Giant cell tumours (GCT) of the synovium and tendon sheath can be classified into two forms: localised (giant cell tumour of the tendon sheath, or nodular tenosynovitis) and diffuse (diffuse-type giant cell tumour or pigmented villonodular synovitis). The former principally affects the small joints. It presents as a solitary slow-growing tumour with a characteristic appearance on MRI and is treated by surgical excision. There is a significant risk of multiple recurrences with aggressive diffuse disease. A multidisciplinary approach with dedicated MRI, histological assessment and planned surgery with either adjuvant radiotherapy or systemic targeted therapy is required to improve outcomes in recurrent and refractory diffuse-type GCT.

Although arthroscopic synovectomy through several portals has been advocated as an alternative to arthrotomy, there is a significant risk of inadequate excision and recurrence, particularly in the posterior compartment of the knee. For local disease partial arthroscopic synovectomy may be sufficient, at the risk of recurrence. For both local and diffuse intra-articular disease open surgery is advised for recurrent disease. Marginal excision with focal disease will suffice, not dissimilar to the treatment of GCT of tendon sheath. For recurrent and extra-articular soft-tissue disease adjuvant therapy, including intra-articular radioactive colloid or moderate-dose external beam radiotherapy, should be considered.

Chondrosarcomas are notorious for their resistance to conventional chemo- and radiotherapy, indicating there are no curative treatment possibilities for patients with inoperable or metastatic disease. We therefore explored the existence of molecular targets for systemic treatment of chondrosarcoma using kinome profiling. Peptide array was performed for 4 chondrosarcoma cell lines and 9 primary chondrosarcoma cultures. Acitivity of kinases was verified using immunoblot and active Src- and PDGFR signaling were further explored using imatinib and dasatinib on chondrosarcoma cell lines and primary cultures. The AKT1/GSK3B pathway was clearly active in chondrosarcoma. In addition, the PDGFR pathway and the Src kinase family were active. PDGFR and Src kinases can be inhibited by imatinib and dasatinib, respectively. While imatinib did not show any effect on chondrosarcoma cell cultures, dasatinib showed a decrease in cell viability at nanomolar concentrations in 3 out of 5 chondrosarcoma cultures. Whereas inhibition of phosphorylated Src (Y419) was found both in responsive and non-responsive cells, caspase-3 related apoptosis was found only in cell line GIST882, suggesting that the mechanism of decreased cell viability in chondrosarcoma by dasatinib is caspase-3 independent. In conclusion, using kinome profiling we found the Src pathway to be active in chondrosarcoma. Moreover, in the chondrosarcoma cell lines and primary cultures we showed that the inhibitor of the Src pathway, dasatinib, may provide a potential therapeutic benefit for chondrosarcoma patients which are not eligible for surgery

Diffuse-type Tenosynovial Giant-Cell Tumour (d-TGCT) of large joints is a rare, locally aggressive, soft tissue tumour affecting predominantly the knee. Previously classified as Pigmented Villonodular Synovitis (PVNS), this monoarticular disease arises from the synovial lining and is more common in younger adults. Given the diffuse and aggressive nature of this tumour, local control is often difficult and recurrence rates are high. Current literature is comprised primarily of small, and a few larger but heterogeneous, observational studies. Both arthroscopic and open synovectomy techniques, or combinations thereof, have been described for the treatment of d-TGCT of the knee. There is, however, no consensus on the best approach to minimize recurrence of d-TGCT of the knee. Some limited evidence would suggest that a staged, open anterior and posterior synovectomy might be of benefit in reducing recurrence. To our knowledge, no case series has specifically looked at the recurrence rate of d-TGCT of the knee following a staged, open, posterior and anterior approach. We hypothesized that this approach may provide better recurrence rates as suggested by larger more heterogeneous series. A retrospective review of the local pathology database was performed to identify all cases of d-TGCT or PVNS of the knee treated surgically at our institution over the past 15 years. All cases were treated by a single fellowship-trained orthopaedic oncology surgeon, using a consistent, staged, open, posterior and anterior approach for synovectomy. All cases were confirmed by histopathology and followed-up with regular repeat MRI to monitor for recurrence. Medical records of these patients were reviewed to extract demographic information, as well as outcomes data, specifically recurrence rate and complications. Any adjuvant treatments or subsequent surgical interventions were noted. Twenty-three patients with a minimum follow-up of two years were identified. Mean age was 36.3 at the time of treatment. There were 10 females and 13 males. Mean follow-up was seven and a half years. Fourteen of 23 (60.9%) had no previous treatment. Five of 23 had a previous arthroscopic synovectomy, one of 23 had a previous combined anterior arthroscopic and posterior open synovectomy, and three of 23 had a previous open synovectomy. Mean time between stages was 87 days (2.9 months). Seven of 23 (30.4%) patients had a recurrence. Of these, three of seven (42.9%) were treated with Imatinib, and four of seven (57.1%) were treated with repeat surgery (three of four arthroscopic and one of four open). Recurrence rates of d-TGCT in the literature vary widely but tend to be high. In our retrospective study, a staged, open, anterior and posterior synovectomy provides recurrence rates that are lower than rates previously reported in the literature. These findings support prior data suggesting this approach may result in better rates of recurrence for this highly recurrent difficult to treat tumour

