Robin Pollock

IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours.

Somatic mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 occur in gliomas and acute myeloid leukaemia (AML). Since patients with multiple enchondromas have occasionally been reported to have these conditions, we hypothesized that the same mutations would occur in cartilaginous neoplasms. Approximately 1200 mesenchymal tumours, including 220 cartilaginous tumours, 222 osteosarcomas and another ∼750 bone and soft tissue tumours, were screened for IDH1 R132 mutations, using Sequenom® mass spectrometry. Cartilaginous tumours and chondroblastic osteosarcomas, wild‐type for IDH1 R132, were analysed for IDH2 (R172, R140) mutations. Validation was performed by capillary sequencing and restriction enzyme digestion. Heterozygous somatic IDH1/IDH2 mutations, which result in the production of a potential oncometabolite, 2‐hydroxyglutarate, were only detected in central and periosteal cartilaginous tumours, and were found in at least 56% of these, ∼40% of which were represented by R132C. IDH1 R132H mutations were confirmed by immunoreactivity for this mutant allele. The ratio of IDH1:IDH2 mutation was 10.6 : 1. No IDH2 R140 mutations were detected. Mutations were detected in enchondromas through to conventional central and dedifferentiated chondrosarcomas, in patients with both solitary and multiple neoplasms. No germline mutations were detected. No mutations were detected in peripheral chondrosarcomas and osteochondromas. In conclusion, IDH1 and IDH2 mutations represent the first common genetic abnormalities to be identified in conventional central and periosteal cartilaginous tumours. As in gliomas and AML, the mutations appear to occur early in tumourigenesis. We speculate that a mosaic pattern of IDH‐mutation‐bearing cells explains the reports of diverse tumours (gliomas, AML, multiple cartilaginous neoplasms, haemangiomas) occurring in the same patient. Copyright

Non-invasive distal femoral expandable endoprosthesis for limb-salvage surgery in paediatric tumours

We report our early experience with the use of a non-invasive distal femoral expandable endoprosthesis in seven skeletally immature patients with osteosarcoma of the distal femur. The patients had a mean age of 12.1 years (9 to 15) at the time of surgery. The prosthesis was lengthened at appropriate intervals in outpatient clinics, without anaesthesia, using the principle of electromagnetic induction. The patients were functionally evaluated using the Musculoskeletal Tumour Society scoring system. The mean follow-up was 20.2 months (14 to 30). The prostheses were lengthened by a mean of 25 mm (4.25 to 55) and maintained a mean knee flexion of 110 degrees (100 degrees to 120 degrees ). The mean Musculoskeletal Tumour Society score was 68% (11 to 29). Complications developed in two patients; one developed a flexion deformity of 25 degrees at the knee joint, which was subsequently overcome and one died of disseminated disease. The early results from patients treated with this device have been encouraging. The implant avoids multiple surgical procedures, general anaesthesia and assists in maintaining leg-length equality.

Elastofibroma dorsi: management, outcome and review of the literature

Elastofibroma dorsi is an uncommon, benign, slow-growing soft-tissue tumour of uncertain aetiology. It classically presents as an ill-defined mass at the inferior pole of the scapula with symptoms which include swelling, discomfort, snapping, stiffness and occasionally pain. We report the symptoms, function and outcome after treatment of 21 elastofibromas in 15 patients. All were diagnosed by MRI and early in the series four also underwent CT-guided biopsy to confirm the diagnosis. In all, 18 tumours were excised and three were observed. After excision, the mean visual analogue score for pain decreased from 4.6 (0 to 10) pre-operatively to 2.4 (0 to 8) post-operatively (p = 0.04). The mean shoulder function, at a mean follow-up of 4.2 years (3 months to 16 years), was 78.1% (30 to 100) using the Stanmore percentage of normal shoulder assessment scoring system. The mean range of forward flexion improved from 135 degrees (70 degrees to 180 degrees ) to 166 degrees (100 degrees to 180 degrees ) after excision (p = 0.005). In four patients a post-operative haematoma formed; one required evacuation. Three patients developed a post-operative seroma requiring needle aspiration and one developed a superficial infection which was treated with antibiotics. Our findings support previous reports suggesting that a pre-operative tissue diagnosis is not necessary in most cases since the lesion can be confidently diagnosed by MRI, when interpreted in the light of appropriate clinical findings. Surgical excision in symptomatic patients, is helpful. It has been suggested that elastofibroma is caused by a local tissue reaction and is not a true neoplastic process. A strong association has been noted between elastofibroma and repetitive use of the shoulder, which is supported by our findings.

