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.

[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.

[Pulmonary artery intimal sarcoma]. / Sarcome intimal de l'artère pulmonaire.

Pulmonary artery sarcoma is a rare tumor. We present a case of intimal sarcoma arising from right pulmonary artery and left lower pulmonary vein observed in a 44-year-old man with a non-productive cough. Computed tomographic scans and magnetic resonance imaging showing filling defect enhancement contributed early, suggesting the diagnosis of primary vascular tumor, hypothesis confirmed by pathologist findings.

[Epilaryngeal tuberculosis: epidemiologic, clinical and healthcare considerations]. / Tuberculose épilaryngée: considérations épidémiologiques, cliniques et sanitaires.

OBJECTIVE: To report a case of laryngeal tuberculosis and to consider tuberculosis management in ENT practice. MATERIAL AND METHODS: A 44-year-old man, a smoker with pulmonary sarcoidosis experienced dysphonia with dysphagia. Laryngeal fibroscopy revealed an ulcerated epiglottic lesion. Direct laryngoscopy was performed to detect carcinoma, laryngeal sarcoidosis or tuberculosis. The histologic study revealed granulomatosis with giant cells and caseous necrosis. Tissue culture identified Mycobacterium tuberculosis. RESULTS: Antituberculosis therapy decreased dysphonia and dysphagia. Isolated ulceration disappeared at three months. Pulmonary infiltration decreased in radiography. The discovery of this case of laryngeal tuberculosis instigated hospital and community tuberculosis surveillance. CONCLUSION: The ENT specialist should be aware of laryngeal tuberculosis in suspicious lesions. Mandatory declaration of such cases can motivate setting up tuberculosis surveillance.

[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.

[Salivary involvement in IgG4-related multifocal fibrosclerosing disease]. / Manifestations salivaires dans la Maladie Fibrosclérosante Multiple à IgG4.

OBJECTIVES: To report a case of IgG4-related multifocal fibrosclerosis, revealed by a multifocal salivary involvement. MATERIAL AND METHODS: A 59-year-old man, with chronic pancreatitis, was managed for fibrotic involvement of the 2 submaxillary glands and the 2 parotids. Clinical, radiological, and histologic features were retrospectively studied. RESULTS: Pathological features of submandibular gland revealed a chronic sclerosing sialadenitis. Retroperitoneal fibrosis in computed tomography and high rate of IgG4 are objectived. The diagnosis of IgG4-related multifocal fibrosclerosis is evoked. The patient's state improved with corticosteroid therapy. CONCLUSION: Salivary involvement in IgG4-related multifocal fibrosclerosis must be recognized in salivary medical pathology.

[Adenoid cystic carcinoma of the external auditory canal]. / Carcinome adénoïde kystique du méat acoustique externe.

OBJECTIVES: To report a case of adenoid cystic carcinoma of the external auditory canal with petrous involvement. MATERIAL AND METHODS: A 50-year-old woman was referred to our department for the management of a necrotizing external otitis. Computed tomography and biopsy revealed an adenoid cystic carcinoma of the external auditory canal. RESULTS: The patient was treated by complete surgical excision. A radiation therapy completed the treatment. Follow-up time was 19 months without evidence of recurrence. Adenoid cystic carcinoma of the external auditory canal is a rare tumor. It's a special type of carcinoma developing from the ceruminous glands. Histogenesis is difficult and unsettled. The most important survival factor is removal of the tumor with histologically free margins. CONCLUSIONS: Lack of specific clinical and radiological signs makes the diagnostic challenging. The adenoid cystic carcinoma is a rare neoplasm of the external auditory canal. An initial aggressive wide "en bloc" surgical resection is mandatory.

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.

Primary lymphoma of the lacrimal sac: an EORTC ophthalmic oncology task force study.