Diffuse-type Tenosynovial Giant-Cell Tumour (d-TGCT) of large joints is a rare, locally aggressive, soft tissue tumour affecting predominantly the knee. Previously classified as Pigmented Villonodular Synovitis (PVNS), this monoarticular disease arises from the synovial lining and is more common in younger adults. Given the diffuse and aggressive nature of this tumour, local control is often difficult and recurrence rates are high. Current literature is comprised primarily of small, and a few larger but heterogeneous, observational studies. Both arthroscopic and open synovectomy techniques, or combinations thereof, have been described for the treatment of d-TGCT of the knee. There is, however, no consensus on the best approach to minimize recurrence of d-TGCT of the knee. Some limited evidence would suggest that a staged, open anterior and posterior synovectomy might be of benefit in reducing recurrence. To our knowledge, no case series has specifically looked at the recurrence rate of d-TGCT of the knee following a staged, open, posterior and anterior approach. We hypothesized that this approach may provide better recurrence rates as suggested by larger more heterogeneous series. A retrospective review of the local pathology database was performed to identify all cases of d-TGCT or PVNS of the knee treated surgically at our institution over the past 15 years. All cases were treated by a single fellowship-trained orthopaedic oncology surgeon, using a consistent, staged, open, posterior and anterior approach for synovectomy. All cases were confirmed by histopathology and followed-up with regular repeat MRI to monitor for recurrence. Medical records of these patients were reviewed to extract demographic information, as well as outcomes data, specifically recurrence rate and complications. Any adjuvant treatments or subsequent surgical interventions were noted. Twenty-three patients with a minimum follow-up of two years were identified. Mean age was 36.3 at the time of treatment. There were 10 females and 13 males. Mean follow-up was seven and a half years. Fourteen of 23 (60.9%) had no previous treatment. Five of 23 had a previous arthroscopic synovectomy, one of 23 had a previous combined anterior arthroscopic and posterior open synovectomy, and three of 23 had a previous open synovectomy. Mean time between stages was 87 days (2.9 months). Seven of 23 (30.4%) patients had a recurrence. Of these, three of seven (42.9%) were treated with Imatinib, and four of seven (57.1%) were treated with repeat surgery (three of four arthroscopic and one of four open). Recurrence rates of d-TGCT in the literature vary widely but tend to be high. In our retrospective study, a staged, open, anterior and posterior synovectomy provides recurrence rates that are lower than rates previously reported in the literature. These findings support prior data suggesting this approach may result in better rates of recurrence for this highly recurrent difficult to treat tumour

Soft tissue sarcomas (STS) include a spectrum of his-tologically and clinically different tumors. Patients are typically relatively young and the course of disease is characterized by early metastasis as well as limited response to chemotherapy. However, a few subtypes such as small round cell tumors (SRCTs) and rhabdomyosarcoma (except from pleomorphic), are considered chemotherapy-sensitive. In addition, reflecting successful translational research of recent years, gastrointestinal stromal tumor (GIST) and dermatofibrosarcoma protuberans have become model diseases for targeted oncological therapy. With a very limited number of active compounds at hand, treatment choices in metastatic STS with inkonsistent genomic alterations were easy to overview until only a few years ago. However, with novel therapeutic strategies such as the antiangiogenic approach and a multitude of novel compounds available both outside and within clinical studies, it may have become more difficult to keep track of currently available treatment options and their clinical safety and efficacy. Anthracyclines with or without ifosfamide are still considered standard of care in most STS-subtypes, especially in high-grade tumors. There is no evidence-based recommendation as to second-line treatment options. However, a number of established compounds, including dacarbazine/temozolomide, gemcitabine, taxanes, trofosfamide, DNA topoisomerase I inhibitors, DNA minor groove binders, and bendamustine, have shown activity. Recently, trabectedin, a DNA minor groove binder initially isolated from a sea sponge, has proven effective and received European approval for use in treatment-refractory STS. In addition, novel compounds such as bevacizumab, multityrosine kinase inhibitors, mTOR inhibitors, imatinib mesylate, and the thrombospondin agonist ABT 510 represent attractive partners for the above-mentioned cytostatic agents or may even be effective single agents in the clinically advanced setting. Novel combinations are being evaluated in clinical studies. In order to be successful, we may have to combine not only different compounds but also different targets beyond the proliferation machinery of sarcoma cells such as tumor angiogenesis, the tumor stromal compartment or tumor cell oncogene products

Aims

Tenosynovial giant cell tumour (TGCT) is one of the most common soft-tissue tumours of the foot and ankle and can behave in a locally aggressive manner. Tumour control can be difficult, despite the various methods of treatment available. Since treatment guidelines are lacking, the aim of this study was to review the multidisciplinary management by presenting the largest series of TGCT of the foot and ankle to date from two specialized sarcoma centres.

