A literature review and expert consensus statement on diagnostics in suspected metal implant allergy.

BACKGROUND: Although rare, allergic reactions to metal implants represent a diagnostic challenge in view of missing guidelines. OBJECTIVES: To develop an European expert consensus on characteristics of metal allergy reactions and the utility of various diagnostic tools in suspected metal implant allergy. METHODS: A nominal group technique (NGT) was applied to develop consensus statements. Initially an online literature database was created on a secure server to enable a comprehensive information. Twenty-three statements were formulated on potential aspects of metal implant allergy with a focus on diagnostics and grouped into five domains. For the consensus development, the panel of 12 experts initially did refine and reformulate those statements that were ambiguous or had unclear wording. By face-to-face (9/12) or virtual participation (3/12), an anonymous online voting was performed. RESULTS: Consensus (≥80% of agreement) was reached in 20/23 statements. The panel agreed that implant allergy despite being rare should be considered in case of persistent unexplained symptoms. It was, however, recommended to allow adequate time for resolution of symptoms associated with healing and integration of an implant. Obtaining questionnaire-aided standardized medical history and standardized scoring of patient outcomes was also considered an important step by all experts There was broad consensus regarding the utility/performance of patch testing with additional late reading. It was recognized that the lymphocyte transformation test (LTT) has to many limitations to be generally recommended. Prior to orthopaedic implant, allergy screening of patients without a history of potential allergy to implant components was not recommended. CONCLUSIONS: Using an expert consensus process, statements concerning allergy diagnostics in suspected metal implant allergy were created. Areas of nonconsensus were identified, stressing uncertainty among the experts around topics such as preoperative testing in assumed allergy, histological correlate of periimplant allergy and in vitro testing, which underscores the need for further research.

[Localized tenosynovial giant cell tumor : Results from the Histopathological Arthritis Register of the German Society for Orthopedic Rheumatology]. / Der lokalisierte tenosynoviale Riesenzelltumor (L-TSRZT) : Ergebnisse aus dem histopathologischen Arthritisregister der Deutschen Gesellschaft für Orthopädische Rheumatologie.

BACKGROUND: The tenosynovial giant cell tumor (pigmented villonodular synovitis) is a proliferative, mainly benign soft tissue tumor of the tendon sheaths, bursae and joints arising from the synovia. It can be divided into circumscribed localized and destructive diffuse types. Approximately 1% of all joint diseases are due to this entity. The tumor is considered as a rarity. Mostly case studies exist. For this study the focus was set on the localized type (L-TSRZT), which accounts for 90% of the diagnoses of this tumor. Given its rarity, data are limited. Therefore, the research aim was to provide data on prevalence, primary location and sensitivity of clinical versus histopathological diagnosis in a German sample. METHODS: Based on the Histopathological Arthritis Register of the German Society for Orthopedic Rheumatology, the data of the L­TSRZT were retrospectively analyzed (time frame 1 January 2018-28 December 2020). RESULTS: This database contained N = 7595 cases of arthropathy. A total of n = 45 patients with the diagnosis L­TSRZT were identified. The prevalence of the tumor was 0.6%, 95% CI [0.4%, 0.8%], or 5.9 cases per 1000. The primary location involved the finger (48.9%). In 14 of 45 cases the diagnosis was correctly determined from the clinical side, corresponding to a sensitivity of 31.1%, 95% CI [18.2%, 46.7%]. CONCLUSION: For the first time, this paper was able to provide data on a large sample for Germany. Notably, the low sensitivity of the clinical diagnosis confirms the importance of histopathology for diagnosing L­TSRZT.

Diagnostic value of the CD 15 focus score in two-stage revision arthroplasty of periprosthetic joint infections : High specificity in diagnosing infect eradication.

