Non-invasive sampling of tumor-derived genetic material in circulation through liquid biopsy may be very beneficial for an accurate diagnosis and evaluation of response to treatment in patients with malignant and benign soft tissue tumors. We previously showed that tumor-derived genomic aberrations can be detected in plasma of patients with leiomyosarcoma (LMS) and leiomyoma (LM). In LMS patients, we also showed that the levels of circulating tumor DNA (ctDNA) correspond with response to treatment. We developed an approach tailored to genomic profile of LMS (characterized by intermediate levels of point mutations and copy number alterations, CNAs). Based on TCGA data, we designed a panel of 89 most frequently mutated genes in LMS, which we profiled in plasma DNA by deep sequencing. In parallel, plasma samples were analyzed by shallow whole genome sequencing for detection of CNAs. With this approach, we detected ctDNA in 71% (20/28) of samples from 6/7 patients with advanced disease with >98% specificity. The combination approach for orthogonal profiling of point mutations and CNAs proved to increase the sensitivity of ctDNA detection. Currently, we seek to further improve the sensitivity of ctDNA detection by refining our capture panel and tracking LMS-specific DNA methylation markers in circulation, in addition to point mutations and CNAs. The ultimate goals of our ctDNA studies are 1) to develop a highly sensitive assay for evaluation of response to therapy and long-term surveillance for patients with LMS, and 2) to develop a blood-based test for accurate pre-operative distinction between LMS and LM. To identify LMS-specific DNA methylation markers, we analyzed a test cohort of 76 LM, 35 uterine LMS and 31 extra-uterine LMS by Illumina Infinium EPIC arrays. We identified differentially methylated CpGs between LM and uterine LMS, and between LM and all LMS using a newly developed custom pipeline in R. The results of this analysis are currently being validated in a new dataset of 41 LM and 153 LMS generated by our group. Recently published (PMID: 34301934) genomic data from new 53 LMS samples are used to refine the panel of the most frequently mutated genes that we identified previously in the LMS TCGA data. Our preliminary analysis of test cohort revealed >270 differentially methylated CpGs between LM and uterine LMS, and >1000 differentially methylated CpGs between LM and all LMS. The preliminary analysis of genomic data shows that the initial panel of 89 frequently mutated genes could be substantially narrowed down to cover only selected tumor suppressor genes. Once validated, these results will be used to refine the ctDNA assay for LMS and LM. Our results point to multiple epigenetic markers that could be used for ctDNA profiling, in addition to point mutations or CNAs. Further validation will allow us to select the most reliable LMS- and LM-specific DNA methylation markers and the most frequently mutated regions across independent datasets, and these markers will be incorporated into our new ctDNA test for a concurrent detection of point mutations, CNAs and DNA methylation markers in circulation

We reviewed 234 benign solitary schwannomas treated between 1984 and 2004. The mean age of the patients was 45.2 years (11 to 82). There were 170 tumours (73%) in the upper limb, of which 94 (40%) arose from the brachial plexus or other nerves within the posterior triangle of the neck. Six (2.6%) were located within muscle or bone. Four patients (1.7%) presented with tetraparesis due to an intraspinal extension. There were 198 primary referrals (19 of whom had a needle biopsy in the referring unit) and in these patients the tumour was excised. After having surgery or an open biopsy at another hospital, a further 36 patients were seen because of increased neurological deficit, pain or incomplete excision. In these, a nerve repair was performed in 18 and treatment for pain or paralysis was offered to another 14. A tender mass was found in 194 (98%) of the primary referrals. A Tinel-like sign was recorded in 155 (81%). Persistent spontaneous pain occurred in 60 (31%) of the 194 with tender mass, impairment of cutaneous sensibility in 39 (20%), and muscle weakness in 24 (12%). After apparently adequate excision, two tumours recurred. No case of malignant transformation was seen

Background. Treatment of aggressive benign bone lesions with curettage, burring, cementation and plate augmentation is a widely accepted treatment. We have used the above method using a locked plate (rather than conventional), facilitating stability and early mobilisation. We hypothesise that this is an alternative to megaprosthetic joint replacement, and provides acceptable functional outcomes at follow-up. Methods. Patients with peri-articular aggressive benign bone lesions of the lower limb were treated with marginal excision, intra-lesional curettage, burring and cementation. This was augmented with a locked plate of varying designs. Where feasible, liquid nitrogen was used as an adjunctive treatment. Functional outcome was evaluated at follow-up using the Musculoskeletal Tumour Society Score (MSTS). Routine X-rays were performed at follow up to determine if there was any radiographic evidence of recurrence or any complications. Results. 13 patients with aggressive benign tumours of the lower limb were treated between 2005 and 2009. All tumours were aggressive benign peri-articular tumours with extension to the articular surface. Several of the tumours had fractured the articular cartilage and extended into the joint. Several pathological fractures were noted. The patients were treated in the manner described. The average MSTS score was 89%. Average follow-up time is 35 months. Patients were discharged 2 weeks post-operatively, a prerequisite being the ability to achieve 90° of knee flexion. To date there have been no complications or evidence of radiological recurrence. Conclusion. Our early results in a small series make us cautiously optimistic that this may be an alternative to immediate megaprosthetic reconstruction in patients with relative joint preservation and form an intermediate step in the treatment of aggressive benign peri-articular bone tumours. These may be amenable to arthroplastic reconstruction at a later stage, if necessary

Introduction:

Subsidence of cementless femoral stems in total hip arthroplasty (THA) has been associated with poor initial fixation and subsequent risk of aspectic loosening. There is limited literature on how subsidence of cementless, proximally porous coated, tapered wedge femoral stems impacts the patient clinically. The aim of our study was to assess whether subsidence with these stems is associated with a decline in clinical function.

