Translocation (2;3)(p21;q26) as the sole anomaly in a case of primary myelofibrosis.

peer reviewedTranslocation t(2p;3q) is a rare but recurrent finding in myeloid disorders. We present the first case of primary myelofibrosis with t(2;3)(p21;q26) as the sole chromosomal anomaly. The comparison with the 11 other previously published myeloid-associated t(2p;3q) cases confirms that this nonrandom translocation involves a pluripotent stem cell and is associated with a poor prognosis

Pathology of immune reconstitution inflammatory syndrome in multiple sclerosis with natalizumab-associated progressive multifocal leukoencephalopathy

Natalizumab is an approved medication for highly active multiple sclerosis (MS). Progressive multifocal leukoencephalopathy (PML) may occur as a severe side effect of this drug. Here, we describe pathological and radiological characteristics of immune reconstitution inflammatory syndrome (IRIS), which occurs in natalizumab-associated PML after the cessation of therapy, and we differentiate it from ongoing PML. Brain biopsy tissue and MRI scans from five MS patients with natalizumab-associated PML were analyzed and their histology compared with non-MS PML. Histology showed an extensive CD8-dominated T cell infiltrate and numerous macrophages within lesions, and in nondemyelinated white and grey matter, in four out of five cases. Few or no virally infected cells were found. This was indicative of IRIS as known from HIV patients with PML. Outstandingly high numbers of plasma cells were present as compared to non-MS PML and typical MS lesions. MRI was compatible with IRIS, revealing enlarging lesions with a band-like or speckled contrast enhancement either at the lesion edge or within lesions. Only the fifth patient showed typical PML pathology, with low inflammation and high numbers of virally infected cells. This patient showed a similar interval between drug withdrawal and biopsy (3.5 months) to the rest of the cohort (range 2.5–4 months). MRI could not differentiate between PML-associated IRIS and ongoing PML. We describe in detail the histopathology of IRIS in natalizumab-associated PML. PML–IRIS, ongoing PML infection, and MS exacerbation may be impossible to discern clinically alone. MRI may provide some clues for distinguishing different pathologies that can be differentiated histologically. In our individual cases, biopsy helped to clarify diagnoses in natalizumab-associated PML

LYMPHOMES T/NK NASAL ET DE TYPE NASAL (ETUDE DE 15 CAS ; ANALYSE EN IMMUNOHISTOCHIMIE DE PARAMETRES POTENTIELS DE CHIMIORESISTANCE)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Endoscopic ultrasonographic characterization of peridigestive lymph nodes: parametric images and quantitive analysis

Objectifs. La précision diagnostique de l'échoendoscopie dans le bilan d'extension ganglionnaire des cancers digestifs pourrait être améliorée par l'analyse paramétrique de la texture des images. Nous avons cherché à évaluer les résultats de cette méthode dans une étude prospective. Méthodes. Cent cinq ganglions péri-digestifs ont été analysés chez 80 malades. Le diagnostic final était obtenu par l'histologie de la pièce opératoire ou par le suivi des patients. Il s'agissait de 41 ganglions inflammatoires bénins et de 64 ganglions métastatiques. Les images étaient obtenues durant une échoendoscopie conventionnelle, numérisées puis transférées sur une station de travail pour l'analyse paramétrique. Deux régions d'intérêt (RI) étaient sélectionnées pour chaque ganglion (ganglion entier et portion périphérique). 21 paramètres étaient étudiés pour chaque RI (2 paramètres de 1er ordre et 19 de second ordre). Les paramètres étaient étudiés par analyse uni- puis multivariée pour définir les paramètres discriminant les ganglions inflammatoires des ganglions métastatiques. Principaux résultats. Sept paramètres, tous de second ordre, pouvaient distinguer les ganglions inflammatoires et métastatiques de façon indépendante. La sensibilité de l'interprétation par l'endoscopiste (qui possédait les informations cliniques et morphologiques pertinentes) était de 83 % et la spécificité de 90 %. La sensibilité et la spécificité de l'analyse de texture étaient de 56 % et 60 %, respectivement. Conclusions. Ces résultats suggèrent que l'analyse paramétrique de la texture des images ganglionnaires d'échoendoscopie n'améliore pas les performances de l'interprétation visuelle d'un opérateur entraîné disposant des éléments habituels du dossier clinique

Break in theBCL1 locus is closely associated with intermediate lymphocytic lymphoma subtype

International audienc

Exome Sequencing in a Swiss Childhood Glaucoma Cohort Reveals CYP1B1 and FOXC1 Variants as Most Frequent Causes

Purpose: The aim of this study was to investigate the molecular basis of childhood glaucoma in Switzerland to recommend future targeted genetic analysis in the Swiss population. Methods: Whole-exome sequencing and copy number variation (CNV) analysis was performed in a Swiss cohort of 18 patients from 14 unrelated families. Identified variants were validated by Sanger sequencing and multiplex ligation-dependent probe amplification. Breakpoints of structural variants were determined by a microarray. A minigene assay was conducted for functional analysis of a splice site variant. Results: A diagnosis of primary congenital glaucoma was made in 14 patients, of which six (43%) harbored pathogenic variants in CYP1B1, one (7%) a frameshift variant in FOXC1, and seven (50%) remained without a genetic diagnosis. Three patients were diagnosed with glaucoma associated with nonacquired ocular anomalies, of which two patients with mild ocular features of Axenfeld-Rieger syndrome harbored a FOXC1 duplication plus an additional FOXC1 missense variant, and one patient with a Barkan membrane remained without genetic diagnosis. A diagnosis of juvenile open-angle glaucoma was made in one patient, and genetic analysis revealed a FOXC1 duplication. Conclusions: Sequencing of CYP1B1 and FOXC1, as well as analysis of CNVs in FOXC1, should be performed before extended gene panel sequencing. Translational Relevance: The identification of the molecular cause of childhood glaucoma is a prerequisite for genetic counseling and personalized care for patients and families

Bone marrow hematons: An access point to the human hematopoietic niche

International audienc