INTRODUCTION: The purpose of this study is to use the CD15 focus score (FS) to determine the sensitivity and specificity of bacterial infection persistence in spacer-based two-stage revision arthroplasty. METHODS: The analysis comprises 112 cases that were subjected to revision due to the presence of infection upon replacement of a joint endoprosthesis. The histopathological data were collected in accordance with the synovial-like interface membrane (SLIM) classification and the CD15-FS and correlated with the microbiological data (MD). The quantifying evaluation of the CD15-FS was performed without knowledge regarding the microbiological data (MD). Correlation with the MD was performed after a 14-day cultivation period. RESULTS: With a single evaluation (1 focus, field area: 1.2 mm2) with a score value of 42, the CD15-FS showed a sensitivity for the eradication of infections of 0.64 and a specificity of 0.79 (PPV = 0.5; NPV = 0.87). With tenfold evaluation (10 foci, field area: 12 mm2) with a score value of 220, the sensitivity for the eradication was 0.68, the specificity 0.91 (PPV = 0.7; NPV = 0.89). No statistically significant correlation between the score values and the different infectious species could be detected. Based on the MD in 112 cases the rate of infection eradication was 75%. Polymethylmethacrylate-particles (PMMA) were detected in the perispacertissue in 64 cases (58%). No significant correlation could be established between microbiological pathogen detection and the presence of PMMA. CONCLUSION: In all cases (n = 112), periimplant synovial tissue (SLIM) with variable fibroblastic cellularity, capillary proliferation, leukocytic infiltration, fibrin deposition, new formation of woven bone and detection of PMMA particles was observed. These cases were classified as type IX perispacer synovialis/SLIM: type IX­A with histopathological infection eradication and type IX­B with histopathological infection persistence.

[Joint tumors: rare but important differential diagnoses of malignant and benign tumors as well as pseudotumors in rheumatology]. / Gelenktumoren: Seltene, aber wichtige Differenzialdiagnosen von malignen und benignen Tumoren sowie Pseudotumoren in der Rheumatologie.

This review article elucidates the differential diagnostics of malignant and benign joint tumors, pseudotumors of the joints and the peri-implant tissue, which are rare but important entities in rheumatology and orthopedic rheumatology. The tissue of origin includes the synovium, peri-implant tissue, peri-articular fibrous tissue and peri-articular osseous tissue. Pseudotumors can be viewed as independent but heterogeneous entities. These are essentially manifested as tumor-like depositions of crystals, calcareous deposits, vascular malformations, ectasia of the synovia and joint capsule tissue and pseudocysts. Other causes for pseudotumors are focal destructive inflammation (e.g. induced by foreign bodies), high grade synovitis and focal fibrinoid necrosis (i.e. rheumatoid nodules). Methodologically, these diagnostics are based on conventional standard staining methods, immunohistochemical analyses of formalin-fixed and paraffin-embedded materials and on molecular diagnostic procedures. The latter are of great importance in cases of benign and malignant joint tumors. The most important immunohistochemical markers with respect to joint tumors are S100, SM-actin, CD68, CD34, STAT6, clusterin, Muc­4, beta-catenin and MDM2-FISH. The following markers are recommended for the differential diagnostics and typing of periarticular tumor metastases in the pathology of rheumatic diseases: AE1/AE3, CK8, p63, TTF­1, TGB, PSA, androgen receptor, GATA, CD56, chromogranin, CDX­2, SAT-B2, SALL4, estrogen and progesterone receptors, CD45LCA, CD30, CD79a and S100. Necrosis, inflammatory infiltrations and reparative inflammatory changes may complicate the histopathological classification. Therefore, a correlation with clinical, microbiological and radiological data in the sense of interdisciplinary synergistic diagnostics may be required.

Diagnostic guidelines for the histological particle algorithm in the periprosthetic neo-synovial tissue.

