Browsing by Author "Nikulshin, Sergey"

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    Anaplastic Large Cell Lymphoma : Clinical and Histologic Features of 16 Patients
    (2015) Nikulshin, Sergey; Nazarovs, Jurijs; Uzars, Arturs; Rudaka, Irina; Sokolova, Ludmila
    Introduction. Anaplastic Large Cell Lymphoma (ALCL) is a rare type of aggressive T-cell lymphoma. Tumor cells are highly anaplastic, strongly positive for antigen CD30 and express reduced phenotype (usually CD3- and CD7-, often CD45-) that may considerably complicate diagnosis. 60−70% of the patients express Anaplastic Lymphoma Kinase (ALK1) that is associated with t(2;5)(p23;q35.1) and better prognosis. ALCL constitutes about 2% of all lymphomas and 12% of childhood lymphomas; primary cutaneous ALCL is diagnosed in 9% of cutaneous lymphomas. WHO classification discerns three types of ALCL: systemic ALK+, systemic ALK- and primary cutaneous ALCL. Systemic cases usually present as a widely disseminated disease with rapid progression. Systemic ALK1+ ALCL has predilection for extranodal infiltrates, ALK1- – to nodal involvement, while primary cutaneous ALCL is isolated to skin. Extranodal sites include bone marrow, bone, soft tissues, lungs, liver, skin and GI tract. Five morphologic patterns can be recognized: common, lymphohystiocytic, small cell, Hodgkinlike and composite. Aims. The aim of the study was to retrospectively analyse clinical features at presentation and histology of ALCL cases diagnosed in the Institute of Pathology of Paul Stradins Clinical University Hospital, Pathology Center of Riga Eastern University Hospital and Pathology Bureau of Children’s Clinical University Hospital. Material and ethods. 16 documented cases were found for the time period of 2003−2014. Patients’ files from the hospital archives were studied, histological and immunohistochemical slides were microscopically reevaluated. Results. Patients’ age varied between 11 and 80 years (mean – 33.5). 10 cases were male (M:F = 1.67:1). All cases were primary systemic and widely disseminated; 11 patients had extranodal infiltrates, including skin in 5 cases and bone marrow in 6, as well as bones, meninges, brain, adrenal gland, lungs, liver, spleen, gastric wall, orbit and muscles. 14 patients had systemic symptoms; blood counts were abnormal in 10 cases, inflammation markers increased in 11 patients. 3 patients were HIV+ with particularly fulminant clinical course. Lymph node biopsy was diagnostic in 10 cases (7 peripheral nodes, 2 abdominal and 1 mediastinal), trephine biopsy in 3, skin biopsy in 2 and bone (vertebral) biopsy in 1. Morphologically, 10 cases showed common pattern, 4 lymphohistiocytic, 1 small cell and 1 Hodgkin-like. Diffuse infiltrate was observed in 9 cases, cell clusters in 4 and intrasinusoidal infiltration in 2. Prominent necrosis was found in 7 cases. All cases were strongly positive for CD30. 14 cases were stained for ALK1, 6 of them were positive and 8 negative, including all HIV+ cases. Median age of patients with ALK+ALCL was 25 years and M : F = 2 : 1; median age of ALK- patients was 56 years and M : F = 3 : 1. CD45 (LCA) was positive in 13 cases (very weak in 2), and negative in 3. The most specific T-cell antigen CD3 was positive in only 2 cases (2 of them weakly). No expression of B-lineage, epithelial and soft tissue antigens was found, except Vimentin was positive in all 6 tested cases and EMA in 12 out of 14 cases. Conclusions. ALCL has been successfully diagnosed in Latvia over the last decade, in spite of considerable diagnostic difficulties. The study revealed an uncommonly high incidence of ALK- systemic ALCL in Latvian population. On the other hand, no primary skin cases have been documented, that could indicate hypodiagnostics. HIV+ ALCL is extremely rare worldwide, 3 cases in this small cohort are unusual. Otherwise, clinical, histologic and phenotypic features of the studied patients, though exotic, were well in accordance with the published data.
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    Characterization of senescence of culture-expanded human adipose-derived mesenchymal stem cells
    (2016) Legzdina, Diana; Romanauska, Anete; Nikulshin, Sergey; Kozlovska, Tatjana; Berzins, Uldis
    Background and Objectives: Adipose-derived mesenchymal stem cells (ADSCs) are promising candidates in regenerative medicine. The need for in vitro propagation to obtain therapeutic quantities of the cells imposes a risk of impaired functionality due to cellular senescence. The aim of the study was to analyze in vitro senescence of previously cryopreserved human ADSCs subjected to serial passages in cell culture. Methods and Results: ADSC cultures from 8 donors were cultivated until proliferation arrest was reached. A gradual decline of ADSC fitness was observed by altered cell morphology, loss of proliferative, clonogenic and differentiation abilities and increased β-galactosidase expression all of which occurred in a donor-specific manner. Relative telomere length (RTL) analysis revealed that only three tested cultures encountered replicative senescence. The presence of two ADSC subsets with significantly different RTL and cell size was discovered. The heterogeneity of ADSC cultures was supported by the intermittent nature of aging seen in tested samples. Conclusions: We conclude that the onset of in vitro senescence of ADSCs is a strongly donor-specific process which is complicated by the intricate dynamics of cell subsets present in ADSC population. This complexity needs to be carefully considered when elaborating protocols for personalized cellular therapy.
