Cobalamin c deficiency associated with antifactor h antibody-associated hemolytic uremic syndrome in a young adult.

BACKGROUND: Thrombotic microangiopathy (TMA) syndromes are characterized by the association of hemolytic anemia, thrombocytopenia and organ injury due to arteriolar and capillary thrombosis. CASE PRESENTATION: We report the first case of adult onset cobalamin C (Cbl C) disease associated with anti-factor H antibody-associated hemolytic uremic syndrome (HUS). A 19-year-old woman was admitted to the nephrology department owing to acute kidney failure, proteinuria, and hemolytic anemia with schizocytes. TMA was diagnosed and plasma exchanges were started in emergency. Exhaustive analyses showed 1) circulating anti factor H antibody and 2) hyperhomocysteinemia, hypomethioninemia and high levels of methylmalonic aciduria pointing towards Clb C disease. Cbl C disease has been confirmed by methylmalonic aciduria and homocystinuria type C protein gene sequencing revealing two heterozygous pathogenic variants. The kidney biopsy showed 1) intraglomerular and intravascular thrombi 2) noticeable thickening of the capillary wall with a duplication aspect of the glomerular basement membrane and a glomerular capillary wall IgM associated with Cbl C disease related TMA. We initiated treatment including hydroxycobalamin, folinic acid, betaine and levocarnitine and Eculizumab. Rituximab infusions were performed allowing a high decrease in anti-factor H antibody rate. Six month after the disease onset, Eculizumab was weaning and vitaminotherapy continued. Outcome was favorable with a dramatic improvement in kidney function. CONCLUSION: TMA with renal involvement can have a complex combination of risk factors including anti-FH autoantibody in the presence of cblC deficiency.

A French retrospective study on clinical outcome in 102 choroid plexus tumors in children.

The aim of this study was to review and describe therapeutic approaches in children with choroid plexus tumor (CPT) based on a nationwide series. The World Health Organization classification subdivides these rare tumors into three histological subtypes corresponding to three grades of malignancy: low grade (grade I) choroid plexus papilloma (CPP), intermediate grade (grade II) atypical choroid plexus papilloma (aCPP) and high grade (grade III) choroid plexus carcinoma (CPC). This retrospective study included 102 French children younger than 18 years, treated from 2000 to 2012: 54 CPP, 26 aCPP and 22 CPC. The 5 year overall survival was 100% in CPP, 96.2% in aCPP and 64.7% in CPC. In patients with localized disease, complete surgical resection was achieved in 48/52 CPP, 20/26 aCPP and 7/14 CPC. In this group, patients with complete surgical resection had better event free survival than patients with partial resection (88.9 vs. 41.6%). 28 patients (1 CPP, 6 aCPP and 22 CPC) had adjuvant chemotherapy. 2 aCPP and 9 CPC had radiotherapy. We underlined the need for a central histological review to accurately analyze clinical data; we reported a much higher overall survival for CPC than in most previous CPT series probably including atypical teratoid rhabdoid tumors. In our series, the 5 years overall survival in CPC (64.7%) was higher than event free survival (25.2%) and could be interpreted as a clue for the efficiency of adjuvant/salvage therapy even if the heterogeneity of applied treatments in this retrospective series does not allow for meaningful statistical comparisons.

P53/Rb inhibition induces metastatic adrenocortical carcinomas in a preclinical transgenic model.

