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.

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.

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.

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.

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.

Primary synovial chondromatosis: a reassessment of malignant potential in 155 cases.

OBJECTIVE: Primary synovial chondromatosis (PSC) is a rare disorder characterised by cartilage formation in synovium-lined joints, tendon sheaths and bursae. It is thought that PSC cartilage arises from the proliferation of mesenchymal cells, which exhibit cartilaginous metaplasia in subintimal connective tissue. There are reports of transformation of PSC to chondrosarcoma, although the precise incidence and nature of this complication is uncertain. In this study we carried out a retrospective review PSC to determine the incidence of sarcomatous change in this condition, in addition to the clinical, radiological and pathological features that characterise this complication MATERIALS AND METHODS: We reviewed 155 cases of PSC and identified 4 cases (3 in the hip joint; 1 in the elbow joint) of aggressive behaviour and chondrosarcoma-like histology. RESULTS: Radiologically, these cases were all reported as showing features consistent with PSC and aggressive extra-articular soft tissue/bone involvement. Histologically, in addition to typical features of PSC, there was morphological evidence of peri-articular soft tissue and, in 2 cases, bone involvement by an infiltrating cartilaginous tumour. These tumours all behaved as locally aggressive neoplasms and did not give rise to metastasis. CONCLUSION: Our findings show that chondrosarcoma arises infrequently in PSC (approximately 2.5 %), and that this complication occurs most commonly in the hip joint (approximately 11 % of cases of hip PSC). These tumours behaved mainly as low-grade, locally aggressive tumours analogous to atypical cartilaginous tumour of bone/grade 1 chondrosarcoma of bone.

The role of calcium and nicotinic acid adenine dinucleotide phosphate (NAADP) in human osteoclast formation and resorption.

Osteoclasts are specialised bone resorbing cells which form by fusion of circulating mononuclear phagocyte precursors. Bone resorption results in the release of large amounts of calcium into the extracellular fluid (ECF), but it is not certain whether changes in extracellular calcium concentration [Ca(2+)]e influence osteoclast formation and resorption. In this study, we sought to determine the effect of [Ca(2+)]e and NAADP, a potent calcium mobilising messenger that induces calcium uptake, on human osteoclast formation and resorption. CD14+ human monocytes were cultured with M-CSF and RANKL in the presence of different concentrations of calcium and NAADP and the effect on osteoclast formation and resorption evaluated. We found that the number of TRAP+ multinucleated cells and the extent of lacunar resorption were reduced when there was an increase in extracellular calcium and NAADP. This was associated with a decrease in RANK mRNA expression by CD14+ cells. At high concentrations (20 mM) of [Ca(2+)]e mature osteoclast resorption activity remained unaltered relative to control cultures. Our findings indicate that osteoclast formation is inhibited by a rise in [Ca(2+)]e and that RANK expression by mononuclear phagocyte osteoclast precursors is also [Ca(2+)]e dependent. Changes in NAADP also influence osteoclast formation, suggesting a role for this molecule in calcium handling. Osteoclasts remained capable of lacunar resorption, even at high ECF [Ca(2+)]e, in keeping with their role in physiological and pathological bone resorption.

Investigation of osteoclastogenic signalling of the RANKL substitute LIGHT.

LIGHT (TNFSF14) is a member of the TNF superfamily and is known to substitute for RANKL to induce osteoclast differentiation. LIGHT binds HVEM and LTßR, but it is not known whether these receptors play a role in osteoclast formation or whether LIGHT acts via RANKL signalling pathways. We found that both RANKL and LIGHT strongly induced phosphorylation of Akt and NFκB but not JNK in mouse osteoclast precursor cells. The addition of an Akt inhibitor showed decreased osteoclast differentiation and resorption mediated by both RANKL and LIGHT. RT-PCR and FACS analysis showed that CD14(+) human osteoclast precursors expressed HVEM and LTßR; expression levels of HVEM increased in the course of osteoclastogenesis and a decrease in LIGHT expression was associated with an increase in HVEM suggesting that there is a feedback loop related to this receptor. Our findings show that LIGHT is not inhibited by the soluble RANKL receptor OPG and that LIGHT is a potent osteoclastogenesis factor that activates the Akt, NFκB and JNK pathways.

