[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.

Quasispecies variant dynamics during emergence of resistance to raltegravir in HIV-1-infected patients.

OBJECTIVES: Raltegravir is the first approved inhibitor of HIV-1 integrase (IN). In most patients, raltegravir failure is associated with mutations in the IN gene, through two different genetic pathways: 155 (N155H) or 148 (Q148K/R/H). The objective of this study was to characterize the dynamics of HIV-1 quasispecies variant populations in patients who failed to respond to raltegravir treatment. PATIENTS AND METHODS: Bulk genotyping and clonal analysis were performed during the follow-up of 10 patients who failed to respond to raltegravir treatment. RESULTS: Treatment failed through the 155 pathway in six patients and through the 148 pathway in two patients; two further patients switched from the 155 to the 148 pathway. In the two patients switching from the 155 to the 148 pathway, clonal analysis showed that Q148R/H and N155H mutations were present on different strands, suggesting that these two pathways are independent. This was consistent with our finding that each genetic profile was associated with different secondary mutations. We observed a greater variability among quasispecies associated with the 155 pathway, and IC(50) determinations showed that the fold resistance to raltegravir, relative to wild-type, was 10 for the N155H mutant and 50 for the G140S+Q148H mutant. CONCLUSIONS: Clonal analysis strongly suggests that the two main genetic pathways, 155 and 148, involved in the development of resistance to raltegravir are independent and exclusive. Moreover, the switch of the resistance profile from 155 to 148 may be related to the higher level of resistance to raltegravir conferred by the 148 pathway and also to the higher instability of the 155 pathway.