Desmoid tumours are a rare fibroblastic proliferation of monoclonal origin, arising in deep soft-tissues. Histologically, they are characterized by locally aggressive behaviour and an inability to metastasize, and clinically by a heterogeneous and unpredictable course. Desmoid tumours can occur in any anatomical site, but commonly arise in the limbs. Despite their benign nature, they can be extremely disabling and sometimes life-threatening, causing severe pain and functional limitations. Their surgical management is complex and challenging, due to uncertainties surrounding the biological and clinical behaviour, rarity, and limited available literature. Resection has been the first-line approach for patients with a desmoid tumour but, during the last few decades, a shift towards a more conservative approach has occurred, with an initial ‘wait and see’ policy. Many medical and regional forms of treatment are also available for the management of this condition, and others have recently emerged with promising results. However, many areas of controversy remain, and further studies and global collaboration are needed to obtain prospective and randomized data, in order to develop an appropriate shared stepwise approach.

Cite this article: Bone Joint J 2023;105-B(7):729–734.

Aims

The aim of this study was to evaluate health-related quality of life (HRQoL) and joint function in tenosynovial giant cell tumour (TGCT) patients before and after surgical treatment.

Pigmented villonodular synovitis (PVNS) is a rare benign neoplastic proliferation of synovial tissue which is typically localised and usually responds well to surgery and/or radiotherapy. We present a case of unusually aggressive of PVNS of the hip in a 73-year-old woman.

Dedifferentiated chordoma is a rare and aggressive variant of the conventional tumour in which an area undergoes transformation to a high-grade lesion, typically fibrous histiocytoma, fibrosarcoma, and rarely, osteosarcoma or rhabdomyosarcoma. The dedifferentiated component dictates overall survival, with smaller areas of dedifferentiation carrying a more favourable prognosis. Although it is more commonly diagnosed in recurrences and following radiotherapy, there have been a few reports of spontaneous development. We describe four such cases, which were diagnosed de novo following primary excision, and discuss the associated clinical and radiological features.

This article provides an overview of the role of genomics in sarcomas and describes how new methods of analysis and comparative screening have provided the potential to progress understanding and treatment of sarcoma. This article reviews genomic techniques, the evolution of the use of genomics in cancer, the current state of genomic analysis, and also provides an overview of the medical, social and economic implications of recent genomic advances.

Pigmented villonodular synovitis (PVNS) is a rare benign disease of the synovium of joints and tendon sheaths, which may be locally aggressive. We present 18 patients with diffuse-type PVNS of the foot and ankle followed for a mean of 5.1 years (2 to 11.8). There were seven men and 11 women, with a mean age of 42 years (18 to 73). A total of 13 patients underwent open or arthroscopic synovectomy, without post-operative radiotherapy. One had surgery at the referring unit before presentation with residual tibiotalar PVNS. The four patients who were managed non-operatively remain symptomatically controlled and under clinical and radiological surveillance. At final follow-up the mean Musculoskeletal Tumour Society score was 93.8% (95% confidence interval (CI) 85 to 100), the mean Toronto Extremity Salvage Score was 92 (95% CI 82 to 100) and the mean American Academy of Orthopaedic Surgeons foot and ankle score was 89 (95% CI 79 to 100). The lesion in the patient with residual PVNS resolved radiologically without further intervention six years after surgery. Targeted synovectomy without adjuvant radiotherapy can result in excellent outcomes, without recurrence. Asymptomatic patients can be successfully managed non-operatively. This is the first series to report clinical outcome scores for patients with diffuse-type PVNS of the foot and ankle.

Cite this article: Bone Joint J 2013;95-B:384–90.

Giant-cell tumour of the synovium is known to affect the fingers or toes of adults. It has seldom been described in the spine and rarely in the thoracic vertebrae or in a child. The lesions of giant-cell tumour of the synovium have a classical radiological appearance, but require a high index of suspicion for correct recognition. Unlike giant-cell tumour of the synovium at other well-known sites, spinal lesions lack the characteristic papillary architecture, thereby raising other diagnostic possibilities. We describe a giant-cell tumour of the synovium of the left facet joint of a thoracic vertebra in a nine-year-old girl. The tumour was treated successfully by surgical excision.