Outcome of intralesional curettage for low-grade chondrosarcoma of long bones

BACKGROUND Different treatment strategies for low-grade chondrosarcomas are reported in the literature with variable outcomes. The aim of this study was to assess the oncological and functional outcomes associated with intralesional curettage and cementation of the lesion as a treatment strategy. PATIENTS AND METHODS We performed a retrospective review of 39 consecutive patients with intramedullary low-grade chondrosarcoma of long bones treated by intralesional curettage and cementation at our institution between 1999 and 2005. RESULTS There were 10 males and 29 females with a mean age of 55.5 years (32-82), and a mean follow-up of 5.1 years (3-8.7). Local recurrence occurred in two patients (5%) within the first two years following index surgery. Both were treated by re-curettage and cementation of the resultant defects. A second local recurrence developed a year later in one of these two patients, for which a further curettage followed by local liquid nitrogen treatment was performed. Overall, there were no cases of post-operative complications or metastases. The patients were assessed using the Musculoskeletal Tumour Society scoring system (MSTS) to determine limb function. The average score achieved was 94% (79-100%). CONCLUSION Intralesional curettage is an effective treatment strategy for low-grade intramedullary chondrosarcoma of long bones, with excellent oncological and functional results. Careful case selection with stringent clinical and radiographic follow-up is recommended.

Femoral diaphyseal endoprosthetic reconstruction after segmental resection of primary bone tumours

Segmental resection of malignant bone disease in the femoral diaphysis with subsequent limb reconstruction is a major undertaking. This is a retrospective review of 23 patients who had undergone limb salvage by endoprosthetic replacement of the femoral diaphysis for a primary bone tumour between 1989 and 2005. There were 16 males and seven females, with a mean age of 41.3 years (10 to 68). The mean overall follow-up was for 97 months (3 to 240), and 120 months (42 to 240) for the living patients. The cumulative patient survival was 77% (95% confidence interval 63% to 95%) at ten years. Survival of the implant, with failure of the endoprosthesis as an endpoint, was 85% at five years and 68% (95% confidence interval 42% to 92%) at ten years. The revision rate was 22% and the overall rate of re-operation was 26%. Complications included deep infection (4%), breakage of the prosthesis (8%), periprosthetic fracture (4%), aseptic loosening (4%), local recurrence (4%) and metastases (17%). The 16 patients who retained their diaphyseal endoprosthesis had a mean Musculoskeletal Tumour Society score of 87% (67% to 93%). They were all able to comfortably perform most activities of daily living. Femoral diaphyseal endoprosthetic replacement is a viable option for reconstruction following segmental resection of malignant bone disease. It allows immediate weight-bearing, is associated with a good long-term functional outcome, has an acceptable complication and revision rate and, most importantly, does not appear to compromise patient survival.

Intercalary diaphyseal endoprosthetic reconstruction for malignant tibial bone tumours

The best method of reconstruction after resection of malignant tumours of the tibial diaphysis is unknown. In the absence of any long-term studies analysing the results of intercalary endoprosthetic replacement, we present a retrospective review of 18 patients who underwent limb salvage using a tibial diaphyseal endoprosthetic replacement following excision of a malignant bone tumour. There were ten men and eight women with a mean age of 42.5 years (16 to 76). Mean follow-up was 58.5 months (20 to 141) for all patients and 69.3 months (20 to 141) for the 12 patients still alive. Cumulative patient survival was 59% (95% confidence interval (CI) 32 to 84) at five years. Implant survival was 63% (95% CI 35 to 90) at ten years. Four patients required revision to a proximal tibial replacement at a mean follow-up of 29 months (10 to 54). Complications included metastases in five patients, aseptic loosening in four, peri-prosthetic fracture in two, infection in one and local recurrence in one. The mean Musculoskeletal Tumor Society score and the mean Toronto Extremity Salvage Score were 23 (17 to 28) and 74% (53 to 91), respectively. Although rates of complication and revision were high, custom-made tibial diaphyseal replacement following resection of malignant bone tumours enables early return to function and provides an attractive alternative to other surgical options, without apparent compromise of patient survival.

Long-term survival of cemented distal femoral endoprostheses with a hydroxyapatite-coated collar: a histological study and a radiographic follow-up.

