INTRODUCTION: Central nervous system lymphoma poses significant diagnostic challenges, with stereotactic biopsy being the gold standard for diagnosis. Intraoperative magnetic resonance imaging and intraoperative histological examination are utilized to enhance biopsy yield, yet their comparative efficacy remains unclear. RESEARCH QUESTION: This study aims to compare the diagnostic yield of intraoperative magnetic resonance imaging and intraoperative histological examination in stereotactic brain biopsies for central nervous system lymphoma. MATERIALS AND METHODS: A retrospective analysis was conducted on 115 patients who underwent stereotactic brain biopsies for central nervous system lymphoma. Diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of intraoperative magnetic resonance imaging and intraoperative histological examination were assessed and compared. RESULTS: Out of 125 surgeries, frameless biopsies were the most common, accounting for 74.4 percent. Intraoperative magnetic resonance imaging demonstrated a sensitivity of 80.00 percent and a specificity of 98.51 percent (AUC = 0.893, p = 0.004), whereas intraoperative histological examination showed a sensitivity of 66.67 percent and a specificity of 59.09 percent (AUC = 0.629, p = 0.459). DISCUSSION AND CONCLUSIONS: The study emphasizes the critical role of intraoperative examinations, thus improving precision and diagnostic yield in the surgical management of central nervous system lymphoma. Intraoperative magnetic resonance imaging outperforms intraoperative histological examination in terms of sensitivity and specificity for confirming positive biopsy yields in central nervous system lymphoma, thereby reducing the need for additional surgeries. These findings support the routine use of intraoperative magnetic resonance imaging in the surgical strategy for central nervous system lymphoma to improve diagnostic accuracy and patient outcomes.

• Publikační typ
• časopisecké články MeSH

Our knowledge of genetic aberrations, that is, variants and copy number variations (CNVs), associated with mantle cell lymphoma (MCL) relapse remains limited. A cohort of 25 patients with MCL at diagnosis and the first relapse after the failure of standard immunochemotherapy was analyzed using whole-exome sequencing. The most frequent variants at diagnosis and at relapse comprised six genes: TP53, ATM, KMT2D, CCND1, SP140, and LRP1B. The most frequent CNVs at diagnosis and at relapse included TP53 and CDKN2A/B deletions, and PIK3CA amplifications. The mean count of mutations per patient significantly increased at relapse (n = 34) compared to diagnosis (n = 27). The most frequent newly detected variants at relapse, LRP1B gene mutations, correlated with a higher mutational burden. Variant allele frequencies of TP53 variants increased from 0.35 to 0.76 at relapse. The frequency and length of predicted CNVs significantly increased at relapse with CDKN2A/B deletions being the most frequent. Our data suggest, that the resistant MCL clones detected at relapse were already present at diagnosis and were selected by therapy. We observed enrichment of genetic aberrations of DNA damage response pathway (TP53 and CDKN2A/B), and a significant increase in MCL heterogeneity. We identified LRP1B inactivation as a new potential driver of MCL relapse.