BACKGROUND: The identification of implant wear particles and non-implant related particles and the characterization of the inflammatory responses in the periprosthetic neo-synovial membrane, bone, and the synovial-like interface membrane (SLIM) play an important role for the evaluation of clinical outcome, correlation with radiological and implant retrieval studies, and understanding of the biological pathways contributing to implant failures in joint arthroplasty. The purpose of this study is to present a comprehensive histological particle algorithm (HPA) as a practical guide to particle identification at routine light microscopy examination. METHODS: The cases used for particle analysis were selected retrospectively from the archives of two institutions and were representative of the implant wear and non-implant related particle spectrum. All particle categories were described according to their size, shape, colour and properties observed at light microscopy, under polarized light, and after histochemical stains when necessary. A unified range of particle size, defined as a measure of length only, is proposed for the wear particles with five classes for polyethylene (PE) particles and four classes for conventional and corrosion metallic particles and ceramic particles. RESULTS: All implant wear and non-implant related particles were described and illustrated in detail by category. A particle scoring system for the periprosthetic tissue/SLIM is proposed as follows: 1) Wear particle identification at light microscopy with a two-step analysis at low (× 25, × 40, and × 100) and high magnification (× 200 and × 400); 2) Identification of the predominant wear particle type with size determination; 3) The presence of non-implant related endogenous and/or foreign particles. A guide for a comprehensive pathology report is also provided with sections for macroscopic and microscopic description, and diagnosis. CONCLUSIONS: The HPA should be considered a standard for the histological analysis of periprosthetic neo-synovial membrane, bone, and SLIM. It provides a basic, standardized tool for the identification of implant wear and non-implant related particles at routine light microscopy examination and aims at reducing intra-observer and inter-observer variability to provide a common platform for multicentric implant retrieval/radiological/histological studies and valuable data for the risk assessment of implant performance for regional and national implant registries and government agencies.

[Pathophysiology of aseptic femoral head necrosis: Pathogenesis and histopathological differential diagnosis]. / Pathophysiologie der aseptischen Hüftkopfnekrose: Pathogenese und histopathologische Differenzialdiagnostik.

BACKGROUND: Aseptic osteonecrosis is characterized by a complete death of the tissue (necrosis), more specifically, an ischemic necrosis of the lamellar bone tissue. The denotation aseptic refers to causal pathogenesis; therefore, it is not a matter of an infectious, septic-induced bone necrosis as in the case of acute infectious osteomyelitis. Formal pathogenesis leads to either (1) a hypoperfusion of the lamellar bone in the sense of an ischemic necrosis or (2) to directly induced damage of osteocytes and osteoblasts, which causes aseptic osteonecrosis. CAUSE: The causes of hypoperfusion/ischemia are manifold and entail vascular malformations, coagulopathies, haemoglobinopathies, thrombotic embolisms, myeloproliferative illnesses, air embolisms, decompression-caused illnesses, macro as well as micro traumata and, finally, vasculitis with necrosis, which complete the vascular-induced spectrum. Direct toxic damage to the osteocytes and osteoblasts is primarily caused by alcohol abuse, medical drug therapies (i. e. chemotherapeutic substances or cortisone) and disorders of the lipid embolism. Contemporary molecular and cellular models of pathogenesis assume a so-called dysbalance of the catabolic and anabolic osseous metabolism in osteocytes and osteoblasts. The RANKL-RANK system, the ROS system and PPAR-gamma signal transduction are involved in the molecular pathogenesis. DIFFERENTIAL DIAGNOSIS: The most relevant histopathologic differential diagnosis entails the complete spectrum of focal osseous changes among which osteonecrosis can occur to a diverse extent: infectious osteomyelitis, chronic immunologic induced osteomyelitis, pseudoarthrosis, infected pseudoarthrosis, bone fractures and malignant metastatic intraosseous diseases and non-metastatic intraosseous malignant diseases.

[Arthur Vick Prize 2017 of the German Society of Orthopaedic Rheumatology]. / Arthur-Vick-Preis der Deutschen Gesellschaft für Orthopädische Rheumatologie 2017.

