Introduction. Intravascular large B-cell lymphoma is a rare variant of large B-cell, highly invasive extranodal tumors of the lymphatic system. The pathogenesis of the disease lies in the ability of tumor cells to penetrate into small vessels and capillaries of various organs. The clinical presentation is atypical for diffuse large B-cell lymphoma. In the relevant literature, information on the diagnosis and treatment of this pathology is extremely rare, therefore each publication makes a significant contribution to expanding the horizons of hematologists and morphologists.Aim – to present a case of diagnosing intravascular B-cell lymphoma.Main findings. A clinical case of a 78-year-old patient who fell ill acutely is presented. At the onset of the disease, febrile fever was noted. In the general blood test: hemoglobin – 104 g/L; erythrocytes – 3.0 × 1012/L; ESR – 24 mm/h; platelets – 112 × 109/L, leukocytes – 4.9 × 109/L, 4 % of cells with lymphoblast morphology were found in the leukocyte formula. Blood serum tests revealed: an increase in uric acid concentrations – up to 639 μmol/L, LDH – up to 1885 U/L, beta-2-microglobulin – up to 8.9 mmol/L, C-reactive protein – up to 0.6 g/L, a decrease in the concentration of total protein – up to 45 g/L, an increase in the concentration of aspartate aminotransferase – up to 48 units/L at normal concentrations of bilirubin and alanine aminotransferase.The histological and immunohistochemical picture, according to the study of bone biopsy, most corresponded to bone marrow damage by intravascular large B-cell lymphoma. Immunophenotyping was carried out – 15.7 % of blast cells with immunophenotype CD19+HLA/DR+CD24+CD37+CD20+CD10+IgM+ were detected. Cytogenetic studies revealed no karyotype abnormalities. The result of fluorescence in situ hybridization of the IGH locus (14q32) was normal. Based on the data obtained, the final clinical diagnosis was established: diffuse large B-cell lymphoma, stage IVB, intravascular variant with bone marrow involvement, aggressive course. The patient was prescribed the first line of therapy according to the R-CHOP scheme (rituximab, cyclophosphamide, vincristine, prednisolone). In the control study of the bone marrow, after the first course of therapy, the number of lymphoid elements was 3.6 %, laboratory parameters returned to normal.
Background. A significant role in the pathogenesis, resistance to treatment and progression of many types of lymphomas, including diffuse large B-cell lymphoma, is assigned to the TP53 gene. Literature data on the prognostic significance of the expression of its product, the p53 protein, and its association with aberrations at the 17p13 locus are ambiguous. Aim. To assess the relationship of p53 protein expression with the presence of a 17p13 locus deletion of the TP53 gene and the survival of patients with diffuse large B-cell lymphoma. Material and methods. The study included 75 patients with newly diagnosed diffuse large B-cell lymphoma who received R-CHOP therapy. The calculation of the relative content of tumor cells expressing p53 was carried out using immunohistochemical and morphometric methods on biopsy samples of lymph nodes. The 17p13/TP53 deletion was determined by fluorescent in situ hybridization. The threshold level of p53-positive tumor cells, corresponding to 43%, was calculated by ROC analysis. The association between p53 protein expression and the presence of a 17p13 deletion was assessed using Fisher's (F) and Pearson's 2 tests. The correlation dependence was evaluated by the Cramer method (V). Five-year overall and progression-free survival was calculated using the KaplanMeier method. Differences between the indicators were considered statistically significant at p 0.05. Results. The frequency of 17p13/TP53 deletion was higher in patients with high expression of p53 (43%) compared to the group of patients with low expression: 87.5 and 12.5%, respectively (p=0.018). A direct correlation between a high level of p53 expression (43%) and the presence of a 17p13/TP53 deletion was found (p=0.018). Five-year overall and progression-free survival in patients with a proportion of p53-positive cells 43% was significantly lower than in patients with its subthreshold value: 54.5 versus 81.0% (p=0.014) and 45.5 versus 66.7% (p=0.022), respectively. Conclusion. High expression of the p53 protein is associated with the presence of a 17p13 locus deletion and a low five-year survival rate in patients with diffuse large B-cell lymphoma.
Background. Diffuse large B-cell lymphoma (DLBCL) amounts for 30-40 % of all adult non-Hodgkin's lymphomas. After R-CHOP immunochemotherapy 40 % of patients develop early relapsed or therapy-refractory disease. The conventional prognostic parameters in DLBCL are not always effective. Therefore, exploring further predictors of disease course remains an issue. Aim. To assess the prognostic value of pAKT1 and рSy< expression in DLBCL. Materials & Methods. The study enrolled 100 patients with newly diagnosed DLBCL treated with R-CHOP first-line immunochemotherapy. The relative count of pAKT1- and pSyk-expressing tumor cells was determined by immunohistochemical and morphometric methods. The expression cutoff of these proteins was calculated by ROC analysis. The relationship of protein expression with clinical parameters of DLBCL was analyzed by Fisher's exact two-tailed test. The 5-year overall (OS) and progression-free (PFS) survivals were estimated by Kaplan-Meier method (log-rank test). Results. High pAKT1 expression was associated with advanced DLBCL stages, International Prognostic Index > 2, serum lactate dehydrogenase concentration above normal, failures of R-CHOP therapy, as well as worse OS and PFS. No correlation between рSyk< expression and clinical lymphoma characteristics was found. The worst 5-year OS (27.6 %) was reported in cases of pAKT1 and pSyk co-overexpression (hazard ratio [HR] 5.2; 95% confidence interval [95% CI] 2.49-10.9; p < 0.001). A similar trend was observed for PFS (HR = 3.3; 95% CI 1.54-7.30; p = 0.002). Conclusion. Overexpression of pAKT1 is an informative indicator of a poor DLBCL prognosis. Co-overexpression of pAKT1 and рSyk< markers is associated with worse OS and PFS compared to their isolated expressions and other co-expression variants.
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