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Systemic mastocytosis is characterised by tissular infiltration and a cytokine storm due to mast cells excessive proliferation and activation. Herein, we report an extraordinary case of AH1N1 influenza post-viral glomerulonephritis occurring in the course of an aggressive systemic mastocytosis with an associated hematological neoplasm. Because of a multisystemic involvement including the liver and lungs, we treated mastocytosis with midostaurin (multiple inhibitor of kinase protein), anti H1/H2 blockers and dexamethasone as first line treatment. One month later and despite vaccination, he developed a severe acute lung injury with respiratory distress due to AH1N1 influenza in association with the nephrotic syndrome. Kidney biopsy disclosed a membranoproliferative glomerulonephritis that was successfully treated with mycophenolate mofetil. Only a few cases of influenza post-viral or post-vaccination glomerulonephritis are documented in the medical literature. This is an exceptional association of uncommon conditions occurring within only a few months in the same patient.

International audience; Primary membranous nephropathy (MN) is an autoimmune glomerular disease in which autoantibodies are directed against podocyte proteins. In about 80% of cases the main targeted antigen is the phospholipase A2 receptor 1 (PLA2R1). Anti-PLA2R1 antibodies are mainly immunoglobulin G type 4 (IgG4). However, the antigenic target remains to be defined in 20% of cases. MN can be associated with chronic inflammatory demyelinating polyneuropathy, an autoimmune disease of the peripheral nervous system where a common antigenic target has yet to be identified. To ascertain a possible novel target antigen, we analyzed kidney biopsies from five patients positive for anti-contactin 1 antibodies and presenting with MN combined with chronic inflammatory demyelinating polyneuropathy. Eluted IgG from biopsy sections against contactin 1 and nerve tissue were screened. Western blot revealed contactin 1 expression in normal kidney glomeruli. Confocal microscopic analysis showed the presence and colocalization of contactin 1 and IgG4 on the glomerular basement membrane of these patients. Glomerular contactin 1 was absent in patients with anti-PLA2R1-associated MN or membranous lupus nephritis or a healthy control. The eluted IgG from contactin 1-positive biopsy sections but not the IgG eluted from patients with PLA2R1 MN bound conactin 1 with the main eluted subclass IgG4. Eluted IgG could bind paranodal tissue (myelinated axon) and colocalized with commercial anti-conactin 1 antibody. Thus, contactin 1 is a novel common antigenic target in MN associated with chronic inflammatory demyelinating polyneuropathy. However, the precise pathophysiology remains to be elucidated.

The pathogenicity of de novo donor-specific antibodies (dnDSA) varies according to their characteristics. While their MFI, complement-fixing ability, and IgG3 subclass are associated with ABMR occurrence and graft loss, they are not fully predictive of outcomes. We investigated the role of the Fc glycosylation of IgG3 dnDSA in ABMR occurrence using mass spectrometry after isolation by single HLA antigen beads. Between 2014 and 2018, we enrolled 54 patients who developed dnDSA (ABMR- n = 24; ABMR+ n = 30) in two French transplant centers. Fucosylation, galactosylation, GlcNAc bisection, and sialylation of IgG3 dnDSA were compared between ABMR+ and ABMR- patients. IgG3 dnDSA from ABMR+ patients exhibited significantly lower sialylation (7.5% vs. 10.5%, p .001) and higher GlcNAc bisection (20.6% vs. 17.4%, p = .008). Fucosylation and galactosylation were similar in both groups. DSA glycosylation was not correlated with DSA MFI. In a multivariate analysis, low IgG3 sialylation, high IgG3%, time from transplantation to kidney biopsy, and tacrolimus-free regimen were independent predictive factors of ABMR. We conclude that a proinflammatory glycosylation profile of IgG3 dnDSA is associated with a risk of ABMR occurrence. Further studies are needed to confirm the clinical interest of DSA glycosylation and to clarify its role in determining the risk of ABMR and graft survival.

BACKGROUND: Membranous nephropathy (MN) is rare in pediatric patients, although its diagnosis may be underestimated in children who are responsive to corticosteroid therapy prescribed for a suspicion of minimal change disease. It is most often associated with an autoimmune disease, predominantly lupus. We previously reported the occurrence of early-onset MN associated with semaphorin 3B in nine children and two adults. METHODS: Biopsies were performed on native kidney and at 1 and 5 months after transplantation. Semaphorin 3B antigen was detected in immune deposits by immunohistochemistry and confocal microscopy on paraffin-embedded biopsies. Anti-semaphorin antibodies were detected by Western blot and analyzed sequentially. RESULTS: We report the first case of early recurrence after transplantation in a 7-year-old boy who presented with severe nephrotic syndrome and advanced kidney failure. There was no evidence of hereditary or associated autoimmune disease. Abundant, almost coalescent deposits were seen by electron microscopy and bright granular, subepithelial staining was observed for semaphorin 3B antigen. Western blot analysis of serum revealed anti-semaphorin 3B antibodies. Recurrence of MN occurred 25 days after transplantation and manifested as nephrotic range proteinuria despite conventional immunosuppressive therapy. Kidney biopsies confirmed histologic MN recurrence with colocalization of semaphorin 3B antigen and IgG. The patient was treated with rituximab. Anti-semaphorin 3B antibodies, which were detected at transplantation, were not detected 40 days after rituximab. CONCLUSION: This case provides evidence that anti-semaphorin 3B antibodies are pathogenic and should be monitored in patients with MN.

