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Introduction Interstitial inflammation and peritubular capillaritis are observed in many diseases on native and transplant kidney biopsies. A precise and automated evaluation of these histological criteria could help stratify patients’ kidney prognoses and facilitate therapeutic management. Methods We used a convolutional neural network to evaluate those criteria on kidney biopsies. 423 kidney samples from various diseases were included. 83 kidney samples were used for the neural network training, 106 for comparing manual annotations on limited areas to automated predictions, and 234 to compare automated and visual gradings. Results The Precision, the Recall, and the F-score for leukocyte detection were respectively 81%, 71% and 76%. Regarding peritubular capillaries detection the Precision, the Recall, and the F-score were respectively 82%, 83%, and 82%. There was a strong correlation between the predicted and observed grading of total inflammation, as for the grading of capillaritis (r = 0.89 and r = 0.82 respectively, all p Conclusion We developed a tool using deep learning that scores the total inflammation and capillaritis, demonstrating the potential of artificial intelligence in kidney pathology.

BACKGROUND AND OBJECTIVES: The prognosis of patients undergoing kidney tumor resection or kidney donation is linked to many histologic criteria. These criteria notably include glomerular density, glomerular volume, vascular luminal stenosis, and severity of interstitial fibrosis/tubular atrophy. Automated measurements through a deep-learning approach could save time and provide more precise data. This work aimed to develop a free tool to automatically obtain kidney histologic prognostic features. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In total, 241 samples of healthy kidney tissue were split into three independent cohorts. The “Training” cohort (n=65) was used to train two convolutional neural networks: one to detect the cortex and a second to segment the kidney structures. The “Test” cohort (n=50) assessed their performance by comparing manually outlined regions of interest to predicted ones. The “Application” cohort (n=126) compared prognostic histologic data obtained manually or through the algorithm on the basis of the combination of the two convolutional neural networks. RESULTS: In the Test cohort, the networks isolated the cortex and segmented the elements of interest with good performances (>90% of the cortex, healthy tubules, glomeruli, and even globally sclerotic glomeruli were detected). In the Application cohort, the expected and predicted prognostic data were significantly correlated. The correlation coefficients r were 0.85 for glomerular volume, 0.51 for glomerular density, 0.75 for interstitial fibrosis, 0.71 for tubular atrophy, and 0.73 for vascular intimal thickness, respectively. The algorithm had a good ability to predict significant (>25%) tubular atrophy and interstitial fibrosis level (receiver operator characteristic curve with an area under the curve, 0.92 and 0.91, respectively) or a significant vascular luminal stenosis (>50%) (area under the curve, 0.85). CONCLUSION: This freely available tool enables the automated segmentation of kidney tissue to obtain prognostic histologic data in a fast, objective, reliable, and reproducible way.

Background Although the MEST-C classification is among the best prognostic tools in immunoglobulin A nephropathy (IgAN), it has a wide interobserver variability between specialized pathologists and others. Therefore we trained and evaluated a tool using a neural network to automate the MEST-C grading. Methods Biopsies of patients with IgAN were divided into three independent groups: the Training cohort (n = 42) to train the network, the Test cohort (n = 66) to compare its pixel segmentation to that made by pathologists and the Application cohort (n = 88) to compare the MEST-C scores computed by the network or by pathologists. Results In the Test cohort, >73% of pixels were correctly identified by the network as M, E, S or C. In the Application cohort, the neural network area under the receiver operating characteristics curves were 0.88, 0.91, 0.88, 0.94, 0.96, 0.96 and 0.92 to predict M1, E1, S1, T1, T2, C1 and C2, respectively. The kappa coefficients between pathologists and the network assessments were substantial for E, S, T and C scores (kappa scores of 0.68, 0.79, 0.73 and 0.70, respectively) and moderate for M score (kappa score of 0.52). Network S and T scores were associated with the occurrence of the composite survival endpoint (death, dialysis, transplantation or doubling of serum creatinine) [hazard ratios 9.67 (P = .006) and 7.67 (P Conclusions This work highlights the possibility of automated recognition and quantification of each element of the MEST-C classification using deep learning methods.