Adrenocortical carcinoma (ACC) is a rare cancer with poor prognosis. Pan-genomic analyses identified p53/Rb and WNT/ß-catenin signaling pathways as main contributors to the disease. However, isolated ß-catenin constitutive activation failed to induce malignant progression in mouse adrenocortical tumors. Therefore, there still was a need for a relevant animal model to study ACC pathogenesis and to test new therapeutic approaches. Here, we have developed a transgenic mice model with adrenocortical specific expression of SV40 large T-antigen (AdTAg mice), to test the oncogenic potential of p53/Rb inhibition in the adrenal gland. All AdTAg mice develop large adrenal carcinomas that eventually metastasize to the liver and lungs, resulting in decreased overall survival. Consistent with ACC in patients, adrenal tumors in AdTAg mice autonomously produce large amounts of glucocorticoids and spontaneously activate WNT/ß-catenin signaling pathway during malignant progression. We show that this activation is associated with downregulation of secreted frizzled related proteins (Sfrp) and Znrf3 that act as inhibitors of the WNT signaling. We also show that mTORC1 pathway activation is an early event during neoplasia expansion and further demonstrate that mTORC1 pathway is activated in ACC patients. Preclinical inhibition of mTORC1 activity induces a marked reduction in tumor size, associated with induction of apoptosis and inhibition of proliferation that results in normalization of corticosterone plasma levels in AdTAg mice. Altogether, these data establish AdTAg mice as the first preclinical model for metastatic ACC.

[Intraocular lymphoma associated with primary malignant lymphoma of the central nervous system: Seven-year experience of a tertiary center]. / Lymphome intraoculaire associé au lymphome primitif non hodgkinien du système nerveux central : expérience d'un centre tertiaire sur une durée de sept ans.

INTRODUCTION: Primary intraocular lymphoma (PIOL), associated with primary central nervous system lymphoma (PCNSL), is a rare malignancy disease. By way of a seven-year experience of a tertiary center, we discuss the presentation and we review the diagnostic and therapeutic modalities. OBSERVATIONS: We report six cases of PIOL associated with PCNSL. For all patients, the clinical presentation was a vitreoretinal syndrome. The diagnosis was histologically confirmed by vitreal sample or brain biopsy. Five patients developed a diffuse large B-cell lymphoma. Only one patient developed a T-cell lymphoma. The treatment consisted of conformational radiation therapy, systemic chemotherapy and intravitreal injections of methotrexate. The median survival after the diagnosis was 24 months. DISCUSSION: PIOL, associated with PCNSL, is the most common type of ocular lymphoma. In most cases, ocular manifestations inaugurate the disease. PIOL is often fatal because of ultimate central nervous system presentation. The role of the ophthalmologist consists in early diagnosis. Typical clinical findings include vitroretinal tumor syndrome but can mascarade other eye pathologies. Diagnosis requires histology. The majority of PIOL is diffused large B-cell lymphoma. Decisions are made through multidisciplinary consultation. PIOL exhibits high responsiveness to methotrexate. CONCLUSION: Through a literature review and many illustrations, we discuss epidemiological, clinical, histological, radiological and treatment characteristics of PIOL associated with PCNSL.

[DSAEK after failed penetrating keratoplasty]. / DSAEK après échec de kératoplastie perforante.

PURPOSE: To report the anatomic and functional outcomes of Descemet's stripping automated endothelial keratoplasty (DSAEK) in 32 eyes after failed penetrating keratoplasty (PK). SUBJECTS AND METHODS: This retrospective, single-center observational study was performed on 32 eyes of 26 patients with failed PK grafts who underwent DSAEK between June 2009 and June 2013 at Clermont-Ferrand University Medical Center. Primary outcomes measured were: graft survival rates, functional improvement (visual acuity), and complications. RESULTS: Mean follow-up was 16.45 months [6-36]. Graft survival at 12 months was 76.1 % [68.1-82.3]. PK grafts cleared in 75 % of cases. Eight primary DSAEKs detached and/or decentered early (prior to day 8, average 6.22 days): 3 underwent repeat DSAEK with a new graft, and 3 underwent conversion to PK. Results were available for 26 patients at 6 months. Mean preoperative best-corrected visual acuity (BCVA) in logMAR increased from 1.48 (counting fingers at 2 meters) to 0.996 logMAR (1/10) at 6 months. BCVA improved in 17 patients (68 %). BCVA improved an average of 5.2 lines (P=0.0006). Eight patients had a large number of comorbid conditions that limited final visual acuity. DISCUSSION: Anatomic outcomes are similar to other studies. Final average BCVA was limited by severe comorbid conditions and performance of DSAEK solely for comfort. Many surgical strategies have been described to decrease graft dislocation and primary graft failure. Adapting graft trephine diameter to the host cornea as measured by AS-OCT, using a nomogram based on posterior corneal curvature obtained on AS-OCT, may be an interesting approach. CONCLUSION: DSAEK allows for quick visual recovery by preserving the anterior corneal curvature. It is an essential option for restoring corneal clarity in PK failure due to endothelial decompensation. A longer follow-up would allow a comparison of graft survival for the two techniques in this context.