Objective To describe the fertility-sparing management of an atypical uterine myoma. Design Step-by-step video explanation of transcervical biopsy using transabdominal ultrasound guidance, highlighting tips and tricks. Patient consent was obtained before the publication of the case. Setting University hospital. Patient(s) A 32-year-old nulliparous woman with a history of dysmenorrhea was found to have an atypical myoma FIGO 6, with suspicion of leiomyosarcoma on magnetic resonance imaging. Intervention(s) A transcervical biopsy of an atypical myoma was done under transabdominal ultrasound guidance. A myomectomy by a minimally invasive approach was performed without morcellation. Main outcome measure(s) Feasibility of transcervical biopsy and correlation with definitive anatomopathological diagnosis. Result(s) The patient was under general anesthesia. A hysteroscopy confirmed the normal appearance of the uterine cavity with no direct access to the myoma. Four core biopsies were performed with a 16-gauge needle transcervically under ultrasound guidance. The preliminary diagnosis of cellular leiomyoma allowed a fertility-sparing surgery. Myomectomy and surgical treatment of endometriosis were performed secondarily. This patient had a successful recovery, and the diagnosis of benign cellular leiomyoma was confirmed on the surgical specimen. Conclusion(s) The current video highlights the safety and feasibility of transcervical ultrasound-guided core biopsy in patients with atypical uterine fibroids.

Systemic mastocytosis is characterised by tissular infiltration and a cytokine storm due to mast cells excessive proliferation and activation. Herein, we report an extraordinary case of AH1N1 influenza post-viral glomerulonephritis occurring in the course of an aggressive systemic mastocytosis with an associated hematological neoplasm. Because of a multisystemic involvement including the liver and lungs, we treated mastocytosis with midostaurin (multiple inhibitor of kinase protein), anti H1/H2 blockers and dexamethasone as first line treatment. One month later and despite vaccination, he developed a severe acute lung injury with respiratory distress due to AH1N1 influenza in association with the nephrotic syndrome. Kidney biopsy disclosed a membranoproliferative glomerulonephritis that was successfully treated with mycophenolate mofetil. Only a few cases of influenza post-viral or post-vaccination glomerulonephritis are documented in the medical literature. This is an exceptional association of uncommon conditions occurring within only a few months in the same patient.

Introduction Myelodysplastic syndromes (MDS) are characterized by a high prevalence of associated autoimmune manifestations. Kidney involvement has been rarely reported in MDS patients. We report on the spectrum of kidney pathological findings in MDS patients. Methods We retrospectively identified MDS patients who had undergone a kidney biopsy between 2001 and 2019 in nine Swiss and French nephrology centres. Results Nineteen patients (median age 74 years [63-83]) were included. At the time of kidney biopsy, eleven (58%) patients had extra-renal auto-immune manifestations and sixteen (84%) presented with acute kidney injury. Median serum creatinine at diagnosis was 2.8 mg/dL [0.6-8.3] and median urinary protein to creatinine ratio was 1.2 g/g [0.2-11]. Acute tubulo-interstitial nephritis (TIN) was present in seven (37%) patients. Immunofluorescence study in one patient with acute TIN disclosed intense IgG deposits along the tubular basement membrane and Bowman’s capsule. Other kidney pathological features included ANCA-negative pauci-immune necrotizing and crescentic glomerulonephritis (n = 3), membranous nephropathy (n = 2), IgA nephropathy (n = 1), IgA vasculitis (n = 1), immunoglobulin-associated membrano-proliferative glomerulonephritis type I (n=1), crescentic C3 glomerulopathy (n = 1), fibrillary glomerulonephritis (n = 1) and minimal change disease (n = 1). Eleven (58%) patients received immunosuppressive treatments, among whom one developed a severe infectious complication. After a median follow-up of 7 month [1-96], nine (47%) patients had chronic kidney disease stage 3 (n = 6) or 4 (n = 3) and five (26%) progressed to end-stage kidney disease. Three patients died. Conclusions MDS are associated to several autoimmune kidney manifestations, predominantly acute TIN. MDS are to be listed among the potential causes of autoimmune TIN., Graphical abstract