AIM: To define the clinical and histopathological characteristics of primary lacrimal sac lymphoma in a predominantly white population. METHODS: Specimens of lacrimal sac lymphoma and follow up data were solicited from members of the Ophthalmic Oncology Task Force of the European Organization for Research and Treatment of Cancer (EORTC) and the European Ophthalmic Pathology Society (EOPS). Specimens were stained with haematoxylin and eosin and an immunohistochemical panel against leucocyte antigens was applied. Diagnosis was reached by consensus of five experienced pathologists according to the World Health Organization classification system. The histopathological findings were correlated with the clinical data. RESULTS: Of 15 primary lacrimal sac lymphomas, five (33%) were diffuse large B cell lymphoma (DLBCL), five (33%) were extranodal marginal zone B cell lymphoma of mucosa associated lymphoid tissue (MALT lymphoma), three were classified as "transitional MALT lymphoma," being in transition from MALT lymphoma to DLBCL, and two were unclassified B cell lymphomas. Nine of the patients were female, and the median age at the time of diagnosis was 71 years (range 45-95 years). The most frequent presenting symptoms were epiphora (85%), swelling in the region of the lacrimal sac (79%), and dacryocystitis (21%). All but one patient presented in stage I. Systemic spread occurred in three of nine patients (33%). The 5 year overall survival was 65%. CONCLUSIONS: DLBCL and MALT lymphoma are equally common in the lacrimal sac in contrast with the remaining periorbital and/or orbital region where MALT lymphoma predominates.

[Adenocarcinomas of the ethmoid sinus: retrospective analysis of prognostic factors]. / Adénocarcinomes de l'ethmoïde: analyse rétrospective des facteurs pronostics.

OBJECTIVES: Determinate the different prognostic factors of survival in ethmoidal sinus adenocarcinomas (ADK). MATERIAL AND METHODS: 60 patients with ethmoidal sinus ADK. 59 men and one woman. Average of 62.2 years (41-82). Retrospective study between 1985 and 2005. The following data were analyzed: exposure time to wood dust, disease incidence, primary clinical symptoms and ASA score. Radiological data were recovered by tomodensitometry and magnetic resonance imaging. Histological groups were described. TNM classification according to UICC 2002 and Roux/Brasnu was established on clinical and radiological constatations. Different treatments used were analyzed. Estimate of survival rate and impact of different prognostic factors were based on Kaplan-Meier actuarial method and multivariate analysis. RESULTS: Incidence rate was 2.86 patients a year. Exposure average time to wood dust was 25.6 years (2-44). T3/T4 stages were predominant (66.7%). the survival rate was 46.5% at 5 years. The survival rate was significantly superior respectively in T1 and T2 stages than in T3 and T4 stages, and in T4a than in T4b stages. Extension of the lesion to the sphenoid sinus was revealed as a significant bad prognostic factor. The ASA score and the exposure time to wood dust were not identified as statistically significant prognosis factors. CONCLUSION: Survival factors of ethmoïd sinus ADK were T stage and the extension of the tumor to the sphenoid sinus. On the results of this study, we consider that extension in sphenoïd sinus could be include in TNM classification of ethmoïd sinus adenocarcinomas.

[Hemorrhagic lumbar juxta facet cyst. A case report]. / Kyste lombaire hémorragique juxta-articulaire. A propos d'un cas.

We report the case of a hemorrhagic lumbar juxta facet cyst (L2-L3), revealed by a chronic right lumbocruralgia, in a 77-year-old woman treated by anticoagulants for cardiac arrhythmia. Computerized tomography and magnetic resonance imaging suggested the diagnosis of benign tumor. During surgical removal of the whole lesion, a hemorrhagic synovial cyst was evoked. The operation dramatically relieved the symptoms. The diagnosis was confirmed by the histopathological analysis confronted with the clinical and the radiological findings. This uncommon observation allows the discussion of the pathogenic mechanism and of the differential diagnosis.

[Tympanic paragangliomas: analysis of a nine cases]. / Paragangliomes tympaniques. Analyse d'une série de neuf cas.