The German Society of Orthopaedic Rheumatology (DGORh) honored Prof. Dr. med. Veit Krenn (MVZ-ZHZMD-Trier) with the Arthur Vick Prize 2017. With this award, scientific results with high impact on the diagnosis, therapy and pathogenetic understanding of rheumatic diseases are honored. In cooperation with pathologists and colleagues from various clinical disciplines Prof. Dr. med. Veit Krenn developed several histopathologic scoring systems which contribute to the diagnosis and pathogenetic understanding of degenerative and rheumatic diseases. These scores include the synovitis score, the meniscal degeneration score, the classification of periprosthetic tissues (SLIM classification), the arthrofibrosis score, the particle score and the CD15 focus score. Of highest relevance for orthopedic rheumatology is the synovitis score which is a semiquantitative score for evaluating immunological and inflammatory changes of synovitis in a graded manner. Based on this score, it is possible to divide results into low-grade synovitis and high-grade synovitis: a synovitis score of 1-4 is called low-grade synovitis and occurs for example in association with osteoarthritis (OA), post-trauma, with meniscal lesions and hemochromatosis. A synovitis score of 5-9 is called high-grade synovitis, e.g. rheumatoid arthritis, psoriatic arthritis, Lyme arthritis, postinfection and reactive arthritis as well as peripheral arthritis with Bechterew's disease (sensitivity 61.7%, specificity 96.1%). The first publication (2002) and an associated subsequent publication (2006) of the synovitis score has led to national and international acceptance of this score as the standard for histopathological assessment of synovitis. The synovitis score provides a diagnostic, standardized and reproducible histopathological evaluation method for joint diseases, particularly when this score is applied in the context with the joint pathology algorithm.

[Histopathological classification principles of rheumatic joint diseases : Contribution of pathology to the diagnosis]. / Histopathologische Klassifikationsprinzipien rheumatischer Gelenkerkrankungen : Beitrag der Pathologie zur Diagnose.

Even though the diagnostics of rheumatic joint diseases are mostly based on clinical, immunoserological and imaging criteria, histopathology can also make a significant contribution. This is particularly true for clinically unclear monoarticular and periarticular diseases. The contribution of histopathology to the diagnosis of rheumatic diseases is manifold since the histopathological differential diagnosis includes the complete spectrum of synovial diseases. This heterogeneous pathogenetic spectrum is described in the joint pathology algorithm, which includes inflammatory and non-inflammatory diseases. To the latter group belong certain benign tumors such as the diffuse variant of the tenosynovial giant cell tumor, lipoma, hemangioma, vascular malformations and synovial chondromatosis. Additionally, the rare group of storage diseases should be kept in mind. Inflammatory diseases can be discriminated into crystal-induced arthropathies mainly such as gout and pseudogout, into granulomatous diseases such as tuberculosis and foreign-body inoculations, and finally into the large group of non-granulomatous, non-infectious synovitis. This large group is by far the most common, and it often causes difficulties in assigning the histopathological findings to a concrete rheumatologic diagnosis. In this context the synovitis score should be applied as a diagnostic device in these cases, leading to the diagnosis of a low-grade synovitis (which is associated with degenerative arthropathies) or of a high-grade synovitis (associated with rheumatic diseases). Identification of crystals and crystal-like deposits should be carried out with the application of the joint particle algorithm which addresses the identification of endogenous and non-endogenous particle deposits in the synovial tissues. Additionally, the synovitis-score may be used for evaluation of arthritis-progresssion and for the evaluation of inflammation-regression as a consequence of therapy with biologicals.

[Endoprosthesis failure in the ankle joint : Histopathological diagnostics and classification]. / Endoprothesenversagen im oberen Sprunggelenk : Histopathologische Diagnostik und Klassifikation.