Molecular identification of rare human infectious pathogens appears to be one of the most relevant current methods for rapid diagnosis and management of patients. PCR techniques, in particular real-time quantitative PCR, are best suited for the detection of DNA from the pathogens, even at low concentrations. Echinococcosis infections are due to helminths of the Echinococcus genus, with closely related species involved in parasitic lesions affecting animals and, accidentally, humans. We developed a multiplex qPCR (MLX qPCR) assay allowing for the detection of four Echinococcus species involved in Europe in alveolar echinococcosis (AE) and cystic echinococcosis (CE) (Echinococcus multilocularis, E. granulosus sensu stricto, E. ortleppi, and E. canadensis), based on short mitochondrial targets. A collection of 81 fresh and formalin-fixed paraffin-embedded tissues (FFPE) of AE and CE lesions was assembled. The qPCR assays were performed in triplex for Echinococcus spp. detection, associated with a qPCR inhibitor control. A duplex qPCR was also designed to enable diagnosis of two other dead-end helminthiases (cysticercosis (Taenia solium), and toxocariasis (Toxocara cati and T. canis)). The sensitivity of the qPCR was assessed and ranged from 1 to 5 × 10−4 ng/μL (seven PCR assays positive), corresponding to 37–42 cycles for quantifiable DNA. The specificity was 100% for all the targets. This multiplex qPCR, adapted to low amounts of DNA can be implemented in the laboratory for the rapid molecular diagnosis of Echinococcosis species.

Confirmed diagnosis of alveolar echinococcosis (AE) is based on pathological criteria and molecular evidence. This parasite-borne disease, caused by the cestode Echinococcus multilocularis, sparingly involves humans as a dead-end host. In humans, the parasite mainly colonizes the liver but can colonize any organ and cause atypical forms, often difficult to characterize clinically. Moreover, molecular methods may be suitable to make the diagnosis of AE in cases of atypical forms, extra-hepatic localizations, or immunosuppressed patients. The aim of this study was to determine the most relevant published PCR techniques, for diagnosis of AE in patients and adopt the best strategy for molecular diagnosis depending on the nature of the tested sample. In this study, we evaluated nine end-point PCR assays and one real-time PCR assay (qPCR), targeting mitochondrial genes, using a total of 89 frozen or formalin-fixed paraffin-embedded (FFPE) samples from either 48 AE or 9 cystic echinococcosis patients. Targeted fragment-genes ranged from 84 to 529 bp. Six PCR assays were able to amplify the DNA of 100% of the frozen AE-samples and for one PCR, 69.8% of the FFPE AE-samples. The 16S rrnL PCR (84 bp) was positive in PCR for 77% of the AE samples and in qPCR for 86.5%. The sensitivity of the PCR assays was higher for fresh samples and FFPE samples stored for less than 5 years. The qPCR assay further increased sensitivity for the tested samples, confirming the need for the development of an Echinococcus spp. qPCR to improve the molecular diagnosis of echinococcoses.Diagnostic moléculaire de l’échinococcose alvéolaire chez les patients à partir d’échantillons de tissus congelés et fixés au formol et inclus en paraffine.La confirmation diagnostique de l’échinococcose alvéolaire (EA) est basée sur des critères anatomo-pathologiques et moléculaires. Cette maladie d’origine parasitaire, causée par le cestode Echinococcus multilocularis, implique sporadiquement l’homme, impasse parasitaire. Chez l’homme, le parasite colonise principalement le foie mais peut coloniser tout organe et causer des formes atypiques, souvent difficiles à caractériser cliniquement. En outre, les méthodes moléculaires permettent de réaliser le diagnostic de l’EA dans les formes atypiques, les localisations extra-hépatiques ou chez les patients immunodéprimés. Le but de cette étude était de déterminer les techniques PCR publiées les plus pertinentes, pour le diagnostic de l’EA chez les patients et adopter la meilleure stratégie par diagnostic moléculaire en fonction de la nature de l’échantillon testé. Dans cette étude nous avons évalué neuf PCR en point-final et une PCR-temps-réel (qPCR), ciblant des gènes mitochondriaux, utilisant 89 échantillons congelés ou fixés en paraffine (FFPE) de patients EA (n = 48) ou présentant une échinococcose kystique (n = 9). Les fragments de gènes ciblés allaient de 84 à 529 pb. Six tests PCR ont permis d’amplifier l’ADN de 100 % des échantillons EA congelés, et pour une PCR, 69,8 % des échantillons EA-FFPE. La PCR 16S rrnL (84 pb) était positive en PCR pour 77 % des échantillons EA et en qPCR pour 86,5 %. La sensibilité des tests PCR était plus importante pour les échantillons congelés et les FFPE stockés moins de 5 ans. Le test qPCR a permis d’augmenter la sensibilité pour les échantillons testés, confirmant le besoin de développement d’une qPCR Echinococcus spp. pour améliorer le diagnostic moléculaire des échinococcoses.