[Apropos of 5 cases of optic nerve tumors diagnosed during a 6-year-period]. / À propos de 5 cas de tumeurs du nerf optique sur une période de 6ans.

INTRODUCTION: Optic nerve tumors are uncommon and rarely described. By way of five patients treated at the University Hospital of Clermont-Ferrand, France, over a six-year-period, we discuss their clinical and radiological characteristics, their treatment and their course. OBSERVATIONS: We report two cases of optic nerve glioma in small children, two cases of optic nerve sheath meningioma and a 57-year-old patient treated for lung cancer with an optic nerve metastasis and choroidal and brain metastases. The diagnosis was confirmed by imaging in all patients and histologically for the cases of optic nerve glioma. RESULTS: The children with glioma were exclusively treated with chemotherapy, the two women with meningioma exclusively with radiation therapy, and the man with the optic nerve metastasis by chemotherapy and radiotherapy. The tumors were stabilized in all cases except for a progression in one case of glioma, one year after treatment. DISCUSSION: Gliomas and meningiomas are the most frequent tumors; other tumors are rare. Through a literature review and many illustrations, we discuss epidemiologic, clinical and radiologic characteristics, treatment and course of these uncommon tumors. CONCLUSION: The diagnosis of optic nerve tumors must be considered in cases of anterior or posterior progressive optic neuropathy. Treatment must be a compromise between effective treatment of the tumor and preservation of visual function. Decisions are made through multidisciplinary consultations, in which the role of the ophthalmologist is crucial for the diagnosis and success of the treatment.

[Multiparametric 3T MRI in the routine staging of prostate cancer]. / L'IRM 3 Tesla multi-paramétrique dans le staging du cancer prostatique en pratique courante.

OBJECTIVE: To analyse the detection ability of a multiparametric 3T MRI with phased-array coil in comparison with the pathological data provided by the prostatectomy specimens. METHODS: Prospective study of 30 months, including 74 patients for whom a diagnosis of prostate cancer had been made on randomized prostate biopsies, and all eligible to a radical prostatectomy. They all underwent multiparametric 3T MRI with pelvic phased-array coil including T2-weighted imaging (T2W), dynamic contrast-enhanced (DCE) and diffusion-weighted imaging (DWI) with an ADC mapping. Each gland was divided in octants. Three specific criteria have been sought (detection ability, capsular contact [CC] and extracapsular extension [ECE]), in comparison with the pathological data provided by the prostatectomy specimens. RESULTS: Five hundred and ninety-two octants were considered with 124 significant tumors (volume ≥ 0.1cm(3)). The general ability of tumor detection had a sensitivity, specificity, PPV and NPV respectively to 72.3%, 87.4%, 83.2% and 78.5%. The estimate of the CC and ECE had a high negative predictive power with specificities and VPN respectively to 96.4% and 95.4% for CC, and 97.5 and 97.7% for ECE. CONCLUSIONS: Multiparametric 3T MRI with pelvic phased-array coil appeared to be a reliable imaging technique in clinical and routine practice for the detection of localized prostate cancer. Estimation of the CC and millimeter ECE remains to be clarified, even if the negative predictive power for these parameters seems encouraging.

[The myeloproliferative neoplasms-related glomerulopathy]. / Les glomérulopathies associées aux néoplasies myéloprolifératives.