Background The kidney is a major target in primary antiphospholipid syndrome. Several types of nephropathy have been reported, the most frequent being acute or chronic specific vascular nephropathies and membranous nephropathy. Case presentation A 59-year-old male presented in our unit with nephrotic syndrome. He had a history of primary antiphospholipid syndrome with lupus anticoagulant treated with vitamin K antagonist therapy. On admission, antiphospholipid (lupus anticoagulant) and anti-PLA2R antibodies were positive. Screening for secondary etiologies was negative. In the context of primary antiphospholipid syndrome treated with vitamin K antagonist therapy, we did not perform a biopsy and we treated the patient with angiotensin-converting-enzyme inhibitor. No remission was observed at 6 months with persistent anti-PLA2R antibodies while antiphospholipid antibody level became negative. Consequently, kidney biopsy was performed showing both membranous nephropathy with PLA2R in deposits on immunohistochemistry with IgG4 dominance and antiphospholipid syndrome chronic vascular nephropathy. Following that, treatment with rituximab was started with secondarily a decrease in serum PLA2R antibody levels and partial remission. Conclusion We report the first association between primary antiphospholipid syndrome and membranous nephropathy with anti-PLA2R antibodies. Our observations could suggest a causal link between primary antiphospholipid syndrome and PLA2R-related membranous nephropathy. Consequently, it would be interesting to screen for anti-PLA2R antibodies for further cases of nephrotic syndrome in patients with primary antiphospholipid syndrome and to search antiphospholipid antibodies in all membranous nephropathies.

International audience; One third of operated breast cancers are clinically occult.1 Nonpalpable breast cancers (NPBC) require accurate intraoperative guidance to achieve complete tumor removal.1 Incomplete removal of lesions increases the rate of reexcision, worsening patient's discomfort, and cosmetic outcomes.1 Localization techniques suffer from various limitations. Indocyanine green (ICG) fluorescence is commonly used for intraoperative identification of sentinel lymph nodes (SLN).2 Its pertinence for NPBC is still underestimated. Darkness required in surgery room with available cameras has been a limitation for its use. We evaluated ICG method for NPBC localization, guided by a probe in ambient light, inspired by radioguided occult lesion localization (ROLL).

Background Essure is an effective method for hysteroscopic sterilization. Reports of adverse effects, the underlying mechanisms of which are unknown, have increased in recent years. Objective The aim of the study was to determine whether there is a relationship between adverse events attributed to Essure and nickel sensitization. Methods Patients presenting alleged adverse reactions to Essure were referred for nickel patch testing before removal. Data regarding medical history of nickel sensitization and symptoms attributed to Essure were collected. Dimethylglyoxime spot tests were performed on the explanted Essure. There was a follow-up at 3 months to evaluate whether there is improvement of the symptoms after Essure removal. Conclusions Nickel sensitization via the classic delayed hypersensitivity pathway did not seem to be responsible for adverse events attributed to Essure. Among systemic symptoms reported, extracutaneous symptoms had the highest prevalence. Systemic contact dermatitis to nickel could not be ruled out in one case.

International audience; Mastitis frequently affects women of childbearing age. Of all the pathological breast conditions requiring specific management, autoimmune mastitis is in the third position after infection and breast cancer. The aim of this literature review was to make a comprehensive description of autoimmune diseases targeting the mammary gland. Four main histological patterns of autoimmune mastitis are described: (i) lymphocytic infiltrates; (ii) ductal ectasia; (iii) granulomatous mastitis; and (iv) vasculitis. Our literature search found that all types of autoimmune disease may target the mammary gland: organ-specific diseases (diabetes, thyroiditis); connective tissue diseases (such as systemic erythematosus lupus or Sjögren’s syndrome); vasculitides (granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, giant cell arteritis, polyarteritis nodosa, Behçet’s disease); granulomatous diseases (sarcoidosis, Crohn’s disease); and IgG4-related disease. Cases of breast-specific autoimmune diseases have also been reported, including idiopathic granulomatous mastitis. These breast-limited inflammatory diseases are sometimes the first symptom of a systemic autoimmune disease. Although autoimmune mastitis is rare, it is probably underdiagnosed or misdiagnosed. Early diagnosis may allow us to detect systemic diseases at an earlier stage, which could help to initiate a prompt, appropriate therapeutic strategy. In case of suspected autoimmune mastitis, we hereby propose a diagnostic pathway and discuss the potential pathophysiological pathways leading to autoimmune breast damage.

International audience; A 33-year-old woman presented with left breast chronic wound. Her past medical history was unremarkable, except tobacco use (

Introduction En dehors du contexte d’hepatites virales, les atteintes hepatiques liees aux vascularites cryoglobulinemiques restent une eventualite rare. Observation Un homme de 65 ans aux antecedents d’accident vasculaire cerebral ischemique, consulte pour une dyspnee progressive, une alteration de l’etat general en lien avec un syndrome inflammatoire. Les premieres explorations revelent des opacites pulmonaires migratrices, quelques adenopathies mediastinales et une hepato-splenomegalie. Les hypotheses infectieuses sont ecartees. Apres quelques mois d’evolution, il est hospitalise. On note une elevation persistante de la CRP a 115 mg/l, une anemie mixte inflammatoire et ferriprive, une hypergammaglobulinemie polyclonale, une glomerulonephrite caracterisee par une majoration progressive de la creatinemie de 90 a 120 μmo/L avec ratio proteine/creatine urinaire a 121 mg/mmoL en presence d’une hematurie microscopique. Le scanner montre une regression spontanee des opacites pulmonaires en faveur d’une pneumonie organisee cryptogenique, alors que la bronchoscopie avec lavage bronchiolo-alveolaire revele une hemorragie intra-alveolaire (score de Golde a 274). Le bilan immunologique decele des anticorps anti-nucleaires positifs a 1/320, avec anti ADN a 41 UI/mL, une consommation des fractions C3 et C4 du complement, un test de Coombs positif sans hemolyse. Il n’y a par ailleurs pas d’ANCA, pas d’anti-MBG, pas de facteur rhumatoide, la recherche d’antiphospholipides est negative. On detecte la presence d’une cryoglobulinemie de type II sur 3 prelevements. Les serologies des hepatites virales sont negatives. Par ailleurs, le syndrome sec est confirme au test de Schirmer et il existe une sialadenite lymphocytaire avec un focus score a 1 sur la biopsie des glandes salivaires accessoires. L’histologie renale montre une glomerulonephrite necrosante focale a depots d’IgM, C1q et C3, compatible avec une atteinte de la cryoglobuline. L’histologie hepatique revele un aspect de syndrome d’obstruction sinusoidale avec depots d’IgM, C1q et C3 similaires a ceux observes au niveau renal, orientant vers une atteinte specifique de la cryoglobulinemie. Par ailleurs, l’ensemble de prelevements, incluant la biopsie osteomedullaire, ecartent un syndrome lympho-proliferatif associe. Nous concluons a une vascularite cryoglobulinemique pulmonaire, hepatique et renale, compliquant un lupus avec Sjogren secondaire. Le traitement par corticotherapie a 1 mg/kg associe au RITUXIMAB 375 mg/m2 hebdomadaire permet une rapide amelioration clinique et paraclinique. Discussion La presentation initiale d’une vascularite systemique avec syndrome pneumo-renal chez un sujet masculin d’âge mur nous a d’abord fait evoquer une vascularite a ANCA. Toutefois, la confrontation du tableau clinique aux resultats immunologiques et a l’histologie a finalement conforte l’hypothese d’une vascularite cryoglobulinemique. L’organomegalie et le terrain pouvaient faire craindre une hemopathie sous-jacente, qui a ete ecartee. Finalement, malgre les atypies, le diagnostic de lupus systemique associe a un syndrome de Sjogren secondaire a ete retenu. L’hemorragie intra-alveolaire est une atteinte rare mais decrite dans le cadre d’une cryoglobulinemie et d’un lupus [1] , [2] , [3] . Par ailleurs, les atteintes hepatiques liees aux cryoglobulinemies ont ete decrites, mais le plus souvent en lien avec une hepatite virale, et rarement documentees. Nous apportons ici une documentation histologique originale d’une atteinte specifique de la cryoglobulinemie au niveau hepatique et renal. Conclusion La survenue d’une vascularite cryoglobulinemique a tropisme pulmonaire, renal et hepatique en association a un lupus et un syndrome de Sjogren reste une eventualite rare chez un sujet masculin d’âge mur, justifiant la recherche de diagnostics alternatifs, et imposant une confrontation anatomo-immuno-clinique.

International audience; Since 1973, a few cases of concomitant inflammatory demyelinating polyradiculoneuropathy and nephrotic syndrome have been reported. The neuropathy was either an acute inflammatory demyelinating polyneuropathy (AIDP) or a chronic inflammatory demyelinating polyneuropathy (CIDP), and the nephrotic syndrome was related to either a focal segmental glomerulosclerosis (FSGS) or a membranous glomerulonephritis (MGN).Time course, severity, and response to treatment were heterogeneous, and evolution of neuropathy and nephropathy could be independent. This suggests that common epitopes are targeted by autoantibodies within the peripheral nerve and the glomerular filtration barrier. However, the antigenic targets are unknown. Here, we report a patient who developed CIDP associated with anti-contactin-1 immunoglobulin G4 (IgG4) antibodies and nephrotic syndrome.

International audience; C4d deposition in peritubular capillaries (PTC) reflects complement activation in antibody-mediated rejection (ABMR) of kidney allograft. However, its association with allograft survival is controversial. We hypothesized that capillary deposition of C5b9-indicative of complement-mediated injury-is a severity marker of ABMR. This pilot study aimed to determine the frequency, location and prognostic impact of these deposits in ABMR. We retrospectively selected patients diagnosed with ABMR in two French transplantation centers from January 2005 to December 2014 and performed C4d and C5b9 staining by immunohistochemistry. Fifty-four patients were included. Median follow-up was 52.5 (34.25-73.5) months. Thirteen patients (24%) had C5b9 deposits along glomerular capillaries (GC). Among these, seven (54%) had a global and diffuse staining pattern. Twelve of the C5b9+ patients also had deposition of C4d in GC and PTC. C4d deposits along GC and PTC were not associated with death-censored allograft survival (p = 0.42 and 0.69, respectively). However, death-censored allograft survival was significantly lower in patients with global and diffuse deposition of C5b9 in GC than those with a segmental pattern or no deposition (median survival after ABMR diagnosis, 6 months, 40.5 months and 44 months, respectively; p = 0.015). Double contour of glomerular basement membrane was diagnosed earlier after transplantation in C5b9+ ABMR than in C5b9- ABMR (median time after transplantation, 28 vs. 85 months; p = 0.058). In conclusion, we identified a new pattern of C5b9+ ABMR, associated with early onset of glomerular basement membrane duplication and poor allograft survival. Complement inhibitors might be a therapeutic option for this subgroup of patients.

Cowden syndrome (CS) is an autosomal dominant mendelian disease related to germline pathogenic variants affecting the PTEN-gene. CS is characterized by macrocephaly, mucocutaneous lesions, and an increased risk of breast and thyroid cancers. Rare ovarian cancer cases (mostly embryonic tumors) associated with PTEN have been described in the literature, but no current CS guidelines are available for ovarian cancer risk management. We report on a woman diagnosed with ovarian clear cell carcinoma (OCCC) at 28 years of age. The patient displayed macrocephaly, trichilemmomas, oral papillomatosis, and acral keratosis. A family history of multiple cancer cases within the PTEN-related tumor spectrum was identified. In addition, PET scan and fine-needle biopsy results led to a diagnosis of thyroid follicular neoplasia. PTEN sequencing revealed that she carried a germline inherited pathogenic variant in exon 5 c.388C>T, p.(Arg130*) (NM_000314). Somatic mismatch repair immunohistochemistry analysis showed normal expression, and germline BRCA1/2 sequencing did not reveal pathogenic or likely pathogenic variants. An ovarian cell immunohistochemistry analysis reported total loss of PTEN expression, which strongly suggested the role of PTEN in the oncogenesis of this cancer. Hence, a total thyroid resection was performed instead of thyroid lobectomy and a risk-reducing bilateral mastectomy was discussed. Co-occurrence of this pathogenic germline mutation in PTEN in this patient, early development of OCCC at age 28 years, and total loss of PTEN expression in the tumor might support the involvement of PTEN in the carcinogenesis of her ovarian cancer. We describe a new ovarian cancer case with an atypical histologic type-clear cell carcinoma-in CS. This observation might be the first indication of the need to expand the PTEN-related tumor spectrum to incorporate OCCC. The CS diagnosis significantly changed the therapeutic outcome of this patient.

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International audience; Sjögren's syndrome is well known to target exocrine glands, especially lacrimal and salivary glands, which share with mammary glands anatomical, histological, and immunological features. Herein, we investigated the mammary involvement in patients with Sjögren's syndrome and compared the histological findings with minor salivary gland involvement. We reviewed the charts of patients with Sjögren's syndrome (followed in Montpellier University Hospital, between January 2000 and January 2015), in whom minor salivary gland and mammary tissues were available. Two expert pathologists analysed retrospectively these tissues in order to identify inflammatory patterns. Immunohistochemical stainings were performed to precise leucocyte distribution. Sixteen Sjögren's syndrome patients with available salivary and breast tissue samples were included. All were women, with a median age of 60.1 ± 11.3 years at Sjögren's syndrome diagnosis. Mammary biopsy was conducted because of breast symptoms in 6 patients and following imaging screening strategies for breast cancer in 10 patients. Nine patients exhibited an inflammatory breast pattern (lymphocytic infiltrates or duct ectasia), close to minor salivary gland histological findings. Immunohistochemical stainings (n = 5) revealed B and T cell infiltrates within breast tissue, with a higher proportion of T CD4+ cells, but no IgG4-secreting plasma cells were found. This is the first series to describe breast inflammatory patterns in Sjögren's syndrome. Mastitis is in line with the classical involvement of exocrine glands in this disease. These findings are consistent with the literature data considering Sjögren's syndrome as an "autoimmune epithelitis".

Resume La classification moleculaire des cancers du sein definit des sous-groupes de cancer de pronostics et therapeutiques differents. A chaque type moleculaire representant la signature intrinseque du cancer correspond a un profil histologique integrant les recepteurs hormonaux, le statut HER2 et l’index de proliferation. Cet article decrit les correlations entre cette classification moleculaire obtenue en pratique clinique quotidienne par les parametres histologiques et l’IRM. Elle montre qu’il existe un profil IRM particulier pour les cancers triple negatif : contours nets, bords reguliers, hypersignal sur les sequences ponderees en T2, et surtout couronne rehaussee. Cette classification moleculaire est importante a connaitre pour le radiologue, d’une part, du fait de ce caractere relativement evocateur des cancers triple negatif de type basal- like dans la classification moleculaire et, d’autre part, et surtout car les cancers chez les patientes mutees BRCA1 sont souvent de caracteristique triple negatif obligeant les criteres de lecture de l’IRM a s’adapter a cette caracteristique des cancers, et enfin car l’efficacite de l’IRM pour evaluer la reponse a la chimiotherapie neoadjuvante depend de la classe moleculaire du cancer traite.

The molecular classification of breast cancers defines subgroups of cancer with different prognoses and treatments. Each molecular type representing the intrinsic signature of the cancer corresponds to a histological profile incorporating hormone receptors, HER2 status and the proliferation index. This article describes the correlations between this molecular classification obtained in routine clinical practice using histological parameters and MRI. It shows that there is a specific MRI profile for triple-negative cancers: distinct demarcation, regular edges, hyperintensity on T2 weighted signals and, particularly, a crown enhancement. It is important for the radiologist to understand this molecular classification, firstly because of the relatively suggestive appearance of triple-negative basal-like cancers in the molecular classification, secondly, and particularly, as cancers in patients with the BRCA1 mutation are often triple-negative meaning that the criteria for reading the MRI needs to be tailored to this feature of the cancers, and finally because the efficacy of MRI in assessing response to neoadjuvant chemotherapy depends on the molecular class of cancer treated.

Introduction La recidive clinique de glomerulopathie a depot de C3 (GC3) ou de glomerulonephrite membranoproliferative a complexes immuns (Ig-GNMP) survient chez 50 % des patients apres transplantation renale et est la premiere cause de perte du greffon chez ces patients. Aucun traitement n’a montre son efficacite en post-transplantation. L’eculizumab (ECZ), a ete utilise dans des cas severes sur rein natif ou sur greffon avec une efficacite variable. L’objectif de ce travail etait d’etudier la reponse et d’identifier des facteurs associes a la reponse a l’ECZ chez les patients traites pour une recidive clinique de GC3/Ig-GNMP. Patients/Materiels et methodes Il s’agit d’une etude retrospective multicentrique nationale francaise, incluant les patients transplantes pour une GC3/Ig-GNMP. La recidive clinique etait definie par une augmentation de la creatininemie > 30 % du nadir et/ou l’apparition d’une proteinurie > 0,5 g/g. Elle devait etre confirmee par la presence de depots de C3 glomerulaires a la biopsie du greffon, sans signes de rejet. La reponse complete (RC) a l’ECZ etait definie par la baisse de la creatininemie au nadir et de la proteinurie ≤ 0,5 g/g, la reponse partielle (RP) par la stabilisation de la creatininemie (± 25 %) et la regression de plus de > 50 % de la proteinurie. Observation/Resultats Nous avons identifie 66 recidives de GC3/Ig-GNMP entre 1986 et 2016, dont 39 recidives cliniques. Quatorze patients sur 39 ont ete traites par ECZ (11 GC3, 3 Ig-GNMP). La recidive survenait apres un delai median de 58 jours dans le groupe ECZ contre 556 jours dans le groupe non traites (p = 0,0017). Le delai median d’introduction de l’ECZ etait de 35 jours apres le diagnostic. A 6 mois de traitement par ECZ, 9/14 (64 %) patients etaient repondeurs (6 RC, 3 RP). Au dernier follow-up, 3/5 non repondeurs avaient perdu leur greffon contre 0/9 repondeurs (p = 0,027). Les repondeurs avaient une fonction renale stable. Le principal facteur associe a une reponse a l’ECZ etait la presence de depots glomerulaires de C5b-9 (7/7 repondeurs ; 2/5 non-repondeurs ; p = 0,045). La survie du greffon semblait meilleure dans le groupe ECZ sans toutefois de difference significative (p = 0,123) Discussion/Conclusion L’ECZ a ete efficace chez 64 % des patients traites pour une recidive clinique de GC3/Ig-GNMP. Les depots de C5b-9 glomerulaires etaient significativement associes a une reponse au traitement. Des essais prospectifs sont necessaires pour confirmer ces resultats.

Purpose The active or aggressive character in certain localisations of aneurysmal bone cysts in children requires either curettage with a considerable recurrence rate or a radical segmental excision, raising complex reconstructive challenges. Cyst maturation with subsequent ossification may be observed either spontaneously or after incisional biopsy. Patients Five new cases of active aneurysmal bone cysts (ABCs) with healing of the cyst after biopsy alone are reported. All patients had no treatment of the cyst after the biopsy. Results In two cases, the lesion initially increases in size immediately after the biopsy, and it is only secondarily that the lesion decreases in size. Four out of five cases of the spontaneous healing occurred in pelvic bone. The cysts healed after, respectively, 36, 24, 12, 32 and 12 months. Conclusions The emergence of these new cases of spontaneous healing encourages promoting clinical and radiological supervision after biopsy in selected cases. Unfortunately, it is impossible to predict a possible aggressive behaviour in ABCs. Then, if the lesion is quickly aggressive with clinically and radiologically increasing size after biopsy, it would be illogical and dangerous to let this ABC evolve. It would be necessary to treat it without delay. On the other hand, if the lesion moderately increased after the biopsy, it is possible to wait and observe the patient during a period of 5 months for a possible healing, if the ABC localisation is not dangerous. Of course, if the lesion does not increase in size after biopsy, there is no delay to treat it.