Various studies have demonstrated that occult metastases may be present in patients with clinical stage II colon cancer. The objective of this prospective investigation was to compare the performance of molecular analysis and histologic ultrastaging in detecting occult metastases in sentinel lymph nodes (SLNs). SLNs were collected ex vivo during surgery in 29 patients. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) assays were constructed. The results were compared with histologic ultrastaging analysis by hemalum and eosin stain and immunohistochemistry on step serial sections. At least 1 SLN was identified in 76% of the cases. The first hemalum and eosin section identified metastases in 23% of the 22 SLNs. Immunohistochemistry identified isolated tumor cells in 24% of the remaining 17 cases. An overall 73% of the SLNs analyzed by qRT-PCR were positive. Four of them were negative for ultrastaging analysis. qRT-PCR is a powerful tool for the detection of occult metastases in colorectal SLN and seems to be more sensitive than histologic ultrastaging analysis. A larger prospective cohort study is necessary to provide further evidence.

Background Infection-related glomerulonephritis with IgA deposits (IRGN-IgA) is a rare disease but it is increasingly reported in the literature. Data regarding epidemiology and outcome are lacking, especially in Europe. We aimed to assess the clinical, pathologic and outcome data of IRGN-IgA. Methods Clinical and outcome data from patients from 11 French centers over the 2007–2017 period were collected retrospectively. We reviewed pathologic patterns and immunofluorescence of renal biopsies and evaluated C4d expression in IRGN-IgA. We analyzed the correlation between histological presentation and outcome. Results Twenty-seven patients (23 men, mean age: 62 ± 15 years) were included. Twenty-one (78%) had Staphylococcus aureus infection and twelve (44%) were diabetic. At the time of biopsy, 95.2% had haematuria, 48.1% had a serum creatinine level of > 4 mg/dL, and 16% had hypocomplementemia. The most common pathologic presentation included mesangial (88.9%) and endocapillary proliferative glomerulonephritis (88.9%) with interstitial fibrosis and tubular atrophy (IF/TA) (85.1%). Diffuse and global glomerular C4d expression was found in 17.8%, mostly in biopsies with acute or subacute patterns, and was associated with a short delay between infection and renal biopsy compared to segmental and focal staining. After median follow-up of 13.2 months, 23.1% died, 46.2% had persistent renal dysfunction and 15.4% reached end-stage renal disease. Renal outcome was correlated to IF/TA severity. Conclusions Infection-related glomerulonephritis with IgA deposits is usually associated with Staphylococcus infections and mainly affects adult men. This entity has a poor prognosis which is correlated to interstitial fibrosis and tubular atrophy severity.

Background: Scapula body fractures are rare injuries with an incidence of 1% of all fractures accounting for 3% to 5% of all upper extremity fractures. Fractures of the scapula commonly result from high-energetic trauma and fall from great height. While several studies focused on concomitant injuries of chest and head as well as the cervical spine, up to now in the common literature, no study exists analyzing the prevalence of concomitant intra-articular glenohumeral injury following extra-articular scapular fracture. Objectives: The aim of this study was to analyze the prevalence of concomitant intra-articular glenohumeral injuries in acute fractures of the scapula by performing magnetic resonance imaging (MRI) of the shoulder joint. Study Design and Methods: This prospective cohort study was performed at our academic Level I trauma center from November 2014 to October 2016. According to our clinical algorithm, all patients suffering from an acute scapula body fracture primarily underwent computed tomography (CT) for assigning the fracture according to the Orthopedic Trauma Association (OTA)-classification and therapy planning. In addition, 3 T MRI-scans of all patients were performed within seven days after trauma. Results: Twenty-one (16 male/5 female, mean age 53 years (25&ndash, 83 y) patients with scapula body fractures (OTA 14.A3.2 80.1%, OTA 14.A3.1 4.8%, OTA14.B3.1 4.8%, OTA14.C3 9.5%) were enrolled. MRI revealed 11 acute intra-articular injuries in 8 of 21 patients (38%). In all 21 patients, hematoma of the rotator cuff and periarticular muscles was present. Three patients (14.3%) presented a partial bursa sided tear of the supraspinatus tendon, whereas in 5 (23.8%), a partial articular sided supraspinatus tendon tear and in 2 (9.5%) patients, a subtotal tear was observed. One patient (4.8%) showed a complete transmural supraspinatus tendon tear. Conclusions: Traumatic concomitant glenohumeral injuries in scapula body fractures seem to be more frequent than generally expected. Subsequent surgical treatment of these formerly missed but therapy-relevant injuries may increase functional outcome and reduce the postoperative complication rate following scapula body fractures.