INTRODUCTION: Endoprostheses of the ankle joint show higher revision rates of 3.29 revisions per 100 component years. The aims of this study were the application and modification of the consensus classification of the synovia-like interface membrane (SLIM) for periprosthetic failure of the ankle joint, the etiological clarification of periprosthetic pseudocysts and a detailed measurement of proliferative activity (Ki67) in the region of osteolysis. MATERIAL AND METHOD: Tissue samples from 159 patients were examined according to the criteria of the standardized consensus classification. Of these, 117 cases were derived from periprosthetic membranes of the ankle. The control group included 42 tissue specimens from the hip and knee joints. Particle identification and characterization were carried out using the particle algorithm. An immunohistochemical examination with Ki67 proliferation was performed in all cases of ankle pseudocysts and 19 control cases. RESULTS: The consensus classification of SLIM is transferrable to endoprosthetic failure of the ankle joint. Periprosthetic pseudocysts with the histopathological characteristics of the appropriate SLIM subtype were detectable in 39 cases of ankle joint endoprostheses (33.3%). The mean value of the Ki67 index was 14% and showed an increased proliferation rate in periprosthetic pseudocysts of the ankle (p-value 0.02037). CONCLUSION: In periprosthetic pseudocysts an above average higher detection rate of type 1 SLIM induced by abrasion (51.3%) with an increased Ki67 proliferation fraction (p-value 0.02037) was found, which can be interpreted as local destructive intraosseus synovialitis. This can be the reason for formation of pseudocystic osteolysis caused by high mechanical stress in ankle endoprostheses. A simplified diagnostic classification scoring system of dysfunctional endoprostheses of the ankle is proposed for collation of periprosthetic pseudocysts, ossifications and the Ki67 proliferation fraction.

[Fifteen years of the histopathological synovitis score : Review and further developments of a diagnostic score]. / 15 Jahre histopathologischer Synovialitis-Score : Rückblick und Weiterentwicklung eines diagnostischen Scores.

The histopathological synovitis score evaluates in a graded approach, as is largely usual for diagnostic histopathological scores, the immunological and inflammatory changes caused by synovitis. A synovitis score of between 1 and ≤ 4 is classified as low-grade (osteoarthritis-related synovitis, post-traumatic synovitis, meniscopathy-related synovitis and synovitis in hemochromatosis). Synovitis scores of between ≥ 5 and 9 are classified as high-grade synovitis (rheumatoid arthritis, psoriatic arthritis, Lyme's arthritis, post-infection/reactive arthritis and peripheral arthritis in Bechterew disease); sensitivity is 61.7% and sensitivity 96.1%. According to receiver operating characteristic (ROC) analysis (AUC: 0.8-0.9), diagnostic value is good. National and international acceptance of the synovitis score has grown since the first publication in 2002 and a related follow-up publication in 2006. PubMed data analysis (as of 11.01.2017) yielded the following citation values according to "cited by PubMed Central articles" for two publications relating to the synovitis score: there were 29 cited-by-PubMed articles for DOI: 10.1078/0344-0338-5710261 , and 44 cited-in-PubMed articles for the second publication, DOI: 10.1111/j.1365-2559.2006.02508 . This makes a total of 73 PubMed citations over a period of 15 years, thereby evidencing the score's international acceptance. Immunohistochemical determination of a number of CD antigens relevant to inflammation has been proposed to further specify the synovitis score for the purposes of risk stratification of high-grade synovitis (e.g., risk of progression and sensitivity to biological agents).

[Adverse reactions to metal orthopedic implants after knee arthroplasty]. / Adverse Reaktionen gegenüber orthopädisch-chirurgischen Metallimplantaten nach Kniegelenkersatz.

Based on several clinical examples, the range of adverse or hypersensitive reactions to metal implants especially after total knee replacement are presented. In general, we found the patients to generally be women who present with pain, swelling, and local or generalized eczema. Some also present with early aseptic loosening mainly in the first 4 years after implantation. For these patients, a detailed allergy-specific history should be taken and a patch test should be performed; if necessary, blood ion levels should be evaluated to exclude cobaltism. Before revision surgery and exchange of the implant we always perform arthroscopic inspection to obtain biopsies for microbiology and histopathology. Using the Consensus Classification a good evaluation for planning revision with the different implant options is possible.

[Histopathological diagnostic work-up of joint endoprosthesis-associated pathologies]. / Histopathologische Diagnostik von Gelenkendoprothesen-assoziierten Erkrankungen.

