[Diagnostic workup in front of an adult thrombocytosis]. / Conduite à tenir devant une thrombocytose de l'adulte.

During a blood test, the discovery of thrombocytosis is a frequent phenomenon with multiple origins. False thrombocytosis linked to analytical interferences is rare but must be eliminated before confirming the anomaly. The reaction origin, often very easily demonstrated by the context and/or the presence of a biological inflammatory syndrome, is the most frequent. More rarely, the diagnosis is oriented towards a clonal hematological pathology not limited to essential thrombocythemia. Currently, many biological tools, which have largely contributed to the recommendations of the latest WHO classification of chronic myeloid neoplasms, are available to classify these pathologies as precisely as possible, allowing optimal management.

[Rare sideroblastic anemias: about 2 cases, review of the literature and reminder of the main etiologies]. / Anémies sidéroblastiques rares : à propos de 2 cas, revue de la littérature et rappel des principales étiologies.

Sideroblastic anemias in adults are often quickly labeled as myelodysplasias. We report two unfrequent observations of secondary acquired forms. The first one is a 15-year-old girl presented with severe cytopenias. The myelogram revealed the presence of vacuolated myeloid and erythroblastic precursors, with ring sideroblasts. Copper deficiency has been demonstrated in front of the association with collapsed cupremia and ceruleoplasminemia, with normal cupruria. The second case is a 70-year-old man, treated for 1 month with several lines of antibiotics for a skin infection, referred for cytopenias. The myelogram found vacuolated erythroblastic precursors and ring sideroblasts. Linezolid's responsibility has been proposed, with a favorable development after treatment has been stopped. These two observations, which describe unfrequent sideroblastic anemias, point out that this discovery should not lead to the diagnosis of myelodysplasia before having considered the many other etiologies.

[Diagnostic workup in front of an hypereosinophilia in 2020]. / Démarche diagnostique devant une hyperéosinophilie en 2020.

The discovery of eosinophilia above 1.5 G/L should not be considered innocuous, requiring monitoring for etiology and possible secondary organ damage. Among these, cardiac localization is the most worrying, sometimes indolent, to be systematically sought by ultrasound and magnetic resonance. The potential etiologies are very numerous, mostly reactive and corticosensitive, much more rarely clonal in relation to a malignant hemopathy usually chronic and myeloid, sometimes sensitive to tyrosine kinase inhibitors.

[Lymphomas in immunocompromised patients]. / Lymphomes de l'immunodéprimé.

Immunosuppression is a well known risk factor for the development of lymphoid pathologies. The classification of these neoplasias is becoming more precise and complex, some features being common to all immunocompromised patients, primarily the important influence of Epstein-Barr virus. Whatever the origin of the immunodepression, these lymphoid proliferations are very heterogeneous, constituting a wide range between polymorphic aspects and clearly lymphomatous morphologies indistinguishable from those observed in immunocompetent subjects. It is important to detect precisely these different categories of proliferation within each group of immunosuppression, to better individualize the prognosis and the management of patients.

[Diagnostic workup in front of an adult monocytosis]. / Conduite à tenir devant une monocytose de l'adulte.

The discovery of a monocytosis is a frequent phenomenon, requiring confirmation by reading under a microscope by an experimented biologist, to overcome usual cytological traps such as the presence of hairy cells, promonocytes or monoblasts. In the vast majority of cases the secondary origin is very easily found by the context and/or the presence of a biological inflammatory syndrome. More rarely the diagnosis is directed towards an eosinophilic pathology or an acute leukemia. In other cases, CMML, MPN or MDS with monocytosis may be highlighted. In the absence of any pathognomonic element and the presence of "borderline" forms the differential diagnosis between these 3 entities is not always straightforward, requiring, according to WHO, molecular investigations and elimination of any reactive cause of monocytosis. Although histological, immunohistochemical and phenotypic flow cytometric studies are not currently recommended by WHO, these investigations could be of interest in the evaluation of difficult cases.

[Monoclonal gammopathy of undetermined significance (MGUS): interpretative shades of analysis and sometimes serious clinical consequences]. / Point sur les GMSI : interprétation des examens complémentaires et complications cliniques.

The etiological assessment of a monoclonal gammopathy is currently standardized, the decisional algorithms allowing a sufficiently precise classification to consider the care, wait or therapeutic. The purpose of this review is to recall the difficulties concerning the interpretation of certain biological investigations and to point out the potential complications of monoclonal gammopathies labeled as "benign". The cooperation between clinicians and biologists is in all cases essential, allowing to propose on a case-by-case basis the best adapted explorations.

Diagnostic workup in front of an adult neutropenia.