• MeSH
• dospělí MeSH
• geny p16 MeSH
• klonální evoluce genetika   MeSH
• lidé MeSH
• lokální recidiva nádoru MeSH
• lymfom z plášťových buněk * diagnóza   farmakoterapie   genetika   MeSH
• variabilita počtu kopií segmentů DNA MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Mature T cell lymphomas (MTCLs) have worse prognosis, and in contrast to B cell lymphomas, there is no universal marker like CD20 with exception of ALK and CD30, which are present in proportion of MTCL only. Up to now, ALK is traditionally associated with good prognosis in ALCLs, and there are some evidences that CD30-positive T cell or B cell lymphomas have better prognosis. In our retrospective, population-based analysis, we analyzed the real clinical value of ALK and CD30 in the most frequent MTCL subtypes. Between 2000 and 2017, we identified 732 patients with newly diagnosed ALCL, AITL, or PTCL-NOS. Among them, 207 ALCL patients were with known ALK, whereas 61 AITL and 238 PTCL-NOS with known CD30 expression. There were 69/207 (33.3%) ALK + ALCLs, who displayed better 5-year PFS (65.6% vs. 36.2%) (p .001) and 5-year OS (71.5% vs. 45.9%) (p .002) compared to ALK - ; ALK + patients were significantly younger (median 48 vs. 60 years; p < 0.001). For patients ≥ 60 years, 5-year PFS (38.5% vs. 31.2%) and 5-year OS (38.5% vs. 39.6%) were similar between ALK + vs. ALK - patients. For AITL and PTCL-NOS, there were 44/61 (72.1%) and 120/238 (50.4%) CD30 + samples, and difference in CD30 expression was significant (p .02). AITL patients had 5-year OS of 43.8% vs. 55.7% (p 0.848) and 5-year PFS of 36.7% vs. 29.4% (p .624) for CD30 + vs. CD30 - patients, whereas PTCL-NOS had 5-year OS of 35.7% vs. 34.3% (p .318) and 5-year PFS of 29.3% vs. 22.5% (p.114) for CD30 + vs. CD30 - cases. We conclude that ALK in ALCLs (≥ 60 years) and CD30 expression in PCTL-NOS and AITL have only limited prognostic value.

• MeSH
• antigen Ki-1 * MeSH
• lidé MeSH
• periferní T-buněčný lymfom * patologie   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• tyrosinkinasové receptory MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Chromosomal translocation t(11;14)(q13;q32) is a characteristic molecular marker of mantle cell lymphoma (MCL) and leads to the fusion of the immunoglobulin heavy chain enhancer-promoter with the cyclin D1 gene. Both aberrant cyclin D1 expression and underlying chromosomal aberration may be used as molecular targets for monitoring minimal residual disease (MRD). The present study aims to assess the usefulness of quantitative cyclin D1 gene expression compared to the standardised but more technologically demanding DNA-based method for immunoglobulin heavy chain (IGH) or t(11;14) clone-specific gene rearrangement quantification in a cohort of bone marrow (BM) and peripheral blood (PB) samples from patients with MCL. We simultaneously evaluated DNA-MRD and cyclin D1 expression levels in 234 samples from 57 patients. We observed that both in DNA-MRD positive and negative BM/PB pairs from the same time points the expression levels of cyclin D1 are lower in PB than in BM (median 19×, BM/PB range 0.41-352). The correlation of cyclin D1 transcript levels with DNA-MRD or with flow cytometry was good only in samples with a very high infiltration. In DNA-MRD-negative BM samples, we observed a significant heterogeneity of cyclin D1 expression (in the range of more than three orders of magnitude). This is in contrast to previous reports demonstrating the usefulness of cyclin D1 for MRD monitoring that did not use DNA-based method as a reference. In PB, the specificity of cyclin D1 expression was better due to a lower physiological background. In conclusion, we show that cyclin D1 is unsuitable for MRD monitoring in BM.

• MeSH
• cyklin D1 genetika   metabolismus   MeSH
• kostní dřeň metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfom z plášťových buněk diagnóza   genetika   patologie   MeSH
• messenger RNA analýza   MeSH
• monitorování fyziologických funkcí metody   MeSH
• nádorové biomarkery analýza   genetika   MeSH
• regulace genové exprese u nádorů MeSH
• reziduální nádor MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Central nervous system (CNS) involvement in mantle cell lymphoma (MCL) is uncommon, and the manifestations and natural history are not well described. PATIENTS AND METHODS: We present the data on 57 patients with MCL who developed CNS involvement, from a database of 1396 consecutively treated patients at 14 institutions. RESULTS: The crude incidence of CNS involvement was 4.1%, with 0.9% having CNS involvement at diagnosis. Blastoid histology, B-symptoms, elevated lactate dehydrogenase, Eastern Cooperative Group performance status >=2 and a high Mantle Cell Lymphoma International Prognostic Index score were enriched in the cohort with CNS involvement, and the presence of >=1 of these features defined a high-risk subset (an actuarial risk of CNS involvement 15% at 5 years) in a single-institution subset. The median time to CNS relapse was 15.2 months, and the median survival from time of CNS diagnosis was 3.7 months. The white blood cell count at diagnosis <10.9 x 109/l, treatment of CNS involvement with high-dose anti-metabolites, consolidation with stem cell transplant and achievement of complete response were all associated with improved survival. CONCLUSIONS: In MCL, CNS involvement is uncommon, although some features may predict risk. Once manifest outlook is poor; however, some patients who receive intensive therapy survive longer than 12 months.

