The management and outcome of large volume liposarcomas encasing the sciatic nerve.

This paper outlines the oncological outcomes of patients with large volume liposarcomas of the posterior thigh who underwent nerve-preserving surgery utilising epineural dissection. Thirty-seven consecutive patients (group I) with a mean age of 66.2 (31-96) were surgically treated with a planned marginal resection and epineurectomy for liposarcoma with known sciatic nerve involvement between March 1997 and January 2015. The mean follow-up was 79 months (15-192). All patients underwent multidisciplinary team (MDT) pre-operative assessment and staging, with follow-up in Sarcoma Clinic. Pre-operative function was assessed by applying the Toronto extremity salvage score (TESS). Oncological and functional outcomes were recorded. In grades 1, 2, and 3, 24, 6, and 7 liposarcomas, respectively, were included with mean volume 1859 cm3. Sciatic nerve involvement extended for 13-30 cm; in one case, the nerve was abutting the tumour throughout its length. Soft tissue reconstructive surgery was required in three cases. The remainder underwent direct primary closure. Seventeen patients underwent post-operative adjuvant radiotherapy 46-60 Gy and three received chemotherapy. There was local recurrence of disease in three patients. One patient had post-radiation wound breakdown treated non-operatively. Three patients died of an unrelated cause. When compared to a cohort of 37 patients without sciatic nerve involvement (group II), there were no significant differences in local and systemic recurrence rate or post-operative survival. In conclusion, sciatic nerve-preserving surgery is both possible and safe when using a planned epineural dissection in large volume tumours encasing the sciatic nerve.

The effect of Imatinib Mesylate in diffuse-type Tenosynovial Giant Cell Tumours on MR imaging and PET-CT.

INTRODUCTION: Recurrence rates remain high after surgical treatment of diffuse-type Tenosynovial Giant Cell Tumour (TGCT). Imatinib Mesylate (IM) blocks Colony Stimulating Factor1 Receptor (CSF1R), the driver mechanism in TGCT. The aim of this study was to determine if IM reduces the tumour metabolic activity evaluated by PET-CT and to compare this response with the response seen on MR imaging. MATERIALS AND METHODS: 25 Consecutive patients treated with IM (off label use) for locally advanced (N = 12) or recurrent (N = 13) diffuse-type TGCT were included, 15 male and median age at diagnosis 39 (IQR 31-47) years. The knee was most frequently affected (n = 16; 64%). The effect of IM was assessed pre- and post-IM treatment by comparing MR scans and PET-CT. MR scans were assessed by Tumour Volume Score (TVS), an estimation of the tumour volume as a percentage of the total synovial cavity. PET-CT scans were evaluated based on maximum standardized uptake value (SUV-max). Partial response was defined as more than 50% tumour reduction with TVS and a decrease of at least 30% on SUV-max. RESULTS: Median duration of IM treatment was 7.0 (IQR 4.2-11.5) months. Twenty patients (80%) discontinued IM treatment for poor response or intended surgery. Twenty patients experienced an adverse event grade 1-2, three patients grade 3 (creatinine increment, neutropenic sepsis, liver dysfunction). MR assessment of all joints showed 32% (6/19) partial response and 63% (12/19) stable disease, with a mean difference of 12% (P = 0.467; CI -22.4-46.0) TVS between pre- and post-IM and a significant mean difference of 23% (P = 0.021; CI 4.2-21.6) in all knee lesions. PET-CT, all joints, showed a significantly decreased mean difference of 5.3 (P = 0.004; CI 1.9-8.7) SUV-max between pre- and post-IM treatment (58% (11/19) partial response, 37% (7/19) stable disease). No correlation between MR imaging and PET-CT could be appreciated in 15 patients with complete radiological data. CONCLUSION: This study confirms the moderate radiological response of IM in diffuse-type TGCT. PET-CT is a valuable additional diagnostic tool to quantify response to tyrosine kinase inhibitor treatment. Its value should be assessed further to validate its efficacy in the objective measurement of biological response in targeted systemic treatment of TGCT.

Correction to: Solochrome cyanine: A histological stain for cobalt-chromium wear particles in metal-on-metal periprosthetic tissues.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Solochrome cyanine: A histological stain for cobalt-chromium wear particles in metal-on-metal periprosthetic tissues.