Background Infection-related glomerulonephritis with IgA deposits (IRGN-IgA) is being more widely recognized but the precise epidemiology and outcome is lacking, particularly in Europe. We aimed to assess clinical, pathologic and outcome data of IRGN-IgA. Methods Clinical and outcome data from patients from 11 French centers over the 2007-2017 period were retrospectively collected. We reviewed pathologic patterns and immunofluorescence of renal biopsies and evaluated C4d expression in IRGN-IgA. We analyzed correlation between histological presentation and outcome using the Chi square test (qualitative data) and Kruskal-Wallis test (quantitative data). Results Twenty-seven patients (23 men, mean age: 62 ± 15 years) were included. Most of them had a Staphylococcus aureus infection (77.8%) and 44.4% were diabetic. At the time of biopsy, 95.2% had haematuria, 48.1% had a serum creatinine >4 mg/dL, and 16% had a hypocomplementemia. The most common pathologic presentation included mesangial (88.9%) and endocapillary proliferative glomerulonephritis (88.9%) with interstitial fibrosis with tubular atrophy (IF/TA) (85.1%). Diffuse and global glomerular C4d expression, found in 17.8% of the cases, was most frequently observed in biopsies with acute or subacute pattern and associated with a shorter delay between infection and renal biopsy compared to segmental and focal staining. After a median follow-up of 13.2 months, 23.1% died, 46.2% had persistent renal dysfunction and 15.4% reached end-stage renal disease. Renal outcome was correlated to IF/TA severity. Conclusions Infection-related glomerulonephritis with IgA deposits is usually associated with Staphyloccus infections and mainly affects adult men. This entity has a poor prognosis which is correlated to interstitial fibrosis and tubular atrophy severity.

Category: Ankle, Trauma Introduction/Purpose: The aim of the study is to clarify whether a novel, minimally invasive intramedullary osteosynthesis system to be implanted leads to an improvement of surgical care in terms of a reduction of postoperative complications after fracture of the distal fibula in older patients. Considering that the population of patients in the western world is getting older and older, a soft tissues-friendly surgical method can not only improve the clinical outcome, the length of stay but also prevent possible postoperative infections. Methods: In our prospective randomized study two study arms were considered. The first arm represents the control group conventionally treated with ORIF in AO technique. Patients in arm 2 were stabilized using the minimally invasive intramedullary Photodynamic Bone Stabilization System (IlluminOss®). The primary target parameter of the clinical outcome is the functionality of the ankle joint, objectified by the Olerud score. Secondary target parameters are the type and severity of postoperative complications. These were divided into minor complications: Superficial wound infection, delayed wound healing, mechanically prominent implant, skin irritations and major complications requiring surgical revision: Deep wound infection, material loosening, loss of reduction. Included were patients > 65 years, with a Charlson comorbidity index = 1 and a distal fibula fracture (according to AO 44 B1.1, B1.2, B1.3), which met the criteria for surgical treatment. Clincal and radiological controls were performed 6 weeks, 12 weeks, 6 months and 1 year postoperatively. Results: 16 patients (10W/6 M), age of 77 J (± 6.65) have been included. Charlson comorbidity index was 2 (±1). Ten patients were treated minimally invasively (62.5%), six patients using the AO technique (37.5%). No minor complications (0%) occurred In the IlluminOss® group. Three minor complications (50%) were detected in the AO group. One patient of the IlluminOss® group (10%) showed a loss of reposition and the procedure changed to the AO treatment. In one case (16%) in the AO group a material loosening with deep wound infection which resulted in a material removal could be detected. At each control time a significantly better olerud score could be obtained in the IlluminOss® group. The length of stay also showed a significant advantage for the minimally invasive group. Conclusion: Our first results are quite positive. We could demonstrate not only the fact that a good clinical function was shown in the IlluminOss® group, but also the absence of minor complications suggests a gentle surgical treatment. The reduced postoperative complication rate has the consequence that the elderly patients can be discharged more quickly into their home environment, the patient’s mobility can be restored faster and the costs for the health care system decrease significantly. However, further investigations and completion of the ongoing study must be awaited.