Increasing classes of joint implants and the combination of materials results in increased and wear-associated pathologies. According to the revised consensus classification, the following types can be recognized at conventional histological examination: Type I, particle-induced type; Type II, infection type; Type III, combination type; Type IV, indifferent type; Type V arthrofibrotic type; Type VI, allergic/immunological/toxic adverse reactions and Type VII, bone pathologies. Wear particles are histopathologically characterized according to the Krenn particle algorithm which focuses on a descriptive identification of wear particles and the differentiation of other nonwear-related particles. Type VII is considered histologically when there is evidence of a perivascular/interstitial lymphocytic CD20- and CD3-positive infiltrate, presence of mast cells and eosinophils, and tissue necrosis/infarction associated with implant wear material. Since wear particle-induced toxicity cannot be differentiated with certainty from hypersensitivity/allergic reaction on histological examination, immunological-allergological and clinical data should be used as supplementary criteria for the differential diagnosis. Tissue sampling should be performed from periprosthetic soft tissue with location mapping and when feasible also from bone tissue. Additional information regarding the type of implant and clinical, radiological, immunological, and microbiology data should be available to the pathologist. Further immunohistochemical studies are recommended in the following settings: infection (CD15, CD20, CD68); prosthesis-associated arthrofibrosis (ß­catenin); allergic/immunologic/toxic adverse reactions (CD20, CD3, CD4, CD8, CD117 and for T­cell characterization T­bet, GATA-3, and FOXP3).

[Supramacroparticulate polyethylene in inflammation of synovial-like interface membranes: Characterization and suggested nomenclature]. / Supramakropartikuläres Polyethylen bei Entzündungen periprothetischer Membranen: Charakterisierung und Nomenklaturvorschlag.

BACKGROUND: The identification of particles of prosthesis material components in the histopathological diagnosis of synovialitis is of great importance in the evaluation of implant failure. MATERIALS AND METHODS: In histopathological particle algorithms, polyethylene (PE) particles with a maximum length of less than 100 µm are designated with the term macroparticles; however, a systematic investigation and characterization are lacking. RESULTS: In SLIM knee specimens (n = 24) a minimum value of 210 µm and a maximum value of 2100 µm were measured; the mathematical mean length varied between 235 µm and 1416 µm. In SLIM hip specimens (n = 11) the minimum value was 290 µm and the maximum value was 1806 µm; the mean length varied between 353 and 1726 µm. Because of this conspicuous size, and to distinguish from PE macroparticles, the designation PE supra-macroparticulate is suggested. This new terminology acknowledges the fact that these PE particles are visible under magnification (e.g., × 12.5) and also macroscopically. The particles were also indirectly proven as there were completely separate and optically clear, column-shaped cavities corresponding to the shape of the PE particles (PE vacuoles). The life of the prosthesis is highly variable at between 12 and 300 months. In all cases loosening of the prosthesis, misalignment of the PE components, and/or damage to the PE inlay occurred. CONCLUSION: The cause and existence of these supra-macroparticulate PE particles (more than 100 µm) is still unclear. A mechanical malfunction seems probable and should be discussed. In prostheses with short lives the proof of supra-macroparticulate PE in SLIM could be a sign of an early mechanical problem. In the wider histopathological particle algorithm supra-macroparticulate PE was considered to fall in the category of macroparticles and should be considered in the histopathological diagnosis of implant failure.

[Revision arthroplasty : Histopathological diagnostics in periprosthetic joint infections]. / Revisionsendoprothetik : Infektionsdiagnostik und Histopathologie.

BACKGROUND: Histopathological differences in synovia and synovial-like interface membrane (SLIM) patterns can be used to differentiate periprosthetic particle-induced reactions, bacterial infections (bacterial synovitis and osteomyelitis), mechanical-induced tissue alterations, adverse reactions to implant material, and arthrofibrosis (SLIM consensus classification). AIM: Because of differences in treatment the diagnosis of a bacterial implant infection is very important. Histopathological tests and scoring systems are important diagnostic tools in identifying deep implant infections in patients with unclear clinical history as well as radiographic and laboratory studies. RESULTS: Modern enzyme PCR-based methods, histochemical- and immune-histopathological techniques (CD3,CD15, CD68) are useful in identifying specific and nonspecific infections, as well as differentiating postsurgical changes from recurrent infections in patients with a spacer. In all histopathological scoring systems for bacterial infection, quantifying the number of neutrophil granulocytes in a defined number of high power fields is crucial. DISCUSSION: Neutrophil granulocytes can be detected through histochemical methods and more specifically by immune-histopathological techniques and by various quantification systems (histopathological scores) leading to the diagnosis of bacterial peri-implant infection. One important function of histopathology, apart from diagnosing infection, is to rule out other mechanisms of implant failure, such as tumor infiltrations, particle-induced reactions, and adverse reactions to implant materials.