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    An Extensive Quality Control and Quality Assurance (QC/QA) Program Significantly Improves Inter-Laboratory Concordance Rates of Flow-Cytometric Minimal Residual Disease Assessment in Acute Lymphoblastic Leukemia : An I-BFM-FLOW-Network Report
    (2021-12-06) Maurer-Granofszky, Margarita; Nikulshin, Sergey; I-BFM-FLOW
    Monitoring of minimal residual disease (MRD) by flow cytometry (FCM) is a powerful prognostic tool for predicting outcomes in acute lymphoblastic leukemia (ALL). To apply FCM-MRD in large, collaborative trials, dedicated laboratory staff must be educated to concordantly high levels of expertise and their performance quality should be continuously monitored. We sought to install a unique and comprehensive training and quality control (QC) program involving a large number of reference laboratories within the international Berlin-Frankfurt-Münster (I-BFM) consortium, in order to complement the standardization of the methodology with an educational component and persistent quality control measures. Our QC and quality assurance (QA) program is based on four major cornerstones: (i) a twinning maturation program, (ii) obligatory participation in external QA programs (spiked sample send around, United Kingdom National External Quality Assessment Service (UK NEQAS)), (iii) regular participation in list-mode-data (LMD) file ring trials (FCM data file send arounds), and (iv) surveys of independent data derived from trial results. We demonstrate that the training of laboratories using experienced twinning partners, along with continuous educational feedback significantly improves the performance of laboratories in detecting and quantifying MRD in pediatric ALL patients. Overall, our extensive education and quality control program improved inter-laboratory concordance rates of FCM-MRD assessments and ultimately led to a very high conformity of risk estimates in independent patient cohorts.
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    Rare Case of Hodgkin Lymphoma Transformation into Diffuse Large B-Cell Lymphoma with Atypical Spread Epidurally, Intradurally and Intramedullary : A Case Report
    (2022-02-25) Balodis, Arturs; Pimenova, Anna; Nikulshin, Sergey; Balode, Ginta; Hasnere, Sigita; Department of Radiology; Department of Infectology
    BACKGROUND Hodgkin lymphoma (HL) transformation into diffuse large B-cell lymphoma (DLBCL) is uncommon, and scant information has been published on transformed high-grade lymphomas. Therefore, it is important to present and discuss cases of lymphoma transformation to make new information on disease progression, diagnosis, and treatment more readily available. In this paper, we present a case of HL transformation into DLBCL with atypical dissemination. CASE REPORT A 39-year-old woman presented with severe hip pain. A computed tomography (CT) scan was performed, which showed massive pathological retroperitoneal and pelvic lymphadenopathy. The lymph nodes were biopsied and revealed HL. The patient then underwent 7 cycles of ABVD therapy; however, clinical concern was raised for persistent disease due to the poor response to therapy. A vertebral body biopsy was performed to clarify the diagnosis, and histological analysis revealed DLBCL. Therefore, specific chemotherapy with the R-CHOP scheme was begun; the patient received 8 cycles of rituximab and residual lymphoma tissue irradiation. Two months later, magnetic resonance imaging later demonstrated radiological disease progression with multiple widespread metastases in the spinal vertebrae as well as prevertebral, epidural, intradural, and intramedullary metastatic spread. The patient underwent intrathecal chemotherapy and radiation therapy, after which, full metabolic remission was observed on PET/CT. CONCLUSIONS Vigilance should be maintained for patients with poor response to HL treatment owing to the possible transformation into DLBCL. However, even in such cases, full metabolic remission can be achieved with appropriate treatment.
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    Significant age- and gender-related variability of main lymphocyte subsets in paediatric patients : Latvian data
    (2018-08) Nikulshin, Sergey; Kundzina, Linda; Tolstikova, Iveta; Gravele, Dagne; Prokofjeva, Tatjana; Gardovska, Dace; Rīga Stradiņš University
    Age- and gender-related variability of main lymphocyte subsets (T, B and NK cell absolute counts and percentages from Ly; T4, T8 and DN cell absolute counts and percentages from lymphocytes and from T cells; T4:T8 and T:B ratios) was studied in a large cohort of paediatric patients (2 days-17 years) at yearly intervals. A total of 4128 six-color TBNK tests performed on BD FACSCanto II flow cytometer were assessed; patients with immune deficiencies and tumours were not included. The study revealed significant age- and gender-related changes in all subsets. Absolute counts of T, B, T4 cells dropped from neonates to adolescents, decrease in T8 and NK cells was milder; relative count of T cells increased with age and that of B cells decreased; T4:T8 ratio went down and T:B ratio grew. Total T, T4 cells and T4:T8 ratio were significantly higher in girls, while T8, NK and DN cells were significantly higher in boys; significantly higher relative and absolute B cell counts in boys appeared in adolescence. We compared our results with reference values for healthy children (Tosato et al, Cytometry A. 2015;87:81); there was a good concordance, except for DN cells. Advantages of using patient cohort instead of healthy children as reference, possibilities for adjusting age- and gender-specific reference ranges and potential international data pooling are discussed.