Metal-on-metal (MoM) hip arthroplasties produce abundant implant-derived wear debris composed mainly of cobalt (Co) and chromium (Cr). Cobalt-chromium (Co-Cr) wear particles are difficult to identify histologically and need to be distinguished from other wear particle types and endogenous components (e.g., haemosiderin, fibrin) which may be present in MoM periprosthetic tissues. In this study we sought to determine whether histological stains that have an affinity for metals are useful in identifying Co-Cr wear debris in MoM periprosthetic tissues. Histological sections of periprosthetic tissue from 30 failed MoM hip arthroplasties were stained with haematoxylin-eosin (HE), Solochrome Cyanine (SC), Solochrome Azurine (SA) and Perls' Prussian Blue (PB). Sections of periprosthetic tissue from 10 cases of non-MoM arthroplasties using other implant biomaterials, including titanium, ceramic, polymethylmethacrylate (PMMA) and ultra-high molecular weight polyethylene (UHMWP) were similarly analysed. Sections of 10 cases of haemosiderin-containing knee tenosynovial giant cell tumour (TSGCT) were also stained with HE, SC, SA and PB. In MoM periprosthetic tissues, SC stained metal debris in phagocytic macrophages and in the superficial necrotic zone which exhibited little or no trichrome staining for fibrin. In non-MoM periprosthetic tissues, UHMWP, PMMA, ceramic and titanium particles were not stained by SC. Prussian Blue, but not SC or SA, stained haemosiderin deposits in MoM periprosthetic tissues and TSGT. Our findings show that SC staining (most likely Cr-associated) is useful in distinguishing Co-Cr wear particles from other metal/non-metal wear particles types in histological preparations of periprosthetic tissue and that SC reliably distinguishes haemosiderin from Co-Cr wear debris.

Correlation of histological and microbiological findings in septic and aseptic knee implant failure.

INTRODUCTION: The Musculoskeletal Infection Society (MSIS) has defined specific clinical and laboratory criteria for the diagnosis of periprosthetic joint infection (PJI). In this study we assessed the diagnostic utility of MSIS microbiological and histological criteria for PJI in 138 cases of septic and aseptic knee implant failure. MATERIALS AND METHODS: Intra-operative samples from 60 cases of knee septic implant failure (SIF) and 78 cases of aseptic implant failure (AIF), defined on the basis of clinical, laboratory and operative findings/surgical management, were analysed microbiologically and histologically. Findings were correlated with the final clinical diagnosis and the specificity, sensitivity, accuracy, positive and negative predictive value of MSIS microbiological and histological criteria for knee PJI were assessed. RESULTS: 80% of SIF cases showed culture of the same organism from two or more samples (ie MSIS microbiological criteria for definite PJI); 8.3% grew an organism from one sample, and 11.7% showed no growth from any sample. 23.1% of AIF cases grew an organism from one sample and 76.9% showed no growth from any sample. MSIS histological criteria for PJI identified 96.7% of SIF cases. The sensitivity, specificity, accuracy and positive and negative predictive value of MSIS histological criteria for PJI were 96.7%, 100%, 98.6%, 100% and 97.5%, respectively. MSIS microbiological and histological criteria identified all AIF cases. CONCLUSIONS: Knee PJI is more often identified by current MSIS histological than microbiological criteria. A significant proportion of SIF cases show either no growth or growth of an organism from only one sample. AIF is identified by both MSIS microbiological and histological criteria. Correlation of clinical, radiological and laboratory findings is required for the diagnosis of knee PJI.

The role of histology in the diagnosis of spondylodiscitis: correlation with clinical and microbiological findings.