Breast inflammation is a difficult clinical problem as it can result from a variety of causes: specific or non-specific infectious mastitis, which may or may not be complicated, primary or secondary inflammatory mastitis or inflammatory cancer. The main objective of radiology is to eliminate an inflammatory cancer. Other objectives are to characterise an inflammatory condition (where the clinical context is valuable in guiding diagnosis but which often requires a micro- or macrobiopsy) or to obtain a microorganism in cases of complicated infectious mastitis (a diagnostic procedure but also comprising the first stage of treatment). Whether for bacteriological or histological purposes, percutaneous samples therefore play a large part in the diagnostic procedure, other than in the clinical context of pregnancy where mastitis is more easily diagnosed because of its frequency. The guidance method is usually ultrasound, and the needle chosen will depend on the radiological or ultrasound signal: puncture with an 18G needle will be used for a bacteriological sample, microbiopsy of a mass or lymph nodes, or macrobiopsy in the case of microcalcifications.

Human tissues are an important source of biological material for the discovery of novel biomarkers. Fresh-frozen tissue could represent an ideal supply of archival material for molecular investigations. However, immediate flash freezing is usually not possible, especially for rare or valuable tissue samples such as biopsies. Here, we investigated the compatibility of RCL2/CS100, a non-crosslinking, non-toxic, and non-volatile organic fixative, with shotgun proteomic analyses. Several protein extraction protocols compatible with mass spectrometry were investigated from RCL2/CS100-fixed and fresh-frozen colonic mucosa, breast, and prostate tissues. The peptides and proteins identified from RCL2/CS100 tissue were then comprehensively compared with those identified from matched fresh-frozen tissues using a bottom-up strategy based on nano-reversed phase liquid chromatography coupled with tandem mass spectrometry (nanoRPLC-MS/MS). Results showed that similar peptides could be identified in both archival conditions and the proteome coverage was not obviously compromised by the RCL2/CS100 fixation process. NanoRPLC-MS/MS of laser capture microdissected RCL2/CS100-fixed tissues gave the same amount of biological information as that recovered from whole RCL2/CS100-fixed or frozen tissues. We next performed MALDI tissue profiling and imaging mass spectrometry and observed a high level of agreement in protein expression as well as excellent agreement between the images obtained from RCL2/CS100-fixed and fresh-frozen tissue samples. These results suggest that RCL2/CS100-fixed tissues are suitable for shotgun proteomic analyses and tissue imaging. More importantly, this alternate fixative opens the door to the analysis of small, valuable, and rare target lesions that are usually inaccessible to complementary biomarker-driven genomic and proteomic research.

International audience; In assisted reproduction, about 30% of embryo implantation failures are related to inadequate endometrial receptivity. To identify molecules involved in endometrial receptivity acquisition, we investigated, using a SELDI-TOF approach, the protein expression profile of early-secretory and mid-secretory endometrium samples. Among the proteins upregulated in mid-secretory endometrium, we investigated the function of S100A10 in endometrial receptivity and implantation process. S100A10 was expressed in epithelial and stromal cells of the endometrium of fertile patients during the implantation windows. Conversely, it was downregulated in the mid-secretory endometrium of infertile patients diagnosed as non-receptive. Transcriptome analysis of human endometrial epithelial and stromal cells where S100A10 was silenced by shRNA revealed the deregulation of 37 and 256 genes, respectively, related to components of the extracellular matrix and intercellular connections. Functional annotations of these deregulated genes highlighted alterations of the leukocyte extravasation signaling and angiogenesis pathways that play a crucial role during implantation. S100A10 silencing also affected the migration of primary endometrial epithelial and stromal cells, decidualization and secretory transformation of primary endometrial stromal cells and epithelial cells respectively, and promoted apoptosis in serum-starved endometrial epithelial cells. Our findings identify S100A10 as a player in endometrial receptivity acquisition.