PURPOSE: Myeloproliferative neoplasms (MPN) are hematological disorders characterized by clonal expansion of one or more medullary lines. Renal complications are rare, chiefly as acute renal failure. Glomerular involvement is exceptional METHODS: We report on a retrospective multicenter case series of eight patients who presented with a glomerulopathy (GP) associated with MPN RESULTS: All GP were revealed by a major proteinuria frequently associated with nephrotic syndrome and oedema. Histology was mainly characterized by lesions of focal segmental glomerulosclerosis associated with increased mesangial cellularity. The pathophysiology is still unclear but platelet-derived growth factor (PDGF) and transforming growth factor-ß (TGF-ß), which play a central role in the MPN may be involved. A majority of patients developed chronic renal failure despite of a therapy intended to block the renin-angiotensin system CONCLUSION: Monitoring of proteinuria during the follow-up of MPN would allow earlier diagnosis of renal involvement. Further studies on a larger scale are needed to specify the pathophysiological mechanisms involved and the management of these complications.

[Recurrent pericarditis related to primary pericardial malignant mesothelioma]. / Péricardite récidivante : traquer le mésotheliome péricardique primitif.

INTRODUCTION: Most of recurrent pericarditis are idiopathic and only 15 to 20% have a specific diagnosis. Primary pericardial mesothelioma is a rare cause of recurrent pericarditis. Diagnosis can be challenging and antedates patient's death in only 10 to 20% of cases. Histology of mesothelioma and immunohistochemistry are mandatory for the diagnosis. Median of survival before using pemetrexed was about 6 months after diagnosis. CASE REPORT: We report the history of a 64-year-old woman for which repeated biopsy for recurrent pericarditis was necessary to diagnose a primary pericardial mesothelioma. The first biopsy had only found mesothelial hyperplasia. CONCLUSION: This case report highlights the necessity of repeat pericardial biopsy in the case of adverse outcome.

Is IgG4-Related Disease a Cause of Xerostomia? A Cohort Study of 60 Patients.

Objective. Immunoglobulin-G4-(IgG4-) related disease (IgG4 RD) is a fibrosing process characterized by a significant infiltration of IgG4-secreting plasma cells. IgG4 RD can affect almost all organs including salivary glands. Whether IgG4 RD plays a role in the development of sicca syndrome and particularly dry mouth syndrome remains to be investigated. Methods. We conducted a monocentric cohort study for two years to search for IgG4 RD features in patients with dry mouth syndrome using immunostainings of labial salivary gland specimens with anti-IgG4 antibody. Results. Among 60 patients presenting with dry mouth syndrome who underwent labial salivary gland biopsy, 18 showed positive immunostaining with the anti-IgG4 antibody including 4 patients with typical systemic IgG4 RD. Five also fulfilled criteria for Sjögren's syndrome. Conclusion. These findings suggest that clinical forms of IgG4 RD salivary involvement without salivary swelling may occur. This salivary involvement is probably overlooked in everyday practice and could represent a mild form of IgG4 RD.

Imaging of inflammatory myofibroblastic cervical tumours: a case report.

Among the family of mesenchymatous tumours, inflammatory myofibroblastic tumours (IMT) are an increasingly recognised and defined lesional group due to the great many studies and recent publications. The aetiopathogenicity is still not fully understood. It seems that an immune origin is involved in the pathological process. These masses result from the proliferation of fibroblast and lymphocyte cells associated with collagen wickerwork. Most often benign, they may affect any organ or supporting tissue. However, these lesions remain non-specific and are difficult to distinguish from malignant tumoral processes. Here resides the value of imaging: to make the diagnosis, guide the biopsy and thereby avoid early damaging surgery or an aggressive medical treatment. This is all the more valid since recent papers have shown that corticotherapy of short duration is currently the first intention treatment We here describe the case of a female patient presenting disseminated erythematous lupus who presented a cervical myofibroblastic tumour. The early diagnosis allowed for the initial medical care, which turned out to be effective without resorting to surgery.

Malignant lacrimal sac tumors.