AIMS: The aim of this study was to determine the diagnostic utility of histological analysis in spinal biopsies for spondylodiscitis (SD). PATIENTS AND METHODS: Clinical features, radiology, results of microbiology, histology, and laboratory investigations in 50 suspected SD patients were evaluated. In 29 patients, the final (i.e. treatment-based) diagnosis was pyogenic SD; in seven patients, the final diagnosis was mycobacterial SD. In pyogenic SD, the neutrophil polymorph (NP) infiltrate was scored semi-quantitatively by determining the mean number of NPs per (×400) high-power field (HPF). RESULTS: Of the 29 pyogenic SD patients, 17 had positive microbiology and 21 positive histology (i.e. one or more NPs per HPF on average). All non-SD patients showed less than one NP per HPF. The presence of one or more NPs per HPF had a diagnostic sensitivity of 72.4%, specificity 100%, accuracy 100%, positive predictive value (PPV) 81.0%, and negative predictive value (NPV) 61.9%. Sensitivity, specificity, and accuracy were greater using the criterion of positive histology and/or microbiology than positive histology or microbiology alone. Granulomas were identified histologically in seven mycobacterial SD patients, and positive microbiology was detected in four. CONCLUSION: The diagnosis of pyogenic SD was more often confirmed by positive histology (one or more NPs per HPF on average) than by microbiology, although diagnostic sensitivity was greater when both histology and microbiology were positive. Cite this article: Bone Joint J 2019;101-B:246-252.

Management and outcome of acral soft-tissue sarcomas.

AIMS: The aim of this study was to evaluate the surgical management and outcome of patients with an acral soft-tissue sarcoma of the hand or foot. PATIENTS AND METHODS: We identified 63 patients with an acral soft-tissue sarcoma who presented to our tertiary referral sarcoma service between 2000 and 2016. There were 35 men and 28 women with a mean age of 49 years (sd 21). Of the 63 sarcomas, 27 were in the hands and 36 in the feet. The commonest subtypes were epithelioid sarcoma in the hand (n = 8) and synovial sarcoma in the foot (n = 11). RESULTS: In 41 patients (65%), the tumour measured less than 5 cm in its largest dimension (median size 3 cm (2 to 6)); 27 patients (43%) were diagnosed after inadvertent excision prior to their referral to the specialist sarcoma unit. After biopsy and staging, primary surgical intervention at the sarcoma unit was excision and limb salvage in 43 (68%), partial (digit or ray) amputation in 14 (22%), and more proximal amputation in six (10%). At final follow up, local recurrence had been treated by one partial amputation and six amputations, resulting in a partial amputation rate of 24% and a proximal amputation rate of 19%. The five-year survival rate was 82%. Patients who underwent inadvertent excision showed no statistically significant difference in survival or local recurrence, but were more likely to undergo amputation (p = 0.008). Large tumour size (> 5 cm) was associated with lower survival (p = 0.04) and a higher risk of local recurrence (p = 0.009;). CONCLUSION: Most acral soft-tissue sarcomas measure less than 5 cm at presentation, indicating that while size can be a useful prognostic factor, it should not be used as a diagnostic threshold for referral. Increased tumour size is associated with a higher rate of local recurrence and reduced survival. Sarcoma excision with limb preservation does not result in an increased risk of local recurrence. Cite this article: Bone Joint J 2018;100-B:1518-23.

Localised foot and ankle amyloid deposition.

BACKGROUND: Localised (transthyretin-associated) amyloid is commonly seen in articular/periarticular tissues of elderly individuals. Whether age-associated, amyloid deposition occurs in foot and ankle (F&A) tissues has not previously been investigated. In this study we assessed the nature and frequency of F&A amyloid deposition and determined whether it is associated with age and/or specific articular/periarticular F&A lesions. METHODS: Histological sections of twenty five normal F&A articular/periarticular tissues (16-71 years) and a range of F&A lesions were stained by Congo Red. The amyloid protein was identified by immunohistochemistry and type of matrix glycosaminoglycans determined by Alcian Blue (critical electrolyte concentration) histochemistry. RESULTS: Amyloid deposits were found in the joint cartilage and capsule of 3/25 normal specimens (57, 62 and 78 years). Amyloid deposits were small, contained transthyretin, and found in areas of matrix degeneration associated with the presence of highly sulphated glycosaminoglycans. In patients older than 47 years, small amyloid deposits were noted in some F&A lesions, including osteoarthritis, Charcot arthropathy, bursa, ganglion, chondrocalcinosis, gout, calcific tendonitis and Achilles tendonitis. CONCLUSION: Small localised amyloid deposits in F&A tissues contain transthyretin and occur in areas of matrix degeneration associated with the presence of highly sulphated glycosaminoglycans; these deposits are age-associated and, although seen more commonly in some F&A lesions, are small and unlikely to be of pathogenic significance.