• MeSH
• antimetabolity antitumorózní terapeutické užití   MeSH
• centrální nervový systém * patologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfom z plášťových buněk * farmakoterapie   MeSH
• nádory centrálního nervového systému farmakoterapie   prevence a kontrola   sekundární   MeSH
• počet leukocytů MeSH
• přežití MeSH
• retrospektivní studie MeSH
• riziko MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Geografické názvy
• Evropa MeSH

Disruption of apoptotic pathways belongs to commonly reported molecular mechanisms that underlie cancer drug resistance. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL, Apo2L) is a cytokine of the TNF family with selective anti-tumor activity and minimal toxicity toward healthy tissues. Primary leukemia cells are, however, largely intrinsically resistant to TRAIL-induced apoptosis. In this study we analyzed molecular differences between TRAIL-resistant K562 cell line and TRAIL-sensitive K562 clones. We demonstrate that TRAIL-sensitive K562 cells differ from the TRAIL-resistant cell line by cell surface downregulation of TRAIL decoy receptor 1, upregulation of both TRAIL death receptors, enhanced assembly and improved functioning of the death-inducing signaling complex, and increased cytoplasmic protein expression of CASP8 and key proapoptotic BCL2 members BID, BIM, BAD and BAK. The molecular basis of the intrinsic leukemia cell TRAIL resistance thus appears a consequence of the multi-level disruption of the extrinsic apoptotic pathway. The results of this study also suggest that the leukemia TRAIL-resistance is functional, leaving a possibility of overcoming the resistance by preexposure of the leukemia cells to potent TRAIL sensitizers, e.g. BH3-mimetics.

• MeSH
• apoptóza * MeSH
• buňky K562 MeSH
• chemorezistence MeSH
• lidé MeSH
• protein TRAIL farmakologie   MeSH
• signální transdukce MeSH
• TNF-alfa farmakologie   MeSH
• TRAIL receptory analýza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• Publikační typ
• abstrakt z konference MeSH

Primary mediastinal B-cell lymphoma (PMBL) seems to be reliably distinguished from diffuse large B-cell lymphoma (DLBCL) with microarray technology. We measured expression of Fcer2, Pdl2 and Blk genes using real-time quantitative polymerase chain reaction (RTqPCR) on formalin fixed, paraffin embedded material (FFPE) and suggested a formula to discriminate PMBL from DLBCL. For 39/82 included patients the diagnosis of PMBL was expected clinico-pathologically. Diagnosis of 10/39 and 2/43 of clinically considered PMBLs and DLBCLs, respectively, was not genetically confirmed. Compared to confirmed PMBLs, unconfirmed ones showed clinical features similar to DLBCLs, e.g. spleen infiltration (p=0,028) and decreased invasiveness in pericardium (p=0,045). They tended to have more common infradiaphragmatic involvement, less often tumor sclerosis or fluidothorax. There were no immunohistochemical differences between genetically confirmed and unconfirmed PMBLs. New approach of distinguishing PMBL and DLBCL is presented. It is based on expression of three genes in routinely available FFPE material using RTqPCR.

• MeSH
• B-buněčný lymfom diagnóza   MeSH
• diferenciální diagnóza MeSH
• difúzní velkobuněčný B-lymfom diagnóza   MeSH
• dospělí MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory mediastina diagnóza   MeSH
• polymerázová řetězová reakce metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH