Aim. To report late development of sarcomas on sites of previously curetted and grafted benign tumours. Rare cases of development of sarcomas in sites of previous benign lesions are documented, and the development is generally considered secondary to progression of benign lesions, even without radiotherapy. Methods and Results. In our files, 12 cases curetted and grafted, without radiotherapy addition developed sarcomas from 6 to 28 years from curettage (median 18). Age at first diagnosis (9 GCT, 1 benign fibrous histiocytoma, ABC and solitary bone cyst) ranged from 13 to 55 (median 30). For all cases radiographic and clinic documentation was available. Histology was available for 7 of the benign lesions and for all malignant lesions. The type of bone used to fill cavities was autoplastic in 4 cases, homoplastic in 2 cases, homoplastic and tricalciumphosphate/hydrossiapatite in 1 case, autoplastic and homoplastic in 1 cases, heteroplastic in 1 case. In 3 cases the origin was not reported. Secondary sarcomas, all high grade, were 8 OS, 3 MFH, and 1 fibrosarcoma. Conclusions. It is impossible to calculate the exact incidence of this transformation, but from a comparison with 137 secondary sarcomas treated in the same years (1975-2005) at the Rizzoli Institute, it is similar to the risk of a sarcoma on fibrous dysplasia or lower than a sarcoma on bone infarcts or on Paget's disease. Recurrence with progression from benign tumours can occur, but the very long intervals reported in the present series suggest a possible different pathogenesis. Recent preclinical papers report development of sarcoma in mice after transplantation of mesenchymal stem cells, independently from the type of scaffold used. The fact that reparative proliferative changes occuring in the area of dead bone, with stimulation of mesenchymal stem cells, could cause malignant transformation, is a new hypothesis

SSX was initially identified as a melanoma associated tumour antigen MEL2 and in the SS18/SSX fusion gene of synovial sarcoma. It consists of a family of nine, highly homologous X chromosome genes, being SSX1, SSX2 and SSX4 the most commonly expressed in tumours. In normal tissue, SSX expression is restricted to germ cells, trophoblasts, and mesenchymal stem cells. In malignant cells, SSX expression is over-represented in sarcomas. SSX expression is epigenetically regulated by methylation and histone deacetylation. Aim. To investigate the oncogenic properties of SSX. Validate it as tumour target and identify lead compounds. Methods. RNAi system for conditional silencing of SSX expression, Protein analysis and Mass Spec, PCR arrays, tumour xenographs and drug library screening. Results. SSX expression peaks at the G1/S phase of the cell cycle where it interacts with histone H3, H4 and β-catenin. This interaction promotes the phosphorylation of β-catenin at tyrosine residues and the transactivation of β-catenin genes MMP2 and cyclin D1. The association of SSX and MMP2 expression resulted in an increased invasion capacity of tumour cells. In vivo, silencing of SSX in tumour xenographs significantly affected the tumour growth. These tumours were characterized by large necrotic areas, impaired vascularization and cytoplasmic β-catenin. In contrast, tumour xenographs expressing SSX were highly proliferative, vascularized and exibited nuclear β-catenin. We further screened a chemical library and have identified lead compounds that target SSX. Conclusion. Our results demonstrate that SSX is a tumour target for drug development. We hypothesise that drugs targeting of SSX could affect functions related with the mesenchymal cell phenotype having potential cytostatic effect in sarcomas and/or epithelial tumour cells that undergo a epithelial-to-mesenchymal transition prior to metastasis

Aims

Bone metastasis ultimately occurs due to a complex multistep process, during which the interactions between cancer cells and bone microenvironment play important roles. Prior to colonization of the bone, cancer cells must succeed through a series of steps that will allow them to gain migratory and invasive properties; epithelial-to-mesenchymal transition (EMT) is known to be integral here. The aim of this study was to determine the effects of G protein subunit alpha Q (GNAQ) on the mechanisms underlying bone metastasis through EMT pathway.

Aims

Massive endoprostheses rely on extra-cortical bone bridging (ECBB) to enhance fixation. The aim of this study was to investigate the role of selective laser sintered (SLS) porous collars in augmenting the osseointegration of these prostheses.

We investigated the clinical outcome of internal fixation for pathological fracture of the femur after primary excision of a soft-tissue sarcoma that had been treated with adjuvant radiotherapy.

A review of our database identified 22 radiation-induced fractures of the femur in 22 patients (seven men, 15 women). We noted the mechanism of injury, fracture pattern and any complications after internal fixation, including nonunion, hardware failure, secondary fracture or deep infection.

The mean age of the patients at primary excision of the tumour was 58.3 years (39 to 86). The mean time from primary excision to fracture was 73.2 months (2 to 195). The mean follow-up after fracture fixation was 65.9 months (12 to 205). Complications occurred in 19 patients (86%). Nonunion developed in 18 patients (82%), of whom 11 had a radiological nonunion at 12 months, five a nonunion and hardware failure and two an infected nonunion. One patient developed a second radiation-associated fracture of the femur after internal fixation and union of the initial fracture. A total of 13 patients (59%) underwent 24 revision operations.

Internal fixation of a pathological fracture of the femur after radiotherapy for a soft-tissue sarcoma has an extremely high rate of complication and requires specialist attention.

Cite this article: Bone Joint J 2013;95-B:1144–8.