The value of quantitative histology in the diagnosis of fracture-related infection.

Aims: This study aimed to investigate the role of quantitative histological analysis in the diagnosis of fracture-related infection (FRI). Patients and Methods: The clinical features, microbiology culture results, and histological analysis in 156 surgically treated nonunions were used to stratify the likelihood of associated infection. There were 64 confirmed infected nonunions (one or more confirmatory criteria: pus, sinus, and bacterial growth in two or more samples), 66 aseptic nonunions (no confirmatory criteria), and 26 possibly infected nonunions (pathogen identified from a single specimen and no confirmatory criteria). The histological inflammatory response was assessed by average neutrophil polymorph (NPs) counts per high-power field (HPF) and compared with the established diagnosis. Results: Assuming a cut-off of over five neutrophils per high-power field to diagnose septic nonunion, there was 80% sensitivity and 100% specificity (accuracy 90%). Using a cut-off of no neutrophils seen in any high-power field to diagnose aseptic nonunion, there was a sensitivity of 85% and a specificity of 98% (accuracy 92%). Conclusion: Histology can be used in a bimodal fashion as a diagnostic test for FRI. The presence of more than five NPs/HPF had a positive predictive value for infected nonunion of 100%, while the complete absence of any NPs is almost always indicative of an aseptic nonunion (positive predictive value of 98%). Cite this article: Bone Joint J 2018;100-B:966-72.

Histopathology in Periprosthetic Joint Infection: When Will the Morphomolecular Diagnosis Be a Reality?

The presence of a polymorphonuclear neutrophil infiltrate in periprosthetic tissues has been shown to correlate closely with the diagnosis of septic implant failure. The histological criterion considered by the Musculoskeletal Infection Society to be diagnostic of periprosthetic joint infection is "greater than five neutrophils per high-power field in five high-power fields observed from histologic analysis of periprosthetic tissue at ×400 magnification." Surgeons and pathologists should be aware of the qualifications introduced by different authors during the last years in the histological techniques, samples for histological study, cutoffs used for the diagnosis of infection, and types of patients studied. Recently, immunohistochemistry and histochemistry studies have appeared which suggest that the cutoff point of five polymorphonuclear neutrophils in five high-power fields is too high for the diagnosis of many periprosthetic joint infections. Therefore, morphomolecular techniques could help in the future to achieve a more reliable histological diagnosis of periprosthetic joint infection.

Angiopoietin-like 4 promotes osteosarcoma cell proliferation and migration and stimulates osteoclastogenesis.

BACKGROUND: Osteosarcoma is the most common primary bone cancer in children and young adults. It is highly aggressive and patients that present with metastasis have a poor prognosis. Angiopoietin-like 4 (ANGPTL4) drives the progression and metastasis of many solid tumours, but has not been described in osteosarcoma tissue. ANGPTL4 also enhances osteoclast activity, which is required for osteosarcoma growth in bone. We therefore investigated the expression and function of ANGPTL4 in human osteosarcoma tissue and cell lines. METHODS: Expression of ANGPTL4 in osteosarcoma tissue microarrays was determined by immunohistochemistry. Hypoxic secretion of ANGPTL4 was tested by ELISA and Western blot. Regulation of ANGPTL4 by hypoxia-inducible factor (HIF) was investigated using isoform specific HIF siRNA (HIF-1α, HIF-2α). Effects of ANGPTL4 on cell proliferation, migration (scratch wound assay), colony formation and osteoblastogenesis were assessed using exogenous ANGPTL4 or cells stably transfected with ANGPTL4. Osteoclastogenic differentiation of CD14+ monocytes was assessed by staining for tartrate-resistant acid phosphatase (TRAP), bone resorption was assessed by lacunar resorption of dentine. RESULTS: ANGPTL4 was immunohistochemically detectable in 76/109 cases. ANGPTL4 was induced by hypoxia in 6 osteosarcoma cell lines, under the control of the HIF-1α transcription factor. MG-63 cells transfected with an ANGPTL4 over-expression plasmid exhibited increased proliferation and migration capacity and promoted osteoclastogenesis and osteoclast-mediated bone resorption. Individually the full-length form of ANGPTL4 could increase MG-63 cell proliferation, whereas N-terminal ANGPTL4 mediated the other pro-tumourigenic phenotypes. CONCLUSIONS: This study describes a role(s) for ANGPTL4 in osteosarcoma and identifies ANGPTL4 as a treatment target that could potentially reduce tumour progression, inhibit angiogenesis, reduce bone destruction and prevent metastatic events.

Pleomorphic liposarcoma of bone: a rare primary malignant bone tumour.

BACKGROUND: Liposarcoma is an extremely rare primary bone sarcoma. CASE PRESENTATION: We report a case of primary pleomorphic liposarcoma that arose in an 18 year old male in the metaphysis of the left tibia. Plain radiographs showed a partly sclerotic lesion and MR imaging a heterogeneous tumour predominantly isointense on T1- and high-signal on T2-weighted sequences with focal areas of increased T1 signal that suppressed with fat saturation. PET/CT showed marked FDG uptake (SUV = 17.1) in the primary tumour as well as a metastasis in the right distal femur and multiple small pulmonary metastases. Histologically, the tumour was a pleomorphic liposarcoma containing large tumour cells with vacuolated cytoplasm and hyperchromatic pleomorphic nuclei as well as numerous lipoblasts and scattered brown fat-like cells. Tumour cells strongly expressed FABP4/aP2, a marker of adipocyte differentiation, and UCP1, a marker of brown fat, but not S100. The case was treated with neoadjuvant MAP chemotherapy, resulting in extensive (> 95%) necrosis in the primary tumour and almost complete resolution of the femoral and pulmonary metastases. CONCLUSIONS: Pleomorphic liposarcoma can present as a sclerotic primary malignant bone tumour; markers of adipose differentiation are useful in histological diagnosis and neoadjuvant MAP chemotherapy results in significant tumor necrosis.

Fracture-related infection: A consensus on definition from an international expert group.

Fracture-related infection (FRI) is a common and serious complication in trauma surgery. Accurately estimating the impact of this complication has been hampered by the lack of a clear definition. The absence of a working definition of FRI renders existing studies difficult to evaluate or compare. In order to address this issue, an expert group comprised of a number of scientific and medical organizations has been convened, with the support of the AO Foundation, in order to develop a consensus definition. The process that led to this proposed definition started with a systematic literature review, which revealed that the majority of randomized controlled trials in fracture care do not use a standardized definition of FRI. In response to this conclusion, an international survey on the need for and key components of a definition of FRI was distributed amongst all registered AOTrauma users. Approximately 90% of the more than 2000 surgeons who responded suggested that a definition of FRI is required. As a final step, a consensus meeting was held with an expert panel. The outcome of this process led to a consensus definition of FRI. Two levels of certainty around diagnostic features were defined. Criteria could be confirmatory (infection definitely present) or suggestive. Four confirmatory criteria were defined: Fistula, sinus or wound breakdown; Purulent drainage from the wound or presence of pus during surgery; Phenotypically indistinguishable pathogens identified by culture from at least two separate deep tissue/implant specimens; Presence of microorganisms in deep tissue taken during an operative intervention, as confirmed by histopathological examination. Furthermore, a list of suggestive criteria was defined. These require further investigations in order to look for confirmatory criteria. In the current paper, an overview is provided of the proposed definition and a rationale for each component and decision. The intention of establishing this definition of FRI was to offer clinicians the opportunity to standardize clinical reports and improve the quality of published literature. It is important to note that the proposed definition was not designed to guide treatment of FRI and should be validated by prospective data collection in the future.

Utility of VS38c in the diagnostic and prognostic assessment of osteosarcoma and other bone tumours/tumour-like lesions.