Introduction Le syndrome de Gougerot-Sjogren (SGS) cible particulierement les glandes exocrines buccales et lacrymales. Ces dernieres partagent avec la glande mammaire des caracteristiques anatomiques (organisation excretrice glandulaire), histologiques (epithelium glandulaire exocrine), et immunologiques (role de defense et role immuno-regulateur). Notre travail visait a decrire, notamment au plan histologique, les lesions mammaires observees parmi des patientes presentant un SGS, et les comparer aux lesions salivaires. Patients et methodes Nous avons etudie retrospectivement les cas de patientes presentant un SGS ayant beneficie d’une biopsie mammaire, et dont les tissus mammaires et salivaires etaient disponibles (patientes suivies au CHRU de Montpellier entre janvier 2000 et janvier 2015). Les caracteristiques cliniques, immunologiques et les modalites therapeutiques de ces patientes ont ete etudiees en parallele des aspects histologiques. Deux anatomopathologistes referents ont analyse retrospectivement les tissus mammaires et salivaires dans l’optique d’identifier des aspects inflammatoires. Des analyses immuno-histochimiques ont permis de preciser la distribution tissulaire des leucocytes dans chacun de ces tissus. Resultats Nous avons identifie 16 patientes presentant un SGS, avec un âge median de 60,1 ± 11,3 ans au diagnostic. Cliniquement, ces 9 patientes presentaient principalement un syndrome sec et des polyarthralgies, associes a de faibles stigmates d’auto-immunite (presence d’anticorps anti-SSa dans 2 cas). L’evolution de la maladie etait benigne dans la plupart des cas, n’entrainant que peu de traitements immunosuppresseurs systemiques chez ces patientes. Les biopsies mammaires etaient realisees en raison de symptomes mammaires pour 6 d’entre elles, et a la suite de la strategie de depistage radiologique du cancer du sein chez 10 patientes. Neuf patientes (56 %) presentaient des signes histologiques d’inflammation du tissu mammaire (infiltrat lymphocytaire et/ou ectasie canalaire), proches de l’atteinte histologique salivaire. Les marquages immuno-histochimiques (n = 5) ont revele des infiltrats lymphocytaire B et T au sein du tissu mammaire, avec une plus forte proportion de cellules CD4+, sans qu’en aucun cas des plasmocytes secreteurs d’IgG4 ne soient identifies. Conclusion Nous rapportons des atteintes histologiques mammaires d’aspect inflammatoire, histologiquement proches des atteintes salivaires, au cours du SGS. Cette atteinte mammaire illustre la diffusion de la maladie aux glandes exocrines, atteinte classique du SGS. Ces observations sont concordantes avec les donnees de la litterature faisant du SGS une « epithelite-auto-immune ».

Up to a quarter of ovarian masses originate from germ cells. Germ cell tumours occur at a higher frequency than epithelial tumours in Oriental and African populations. Mature cystic teratomas (MCTs), or the so-called dermoid cysts because of the overall predominance of skin elements, are not only the most common germ cell tumours but also the most common benign ovarian neoplasms in women under 45 years old. This chapter will cover CT and MR appearance of the more common teratomas: mature cystic teratomas; immature teratomas and struma ovarii.

Background Leiomyomas are benign smooth muscle cell tumours. They are the most common uterine neoplasms, although they may also occur elsewhere, such as in the gastrointestinal and urinary tracts. Leiomyomas are uncommon in von Recklinghausen's neurofibromatosis (NF1). However, the literature suggests that the association of NF1 and leiomyomas or leiomyosarcoma is not entirely coincidental. Case Report We report here the unusual case of a 47-year-old woman with NF1 who presented menorrhagias and a hard, tender pelvic mass composed of uterine leiomyomas. Positron emission tomography/computed tomography disclosed an area of increased 18-fluorodeoxyglucose (FDG) uptake in the upper right part of the mass that raised the suspicion of malignancy. Magnetic resonance imaging revealed numerous intramural leiomyomas ranging from 1 to 6 cm, including a 6-cm submucosal leiomyoma that had abundant cellularity, matching FDG uptake. Abdominal hysterectomy was performed and microscopic examination confirmed the diagnosis of multiple benign smooth muscle tumours (uterine leiomyomatosis). Conclusion Our case illustrates several diagnostic issues that arose while exploring this pelvic mass. Moreover, the association of uterine leiomyoma and NF1 may not be fortuitous.

Main problem The number of kidney transplant candidates with prosthetic heart valves (PHVs) is increasing. Yet, outcomes of kidney transplantation in these patients are still unclear. This is the first report of post-transplant outcomes in patients with PHVs at time of kidney transplantation. Methods We conducted a matched cohort study among recipients from the multicentric and prospective DIVAT cohort to compare outcomes in patients with left-sided PHVs at time of transplantation and a group of recipients without PHV matched according to age, dialysis time, initial disease, pre-transplant DSA, diabetes and cardiovascular events. Results Of 23018 patients, 92 patients with PHVs were included and compared to 276 patients without PHV. Delayed graft function and post-operative bleeding occurred more frequently in patients with PHVs. Kidney graft survival was similar between groups. 5-year overall survival was 68.5 % in patients with PHV versus 87.9 % in patients without PHV (HR, 2.72[1.57-4.70], p=0.0004). Deaths from infection, endocarditis and bleeding were more frequent in patients with PHV. Mechanical valves, but not bioprosthetic valves, were independent risk factors for mortality (HR, 2.89[1.68-4.97], p=0.0001). Conclusions Patients with PHV have high mortality rates after kidney transplantation. These data suggest that mechanical valves, but not biological valves, increase risks of post-transplant mortality.