[CD15 focus score for diagnostics of periprosthetic joint infections : Neutrophilic granulocytes quantification mode and the development of morphometric software (CD15 quantifier)]. / CD15-Fokus-Score zur Diagnostik der periprothetischen Gelenkinfektion : Neutrophile-Granulozyten-Quantifizierungs-Modus und Entwicklung einer morphometrischen Software ("CD15-Quantifier").

BACKGROUND: The aim of this project was to devise a quantification method for neutrophils within a single focal point through the development of a CD15 focus score which enables bacterial infections in synovial-like interface membranes (SLIM) to be diagnosed. METHODS: In this study a histopathological classification of 91 SLIM removed during revision surgery from the hips (n = 59) and knees (n = 32) was performed. Neutrophils were identified immunohistochemically by means of a CD15-specific monoclonal antibody. The quantitative evaluation of CD15-positive neutrophils (CD15Ne) used the principle of maximum focal infiltration (focus) together with an assessment of a single focal point (0.3 mm(2)). This immunohistochemical approach made it possible to develop the CD15 quantifier software, which automatically quantifies CD15Ne. RESULTS: The SLIM cases with positive microbiological findings (n = 47) had significantly (p < 0.001, Mann-Whitney U-test) more CD15Ne/focal point than cases with negative microbiological findings (n = 44). A count of 50 CD15Ne/focal point was identified as the optimum threshold when diagnosing periprosthetic joint infections (PJI) using the CD15 focus score. If the microbiological findings are used as a gold standard, the diagnostic sensitivity is 0.83, and the specificity is 0.864 with a positive predictive value (PPV) of 0.87, a negative predictive value (NPV) of 0.83, an accuracy of 0.846 and an area under the curve (AUC) of 0.878. The evaluation of findings for the preparations using the CD15 quantifier software (n = 31) deviated by an average of 12 cells from the histopathological evaluation findings (CD15 focus score). Above a cell count of 62, the CD15-quantifier needs on average 32 s less than the pathologist. CONCLUSION: The immunohistochemical CD15 focus score has a high diagnostic value and allowed the development of the CD15 quantifier software. This provides an automated procedure, which shortens the mentally tiring and time-consuming process of microscopic cell counting and thus makes a contribution towards the standardization of tools for diagnosing PJI.

[The spectrum of histomorphological findings related to joint endoprosthetics]. / Das Spektrum histopathologischer Veränderungen in endoprothetisch versorgten Gelenken.

Approximately 230,000 total hip and 170,000 knee joint endoprostheses are implanted in Germany annually of which approximately 10% (i.e. 40,000 interventions per year) are cases of revision surgery. These interventions involve removal of a previously implanted prosthesis which has resulted in complaints and replacement with a new prosthesis. There are manifold reasons for revision surgery, the most common indication being so-called endoprosthesis loosening, which is subdivided into septic and aseptic loosening. Histomorphological studies revealed that periprosthetic tissue from endoprosthesis loosening can be classified into four types (I) wear-particle induced type, (II) infectious type, (III) combined type and (IV) fibrous type. Types I and IV represent aseptic loosening and types II and III septic loosening. Recently, the topic of implant allergy has emerged. The detection of cellular, mostly perivascular lymphocytic infiltrates is discussed as being a sign of an allergic tissue reaction. It has most frequently been observed in type I periprosthetic membranes with a dense load of metal wear, which occurs with metal-on-metal bearings. Apart from endoprosthesis loosening, arthrofibrosis is another complication of joint endoprosthetics and can cause pain and impaired function. Histopathologically, arthrofibrosis can be evaluated by a three-tiered grading system. Furthermore, bone pathologies, such as ossification, osteopenia or osteomyelitis can occur as complications of joint endoprosthetics. This review gives an overview of the whole spectrum of pathological findings in joint endoprosthetics and offers a comprehensive and standardized classification system for routine histopathological diagnostics.