BACKGROUND: VS38c is a monoclonal antibody that recognises a rough endoplasmic reticulum (rER) intracellular antigen termed cytoskeleton-linking membrane protein 63. rER is typically found in viable tumour cells and is abundant in osteosarcoma cells. The aim of this study was to determine the diagnostic and prognostic utility of VS38c in the histological assessment of osteosarcoma and other bone tumours/tumour-like leisons. METHODS: Immunohistochemical staining with VS38c was carried out on formalin-fixed specimens of osteosarcoma (pre/post-chemotherapy) and a wide range of benign and malignant bone lesions. In addition, VS38c staining of cultures of MG63 and Sa0S2 osteosarcoma cell cultures. (±cisplatin and actinomycin D-treatment) was analysed. RESULTS: VS38c strongly stained tumour cells in all low-grade and high-grade osteosarcomas and in undifferentiated sarcomas and high-grade chondrosarcomas. There was little or no VS38c staining of low-grade chondrosarcomas or chordomas and variable staining of Ewing sarcomas. Osteoblasts in benign bone-forming tumours and mononuclear stromal cells in chondroblastomas, giant cell tumours and non-ossifying fibromas strongly stained for VS38c. VS38c staining was absent in cisplatin and actinomycin D treated Sa0S2 and MG63 cells. In specimens of osteosarcoma post-neoadjuvant therapy, VS38c staining was absent in most morphologically necrotic areas of tumor although some cells with pyknotic nuclei stained for VS38c in these areas. Most tumour cells exhibiting atypical nuclear forms were not stained by VS38c. CONCLUSIONS: Our findings show that VS38c is a sensitive but not specific diagnostic marker of osteosarcoma. Staining with VS38c identifies viable osteosarcoma cells, a feature which may be useful in the assessment of percentage tumour necrosis post-neoadjuvant chemotherapy.

Metal wear-induced pseudotumour following an endoprosthetic knee replacement for Ewing sarcoma.

Pseudotumours are well recognised as a complication of metal-on-metal hip arthroplasties and are thought to develop on the basis of an innate and adaptive immune response to cobalt-chrome (Co-Cr) wear particles. We report a case of a large pseudotumour that developed following a knee endoprosthetic replacement (EPR) undertaken for Ewing sarcoma. The lesion contained necrotic and degenerate connective tissue in which there were numerous scattered metal wear-containing macrophages, eosinophil polymorphs, lymphocytes, plasma cells and aseptic lymphocyte-dominated vascular-associated lesion-like lymphoid aggregates. Metal ion levels were elevated. No evidence of infection or tumour was noted and it was concluded that the lesion was most likely an inflammatory pseudotumour developing on the basis of an innate and adaptive immune response to components of Co-Cr metal wear derived from the knee EPR.

Development of malignant lymphoma after metal-on-metal hip replacement: a case report and review of the literature.

A number of previous studies have reported a potential risk of malignancy, particularly hematological malignancy, developing in patients receiving a metal-on-metal (MoM) hip replacement. We report a case of malignant lymphoma that arose in a patient who had an MoM hip arthroplasty complicated by development of a pseudotumour. The tumour was a B cell follicular lymphoma that involved lymph nodes and bone. Metal ions are known to have a genotoxic effect on lymphoid cells. Although epidemiological studies have not established that there is an increased risk of lymphoma associated with MoM implants, only a relatively short time period has elapsed since re-introduction of this type of implant and long-term follow-up of patients with MoM implants is indicated.

Comparison of outcomes after UKA in patients with and without chondrocalcinosis: a matched cohort study.

PURPOSE: Chondrocalcinosis can be associated with an inflammatory arthritis and aggressive joint destruction. There is uncertainty as to whether chondrocalcinosis represents a contraindication to unicompartmental knee arthroplasty (UKA). This study reports the outcome of a consecutive series of patients with chondrocalcinosis and medial compartment osteoarthritis treated with UKA matched to controls. METHODS: Between 1998 and 2008, 88 patients with radiological chondrocalcinosis (R-CCK) and 67 patients with histological chondrocalcinosis (H-CCK) were treated for end-stage medial compartment arthritis with Oxford UKA. One-to-two matching was performed to controls, treated with UKA, but without evidence of chondrocalcinosis. Functional outcome and implant survival were assessed in each group. RESULTS: The mean follow-up was 10 years. The mean Oxford Knee Score (OKS) at final follow-up was 43, 41 and 41 in H-CCK, R-CCK and control groups (change from baseline OKS was 21, 18 and 15, respectively). The change was significantly higher in H-CCK than in control but was not significantly different in R-CCK. Ten-year survival was 96 % in R-CCK, 86 % in H-CCK and 98 % in controls. Although the survival in H-CCK was significantly worse than in control, only one failure was due to disease progression. CONCLUSION: The presence of R-CCK does not influence functional outcome or survival following UKA. Pre-operative radiological evidence of CCK should not be considered to be a contraindication to UKA. H-CCK is associated with significantly improved clinical outcomes but also a higher revision rate compared with controls. LEVEL OF EVIDENCE: Case control study, Level III.