Before molecular analysis is performed, morphological control with an estimation of the tumour cell percentage (%TC) could have a major impact on mutation detection. Accreditation according to NF EN ISO 15189 commands an authorization through evaluation of skills. The objective of this work was to validate the empowerment of pathologists to estimate %TC in tissue sample prior to molecular analysis. The accreditation technical guidance methods in Medical biology and histopathology were taken as references. %TC was the ratio of tumour cell nuclei on all nuclei within the area selected for the DNA extraction. External evaluations quality scores were used for accuracy. In order to assess the intermediate precision, 35 %TC estimation were performed 15 days apart in 4 samples (biopsies, transparietal biopsies or surgical specimen, either fixed or frozen) by 7 pathologists. Three other cases with interference (inflammation, mucus, necrosis) were evaluated. A result was satisfactory if %TC were within ±20 % of expected percentage obtained by the average of 35 estimates. The performances were satisfactory since no estimate was made more than 20 % of the expected percentage. Low interpathologists reproducibility has been reported in the literature and can have a consequence on molecular analysis in samples with low %TC, where the value reach the analytical sensitivity thresholds of molecular techniques. The current report is an example of a step of the accreditation process, which is a challenge for pathologists' activity in the future.

Peritoneal malignant mesothelioma is a rare and extremely aggressive tumor that is sometimes difficult to diagnose. We report two cases of metastatic malignant peritoneal mesothelioma. In one case, malignant metastatic cells were identified in cervical lymph nodes while in the other case, the cells were found in the liver. In both cases, metastases were identified before discovering the primary tumor. This led to the misdiagnosis of carcinoma of unknown origin. Nevertheless, the histological and immuno-histochemical patterns were typical of malignant mesothelioma. Regarding metastasis of unknown origin, a differentiation of epithelioid peritoneal malignant mesothelioma and adenocarcinoma proved to be difficult. Therefore, we discuss the diagnostic usefulness of immuno-histochemical mesothelioma markers.

Beckenfrakturen sind seltene, jedoch potenziell lebensbedrohliche Verletzungen. Der Blutverlust bei instabilen Beckenverletzungen ist die fuhrende Todesursache. Das initiale Erkennen der pelvinen Blutung ist ausschlaggebend fur das Uberleben des Patienten und erfordert eine sofortige Notfallbehandlung mit dem Ziel der Blutungskontrolle. Dabei kommt der detaillierten Kenntnis der anatomischen und pathophysiologischen Grundlagen grose Bedeutung zu; der Grosteil der verletzungsbedingten pelvinen Blutungen ist venosen Ursprungs. Deren Kontrolle gelingt am besten uber Tamponade, die jedoch bei frakturbedingter Instabilitat zunachst nicht gelingen kann. Daher kommt dem Konzept der Stabilisierung gefolgt von Tamponade immer grosere Bedeutung zu, was sich auch in den neuesten Empfehlungen der Literatur widerspiegelt. Diese werden im folgenden Beitrag dargestellt, aktuelle Entwicklungen in der Therapie ausgedehnter Beckenverletzungen werden besprochen, und es wird versucht, einen klar strukturierten Handlungsablauf zu skizzieren.