OBJECTIVE: The purpose of this work was to evaluate the diagnostic strategy and outcome of patients treated for tympanic paraganglioma. PATIENTS AND METHODS: Nine patients presented with tympanic paraganglioma were treated in our unit from 1996 to 2003. There were eight women and one man, mean age 65 years. Surgery was performed in all nine patients. This retrospective analysis focused on revealing signs, diagnostic tools, surgical procedure for tumor resection, and short-, mid-, and long-term functional outcome. RESULTS: The surgical procedure was well tolerated by all patients. There were no cases of postoperative mastoiditis. None of the patients experienced postoperative dizziness. Total tumor removal was achieved in seven patients. In one patient, incomplete tumor resection was decided in order to preserve facial motion. All patients but one were relieved from their tinnitus in the early postoperative period. In four patients, preoperative hearing levels were worsened by the surgical procedure, essentially through an alteration of preoperative conductive hearing loss. CONCLUSION: MRI is highly contributive to the diagnosis of tympanic paraganglioma, which should be evoked in patients with pulsatile tinnitus. Diagnosis should be established as early as possible to lower the postoperative morbidity. While surgery can provide cure and relieve tinnitus, there is a high risk of auditory deterioration.

[Nasal leishmaniasis: a case report]. / Leishmaniose nasale. A propos d'un cas.

OBJECTIVE: To report a nasal leishmaniasis diagnosed by septal perforation biopsy. MATERIAL AND METHODS: We report a case of septal perforation with crusty rhinosinusitis and nasal vestibulitis in a 54-year-old woman with cirrhosis. RESULTS: Mucocartilaginous biopsy revealed a mucosal leishmaniasis. Biological and radiologic findings were normal. Clinical follow-up with anti-parasitical treatment showed a regression of the patient's muco-cutaneous lesion and regression of her hepatic insufficiency. CONCLUSION: Biopsy of septal perforation is a useful diagnostic tool, advocated for differentiate infectious, neoplasic and inflammatory pathology. Leishmaniasis may be evoked in rhinologic pathology.

[Cervical and para-pharyngeal bone tumors: two cases report]. / Tumeurs cervicales et para-pharyngées d'origine osseuse.

OBJECTIVE: The purpose of the study was to report two cases of cervical and para-pharyngeal bone tumors. MATERIAL AND METHODS: Patients were two 29 and 67-year-old men. Presentation of the lesions included respectively a right cervical mass and a left para-pharyngeal mass. Clinical features and radiological, anatomopathological and therapeutic characteristics of the tumors were retrospectively studied. RESULTS: A cervical approach was made in both cases. Tumor biopsies revealed a vertebral aneurismal cyst and a corporeo-pedicular chordoma respectively. CONCLUSION: Vertebral bone tumors with cervical expression are very uncommon entities. Diagnosis could be systematically evoked in patients with a cervical or para-pharyngeal tumor presenting vertebral lysis.

[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.

[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.

Adult sphingomyelinase deficiency: report of 2 patients who initially presented with psychiatric disorders.

We studied 2 unrelated adult patients under neuroleptic treatment who met all phenotypic and biochemical criteria for Niemann-Pick disease type B. In addition, they had chronic psychiatric disorders and low blood levels of HDL cholesterol. The marked and persistent deficiency of acid sphingomyelinase and the disturbance of sphingomyelin metabolism in skin fibroblast subcultures ruled out a pure drug-induced lipidosis. The association of Niemann-Pick disease type B with psychiatric disorders and with low levels of HDL cholesterol could be a chance association of 2 diseases, a new phenotype of Niemann-Pick type B, or the revelation by the neuroleptic treatment of a subclinical inborn sphingomyelinase deficiency.

Long-term survival after gene therapy for a recurrent glioblastoma.

A patient presenting with a recurrent glioblastoma (GBM) survived 3 years after suicide gene therapy and finally died of a disseminated breast cancer with no indication of tumor recurrence on MRI. Postmortem analysis showed no evidence of recurrence of the GBM, neither near the initial tumor localization nor in any other area of the brain. Such an evolution is unusual in the course of this disease and may suggest in this particular case a cure of the GBM.