Giant-cell-rich pseudotumour in Paget's disease.

Paget's disease (PD) of the bone is a disorder of bone remodelling that may be polyostotic or monostotic. Although development of a sarcoma in PD is well-recognised, it is less well recognised that pseudosarcomas in bone and soft tissue can also arise in this condition. In this report we document the case of a large giant-cell-rich pseudotumour that developed in the tibia and overlying soft tissues in a case of polyostotic PD. Bone and soft tissues were highly vascular and contained abundant haemorrhage with focal areas of new bone formation and a diffuse infiltrate of osteoclastic giant cells. The lesion has not recurred or produced metastases 3 years after removal. Clinicians should be aware that a benign giant-cell-rich pseudotumour can develop in PD and that it needs to be distinguished from other giant-cell-rich tumours.

Intraosseous schwannoma in schwannomatosis.

This study investigates the clinical, radiological, and pathological features of two cases of intraosseous schwannoma that arose in patients with multiple soft tissue schwannomas. In both cases, the patients were adult females and the tibial bone was affected. Vestibular schwannomas were not identified, indicating that these were not cases of neurofibromatosis 2 (NF2). Radiographs showed a well-defined lytic lesion in the proximal tibia; in one case, this was associated with a pathological fracture. Histologically, both cases showed typical features of benign schwannoma. Molecular analysis of one of the excised tumors showed different alterations in the NF2 gene in keeping with a diagnosis of schwannomatosis. Our findings show for the first time that intraosseous schwannomas can occur in schwannomatosis.

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.

In vitro generation of mature human osteoclasts.

Mononuclear precursors of human osteoclasts are found in the CD14(+) monocyte fraction of circulating peripheral blood mononuclear cells (PBMCs). It is possible to generate osteoclasts in vitro from PBMCs cultured with macrophage colony-stimulating factor and receptor activator for nuclear factor κB ligand. In these cultures, however, it is not possible to distinguish the effect of a specific agent on osteoclast resorption activity as opposed to osteoclast differentiation. To produce a population of mature human osteoclasts to study osteoclast lacunar resorption specifically, we cultured CD14(+) human monocytes on hydrophobic dishes in order to generate and maintain osteoclasts in suspension prior to culturing them on coverslips and dentine slices. Multinucleated cells formed in these cultures expressed vitronectin receptor, tartrate-resistant acid phosphatase, and cathepsin K. These cells also produced F-actin rings and were capable of extensive lacunar resorption on dentine slices after 24 h in culture. Lacunar resorption was inhibited by calcitonin and zoledronate but not by osteoprotegerin. This method of generating a highly enriched population of mature human osteoclasts should provide a valuable means of specifically assessing the effect of molecular factors (e.g., cytokines, growth factors, hormones) and therapeutic agents on osteoclast resorption activity.

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.

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.

Fine mapping of the MHC Class III region demonstrates association of AIF1 and rheumatoid arthritis.