[Histopathological particle algorithm. Particle identification in the synovia and the SLIM]. / Histopathologischer Partikelalgorithmus. Partikelidentifikation in der Synovialis und in der SLIM.

BACKGROUND: In the histopathological diagnostics of synovitis and the synovium-like interface membrane (SLIM) the identification of crystals and crystal-like deposits and the associated inflammatory reactions play an important role. The multitude of endogenous crystals, the range of implant materials and material combinations, and the variability in the formation process of different particles explain the high morphological particle heterogeneity which complicates the diagnostic identification of diagnostic particles. STUDY DESIGN AND METHODS: A simple histopathological particle algorithm has been designed which allows methodological particle identification based on (1) conventional transmitted light microscopy with a guide to particle size, shape and color, (2) optical polarization criteria and (3) enzyme histochemical properties (oil red staining and Prussian blue reaction). These methods, the importance for particle identification and the differential diagnostics from non-prosthetic materials are summarized in the so-called histopathological particle algorithm. RESULTS: A total of 35 cases of synovitis and SLIM were analyzed and validated according to these criteria. Based on these criteria and a dichotomous differentiation the complete spectrum of particles in the SLIM and synovia can be defined histopathologically. CONCLUSION: For histopathological diagnosis a particle score for synovitis and SLIM is recommended to evaluate (1) the predominant type of prothetic wear debris with differentiation between microparticles, and macroparticles, (2) the presence of non-prosthesis material particles and (3) the quantification of particle-association necrosis and lymphocytosis. An open, continuously updated web-based particle algorithm would be helpful to address the issue of particle heterogeneity and include all new particle materials generated in a rapidly changing field.

[Histopathology and microbiology of joint infections: extension of diagnostic safety in patients with chronic polyarthritis]. / Histopathologie und Mikrobiologie bei Gelenkinfekten : Erweiterung der Diagnostiksicherheit bei Patienten mit chronischer Polyarthritis.

BACKGROUND: It can be difficult to distinguish between synovitis due to rheumatism and synovitis due to a bacterial infection. Microbiological detection of bacteria is not always successful and the clinical significance of low virulent bacteria often remains uncertain. Therefore, the histopathological finding of inflammatory reactions is very important. STUDY DESIGN AND METHODS: From patients with clinically clear signs of infections and rheumatoid arthritis who underwent surgery between April and August 2011, samples were taken during surgery. Histopathological diagnosis was carried out by conventional enzyme and immunohistochemical techniques based on defined criteria of bacterial infection in tissues, synovial tissue and bone. RESULTS: A total of 20 patients were included, 10 males and 10 females with a mean age of 61.7 years. Staphylococcus aureus was the most commonly detected bacteria and in 4 cases bacteria could not be demonstrated. The correlation between the histopathological signs of an infection and microbiological detection of bacteria was 93.3 %. CONCLUSIONS: In patients with rheumatoid arthritis the combination of histopathology and microbiology significantly increased the safety of detecting an infection or contamination.

[Allergy diagnostics in suspected metal implant intolerance]. / Allergiediagnostik bei Verdacht auf Metallimplantatunverträglichkeit.

Allergy diagnostics may be requested before implantation or in cases of complications by implants. Preimplant allergy testing by patch test should only be done in patients with a reported history of potential allergies to metal or bone cement components and prophetic prophylactic testing should not be done. For baseline diagnostics of suspected implant allergy a patch test with the standard series (containing Ni, Co and Cr preparations) and with bone cement components and peri-implant histology should be performed after exclusion of frequent complication elicitors (in particular low grade infections). This can show a peri-implant T-lymphocyte dominated inflammation. Additional information on a scientific level is given by the lymphocyte transformation test (LTT) assessing metal sensitivity and by peri-implant molecular cytokine profiling giving the inflammatory pattern.