Cartilage lesions vary in the spectrum from benign enchondromas to highly malignant dedifferentiated chondrosarcomas. From the treatment perspective, enchondromas are observed, Grade 1 chondrosarcomas are curetted like aggressive benign tumors, and rest are resected like other sarcomas. Although biopsy for tissue diagnosis is the gold standard for diagnosis and grade determination in chondrosarcoma, tumor heterogeneity limits the grading in patients following a biopsy. In the absence of definite pre-treatment grading, a surgeon is therefore often in a dilemma when deciding the best treatment option. Radiology has identified aggressive features and aggressiveness scores have been used to try and grade these tumors based on the imaging characteristics but there have been very few published reports with a uniform group and large number of cases to derive a consistent scoring and correlation. The authors asked these study questions :(1) Does Radiology Aggressiveness and its Score correlate with the grade of chondrosarcoma? (2) Can a cut off Radiology Agressiveness Score value be used to guide the clinician and add value to needle biopsy information in offering histological grade dependent management?. A retrospective analysis of patients with long bone extremity intraosseous primary chondrosarcomas were correlated with the final histology grade for the operated patients and Radiological parameters with 9 parameters identified a priori and from published literature (radiology aggressiveness scores - RAS) were evaluated and tabulated. 137 patients were identified and 2 patients were eliminated for prior surgical intervention. All patients had tissue diagnosis available and pre-treatment local radiology investigations (radiographs and/or CT scans and MRI scans) to define the RAS parameters. Spearman correlation has indicated that there was a significant positive association between RAS and final histology grading of long bone primary intraosseous chondrosarcomas. We expect higher RAS values will provide grading information in patients with inconclusive pre-surgery biopsy to tumor grades and aid in correct grade dependant surgical management of the lesion. Prediction of dedifferentiated chondrosarcoma from higher RAS will be attempted and a correlation to obtain a RAS cut off, although this may be challenging to achieve due to the overlap of features across the intermediate grade, high grade and dedifferentiated grades. Radiology Aggressiveness correlates with the histologic grade in long bone extremity primary chondrosarcomas and the correlation of radiology and biopsy can aid in treatment planning by guiding us towards a low-grade neoplasm which may be dealt with intralesional extended curettage or high-grade lesion which need to be resected. Standalone RAS may not solve the grading dilemma of primary long bone intraosseous chondrosarcomas as the need for tissue diagnosis for confirming atypical cartilaginous neoplasm cannot be eliminated, however in the event of a needle biopsy grade or inconclusive open biopsy it may guide us towards a correlational diagnosis along with radiology and pathology for grade based management of the chondrosarcoma

PVNS or TGCT (Pigmented Villonodular Synovitis, or Tenosynovial Giant Cell tumour) is a benign tumour affecting the synovial lining of joints and tendon sheaths, historically treated with surgical excision or debridement. We have shown previously this management is fraught with high recurrence rates, especially in its diffuse form. We present the encouraging early results of medical management for this condition with use of a CSF1 inhibitor, in comparison to a cohort of 137 cases previously treated at our institution

