Vacuoles in bone marrow progenitors: VEXAS syndrome and beyond.

The presence of vacuoles in myeloid and erythroid progenitor cells in bone marrow aspirates is a key feature of vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome. The mere observation of vacuolated progenitor cells is not specific to VEXAS syndrome; in this Viewpoint, we point out the causes to be considered in this situation. Vacuoles, in particular, can be observed in individuals with wild-type UBA1 and with persistent inflammatory features or myelodysplastic syndromes.

Vacuoles in circulating immature myeloid cells in VEXAS syndrome and comparison with UBA1-wild type patients.

We did not identify any vacuole-related differences in circulating immature myeloid cells between VEXAS patients and UBA1-WT 'VEXAS-like' patients. The similar vacuolization of circulating immature myeloid cells between VEXAS and UBA1-WT patients is explained by the main bloodstream passage of late precursors, in which the vacuolization is already similar in bone marrow in both cases.

Accurate stratification between VEXAS syndrome and differential diagnoses by deep learning analysis of peripheral blood smears.

Objectives: VEXAS syndrome is a newly described autoinflammatory disease associated with somatic mutations and vacuolization of myeloid precursors. This disease possesses an increasingly broad spectrum, leading to an increase in the number of suspected cases. Its diagnosis via bone-marrow aspiration and -gene sequencing is time-consuming and expensive.

When Ring Sideroblasts on Bone Marrow Smears Are Inconsistent with the Diagnosis of Myelodysplastic Neoplasms.

Ring sideroblasts are commonly seen in myelodysplastic neoplasms and are a key condition for identifying distinct entities of myelodysplastic neoplasms according to the WHO classification. However, the presence of ring sideroblasts is not exclusive to myelodysplastic neoplasms. Ring sideroblasts are as well either encountered in non-clonal secondary acquired disorders, such as exposure to toxic substances, drug/medicine, copper deficiency, zinc overload, lead poison, or hereditary sideroblastic anemias related to X-linked, autosomal, or mitochondrial mutations.

Perls' Stain Guidelines from the French-Speaking Cellular Hematology Group (GFHC).

In order to standardize cellular hematology practices, the French-speaking Cellular Hematology Group (Groupe Francophone d'Hématologie Cellulaire, GFHC) focused on Perls' stain. A national survey was carried out, leading to the proposal of recommendations on insoluble iron detection and quantification in bone marrow. The criteria presented here met with a "strong professional agreement" and follow the suggestions of the World Health Organization's classification of hematological malignancies.

Proteinuria Increases the PLASMIC and French Scores Performance to Predict Thrombotic Thrombocytopenic Purpura in Patients With Thrombotic Microangiopathy Syndrome.

Introduction: PLASMIC and French scores have been developed to help clinicians in the early identification of patients with thrombotic thrombocytopenic purpura (TTP). Nevertheless, the validity of these scores in thrombotic microangiopathy (TMA) cohorts with low TTP prevalence remains uncertain. We aimed to evaluate their diagnostic value in routine clinical practice using an unselected cohort of patients with TMA.

Iron Deficiency without Anemia Decreases Physical Endurance and Mitochondrial Complex I Activity of Oxidative Skeletal Muscle in the Mouse.

Iron deficiency (ID), with or without anemia, is responsible for physical fatigue. This effect may be linked to an alteration of mitochondrial metabolism. Our aim was to assess the impact of ID on skeletal striated muscle mitochondrial metabolism.

Retrospective and Systematic Analysis of Causes and Outcomes of Thrombotic Microangiopathies in Routine Clinical Practice: An 11-Year Study.

Thrombotic microangiopathies (TMAs) are highly suspected in patients showing mechanical hemolytic anemia, thrombocytopenia, and haptoglobin consumption. Primary [thrombotic thrombocytopenic purpura (TTP) and atypical hemolytic uremic syndrome] and secondary TMA are considered. Even if ADAMTS13 measurements and alternative complement pathway explorations have greatly improved the ability to identify primary TMA, their diagnosis remains difficult, and their frequency relative to that of secondary TMA is undetermined.

Multicentric MFI30 study: Standardization of flow cytometry analysis of CD30 expression in non-Hodgkin lymphoma.

CD30 transmembrane receptor, a member of the tumor necrosis factor receptor family, is expressed in different lymphomas. Brentuximab vedotin (BV), a CD30 monoclonal antibody (Ab)-drug conjugate, is effective in CD30-positive lymphomas. However, the response to BV is not always correlated to CD30 expression detected by immunohistochemistry (IHC).

Platelet Counting: Ugly Traps and Good Advice. Proposals from the French-Speaking Cellular Hematology Group (GFHC).

Despite the ongoing development of automated hematology analyzers to optimize complete blood count results, platelet count still suffers from pre-analytical or analytical pitfalls, including EDTA-induced pseudothrombocytopenia. Although most of these interferences are widely known, laboratory practices remain highly heterogeneous. In order to harmonize and standardize cellular hematology practices, the French-speaking Cellular Hematology Group (GFHC) wants to focus on interferences that could affect the platelet count and to detail the verification steps with minimal recommendations, taking into account the different technologies employed nowadays.

How should we diagnose and treat blastic plasmacytoid dendritic cell neoplasm patients?

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive leukemia for which we developed a nationwide network to collect data from new cases diagnosed in France. In a retrospective, observational study of 86 patients (2000-2013), we described clinical and biological data focusing on morphologies and immunophenotype. We found expression of markers associated with plasmacytoid dendritic cell origin (HLA-DRhigh, CD303+, CD304+, and cTCL1+) plus CD4 and CD56 and frequent expression of isolated markers from the myeloid, B-, and T-lymphoid lineages, whereas specific markers (myeloperoxidase, CD14, cCD3, CD19, and cCD22) were not expressed.

How I investigate basophilia in daily practice.

Basophilia is a rare disorder of the complete blood count (CBC) and its management in daily practice remains unclear. Two main factors explain this situation. On the one hand, the reliability of the basophil count is insufficient, whether it is performed by a microscopic slide examination or by a hematology analyser.

Standardization of Flow Cytometric Immunophenotyping for Hematological Malignancies: The FranceFlow Group Experience.

Flow cytometry is broadly used for the identification, characterization, and monitoring of hematological malignancies. However, the use of clinical flow cytometry is restricted by its lack of reproducibility across multiple centers. Since 2006, the EuroFlow consortium has been developing a standardized procedure detailing the whole process from instrument settings to data analysis.

Harmonisation of full blood count reports, recommendations of the French-speaking cellular haematology group (GFHC).

Aims: To propose recommendations related to the presentation, content and formulation of full blood count analysis reports.

Methods: Strong professional agreement among a group of experts from the French-Speaking Cellular Haematology Group (GFHC) was obtained.

Results: The following two proposals emerged from the consensus: (1) stratification of comments into three parts upon the discovery of an anomaly in blood cell analysis and (2) selection and/or redefinition of the terms recommended for designating the cell types found in normal and pathological peripheral blood.