Background Fractures of the proximal humerus are often associated with lesions of the long head of the biceps (LHB) tendon. This often leads to prolonged shoulder pain. Hence, many surgeons decide to perform a tenodesis of the LHB tendon simultaneous to ORIF. The purpose of this study was to evaluate the postoperative outcome after interlocking plate fixation and biceps tenodesis for treating proximal humerus fractures. Methods 56 patients (38 females, 18 male) suffering from proximal humerus fractures who underwent surgery were retrospectively included. 26 of these 56 patients (19% Neer II, 38% Neer III, 43% Neer IV) were treated with simultaneous tenodesis of the LHB tendon when ORIF using interlocking plate fixation was performed. 30 patients (17% Neer II, 40% Neer III, 43% Neer IV) served as control group receiving only interlocking plate fixation. The patients were asked to complete the Munich Shoulder Questionnaire (MSQ) for evaluation of postoperative shoulder function. Results of the Disabilities of the Arm, Shoulder and Hand (DASH) Score and Shoulder Pain and Disability Index (SPADI) were calculated from the MSQ. Patients were clinically evaluated for a positive O’Brien test and Popeye sign. Results The tenodesis group demonstrated significant superior outcome regarding the MSQ (mean 90.47 points vs. 79.41 points, p = 0.006), DASH Score (mean 4.2 points vs. 16.81 points, p = 0.017) and SPADI (mean 94.59 points vs. 83.56, p = 0.045). Flexion, external rotation and the capability of throwing a soft ball were significantly improved in the tenodesis group compared to the control group. The O’Brien test as indicator for lesions of the LHB was positive in fewer patients of the tenodesis group (2/26, vs. 21/30, p = 0.001). There was no significant difference of a positive Popeye Sign. Conclusion Our results show evidence of an improved shoulder function when a simultaneous tenodesis of the LHB tendon is performed during treatment of proximal humerus fractures using interlocking plate fixation.

Immune-evasion and immune checkpoints are promising new therapeutic targets for several cancer entities. In ovarian cancer, the clinical role of programmed cell death receptor ligand 1 (PD-L1) expression as mechanism to escape immune recognition has not been clarified yet. We analyzed PD-L1 expression of primary ovarian and peritoneal tumor tissues together with several other parameters (whole transcriptomes of isolated tumor cells, local and systemic immune cells, systemic cytokines and metabolites) and compared PD-L1 expression between primary tumor and tumor recurrences. All expressed major histocompatibility complex (MHC) I genes were negatively correlated to PD-L1 abundances on tumor tissues, indicating two mutually exclusive immune-evasion mechanisms in ovarian cancer: either down-regulation of T-cell mediated immunity by PD-L1 expression or silencing of self-antigen presentation by down-regulation of the MHC I complex. In our cohort and in most of published evidences in ovarian cancer, low PD-L1 expression is associated with unfavorable outcome. Differences in immune cell populations, cytokines, and metabolites strengthen this picture and suggest the existence of concurrent pathways for progression of this disease. Furthermore, recurrences showed significantly increased PD-L1 expression compared to the primary tumors, supporting trials of checkpoint inhibition in the recurrent setting.

Resume L’angiosarcome est une tumeur maligne developpee aux depens des cellules endotheliales. La localisation hepatique primitive est rare. L’exposition toxique chronique est classiquement decrite comme responsable du developpement de cette tumeur. Le diagnostic repose sur l’examen anatomopathologique. Les symptomes revelateurs sont aspecifiques : douleurs abdominales, alteration de l’etat general et fievre. L’angiosarcome hepatique primitif est une tumeur a croissance rapide et le diagnostic est generalement effectue a un stade avance de la maladie. Le pronostic est sombre. L’exerese chirurgicale est la premiere option therapeutique, suivie de la radiotherapie, aucune chimiotherapie n’ayant prouve son efficacite. L’intervention de la medecine du travail concourt a ameliorer le pronostic lorsque les tumeurs sont diagnostiquees a un stade plus precoce et qu’elles se presentent sous une forme localisee, accessibles a un geste chirurgical. Nous rapportons une serie de huit cas d’angiosarcomes hepatiques primitifs recenses au CHRU de Besancon entre 2001 et 2012 avec une analyse des donnees cliniques, radiologiques, histologiques et therapeutiques.

Hormonal factors, like oral contraceptives, create a predisposition to hepatocellular adenoma. We present the case of a young woman with an inflammatory hepatocellular adenoma occurring in the context of a polycystic ovary syndrome. In view of this possible relationship, it would be recommended to follow up patients with hyperandrogenism with repeated liver tests and ultrasonographics. Furthermore, this observation illustrated some difficulties to differentiate remodelled inflammatory hepatocellular adenoma and focal nodular hyperplasia and underlined the interest of immunohistochemical markers for the right diagnosis.