BACKGROUND The objective of this study was to examine the degree of osteointegration into a hydroxyapatite-coated collar and relate this finding to aseptic loosening in patients with a distal femoral replacement used to treat primary bone cancer. Our hypothesis was that the implant collar would increase osteointegration and reduce the rate of aseptic implant loosening. METHODS Sixty-one patients treated with a primary cemented distal femoral prosthesis between 1992 and 2001 were included in this study. The mean duration of follow-up was 8.5 years (range, two to eighteen years). Extracortical bone growth into the grooved hydroxyapatite-coated collar was quantified radiographically. Histological sections through four hydroxyapatite-coated collars and four implants with no collar, retrieved following amputation due to local recurrence or at autopsy at a mean of 3.5 years (range, 1.4 to 6.1 years) after implantation, were evaluated as well. RESULTS Five (8%) of the implants were revised because of aseptic loosening, 3% of the implants fractured, and 3% were revised because of infection. Six limbs (10%) required amputation because of local tumor recurrence. On radiographs, osteointegration into the collar was seen to have occurred in 70% of the patients and did not correlate with sex, age, diagnosis, or length of time postoperatively. Histological analysis showed mature lamellar bone within the grooves of the hydroxyapatite-coated collar, and bone was observed in direct contact with the hydroxyapatite coating. Extracortical bone failed to make direct contact with the surface of the implants manufactured without a collar. CONCLUSIONS The use of cemented distal femoral massive bone tumor prostheses with a hydroxyapatite-coated collar located at the shoulder of the implant was followed by a low (8%) rate of revision due to aseptic loosening. The use of hydroxyapatite grooved collars may lead to osteointegration of the implant shoulder (collar) and may reduce the rate of aseptic loosening.

The clinical significance of the FUS-CREB3L2

BackgroundLow-grade fibromyxoid sarcoma (LGFMS) is a rare soft-tissue neoplasm with a deceptively benign histological appearance. Local recurrences and metastases can manifest many years following excision. The FUS-CREB3L2 gene translocation, which occurs commonly in LGFMS, may be detected by reverse-transcriptase polymerase chain reaction (RT-PCR) and fluorescence in situ hybridisation (FISH). We assessed the relationship between clinical outcome and translocation test result by both methods.MethodsWe report genetic analysis of 23 LGFMS cases and clinical outcomes of 18 patients with mean age of 40.6 years. During follow-up (mean 24.8 months), there were no cases of local recurrence or metastasis. One case was referred with a third recurrence of a para-spinal tumour previously incorrectly diagnosed as a neurofibroma.ResultsResults showed 50% of cases tested positive for the FUS-CREB3L2 translocation by RT-PCR and 81.8% by FISH, suggesting FISH is more sensitive than RT-PCR for confirming LGFMS diagnosis. Patients testing positive by both methods tended to be younger and had larger tumours. Despite this, there was no difference in clinical outcome seen during short and medium-term follow-up.ConclusionsRT-PCR and FISH for the FUS-CREB3L2 fusion transcript are useful tools for confirming LGFMS diagnosis, but have no role in predicting medium-term clinical outcome. Due to the propensity for late recurrence or metastasis, wide excision is essential, and longer-term follow-up is required. This may identify a difference in long-term clinical outcome between translocation-positive and negative patients.

Bizarre parosteal osteochondromatous proliferation of bone: CLINICAL MANAGEMENT OF A SERIES OF 22 CASES

We describe 22 cases of bizarre parosteal osteochondromatous proliferation, or Noras lesion. These are surface-based osteocartilaginous lesions typically affecting the hands and feet. All patients were identified from the records of a regional bone tumour unit and were treated between 1985 and 2009. Nine lesions involved the metacarpals, seven the metatarsals, one originated from a sesamoid bone of the foot and five from long bones (radius, ulna, tibia, and femur in two). The mean age of the patients was 31.8 years (6 to 66), with 14 men and eight women. Diagnosis was based on the radiological and histological features. The initial surgical treatment was excision in 21 cases and amputation of a toe in one. The mean follow-up was for 32 months (12 to 162). Recurrence occurred in six patients (27.3%), with a mean time to recurrence of 49 months (10 to 120). Two of the eight patients with complete resection margins developed a recurrence (25.0%), compared with four of 14 with a marginal or incomplete resection (28.6%). Given the potential surgical morbidity inherent in resection, our data suggest that there may be a role for a relatively tissue-conserving approach to the excision of these lesions.

A knee-sparing distal femoral endoprosthesis using hydroxyapatite-coated extracortical plates: PRELIMINARY RESULTS

We used a knee-sparing distal femoral endoprosthesis in young patients with malignant bone tumours of the distal femur in whom it was possible to resect the tumour and to preserve the distal femoral condyles. The proximal shaft of the endoprosthesis had a coated hydroxyapatite collar, while the distal end had hydroxyapatite-coated extracortical plates to secure it to the small residual femoral condylar fragment. We reviewed the preliminary results of this endoprosthesis in eight patients with primary bone tumours of the distal femur. Their mean age at surgery was 17.years (14 to 21). The mean follow-up was 24 months (20 to 31). At final follow-up the mean flexion at the knee was 102 degrees (20 degrees to 120 degrees) and the mean Musculoskeletal Tumour Society score was 80% (57% to 96.7%). There was excellent osteointegration at the prosthesis-proximal bone interface with formation of new bone around the hydroxyapatite collar. The prosthesis allowed preservation of the knee and achieved a good functional result. Formation of new bone and remodelling at the interface make the implant more secure. Further follow-up is required to determine the long-term structural integrity of the prosthesis.