapy. We constructed tissue microarrays (TMAs) with 2mm cores of 45 DDCS (WD and DD), 24 CCS, and 25 MCS, in triplicate. Using immunohistochemistry, we investigated protein expression of estrogen-signaling molecules, growth plate-signaling molecules, and other molecules which might be potential targets for therapy. In addition, we gathered genomic information using Agilent 44K oligo arrays. 30% of the WD components were positive for Cox-2. Almost all others were negative. For Bcl2, 88% of the small cells and 32% of the cartilage in MCS were positive. In CCS, WD, and DD 48%, 4%, and 12% were positive, respectively. We demonstrated the presence of ESR1 and aromatase protein in the majority of tumours in all subtypes. Using array CGH, we observed similar aberrations in the two components of DDCS, with additional aberrations in the DD. Celecoxib treatment is not recommended, as most of the tumours are negative for Cox-2. However, the presence of ESR1 and aromatase support a possible effect of anti-estrogen treatment in all subtypes, and application of Bcl2 inhibitors might chemosensitise MCS.
Giant cell tumour of bone (GCTB) is a primary tumour of bone characterised by a proliferation of mononuclear stromal cells and infiltrating macrophages and osteoclast-like giant cells. GCTB has a variable and unpredictable course and can produce metastatic lesions, mostly in the lungs, in up to 3% of cases. Whether these represent tumour implants rather than true neoplastic secondaries is uncertain. In this study, we analysed morphological and immunophenotypic features of primary GCTBs which metastasised to the lung as well as the metastatic lesions themselves in order to determine if these would provide a clue as to the mechanism of lung metastasis in GCTB. 17 cases of primary GCTB which metastasised to the lung and the lung metastases in these cases were obtained from IOR, Bologna. Morphologically, primary tumours showed variable features, often containing both giant cell-rich and mononuclear stromal cell-rich areas. Mononuclear cells showed frequent mitotic activity and a degree of nuclear pleomorphism; none of the tumours showed cytological features of malignancy. The tumours were highly vascular and frequently contained dilated thin-walled blood vessels and large areas of haemorrhage. GCTB lung metastases were generally small and contained osteoclast-like giant cells and mononuclear stromal cells which showed typical mitotic activity; cytologically, the metastatic tumours were relatively bland and showed little nuclear pleomorphism. Expression of HLA-DR (an allele of which has been associated with a more aggressive GCTB phenotype) and smooth muscle actin (SMA) was noted in stromal cells in primary and secondary GCTBs; frequently, the same pattern of SMA expression was seen in both primary and secondary lesions. Osteoclasts were vitronectin receptor+, CD14-HLA-DR- in both primary and secondary GCTBs. Our findings indicate that mononuclear stromal cells in lung metastases of GCTB often recapitulate the immunophenotype of the primary tumours from which they derive. Taken with the morphological finding that many primary GCTBs are highly vascular and contain areas of haemorrhage, it is possible that the lung “secondaries” of GCTB more likely represent tumour implants than true neoplastic metastases.