OBJECTIVES: Lacrimal sac tumors are usually primary and of epithelial origin. Overall, 55% of lacrimal sac tumors are malignant. Mortality rates for malignant tumors depend on tumor stage and type, with a mean rate of 38%. The main objective of this study was to review our experience with these malignancies and to compare this with the published literature. PATIENTS AND METHODS: A 15-year retrospective review of all malignant lacrimal sac tumor patients was completed in our department. Seven patients were found to have malignant sac tumors. The mean age was 53 years (range, 32-74 years) with six women and one man. The patients' clinical records were reviewed for data regarding patient symptoms, preoperative investigations, pathology reports, treatment results, and outcome. These data were compared with the available literature. RESULTS: All patients presented with epiphora and a palpable lump of the internal canthus. In two cases, a history of recurrent dacryocystitis was noted. The histological types were as follows: squamous cell carcinoma (n=5), one case of adenoid cystic carcinoma, and one case of malignant lymphoma. Surgery was performed in six cases with additional radiotherapy in four. One patient was treated exclusively with external radiotherapy. The mean follow-up was 68 months (range, 6-204 months). Two patients developed recurrences: three were disease-free at the time of the study. CONCLUSIONS: Malignant epithelial lacrimal sac tumors are rare cancers with significant recurrence rates. Correct diagnosis and appropriate therapy require a multidisciplinary management approach. Treatment of these malignant epithelial tumors is first and foremost complete surgical removal with wide excision.

Sinonasal mucosal melanomas.

OBJECTIVES: Sinonasal mucosal melanomas account for approximately 1% of all melanomas. These tumors are particularly aggressive, with a recurrence rate between 37 and 54% and a 5-year survival rate between 20 and 46%. Metastases are frequent. The main objective of this study was to analyze all of our cases of sinonasal mucosal melanomas and determine any prognostic factors. PATIENTS AND METHODS: All our cases of sinonasal mucosal melanoma over a period of 10 years were included. Ten cases were analyzed. The mean age was 71 years (range: 61-85 years) for seven women and three men. The clinical, radiological, anatomopathological, and surgical data as well as the characteristics of disease progression were analyzed. These data were compared to those reported in the literature. RESULTS: The mean follow-up was 36.3 months (range: 2-96 months). The 5-year overall survival was 40%. Seven patients developed local recurrences after a mean follow-up of 16 months (range: 2-27 months) with associated metastases in three cases. Analysis of the prognostic factors showed that tumors classified as T1 and limited to the nasal fossae had a better prognosis. CONCLUSION: Sinonasal mucosal melanomas are rare tumors with a high mortality rate. Treatment of these tumors requires extensive surgical treatment associated with external radiotherapy.

[An optic nerve glioma in a 4-month-old child]. / Gliome du nerf optique chez un enfant de 4 mois.

The optic nerve glioma is a relatively rare pathology in children and only a few cases have been described in infants. This paper reports the symptoms of this exceptional case in a 4-month-old child and reviews the differential diagnoses at this age. Finally, we discuss the diagnosis and therapeutic possibilities.

[Tracheopathia osteoplastica]. / Trachéopathie ossifiante.

OBJECTIVES: Report a case of tracheopathia osteoplastica and describe from a literature analysis the main clinical, radiological, and therapeutic features of this rare disease based on literature review. MATERIAL AND METHODS: A 74-year-old patient suffering from a nasal polyposis that had been repeatedly operated was admitted for surgery of the frontal sinus. The day of surgery, the difficult intubation required a laryngotracheoscopy, which found a dystrophic trachea, with a sprinkling of whitish nodules, and hard swelling. The pathologic exams of a large biopsy specimen using a rigid bronchoscopy provided the diagnosis of tracheopathia osteoplastic. A complementary workup to search for the etiology was undertaken. The risk and the difficulty of the intubation led to suspending the surgery. RESULTS: The CT scan as well as the histological, bacteriological, and immunological tests showed nothing specific. The etiopathogenic hypothesis was the association of chronic disease of the upper airways such as the ozena or the chronic inflammation of the respiratory tract, an endocrine factor, dermatomyositis, exposure to toxic substances such as silica, or tracheobronchial amyloidosis. The bronchial microbiology test is positive in more than 50% of patients, and often Klebsiella ozaenae or Pseudomonas aeruginosa is found. CONCLUSION: Tracheopathia osteoplastica is a rare tumor, with unknown etiology and physiopathology. The discovery is most often incidental. Progession is slow and it does not compromise the vital prognosis. The treatment is symptomatic. Few surgical tracheal operations are described in the literature.