Case Report: Evolution of a Severe Vascular Refractory Form of ECD Requiring Liver Transplantation Correlated With the Change in the Monocyte Subset Analysis

Erdheim–Chester disease is a rare histiocytosis characterized by iconic features associated with compatible histology. Most patients have somatic mutations in the MAP-kinase pathway gene, and the mutations occur in CD14+ monocytes. Differentiation of the myeloid lineage plays a central role in the pathogenesis of histiocytosis. Monocytes are myeloid-derived white blood cells, divided into three subsets, but only the CD14++CD16− “classical monocyte” can differentiate into dendritic cells and tissue macrophages. Since most mutations occur in CD14+ cells and since ECD patients have a particular monocytic phenotype resembling CMML, we studied the correlation between disease activity and monocytic subset distribution during the course of a severe vascular form of ECD requiring liver transplantation. During early follow-up, increased CD14++CD16− “classical monocyte” associated with decreased CD14lowCD16++ “non-classical monocyte” correlated with disease activity. Further studies are needed to confirm the use of monocyte as a marker of disease activity in patients with ECD.

Download Full-text

Peritoneal or mesenteric tumours revealing histiocytosis

BMJ Open Gastroenterology ◽

10.1136/bmjgast-2021-000622 ◽

2021 ◽

Vol 8 (1) ◽

pp. e000622

Author(s):

Fleur Cohen-Aubart ◽

Irena Ungureanu ◽

Jerome Razanamahery ◽

Frédéric Charlotte ◽

Séverine Valmary-Degano ◽

...

Keyword(s):

Diagnostic Delay ◽

Rare Condition ◽

Final Diagnosis ◽

Diagnostic Process ◽

Sclerosing Mesenteritis ◽

Diagnostic Difficulties ◽

Map Kinase Pathway ◽

Important Time ◽

Kinase Pathway ◽

Erdheim Chester

ObjectivePeritoneal or mesenteric tumours may correspond to several tumour types or tumour-like conditions, some of them being represented by histiocytosis. This rare condition often poses diagnostic difficulties that can lead to important time delay in targeted therapies. Our aim was to describe main features of histiocytoses with mesenteric localisation that can improve the diagnostic process.DesignWe performed a retrospective study on 22 patients, whose peritoneal/mesenteric biopsies were infiltrated by histiocytes.ResultsAbdominal pain was the revealing symptom in 10 cases, and 19 patients underwent surgical biopsies. The diagnosis of histiocytosis was proposed by initial pathologists in 41% of patients. The other initial diagnoses were inflammation (n=7), sclerosing mesenteritis (n=4) and liposarcoma (n=1). The CD163/CD68+CD1a- histiocytes infiltrated subserosa and/or deeper adipose tissues in 16 and 14 cases, respectively. A BRAFV600E mutation was detected within the biopsies in 11 cases, and two others were MAP2K1 mutated. The final diagnosis was histiocytosis in 18 patients, 15 of whom had Erdheim-Chester disease. The median diagnostic delay of histiocytosis was 9 months. Patients treated with BRAF or MEK inhibitors showed a partial response or a stable disease. One patient died soon after surgery, and five died by the progression of the disease.ConclusionDiagnosis of masses arising in the mesentery should be carefully explored as one of the possibilities in histiocytosis. This diagnosis is frequently missed on mesenteric biopsies. Molecular biology for detecting the mutations in BRAF or in genes of the MAP kinase pathway is a critical diagnostic tool.

Download Full-text

Role of Tec1 in the Development, Architecture, and Integrity of Sexual Biofilms of Candida albicans

Eukaryotic Cell ◽

10.1128/ec.00224-14 ◽

2015 ◽

Vol 14 (3) ◽

pp. 228-240 ◽

Cited By ~ 12

Author(s):

Karla J. Daniels ◽

Thyagarajan Srikantha ◽

Claude Pujol ◽

Yang-Nim Park ◽

David R. Soll

Keyword(s):

Map Kinase ◽

White Blood Cells ◽

Silicone Elastomer ◽

Minor Role ◽

Matrix Deposition ◽

Initial Adhesion ◽

Map Kinase Pathway ◽

Biofilm Development ◽

Kinase Pathway

ABSTRACTMTL-homozygous (a/aor α/α) white cells form a complex sexual biofilm that exhibits the same architecture as that ofMTL-heterozygous (a/α) pathogenic biofilms. However, the former is regulated by the mitogen-activated protein (MAP) kinase pathway, while the latter is regulated by the Ras1/cyclic AMP (cAMP) pathway. We previously demonstrated that in the formation of anMTL-homozygous, mature (48 h) sexual biofilm in RPMI 1640 medium, the MAP kinase pathway targets Tec1 rather than Cph1, the latter of which is the target of the same pathway, but for the opaque cell mating response. Here we continued our analysis of the role of Tec1 by comparing the effects of deletingTEC1on initial adhesion to silicone elastomer, high-resolution confocal microscopy assessments of the stages and cellular phenotypes during the 48 h of biofilm development, human white cell penetration, and biofilm fragility. We show that although Tec1 plays only a minor role in initial adhesion to the silicone elastomer, it does play a major role in the growth of the basal yeast cell polylayer, vertical extension of hyphae and matrix deposition in the upper portion of the biofilm, final biofilm thickness, penetrability of human white blood cells, and final biofilm integrity (i.e., resistance to fluid flow). These results provide a more detailed description of normal biofilm development and architecture and confirm the central role played by the transcription factor Tec1 in the biofilm model employed here.

Download Full-text