Before molecular analysis is performed, morphological control with an estimation of the tumour cell percentage (%TC) could have a major impact on mutation detection. Accreditation according to NF EN ISO 15189 commands an authorization through evaluation of skills. The objective of this work was to validate the empowerment of pathologists to estimate %TC in tissue sample prior to molecular analysis. The accreditation technical guidance methods in Medical biology and histopathology were taken as references. %TC was the ratio of tumour cell nuclei on all nuclei within the area selected for the DNA extraction. External evaluations quality scores were used for accuracy. In order to assess the intermediate precision, 35 %TC estimation were performed 15 days apart in 4 samples (biopsies, transparietal biopsies or surgical specimen, either fixed or frozen) by 7 pathologists. Three other cases with interference (inflammation, mucus, necrosis) were evaluated. A result was satisfactory if %TC were within ±20 % of expected percentage obtained by the average of 35 estimates. The performances were satisfactory since no estimate was made more than 20 % of the expected percentage. Low interpathologists reproducibility has been reported in the literature and can have a consequence on molecular analysis in samples with low %TC, where the value reach the analytical sensitivity thresholds of molecular techniques. The current report is an example of a step of the accreditation process, which is a challenge for pathologists' activity in the future.

Fluindione is well known to induce acute drug-induced interstitial nephritis (IN). Most cases occurred soon after the onset of treatment. We report a unique case of severe subacute fluindione-induced IN diagnosed 2 years after the treatment was begun. Renal function dramatically improved after fluindione withdrawal and steroid therapy.

Peritoneal malignant mesothelioma is a rare and extremely aggressive tumor that is sometimes difficult to diagnose. We report two cases of metastatic malignant peritoneal mesothelioma. In one case, malignant metastatic cells were identified in cervical lymph nodes while in the other case, the cells were found in the liver. In both cases, metastases were identified before discovering the primary tumor. This led to the misdiagnosis of carcinoma of unknown origin. Nevertheless, the histological and immuno-histochemical patterns were typical of malignant mesothelioma. Regarding metastasis of unknown origin, a differentiation of epithelioid peritoneal malignant mesothelioma and adenocarcinoma proved to be difficult. Therefore, we discuss the diagnostic usefulness of immuno-histochemical mesothelioma markers.

International audience; Perforin (P), Granzyme B (GB) and Fas-Ligand (FAS-L) are cytotoxic molecules involved in acute rejection (AR) after renal transplantation. A noninvasive diagnostic test to monitor AR and other complications could improve clinical management. We investigated the predictive and diagnostic interest of target mRNA measurements, with a quantitative PCR assay, in AR, as well as in other clinical complications recurrent in kidney transplantation. One hundred and sixty-two urine specimens from 37 allograft recipients were investigated. Clinical settings were AR, urinary tract infection (UTI), cytomegalovirus infection (CMVi) or disease (CMVd), chronic allograft nephropathy (CAN), delayed graft function (DGF) and stable graft course (controls). In the case of AR, mRNA levels of all three molecules were significantly higher than in recipients not showing any clinically evident signs of complication. Indeed, it was observed that expression levels of P, GB and Fas-L mRNA also increase in other clinical situations such as UTI, CMV and DGF. Finally, kinetic studies in three patients with AR revealed that increased P, GB and Fas-L mRNA levels could precede or were concomitant with increased serum creatinin levels. P, GB and Fas-L gene expression in urine specimens were upregulated in AR episodes but also in UTI, CMV infection and DGF. Therefore, this technique would appear to be of limited clinical value as a noninvasive method of diagnosing AR.

International audience; The ABCB4 gene codes for a protein involved in the transport of phosphatidylcholine across the canalicular membrane of the hepatocyte. ABCB4 gene defects have been associated with progressive familial intrahepatic cholestasis type 3, intrahepatic cholestasis of pregnancy, adult biliary cirrhosis and the more recently described low phospholipid associated cholelithiasis syndrome. The present paper describes 2 probands with a long history of recurrent pancreatitis and cholelithiasis and the same heterozygous, as yet undescribed del 3683>3688 within exon 28 of the ABCB4 gene resulting in a loss of function. This report shows that ABCB4 mutations may cause acute recurrent biliary pancreatitis.