Temporal and spatial heterogeneity of HER2 status in metastatic colorectal cancer.

BACKGROUND: HER2-targeted therapies have recently emerged as an option in the management of metastatic colorectal cancer (mCRC) overexpressing HER2. However, data regarding HER2 status in primary CRC and its corresponding liver metastases are limited, potentially influencing clinical decisions. Therefore, the aim of this study was to compare the HER2 status in primary CRC and paired liver metastases. METHODS: Patients with mCRC who were operated from their primary colorectal cancer and their corresponding synchronous or metachronous liver metastases, in the digestive surgery department of Besançon University Hospital, between April 1999 and October 2021, were included. Tissue microarrays were constructed from matched primary CRC and liver metastastic tissue samples. HER2 status was assessed by immunohistochemistry and in situ hybridization according to Valtorta's criteria. RESULTS: A series of 108 paired primary CRC and liver metastases, including a series of multiple liver metastases originating from the same patients (n = 24), were assessed. Among the primary CRC, 89 (82.4%), 17 (15.8%) and 2 (1.8%) cases were scored 0, 1 + and 2 + respectively. In liver metastases, 99 (91.7%), 7 (6.5%) and 2 (1.8%) were scored 0, 1 + and 2, respectively. Overall, there was a 19% discrepancy rate in HER2 status between primary CRC and metastases, which increased to 21% in cases with multiple synchronous or metachronous liver metastases in a given patient. No significant difference was found between metachronous and synchronous metastases regarding the HER2 status (p = 0.237). CONCLUSIONS: Our study highlights the temporal and spatial heterogeneity of HER2 status between primary CRC and corresponding liver metastases. These findings raise the question of a sequential evaluation of the HER2 status during disease progression, to provide the most suitable treatment strategy.

Immune checkpoint inhibitor therapy associated with IgA nephropathy: a case report and literature review.

Immune checkpoint inhibitors (ICIs) dramatically improve the prognosis of many malignancies but at the cost of numerous side effects, which may limit their benefits. Acute kidney injury associated with immune checkpoint inhibitors most frequently are acute tubulointerstitial nephritis (ATIN), but various cases of glomerulonephritis have also been reported. Herein, we report a case of severe IgA nephropathy (IgAN) associated with ICIs and carry out a literature review. IgAN was diagnosed in a median time of 5 months (range 1-12 months) after the initiation of ICIs, with heterogeneous severity, and usually treated by corticosteroid and discontinuation of ICIs. In contrast to our case, renal outcomes in literature were often favorable, with recovery of renal function and a reduction in proteinuria on treatment. Although IgAN related to ICIs is a much rarer complication than ATIN, it may still be underdiagnosed. Careful questioning and screening for asymptomatic hematuria should be performed before using ICIs.

Recognition of intraglomerular histological features with deep learning in protocol transplant biopsies and their association with kidney function and prognosis.

Background: The Banff Classification may not adequately address protocol transplant biopsies categorized as normal in patients experiencing unexplained graft function deterioration. This study seeks to employ convolutional neural networks to automate the segmentation of glomerular cells and capillaries and assess their correlation with transplant function. Methods: A total of 215 patients were categorized into three groups. In the Training cohort, glomerular cells and capillaries from 37 patients were manually annotated to train the networks. The Test cohort (24 patients) compared manual annotations vs automated predictions, while the Application cohort (154 protocol transplant biopsies) examined predicted factors in relation to kidney function and prognosis. Results: In the Test cohort, the networks recognized histological structures with Precision, Recall, F-score and Intersection Over Union exceeding 0.92, 0.85, 0.89 and 0.74, respectively. Univariate analysis revealed associations between the estimated glomerular filtration rate (eGFR) at biopsy and relative endothelial area (r = 0.19, P = .027), endothelial cell density (r = 0.20, P = .017), mean parietal epithelial cell area (r = -0.38, P < .001), parietal epithelial cell density (r = 0.29, P < .001) and mesangial cell density (r = 0.22, P = .010). Multivariate analysis retained only endothelial cell density as associated with eGFR (Beta = 0.13, P = .040). Endothelial cell density (r = -0.22, P = .010) and mean podocyte area (r = 0.21, P = .016) were linked to proteinuria at biopsy. Over 44 ± 29 months, 25 patients (16%) reached the primary composite endpoint (dialysis initiation, or 30% eGFR sustained decline), with relative endothelial area, mean endothelial cell area and parietal epithelial cell density below medians linked to this endpoint [hazard ratios, respectively, of 2.63 (P = .048), 2.60 (P = .039) and 3.23 (P = .019)]. Conclusion: This study automated the measurement of intraglomerular cells and capillaries. Our results suggest that the precise segmentation of endothelial and epithelial cells may serve as a potential future marker for the risk of graft loss.