Intraosseous hibernoma: a rare adipocytic bone tumour.

Hibernoma is a benign adipose tumour that contains foetal brown fat cells. We report a case of hibernoma arising in the left ischium of a 65-year-old female with a past history of ovarian carcinoma. The patient presented with a relatively short history of left sacral/hip pain. Radiologically, the lesion, which was large (5 cm) and sclerotic, had been stable for a number of years. Histologically, it was composed mainly of plump cells with foamy, multivacuolated cytoplasm. These cells showed no reaction for epithelial, melanoma or leucocyte markers but expressed FABP4/aP2 and S100, indicating that they were brown fat cells. There was no mitotic activity or nuclear pleomorphism and the lesion was diagnosed as a benign intraosseous hibernoma (IOH). IOH is a recently identified benign adipocytic lesion that presents typically as a sclerotic bone lesion. It has characteristic morphological and immunophenotypic features and should be regarded as a discrete primary bone tumour that needs to be distinguished from metastatic carcinoma/melanoma, chondrosarcoma and metabolic storage diseases containing numerous foamy macrophages.

Dendritic and mast cell involvement in the inflammatory response to primary malignant bone tumours.

BACKGROUND: A chronic inflammatory cell infiltrate is commonly seen in response to primary malignant tumours of bone. This is known to contain tumour-associated macrophages (TAMs) and lymphocytes; dendritic cells (DCs) and mast cells (MCs) have also been identified but whether these and other inflammatory cells are seen commonly in specific types of bone sarcoma is uncertain. METHODS: In this study we determined the nature of the inflammatory cell infiltrate in 56 primary bone sarcomas. Immunohistochemistry using monoclonal antibodies was employed to assess semiquantitatively CD45+ leukocyte infiltration and the extent of the DC, MC, TAM and T and B lymphocyte infiltrate. RESULTS: The extent of the inflammatory infiltrate in individual sarcomas was very variable. A moderate or heavy leukocyte infiltrate was more commonly seen in conventional high-grade osteosarcoma, undifferentiated pleomorphic sarcoma and giant cell tumour of bone (GCTB) than in Ewing sarcoma, chordoma and chondrosarcoma. CD14+/CD68+ TAMs and CD3+ T lymphocytes were the major components of the inflammatory cell response but (DC-SIGN/CD11c+) DCs were also commonly noted when there was a significant TAM and T lymphocyte infiltrate. MCs were identified mainly at the periphery of sarcomas, including the osteolytic tumour-bone interface. DISCUSSION: Our findings indicate that, although variable, some malignant bone tumours (e.g. osteosarcoma, GCTB) are more commonly associated with a pronounced inflammatory cell infiltrate than others (e.g. chondrosarcoma. Ewing sarcoma); the infiltrate is composed mainly of TAMs but includes a significant DC, T lymphocyte and MC infiltrate. CONCLUSION: Tumours that contain a heavy inflammatory cell response, which includes DCs, TAMs and T lymphocytes, may be more amenable to immunomodulatory therapy. MCs are present mainly at the tumour edge and are likely to contribute to osteolysis and tumour invasion.

Primary intraosseous meningioma: an osteosclerotic bone tumour mimicking malignancy.

BACKGROUND: Sclerotic tumours of the calvarial bones are rare and may be due to primary and secondary bone tumours as well as extradural tumours of meningeal origin. CASE PRESENTATION: We report a case of primary intraosseous meningioma (PIM) which arose in the frontal bone of a 63 year old woman who complained of progressive pain and thickening of the right skull. Radiology showed a large osteosclerotic lesion in the right frontal bone. Histology showed an intraosseous lesion containing dense fibrous tissue in which there were scattered cells that expressed epithelial membrane antigen and progesterone receptor. The tumour was partially resected and 3 years after operation has not recurred. CONCLUSIONS: PIM is a rare tumour which needs to be distinguished from primary/secondary osteosclerotic calvarial bone tumours.