Molecular classification of tumour cells in a patient with intravascular large B-cell lymphoma.

BACKGROUND: Intravascular large B-cell lymphoma (IVLBCL) is a rare type of extranodal LBCL. It is characterized by the proliferation of tumour cells exclusively intraluminally in small blood vessels of different organs. The clinical manifestation depends on the type of organ affected; additionally, a haemophagocytic syndrome can be observed in some patients. OBJECTIVES: The aim was to further understand the nosology of this lymphoma as, due to its rarity and in spite of detailed immunohistochemical investigations, its exact nosology is only incompletely understood. METHODS: We used microarray-based analysis of gene expression of tumour cells isolated from a patient with primary manifestation of the lymphoma in the skin and compared it with various other diffuse LBCLs (DLBCLs) as well as a previously published DLBCL classifier. RESULTS: In unsupervised analyses, the tumour cells clustered together with non-germinal centre B-cell (non-GCB) DLBCL samples but were clearly distinct from GCB-DLBCL. Analogous to non-GCB DLBCL, molecular cell-of-origin classification revealed similarity to bone-marrow derived plasma cells. CONCLUSIONS: The IVLBCL of this patient showed molecular similarity to non-GCB DLBCL. Due to the prognostic and increasingly also therapeutic relevance of molecular subtyping in DLBCL, this method, in addition to immunohistochemistry, should also be considered for the diagnosis of IVLBCL in the future.

The association of smoking with IGRA and TST results in HIV-1-infected subjects.

OBJECTIVE: To assess the association of smoking with the interferon-gamma (IFN-γ) release assay and tuberculin skin test (TST) results in a comparative study on the detection of latent tuberculous infection (LTBI) in human immunodeficiency virus (HIV) 1-infected individuals. METHODS: In this cross-sectional study, 305 HIV-1-infected subjects were tested by the QuantiFERON-TB Gold In-Tube assay (QFT-GIT) and the TST. We evaluated the impact of smoking and other LTBI risk factors on QFT-GIT and TST results. RESULTS The concordance of both tests was 93% (κ = 0.71, P < 0.001). The following independent risk factors for both QFT-GIT and TST positivity were identified: birth in a high TB incidence country, self-reported contact with an active TB case and elevated CD4(+) T-cell count (P < 0.001). While smoking was not independently associated with a positive QFT-GIT (OR 1.2, 95%CI 0.5-2.8) or TST result (OR 1.8, 95%CI 0.6-5.9), there was an inverse correlation of the number of cigarettes smoked with IFN-γ levels measured using QFT-GIT (ρ = -0.14, P = 0.027). In addition, smoking was independently associated with a quantitative QFT-GIT response in linear regression analysis (ß = 0.129, P = 0.025). CONCLUSIONS: Although smoking may have a minor inhibitory effect on QFT-GIT response, QFT-GIT results seem not to be affected by smoking to a clinically significant extent.

Revisiting predictors of virologic response to PEGIFN + RBV therapy in HIV-/HCV-coinfected patients: the role of metabolic factors and elevated GGT levels.

Evaluation of metabolic factors and elevated γ-glutamyltransferase (GGT) levels as independent predictors of treatment failure in a thoroughly documented cohort of HIV-/HCV-coinfected patients (HIV/HCV). Sixty-four HIV/HCV patients treated with pegylated interferon-α-2a plus ribavirin (PEGIFN + RBV) at the Medical University of Vienna within a prospective trial were included in this study. In addition, 124 patients with HIV/HCV from the AIFA-HIV and AHIVCOS cohorts were included as a validation cohort. Advanced liver fibrosis, GGT elevation, insulin resistance (IR) and low CD4+ nadir were defined as METAVIR F3/F4, GGT levels >1.5× sex-specific upper limit of normal, homoeostasis model assessment of insulin resistance >2 and CD4+ nadir <350 cells/µL, respectively. HCV-genotype 1/4 (OR26.3; P = 0.006), advanced liver fibrosis (OR20.2; P = 0.009), interleukin 28B rs12979860 non-C/C SNP (OR8.27; P = 0.02) and GGT elevation (OR7.97; P = 0.012) were independent predictors of treatment failure, while both IR (OR3.51; P = 0.106) and low CD4 + nadir (OR2.64; P = 0.263) were not independently associated with treatment failure. A statistically significant correlation between GGT elevation and prior alcohol abuse (r = 0.259; P = 0.039), liver steatosis (r = 0.301; P = 0.034) and low-density lipoprotein-cholesterol (r = -0.256; P = 0.041) was observed. The importance of GGT elevation as an independent predictor of treatment failure was confirmed in a validation cohort (OR2.76; P = 0.026). While GGT elevation emerged as an independent predictor of treatment failure in both the derivation and the validation cohort, no independent associations between metabolic factors and treatment failure were observed. Thus, our findings suggest that GGT elevation is an independent predictor of treatment failure in HIV/HCV that can easily be incorporated into predictive algorithms.

Primary syphilitic chancre on the upper arm in an HIV-1-infected patient.

A 32-year-old HIV-infected man presented with an ulcerating skin lesion with indurated borders on the upper right arm. Both dark-field microscopy and syphilis serology confirmed the diagnosis of primary syphilis. Extragenital syphilitic chancres are uncommon but nevertheless have to be kept in mind as they often delay diagnosis.

The risk of infections in HIV-HCV coinfected patients during antiviral therapy with pegIFN+RBV.

OBJECTIVES: Antiviral treatment with pegIFN/RBV decreases ANC and CD4+ cell count. An association between neutropenia, a low CD4+ cell count and infections has not been demonstrated so far in HIV-HCV coinfected patients. METHODS: The incidence, type, and severity of infections were recorded in 85 HIV-HCV coinfected and 164 monoinfected patients receiving pegIFN/RBV for 48 weeks. ANC and CD4+ cell count were assessed every 4 weeks during therapy. RESULTS: The incidence of infections was significantly higher in HIV-HCV than HCV-Mono (38% vs. 15%; p = 0.001). Types of infections: pneumonia (n = 16/n = 24), bacteraemia/sepsis (n = 5/n = 2), skin infections (n = 15/n = 12), urinary tract infections (n = 4/n = 1), OIs (n = 10/n = 1). The incidence of neutropenia grade 1, 2 3 or 4 was similar in HIV-HCV and HCV-Mono, respectively. The incidence of infections was not associated with neutropenia (HCV-Mono: p = 0.584; HIV-HCV: p = 0.23) or with CD4+ cell counts <200/µL (HIV-HCV: p = 0.29). OIs occurred more often in HIV-HCV patients with CD4+ cell count <200/µL (p = 0.024). CONCLUSIONS: Up to 38% and 15% of HIV-HCV coinfected and HCV-monoinfected patients develop infections during pegIFN+RBV therapy but without any correlation to neutropenia. Antibacterial prophylaxis/treatment should be considered early in HIV-HCV coinfected patients developing CD4+ cell counts <200/µL during antiviral therapy as these patients have an increased risk of OIs.