Transjugular Intrahepatic Portosystemic Shunt is effective to treat portal hypertension due to sinusoidal obstructive syndrome.

Transjugular Intrahepatic Portosystemic Shunt (TIPS) is an established procedure for the complications of portal hypertension, such as variceal bleeding, refractory ascites and hepatic hydrothorax. We report an original case of a renal transplant patient successfully treated with TIPS for portal hypertension due to sinusoidal obstructive syndrome (SOS) induced by azathioprine (AZA). By reporting this case, we wish to draw the attention of healthcare professionals managing organ transplant patients, especially nephrologists, to the possible occurrence of liver toxicity due to AZA, and to emphasize the role of TIPS as an effective therapeutic option for portal hypertension-related complications.

Automated evaluation with deep learning of total interstitial inflammation and peritubular capillaritis on kidney biopsies.

BACKGROUND: 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. A total of 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, recall and F-score for leukocyte detection were, respectively, 81%, 71% and 76%. Regarding peritubular capillaries detection the precision, recall and 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 < .0001). The areas under the receiver operating characteristics curves for the prediction of pathologists' Banff total inflammation (ti) and peritubular capillaritis (ptc) scores were respectively all above 0.94 and 0.86. The kappa coefficients between the visual and the neural networks' scores were respectively 0.74, 0.78 and 0.68 for ti ≥1, ti ≥2 and ti ≥3, and 0.62, 0.64 and 0.79 for ptc ≥1, ptc ≥2 and ptc ≥3. In a subgroup of patients with immunoglobulin A nephropathy, the inflammation severity was highly correlated to kidney function at biopsy on univariate and multivariate analyses. CONCLUSION: We developed a tool using deep learning that scores the total inflammation and capillaritis, demonstrating the potential of artificial intelligence in kidney pathology.

Deep learning automation of MEST-C classification in IgA nephropathy.

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 < .001), respectively]. CONCLUSIONS: This work highlights the possibility of automated recognition and quantification of each element of the MEST-C classification using deep learning methods.

Real-time multiplex PCR for human echinococcosis and differential diagnosis.

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.

Title: PCR multiplex en temps-réel pour le diagnostic de l'échinococcose humaine et diagnostic différentiel. Abstract: L'identification moléculaire des pathogènes infectieux humains rares semble être l'une des méthodes actuelles les plus pertinentes pour un diagnostic et une prise en charge rapides des patients. Les techniques de PCR, en particulier la PCR quantitative en temps réel, sont bien adaptées à la détection d'ADN de pathogènes, même pour de faibles concentrations. Les infections à échinocoque sont dues à des helminthes du genre Echinococcus, des espèces étroitement apparentées, impliquées dans des lésions parasitaires affectant les animaux et accidentellement l'homme. Une qPCR multiplex (MLX qPCR), permettant la détection de quatre espèces d'Echinococcus impliquées en Europe dans l'échinococcose alvéolaire (EA) et kystique (EK) (Echinococcus multilocularis, E. granulosus sensu stricto, E. ortleppi et E. canadensis), basée sur de courtes cibles mitochondriales a été développée ici. Une collection a été constituée de 81 tissus frais ou fixés en paraffine (FFPE) de lésions d'EA et EK. Les essais de qPCR ont été réalisées en triplex pour la détection d'Echinococcus spp., associés à une qPCR de contrôle d'inhibition. Une PCR duplex a été développée pour le diagnostic de deux autres helminthiases en impasse chez l'Homme (cysticercose (Taenia solium), et toxocarose (Toxocara cati et T. canis). La sensibilité de la qPCR a été évaluée et s'échelonne de 1 à 5 × 10−4 ng/µl (sept essais de qPCR positifs), correspondant à 37 à 42 cycles pour l'ADN quantifiable. La spécificité était de 100 % pour toutes les cibles. Cette qPCR multiplex, adaptée à de faibles quantités d'ADN peut être mise en œuvre au laboratoire pour un diagnostic moléculaire rapide des espèces d'Echinococcus.

Molecular diagnosis of alveolar echinococcosis in patients based on frozen and formalin-fixed paraffin-embedded tissue samples.

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.

TITLE: Diagnostic moléculaire de l'échinococcose alvéolaire chez les patients à partir d'échantillons de tissus congelés et fixés au formol et inclus en paraffine. ABSTRACT: 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.

Automatic Evaluation of Histological Prognostic Factors Using Two Consecutive Convolutional Neural Networks on Kidney Samples.

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.