The poor prognosis of patients with soft-tissue sarcoma as not changed in the past several decades, highlighting the necessity for new therapeutic approaches. T-cell based immunotherapies are a promising alternative to traditional cancer treatments due to their ability to target only malignant cells, leaving benign cells unharmed. The development of successful immunotherapy requires the identification and characterization of targetable immunogenic tumor antigens. Cancer-testis antigens (CTA) are a group of highly immunogenic tumor-associated proteins that have emerged as potential targets for CD8+ T-cell recognition. In addition to identifying a targetable antigen, it is crucial to understand the tumor immune microenvironment. The level of immune infiltration and mechanisms of immune suppression within the tumor play important roles in the outcome of immunotherapy. The goal of this study is to identify targetable immunogenic antigens for T-cell based immunotherapy and to characterize the tumor immune microenvironment in human dedifferentiated liposarcoma (DDLS) by Nanostring and IHC. To assess the complexity of the human DDLS tumor immune microenvironment and to identify target antigens we used the nCounter NanoString platform to generate a gene expression profile for hundreds of genes from RNA obtained from 29 DDLS and 10 control fat FFPE samples. To classify inflammatory status of DDLS tumors, we performed hierarchical clustering based on expression levels of selected tumor inflammatory signature genes (CCL5, CD27, CD274, CD276, CD8A, CMKLR1, CXCL9, CXCR6, HLA-DQA1, HLA-E, IDO1, LAG3, PDCDILG2, PSMB10, STAT1, TIGIT). To confirm protein expression and distribution of identified antigens, we performed immunohistochemistry on human tissue micro-arrays encompassing DDLPS tumor tissues and matched normal control tissue from 63 patients. IHC for the cancer testis antigens PBK, SPA17, MAGE-A3, NY-ESO-1 and SSX2 was performed, and the staining results were scored by two authors based on maximal staining intensity on a scale of zero to three (absent=0, weak=1, moderate=2, or strong=3) and the percentage of tumor cells that stained. Hierarchical clustering of DDLS tumors based on expression of tumor inflammation signature genes revealed two distinct groups, consisting of 15 inflamed tumor and 14 non-inflamed tumors, demonstrating tumor heterogeneity within the DDLS sarcoma subtype. All antigens were found to be expressed in DDLS at an mRNA level. SPA17 was expressed at the highest levels in DDLS, however, this antigen was expressed at high levels in normal fat. Notably, antigens PBK and TTK had the largest fold change increase in expression in DDLS compared to normal fat controls. Immunohistochemical analysis of selected antigens revealed that PBK was found to be expressed in 96% (52/54) of DDLS samples at high levels. Other antigens were absent or expressed at low levels in DDLS; MAGEA3 in 15.87% (10/63) NY-ESO-1 in 6.35% (4/62) and SSX2 in 12.7% (8/63) and SPA17 in 5.5% (3/54). This data shows considerable inter-tumoral heterogeneity of inflammation, which should be taken into consideration when designing an immunotherapy for DDLS. To date, these results show promising expression of PBK antigen in DDLS, which may be used as a target in the future development of an immunotherapy for sarcoma

The reconstruction of peri-acetabular defects after severe bone loss or pelvic resection for tumor is among the most challenging surgical intervention. The Lumic® prosthesis (Implantcast, Buxtehude, Germany) was first introduced in 2008 in an effort to reduce the mechanical complications encountered with the classic peri-acetabular reconstruction techniques and to improve functional outcomes. Few have evaluated the results associated with the use of this recent implant. A retrospective study from five Orthopedic Oncology Canadian centers was conducted. Every patient in whom a Lumic® endoprosthesis was used for reconstruction after peri-acetabular resection or severe bone loss with a minimal follow-up of three months was included. The charts were reviewed and data concerning patients’ demographics, peri-operative characteristics and post-operative complications was collected. Surgical and functional outcomes were also assessed. Sixteen patients, 11 males and five females, were included and were followed for 28 months [3 – 60]. Mean age was 55 [17–86], and mean BMI reached 28 [19.6 – 44]. Twelve patients (75%) had a Lumic® after a resection of a primary sarcoma, two following pelvic metastasis, one for a benign tumor and one after a comminuted acetabular fracture with bone loss. Twelve patients (75%) had their surgery performed in one stage whereas four had a planned two-stage procedure. Mean surgical time was 555 minutes [173-1230] and blood loss averaged 2100 mL [500-5000]. MSTS score mean was 60.3 preoperatively [37.1 – 97] and 54.3 postoperatively [17.1-88.6]. Five patients (31.3%) had a cemented Lumic® stem. All patients got the dual mobility bearing, and 10 patients (62.5%) had the largest acetabular cup implanted (60 mm). In seven of these 10 patients the silver coated implant was used to minimize risk of infection. Five patients (31.3%) underwent capsular reconstruction using a synthetic fabric aiming to reduce the dislocation risk. Five patients had per-operative complications (31.3%), four were minor and one was serious (comminuted iliac bone fracture requiring internal fixation). Four patients dislocated within a month post-operatively and one additional patient sustained a dislocation one year post-operatively. Eight patients (50%) had a post-operative surgical site infection. All four patients who had a two-stage surgery had an infection. Ten patients (62.5%) needed a reoperation (two for fabric insertion, five for wash-outs, and three for implant exchange/removal). One patient (6.3%) had a septic loosening three years after surgery. At the time of data collection, 13 patients (81.3%) were alive with nine free of disease. Silver coating was not found to reduce infection risk (p=0.2) and capsuloplasty did not prevent dislocation (p=1). These results are comparable to the sparse data published. Lumic® endoprosthesis is therefore shown to provide good functional outcomes and low rates of loosening on short to medium term follow-up. Infection and dislocation are common complications but we were unable to show benefits of capsuloplasty and of the use of silver coated implants. Larger series and longer follow-ups are needed

The reconstruction of peri-acetabular defects after severe bone loss or pelvic resection for tumor is among the most challenging surgical intervention. The Lumic® prosthesis (Implantcast, Buxtehude, Germany) was first introduced in 2008 in an effort to reduce the mechanical complications encountered with the classic peri-acetabular reconstruction techniques and to improve functional outcomes. Few have evaluated the results associated with the use of this recent implant. A retrospective study from five Orthopedic Oncology Canadian centers was conducted. Every patient in whom a Lumic® endoprosthesis was used for reconstruction after peri-acetabular resection or severe bone loss with a minimal follow-up of three months was included. The charts were reviewed and data concerning patients’ demographics, peri-operative characteristics and post-operative complications was collected. Surgical and functional outcomes were also assessed. Sixteen patients, 11 males and five females, were included and were followed for 28 months [3 – 60]. Mean age was 55 [17-86], and mean BMI reached 28 [19.6 – 44]. Twelve patients (75%) had a Lumic® after a resection of a primary sarcoma, two following pelvic metastasis, one for a benign tumor and one after a comminuted acetabular fracture with bone loss. Twelve patients (75%) had their surgery performed in one stage whereas four had a planned two-stage procedure. Mean surgical time was 555 minutes [173-1230] and blood loss averaged 2100 mL [500-5000]. MSTS score mean was 60.3 preoperatively [37.1 – 97] and 54.3 postoperatively [17.1-88.6]. Five patients (31.3%) had a cemented Lumic® stem. All patients got the dual mobility bearing, and 10 patients (62.5%) had the largest acetabular cup implanted (60 mm). In seven of these 10 patients the silver coated implant was used to minimize risk of infection. Five patients (31.3%) underwent capsular reconstruction using a synthetic fabric aiming to reduce the dislocation risk. Five patients had per-operative complications (31.3%), four were minor and one was serious (comminuted iliac bone fracture requiring internal fixation). Four patients dislocated within a month post-operatively and one additional patient sustained a dislocation one year post-operatively. Eight patients (50%) had a post-operative surgical site infection. All four patients who had a two-stage surgery had an infection. Ten patients (62.5%) needed a reoperation (two for fabric insertion, five for wash-outs, and three for implant exchange/removal). One patient (6.3%) had a septic loosening three years after surgery. At the time of data collection, 13 patients (81.3%) were alive with nine free of disease. Silver coating was not found to reduce infection risk (p=0.2) and capsuloplasty did not prevent dislocation (p=1). These results are comparable to the sparse data published. Lumic® endoprosthesis is therefore shown to provide good functional outcomes and low rates of loosening on short to medium term follow-up. Infection and dislocation are common complications but we were unable to show benefits of capsuloplasty and of the use of silver coated implants. Larger series and longer follow-ups are needed

Solitary fibrous tumor (SFT) is a rare mesenchymal tumor with an intermediate tendency to metastasize, which is found in many different locations including head and neck, abdomen, chest cavity and extremities. Also, meningeal hemangiopericytoma (HPC) is considered an SFT which arises in the meningeal membranes. SFT family shows an undetermined biologic behavior varying from a silent indolent tumor to an aggressive malignant form; however, benign and malignant variants of SFT may have similar cytopathologic characteristics. In this study, we defined the factors correlated with SFT's aggressive behavior and patient's survival. This is a retrospective study based on medical records of 85 patients who were suffering from SFT and had been treated at McGill University Health Centre (MUHC) between 1984 and 2017. We used multivariate logistic regression analysis to address any association between the variables including patient's demographics, tumor size, primary location of the tumor, pathological features, treatment methods and outcomes. The median of the follow-up period was 60 months. The patient's age or gender had no association with tumor aggressive behavior or patient's survival. Anatomical origin of primary tumor had no strong correlation with the patient's disease related death (DRD); however, tumors originated from CNS showed more aggressive behavior. There was an association between tumor size more than 7 cm and distant metastasis (MT) (p= 0.03) and DRD (p=0.03). The tumor size also correlated with the 5-year disease-free survival (p=0.017). We had three histologic groups: 1- Benign SFT (30 cases), 2- cellular SFT or HPC (29 cases), 3- malignant SFT or anaplastic HPC (26 cases). Although univariate analysis demonstrates that patients suffering from cellular SFT and malignant SFT showed increased aggressive behavior of the tumor, multivariate analysis didn't verify the mentioned association. Patients with positive margins had increased odds ratio to experience tumor local recurrence (LR) (p= 0.05) and LR was correlated with DRD in our patients (p=0.006). Radiotherapy had no statistical association with LR, MT or DRD. Frequency of LR and MT in the study were 25.7% and 29.8% respectively. 5-year disease-free survival in our patients was 76%. The size of SFT is the most correlative predictor of the tumor's aggressive behavior. The local recurrence of SFT is associated with disease related death; therefore, resection of the tumor with negative margins provides the highest chance of cure. In addition, a cellular SFT should be treated like a malignant variant of the tumor

Myxofibrosarcoma (MFS) is the second most common subtype of soft tissue sarcoma (STS) and is associated with a high rate of local recurrence after resection. These tumours frequently present with peri-lesional edema, termed “tumour tails” on staging MRI scans [1]. Tumour tails(TT) may contain satellite neoplastic cells or can represent benign reactive edema. There are no clear radiological features to distinguish malignant from reactive peri-lesional edema which limits accurate surgical planning, resulting in either high rates of inadvertently positive resection margins and local recurrences or overly-aggressive resections which negatively impact function and increase morbidity [2]. The objective of this pilot study was to prospectively study a cohort of MFS patients with TTs in an attempt to identify radiological features that predict which type of edema is malignant and requires resection together with the main tumour mass. Patients diagnosed with MFS on biopsy at an orthopaedic oncology referral centre between January 1-December 31 2018 who also had TTs on staging MRI scans were prospectively recruited for the study. Tumours were treated with wide surgical excision, including the TTs, and (neo)adjuvant radiotherapy as per institutional protocol. Staging MRI scans were reviewed in a blinded fashion by two musculoskeletal radiologists to distinguish malignant from reactive TTs. The main tumour mass underwent standard histological evaluation while the regions encompassing the TTs were photographed and sectioned into grids. Each tissue section was examined histologically for the presence of satellite neoplastic cells based on morphological criteria. Radiological and histological findings were compared. Six patients met the inclusion criteria and underwent analysis. All tumours were located in the extremities and were deep to fascia. Mean age at presentation was 67 years (range 51 – 85), with a male:female ratio of 4:2. All patients received radiotherapy (50 Gy), either pre- (n=4) or post-operatively (n=2) based on multidisciplinary tumor board discussion or enrolment in a prospective clinical trial. Radiologically, TTs were labelled as malignant in four patients (66.7%) and as benign TTs in two others. The tails were recognised to be malignant due to the differing signal characteristics to reactive edema on mixed MRI sequences. The radiological evaluation correlated exactly with histological analysis, as satellite neoplastic cells were identified microscopically in the same four cases in which the TTs were designated to be malignant by MRI (specificity&sensitivity=100%). Surgical resection margins were microscopically positive in 50% of cases in the TTs themselves, and 75% of cases in which TTs were designated as malignant on staging MRI. “The malignant nature of peri-lesional edema in MFS, also known as the TT, was accurately predicted in this small pilot study based on specific radiological features which correlated exactly with histologic identification of isolated tumor cells. These findings validate development of a larger prospective study to recruit additional patients with tumor tails beyond just MFS, in order to more robustly study the correlation between the MRI appearance and histological distribution of satellite sarcoma cells in peri-lesional edema in STS. We are already recruiting to this expanded radiological-histological investigation including evaluation of additional novel MRI sequences

The use of peritumoral oedema on magnetic resonance (MR) imaging to predict soft tissue tumour grade is controversial. The clinical significance of oedema visualised on MR scans is poorly defined in the literature. We undertook this study to ascertain a diagnostic relationship between peritumoral oedema surrounding soft tissue sarcomas and the histological grade of the tumour. One hundred and ten consecutive soft tissue tumours were extracted from the New Zealand Bone and Soft Tissue Tumour Registry. Key inclusion criteria were tumours deep to fascia, measuring more than 5cm in any dimension. Both benign and malignant sarcomas were included. MR scans and histology were reviewed, separately and in random order by a single author. Histology was graded as benign, low or high grade (based on the American Joint Committee on Cancer grading system). Peritumoral oedema was defined as the increased signal intensity, on T2 or STIR images, immediately surrounding a discrete lesion. It was measured on two or more planes with the largest value used in diagnostic calculations. Oedema greater than or equal to 20mm was defined as a positive test result. Twenty five random scans were double read to ensure inter-observer reliability. Data was obtained for 83 tumours, 36 benign and 47 malignant (34 high grade and 13 low grade). The tumours in all groups were matched for size. The mean peritumoral oedema was 10.5mm for benign tumours, 20.6mm for low grade sarcomas (p<0.1), 28.1mm for high grade tumours (p<0.01) and 26.1mm if all malignant tumours were included as a single group (p<0.01). Using peritumoral oedema as a diagnostic test for tumour grade resulted in a specificity of 72%. The highest diagnostic ability was found when comparing benign to high grade tumours which yielded sensitivity of 59% and a positive likelihood ratio of 2.1. This data suggests a high false negative rate and that the test adds little to the diagnostic process. To our knowledge this is the first study which assesses the diagnostic accuracy of peritumoral oedema to predict the histological grade of soft tissue sarcomas. Our results show a statistically significant difference, in surrounding peritumoral oedema, exists when comparing benign to high grade sarcomas and to all malignant tumours. This relationship is not apparent for low grade tumours. As a diagnostic test, using only peritumoral oedema to predict histological grade is unreliable

The poor prognosis of patients with advanced bone and soft-tissue sarcoma has highlighted the necessity for new therapeutic approaches. T-cell based immunotherapies are a promising alternative to traditional cancer treatments due to their ability to target only malignant cells, leaving benign cells unharmed. The development of successful immunotherapy requires the identification of targetable immunogenic tumor antigens. Cancer-testis antigens (CTA) are a group of highly immunogenic tumor-associated proteins that have emerged as potential targets for CD8+ T-cell recognition. The goal of this study is to screen for CTA expression, HLA expression, and tumor T-cell infiltration in human dedifferentiated liposarcoma (DDLPS) and osteosarcoma (OS) to establish their immune profile and to identify targetable immunogenic antigens for T-cell based immunotherapy. Human tissue micro-arrays composed of 78 cores of OS and 50 cores of DDLPS were obtained, along with matched control tissues from the same patients. IHC for the cancer testis antigens NY-ESO-1, MAGE-A3, and SSX2, was performed, and the staining results were scored by two authors based on maximal staining intensity on a scale of zero to three (absent=0, weak=1, moderate=2, or strong=3) and the percentage of tumor cells that stained. IHC for CD8 and CD3 was also performed, and T-cell tumor infiltration was defined as either brisk, nonbrisk, or absent, as described in melanoma literature. Concurrently, evaluation of 38 human DDLPS specimens and 10 healthy human fat specimens by the Nanostring nCounter platform is underway for identification of novel antigen targets and to establish the immune profile of DDLPS. Immunohistochemical analysis of CTA expression showed considerable inter- and intra-tumoral heterogeneity. DDLPS showed relatively low expression of all CTAs tested, with only 22% of samples exhibiting MAGE-A3 and one sample each (3.1%) showing expression of SSX2 and NY-ESO-1 in low percentages of tumor cells. By contrast, in osteosarcoma, 74% of samples expressed MAGE-A3 and 68% expressed SSX, both with >80% of positive cases showing moderate to high expression. NY-ESO-1 was expressed in 41% of OS samples, predominantly at low levels. Brisk infiltration of CD8+ T cells was observed in over 70% of both sarcoma types tested. Furthermore, all sarcoma samples tested were positive for HLA expression. To date, these results show promising expression of CTAs MAGE-A3 and SSX in OS, which may be used as targets in the future development of an immunotherapy for sarcoma. DDLPS shows relatively low expression, highlighting the need for more exploratory study with NanoString. The data generated throughout this project will provide insight into the immune profile of DDLPS

Benign aggressive tumors are common and can be debilitating for patients especially if they are in peri-articular regions or cause pathological fracture as is common for giant cell tumor of bone (GCT). Although GCT rarely metastasize, the literature reports many series with high rates of local recurrence, and evidence about which risk factors influence recurrence is lacking. This study aims to evaluate the recurrence rate and identify local recurrence risk factors by reviewing patient data from a single high-volume orthopedic oncology center. A retrospective analysis of all patients treated for GCT at a tertiary orthopedic oncology center was conducted. In total 413 patients were treated for GCT between 1989 and 2017. Multiple patient and tumour characteristics were analysed to determine if they influenced local recurrence including: age, gender, anatomical site, Campanacci stage, soft tissue extension, presence of metastasis, pathologic fractures, and prior local recurrence. Additional variables that were analysed included type of treatment (en bloc resection or aggressive intralesional curettage) and use of local adjuvants. The main outcome parameters were local recurrence- free survival, metastasis-free survival and complications. Patients treated with Denosumab were excluded from analysis given its recently documented association with high rates of local recurrence. “There were 63/413 local recurrences (15.3%) at a mean follow-up of 30.5 months. The metastatic rate was 2.2% at a mean 50.6 months follow-up and did not vary based on type of treatment. Overall complication rate of 14.3% was not related to treatment modality. Local recurrence was higher (p=0.019) following curettage (55/310; 17.7%) compared to resection (8/103; 7.8%) however, joint salvage was possible in 87% of patients (270/310) in the curettage group. Use of adjuvant therapy including liquid nitrogen, peroxide, phenol, water versus none did not show any effect on local recurrence rates (p= 0.104). Pathological fracture did not affect local recurrence rates regardless of treatment modality (p= 0.260). Local recurrence at presentation was present in 16.3% (58/356) patients and did not show any significance for further local recurrence (p= 0.396). Gender was not associated with local recurrence (p=0.508) but younger patient age, below 20 years (p = 0.047) or below 30 years (p = 0.015) was associated with higher local recurrence rates. GCT in distal radius demonstrated the highest rate of local recurrence at 31.6% compared to other sites, although this was not significant (p=0.098). In addition, Campanacci stage and soft tissue extension were not risk factors for recurrence. The overall GCT local recurrence rate was 15.3%, but varied based on the type of resection: 17.7% following joint sparing curettage compared to 7.8% following resection. Local recurrence was also higher with younger patient age (30 years or less) and in distal radius lesions. In addition, neither Campanacci stage, soft tissue extension or presence of a pathologic fracture affected local recurrence. Most patients with GCT can undergo successful curettage and joint sparing, while only a minority require resection +/− prosthetic reconstruction. Even in the presence of soft tissue extension or a pathologic fracture, most joints can be salvaged with curettage

The primary goal of this study was to understand the subjective impact of a diagnosis of Simple Bone Cyst on children with regards to activity participation and psychosocial development. We aimed to explore the concepts of labeling, embodiment and activity participation to understand the impact of SBC. This was a qualitative study. Ten children between the ages of 4 and 17 years with SBC and their families participated in semi-structured interviews related to activity participation, social interactions and psychological impact of SBC. Interview questions were derived from psychology, sociology and philosophy literatures pertaining to illness and activity, sense of embodiment, self-concept and interactions with the social environment. Interviews were transcribed and analyzed using thematic analysis. First, children and families view SBC as an injury more than an illness and did not experience labeling or significant changes in embodiment. Second, SBCs cause anxiety in children related fear of fracture or pain, however normal function and activity participation were maintained. Third, there were significant shortcomings identified in the communication and the decision-making process between families and physicians regarding SBC management. SBC as a benign disease does not neatly fit into the category of illness or injury based on children's experiences. Children who previously perceived themselves as normal feel different and not normal following diagnosis with SBC. The experience of parents is largely one of anxiety, and much of that anxiety is derived from the uncertainty over the treatment plans for their child. The proposed framework of normality allows for the more temporary and fluid changes in perception experienced by the children in our study. The results of this study suggest that the current decision-making process in SBC is unsatisfactory leading to anxiety and worry. Parents felt pressure to make decisions regarding surgery without feeling that they sufficient information. Though understanding how children experience SBCs and how parents experience the treatment course of their child with SBC, we can shared decision-making as a potential way to reduce parents' anxiety and limit negative experience in children

Introduction. Bony tumours of the foot account for approximately 3% of all osseous tumours. However, literature regarding os calcis and talar tumours comprises individual case reports, short case series or literature reviews with no recent large series. Methods. We retrospectively reviewed the medical notes and imaging for all patients with calcaneal or talar tumours recorded in the Scottish Bone Tumour Registry since the 1940's. Demographics, presentation, investigation, histology, management and outcome were reviewed. Results. 34 calcaneal tumours and 23 talar tumours were identified. Calcaneal tumours. 2:1 male prevalence, mean age at presentation 30, average length of symptoms 9 months. 4 cases presented with pathological fracture. 21 benign tumours including 6 unicameral bone cysts, 3 chondroblastoma, and a wide variety of individual lesions. 13 malignant tumours comprising 6 osteosarcoma, 5 chondrosarcoma and 2 Ewings sarcoma. Talar Tumours. male to female ratio 3:1, mean age at presentation 28, average length of symptoms 5 months. 20 benign cases including 7 osteoid osteoma, 4 chondroblastoma, and several individual lesions. 3 malignant lesions comprising 2 chondrosarcoma, 1 osteosarcoma. Discussion. Tumours of the hindfoot frequently are delayed in diagnosis due to their rarity and lack of clinician familiarity. They are more common in men, especially talar tumours, which are most commonly benign osteoid osteoma or chondroblastoma. Calcaneal tumours have 1 in 3 risk of malignancy and cover a wider variety of lesions. Osteosarcoma of the foot tends to present later than other anatomical regions. Outcome is dependant on early diagnosis, timely surgery and most importantly neo-adjuvant chemotherapy. Diagnosis is often made on plain radiograph but MRI is the gold standard. Despite their rarity clinicians should maintain a high index of suspicion as accurate and timely diagnosis is important to management and outcome

Background. Stress fractures at tracker after computer navigated total knee replacement are rare. Periprosthetic fracture after Minimally Invasive Plate Osteosynthesis (MIPO) of stress fracture through femoral tracker is unique in orthopaedic literature. We are reporting this unique presentation of periprosthetic fractures after MIPO for stress fracture involving femoral pin site track in computer assisted total knee arthroplasty, treated by reconstruction nail (PFNA). Methods. A 75-year old female, who had computer navigated right total knee replacement, was admitted 6 weeks later with increasing pain over distal thigh for 3 weeks without trauma. Prior to onset of pain, she achieved a range of movements of 0–105 degrees. Perioperative radiographs did not suggest obvious osteoporosis, pre-existent benign or malignant lesion, or fracture. Radiographs demonstrated transverse fracture of distal third of femur through pin site track. We fixed the fracture with 11-hole combihole locking plate by MIPO technique. Eight weeks later, she was readmitted with periprosthetic fracture through screw hole at the tip of MIPO Plate and treated by Reconstruction Nail (PFNA), removal of locking screws and refixation of intermediate segment with unicortical locking screws. Then she was protected with plaster cylinder for 4 weeks and hinged brace for 2 months. Results. Retrograde nail for navigation pin site stress fracture entails intraarticular approach with attendant risks including scatches to prosthesis and joint infection. So we opted to fix by MIPO technique. Periprosthetic fracture at the top of MIPO merits fixation with antegrade nail in conjunction with conversion of screws in the proximal part of the plate to unicortical locking screws. Overlap of at least 3cms offers biomechanical superiority. She made an uneventful recovery and was started on osteoporosis treatment, pending DEXA scan. Conclusion. Reconstruction Nail (PFNA), refixation of intermediate segment with unicortical locking screws constitutes a logical management option for the unique periprosthetic fracture after MIPO of stress fracture involving femoral pin site track in computer assisted total knee replacement