OBJECTIVES: The heritability of RA has been estimated to be approximately 55%, of which the MHC contributes about one-third. HLA-DRB1 alleles are strongly associated with RA, but it is likely that significant non-DRB1 MHC genetic susceptibility factors are involved. Previously, we identified two three-marker haplotypes in a 106-kb region in the MHC class III region immediately centromeric to TNF, which are strongly associated with RA on HLA-DRB1*0404 haplotypes. In the present study, we aimed to refine these associations further using a combination of genotyping and gene expression studies. METHODS: Thirty-nine nucleotide polymorphisms (SNPs) were genotyped in 95 DRB1*0404 carrying unrelated RA cases, 125 DRB1*0404-carrying healthy controls and 87 parent-case trio RA families in which the affected child carried HLA-DRB1*04. Quantitative RT-PCR was used to assess the expression of the positional candidate MHC class III genes APOM, BAT2, BAT3, BAT4, BAT5, AIF1, C6orf47, CSNK2beta and LY6G5C, and the housekeeper genes, hypoxanthine-guanine phosphoribosyltransferase (HPRT) and beta(2)-microglobulin (B2M) in 31 RA cases and 21 ethnically, age- and sex-matched healthy controls. Synovial membrane specimens from RA, PsA and OA cases were stained by an indirect immunoperoxidase technique using a mouse-anti-human AIF1 monoclonal antibody. RESULTS: Association was observed between RA and single markers or two marker haplotypes involving AIF1, BAT3 and CSNK. AIF1 was also significantly overexpressed in RA mononuclear cells (1.5- to 1.9-fold difference, P = 0.02 vs HPRT, P = 0.002 vs B2M). AIF1 protein was clearly expressed by synovial macrophages in all the inflammatory synovial samples in contrast to the non-inflammatory OA samples. CONCLUSIONS: The results of the genotyping and expression studies presented here suggest a role for AIF1 in both the aetiology and pathogenesis of RA.

Intratumoural lymphatics in benign and malignant soft tissue tumours.

Soft tissue sarcomas do not generally metastasise via lymphatics, and the presence or absence of lymphatic vessels within sarcomas and benign soft tissue tumours is not known. In this study, we determined whether lymphatic vessels were present in a wide range of benign and malignant soft tissue lesions by examining intratumoural expression of the lymphatic endothelial cell markers, Lyve-1 and podoplanin. Intratumoural Lyve-1+/podoplanin+ lymphatics were not identified in sarcomas apart from all cases of epithelioid sarcoma (a tumour which is known to metastasise to lymph nodes) and a few cases of leiomyosarcoma, rhabdomyosarcoma and synovial sarcoma. Intratumoural lymphatics were also absent in most benign soft tissue tumours. Reparative and inflammatory soft tissue lesions contained lymphatics, as did all (pseudosarcomatous) proliferative myofibroblastic lesions including nodular, proliferative and ischaemic fasciitis, elastofibroma, nuchal fibroma and deep fibromatosis. Our results show that most soft tissue sarcomas do not contain intratumoural lymphatics, a finding which is consistent with the infrequent finding of sarcoma metastasis to lymph nodes. In contrast to fibrosarcoma and a number of other malignant spindle cell tumours, proliferative fibroblastic/myofibroblastic lesions of soft tissue contain intralesional lymphatic vessels.

Necrotic granulomatous pseudotumours in bilateral resurfacing hip arthoplasties: evidence for a type IV immune response.

Clinical, radiological and histological findings were analysed in four patients who developed bilateral pseudotumours following metal-on-metal (MoM) resurfacing arthroplasties of both hips. Using a panel of monoclonal antibodies directed against HLA-DR, macrophages (CD14, CD68), dendritic cells (DC-SIGN, S100, CD11c), B cells (CD20), and T cells (CD3, CD4, CD8), the nature of the heavy inflammatory response seen in these cases was examined. Bilateral masses developed in periprosthetic soft tissues following the second MoM arthroplasty; these were characterised histologically by extensive coagulative necrosis, a heavy macrophage infiltrate and the presence of granulomas containing macrophages and giant cells; there was also a diffuse lymphocyte and variable plasma cell and eosinophil polymorph infiltrate. Immunohistochemistry showed strong expression of HLA-DR, CD14 and CD68 in both granulomatous and necrotic areas; lymphocytes were predominantly CD3+/CD4+ T cells. The clinical, morphological and immunophenotypic features of these necrotic granulomatous pseudotumours, which in all cases develop following a second resurfacing hip arthroplasty, is suggestive of a type IV immune response, possibly to MoM metal alloy components.