Clinical characteristics and outcomes of patients with hepatic angiomyolipoma: A literature review.

First reported in 1976, hepatic angiomyolipoma (HAML) is a rare mesenchymal liver tumor occurring mostly in middle-aged women. Diagnosis of the liver mass is often incidental on abdominal imaging due to the frequent absence of specific symptoms. Nearly 10% of HAMLs are associated with tuberous sclerosis complex. HAML contains variable proportions of blood vessels, smooth muscle cells and adipose tissue, which renders radiological diagnosis hazardous. Cells express positivity for HMB-45 and actin, thus these tumors are integrated into the group of perivascular epithelioid cell tumors. Typically, a HAML appears on magnetic resonance imaging (or computed tomography scan) as a hypervascular solid tumor with fatty areas and with washout, and can easily be misdiagnosed as other liver tumors, particularly hepatocellular carcinoma. The therapeutic strategy is not clearly defined, but surgical resection is indicated for symptomatic patients, for tumors showing an aggressive pattern (i.e., changes in size on imaging or high proliferation activity and atypical epithelioid pattern on liver biopsy), for large (> 5 cm) biopsy-proven HAML, and if doubts remain on imaging or histology. Conservative management may be justified in other conditions, since most cases follow a benign clinical course. In summary, the correct diagnosis of HAML is challenging on imaging and relies mainly on pathological findings.

Clinicopathologic features of infection-related glomerulonephritis with IgA deposits: a French Nationwide study.

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.

Concomitant Intra-Articular Glenohumeral Lesions in Fractures of the Scapula Body.

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 (25-83 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.

Comparison of Molecular and Histologic Ultrastaging Methods in Sentinel Lymph Node Analysis from Clinical Stage II Colon Cancers.

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.

[Methotrexate induced crystalline nephropathy: A rare histological finding on renal biopsy]. / Néphropathie cristalline secondaire au méthotrexate : une entité rarement objectivée sur biopsie rénale.

Drug-induced crystalline nephropathies are secondary to abnormal accumulation of crystals leading to parenchymal renal injuries. Methotrexate, used to treat a wide range of malignancies, is one of the various drugs accountable in this particular condition. We report a case of acute renal injury during the course of high-dose methotrexate therapy in a patient presenting primary cerebral diffuse large B-cell lymphoma. Interestingly, the kidney biopsy revealed intratubular methotrexate crystal formations. We also summarize the distinctive characteristics of main crystalline nephropathies in order to guide pathologists toward the many types of crystals encountered on renal biopsy.

Fabry Nephropathy.

Fabry disease is a rare X-linked recessive lysosomal storage disease. Multiple mutations of the GLA gene lead to a deficient or absent activity of the lysosomal enzyme α-galactosidase A, resulting in progressive glycotriaosylceramide accumulation in many organs. Low α-galactosidase A activity and mutations in the GLA gene confirm the diagnosis. Clinical signs are multisystemic, heterogeneous, and progressive. Renal, cardiac, and neurovascular involvements are the main life-threatening complications, highlighting the importance of an early initiation of enzyme replacement therapy improving long-term outcome. Fabry nephropathy lesions are characterized by a cell vacuolization of glomeruli, tubules, interstitium, and arteries and by ultrastructural myelin bodies. The main histologic differential diagnoses are toxicity of lysosomal inhibitors and other renal lipidoses. Renal biopsies are not necessary for diagnosis but have an important role in the evaluation of disease evolution and treatment efficiency, which is a major challenge for improving outcome and quality of life.

Absence of PD-L1 on tumor cells is associated with reduced MHC I expression and PD-L1 expression increases in recurrent serous ovarian cancer.

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.

Hints for control of infection in unique extrahepatic vertebral alveolar echinococcosis.

The prognosis of vertebral alveolar echinococcosis (AE) is poor. We report on the unique outcome of a patient with preexisting liver cirrhosis, in whom a diagnosis of vertebral AE was established on vertebral histopathology (D4 corporectomy in 2010 for paraplegia). Therapeutic drug monitoring of albendazole (ABZ) showed that a low dosage was appropriate. The patient recovered and ABZ withdrawal was decided in 2014, with no relapse 18 months later. In this patient, infection was purely or mainly localized in the dorsal spine, and this may have been favored by liver cirrhosis. A longer follow-up is, however, needed to confirm cure.

[Authorization of pathologists for the estimation of the tumor cell percentage on tissue sample for molecular analysis purpose]. / Habilitation des pathologistes pour l'évaluation du pourcentage de cellules tumorales lors du contrôle morphologique avant extraction d'acides nucléiques.

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.

Reversible Fluindione-Induced Chronic Interstitial Nephritis.

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.