Introduction. The femoral neck in children is a common site for bone lesions. The majority are benign. However these lesions can cause diagnostic problems. Aim. To present a spectrum of chronic lesions of the femoral neck in children and emphasize the importance of tissue diagnosis. Materials and methods. Thirty two children with isolated chronic bone lesions in the femoral neck treated between 1994 and 2013were retrospectively reviewed. The ages ranged between 1–13 years. Clinical features were pain and limp. Routine blood tests, x-rays and CT scans were done in all and MRI scans in 5 cases. All diagnoses were confirmed histologically. Results. Three radiological patterns were seen: lucent or cystic in 22, infiltrative (permeative)in 2, and localized densities with nidus in 8 cases. Histologically the lesions were subacute osteomyelitis in 4, tuberculosis in 9, simple bone cyst in 7, osteoid osteoma in 7, chondroblastoma in 1, monostotic fibrous dysplasia in 2 and eosinophilic granuloma in 2 cases. Two tuberculous lesions were associated with subluxation of the hip and involvement of the head occurred in 2 others. Treatment and outcome. All lesions were curetted. Bone grafting was done in 10. Immobilisation was by internal fixation in 1, traction in 2 and spica cast in 29 cases. Follow up was 9 months to 11 years. Healing occurred in the majority. Recurrence occurred in 2 cases. Coxa vara developed in 6, and growth disturbance with shortening in 9 patients. Discussion. Femoral neck lesions are mainly benign, present diagnostic difficulty and treatment is challenging. There are problems with immobilization and of purchase with fixation devices due to poor bone stock on the neck of femur. The spica cast is a reliable method of immobilization in children under 10years. Growth disturbance and coxa vara can result after healing. CT scan is useful in assessing the architecture of the bone. NO DISCLOSURES

Background. Acromegaly, which stems from high level of serum growth hormone secreted by a benign tumour in the anterior pituitary gland, is likely to cause severe peripheral joint pains due to hypertrophic changes in such joints. Recently, the life expectancy of such patients has been improved and more patients with acromegaly have undergone joint surgeries to mitigate joint pain and malfunctions. However, little is known about to what extent surgical procedures can improve the joint functions of acromegalic patients compared to non-acromegalic cases. Methods. First, we qualitatively analysed prognosis of total hip arthroplasty (THA) of acromegalic patients by investigating 11 cases in which direct anterior approach (DAA) THAs were performed to 8 acromegalic patients in our hospital between 2012 and 2015. Second, we quantitatively compared the functional prognosis of the 11 cases with that of 107 non-acromegalic cases. Technically, to control the difference in age, sex, height, and weight between the two patient groups, we first identified a model that could predict 3month-/6month-/12month-functional prognosis in the control cases. We estimated differences in functional outcomes between the two groups by calculating how accurately the control-case-based model could predict the prognosis of the acromegalic cases. Results. In the qualitative analysis, we found that compared to the control, the most acromegalic cases had atypically advanced degenerative arthritides with osteophytes and enthesophytes proliferations. In addition, some cases showed other signs, such as flattering of femoral head and arthritis with slight osteophytes. Regarding surgical procedures, acromegalic cases were likely to require longer operation time and larger amounts of blood loss compared to the control. In the quantitative analysis, we first identified a model in which age and body height could predict the functional prognosis of DAA THA in the non-acromegalic cases (F[2,104] = 6.7, P = 0.0017). We then found that the actual functional outcomes of the acromegalic cases were not significantly different from those predicted by this control-case-based model (P = 0.18). Conclusions. The qualitative analysis shows the atypical joint structures and resultant prolonged operation time and blood loss in the acromegalic cases. However, the quantitative analysis could not find significant differences in prognosis between the acromegalic and non-acromegalic cases. Although these observations and analyses need to be examined in studies with large sample sizes, this work suggests that functional outcomes of DAA THA to acromegalic patients can be comparable to that to non-acromegalic patients

Background:. Glomus tumours of the hand are rare benign vascular tumours. The literature shows a limited number of case series with few patients treated over several years. Methods:. Patient records and the literature were reviewed. Case Series:. We present a series of 5 patients with glomus tumour treated over a period of 1 year. All 5 patients presented with a similar history. They were all seen by various medical practitioners for an extended period of time before presenting to the Hand Unit of our institution. All 5 patients had classical symptoms and signs of glomus tumour i.e. pain, cold intolerance and pin-point tenderness over the nail bed, while 4 of the 5 had a purplish spot seen through the nail plate. All 5 tumours were excised and the histology confirmed our pre-operative diagnosis of glomus tumour. In all of them, complete resolution of symptoms was the final outcome and there was no reported recurrence of symptoms in the short period of follow-up. Discussion and conclusion:. Glomus tumours are rare benign vascular tumours. The limited number of case series in the literature report small numbers of patients treated at institutions over long periods of time. It can occur anywhere in the body, but up to three quarters of them are found in the hand. It arises from the neuromyoarterial glomus cells of the nailbed dermis. The triad of pain, cold intolerance and pin-point tenderness is highly suggestive of the condition. Subjective symptoms typically exceed clinical signs for which the diagnosis is delayed for months. Sometimes the tumour is visible through the nail plate appearing as reddish or purplish spot of few millimeters or as longitudinal streaks. Imaging studies except MRI are not very helpful and one must rely on a history of cold intolerance and clinical findings like pin-point tenderness for diagnosis