Adult neutropenia, defined as a blood neutrophil count below 1.5 G/L, is a common condition. The most common cause of acute neutropenia is a drug-related reaction or an acute infectious disease. In chronic forms many etiologies are possible, sometimes poorly-defined, requiring precise explorations. The purpose of this article is to recall the required criteria for exploring neutropenia and to point out the algorithm of explorations in order to find the cause. Etiologies of acute and chronic forms are also detailed.

[How I do in front of an hemolytic anemia of unknown etiology?] / Que faire devant une anémie hémolytique sans étiologie retrouvée ?

The most frequent causes of hemolytic anemias are immune or infectious diseases, drug induced hemolysis, thrombotic microangiopathies, hereditary spherocytosis, glucose-6-phosphate dehydrogenase or pyruvate kinase deficiencies, thalassemia's and sickle cell disease. Sometimes no cause is found because a rarer etiology is involved. The goal of this review is to remember some unfrequent constitutional or acquired causes and to point out difficulties to avoid wrong interpretations of analysis results.

[IgM Myeloma: case report and literature review]. / Myélome à IgM : à propos d'un cas et revue de littérature.

The presence of serum monoclonal IgM is often associated with the diagnosis of Waldenström macroglobulinemia (WM) or other chronic lymphoproliferative disorders. IgM myeloma is a rare entity (0.5%). We report the case of an IgM myeloma complicated by systemic amyloidosis AL, with an impure nephrotic syndrome and a factor FX deficiency.

A new case of IgE multiple myeloma with review of literature.

IgE myeloma is an extremely rare disease characterized by frequent plasma cell leukemia, little monoclonal-spike on electrophoresis, an high incidence of t(11;14) translocation and a worse survival than those with common myelomas. We report here a new case of IgE myeloma and discuss clinical presentation, biological features and therapeutic option.

Structure and assembly of the pseudopilin PulG.

The pseudopilin PulG is one of several essential components of the type II pullulanase secretion machinery (the Pul secreton) of the Gram-negative bacterium Klebsiella oxytoca. The sequence of the N-terminal 25 amino acids of the PulG precursor is hydrophobic and very similar to the corresponding region of type IV pilins. The structure of a truncated PulG (lacking the homologous region), as determined by X-ray crystallography, was found to include part of the long N-terminal alpha-helix and the four internal anti-parallel beta-strands that characterize type IV pilins, but PulG lacks the highly variable loop region with a disulphide bond that is found in the latter. When overproduced, PulG forms flexible pili whose structural features, as visualized by electron microscopy, are similar to those of bacterial type IV pili. The average helical repeat comprises 17 PulG subunits and four helical turns. Electron microscopy and molecular modelling show that PulG probably assembles into left-handed helical pili with the long N-terminal alpha-helix tightly packed in the centre of the pilus. As in the type IV pilins, the hydrophobic N-terminal part of the PulG alpha-helix is necessary for its assembly. Subtle sequence variations within this highly conserved segment seem to determine whether or not a type IV pilin can be assembled into pili by the Pul secreton.

Type IV-like pili formed by the type II secreton: specificity, composition, bundling, polar localization, and surface presentation of peptides.

The secreton or type II secretion machinery of gram-negative bacteria includes several type IV pilin-like proteins (the pseudopilins) that are absolutely required for secretion. We previously reported the presence of a bundled pilus composed of the pseudopilin PulG on the surface of agar-grown Escherichia coli K-12 cells expressing the Klebsiella oxytoca pullulanase (Pul) secreton genes at high levels (N. Sauvonnet, G. Vignon, A. P. Pugsley, and P. Gounon, EMBO J. 19:2221-2228, 2000). We show here that PulG is the only pseudopilin in purified pili and that the phenomenon is not restricted to the Pul secreton reconstituted in E. coli or to PulG. For example, high-level expression of the endogenous E. coli gsp secreton genes caused production of bundled pili composed of the pseudopilin GspG, and the Pul secreton was able to form pili composed of PulG-like proteins from secreton systems of other bacteria. PulG derivatives in which the C terminus was extended by the addition of eight different peptides were also assembled into pili and functioned in secretion. Three of the C-terminal peptides were shown to be exposed along the entire length of the assembled pili. Hence, the C terminus of PulG may represent a permissive site for the insertion of immunogenic epitopes or other peptide sequences. One of these PulG variants, with a six-histidine tag at its C terminus, formed nonpolar, nonbundled pili, suggesting that bundle formation and polar localization are not correlated with the ability of PulG to function in secretion. We propose that the PulG pilus is an artifactual manifestation of a periplasmic "pseudopilus" and that cycles of pseudopilus extension and retraction within the periplasm propel pullulanase through secretin channels in the outer membrane. Abnormally long pili that extend beyond the outer membrane are produced only when pilus length control and retraction are deregulated by overproduction of the major pseudopilus subunit (PulG).