Waldenströmova makroglobulinémie (WM) patří k low-grade B-lymfomům. Je definována přítomností lymfoplazmocytárního lymfomu v kostní dřeni a monoklonálního imunoglobulinu typu IgM (M-IgM) v séru. Příznaky nemoci, anémie a trombocytopenie, mohou souviset s masou patologických buněk, stejně jako systémové zánětlivé projevy (B-symptomy). Velké spektrum symptomů však způsobuje M-IgM. Koncentrace M-IgM u WM nekoreluje s masou patologických buněk. Spektrum poruch způsobených M-IgM je vzhledem k diverzitě patofyziologických mechanizmů a lokalizaci poškození značně široké. Poškození může vzniknout depozicí kompletní molekuly nebo její části ve formě agregátů, amorfních, krystalických, mikrotubulárních či fibrilárních struktur. M-IgM může také pacienta poškozovat autoprotilátkovou aktivitou namířenou proti antigenům vlastních tkání. Dále může M-IgM tvořit imunitní komplexy a aktivovat komplement. Výjimečně může B buněčný klon indukovat tvorbu cytokinů. Proto je velmi obtížené včas rozpoznat symptomatickou formu WM. V této publikaci popisujeme pacientku poškozenou depozity M-IgM a řetězců lambda. Diskuze je zaměřena na přehled všech forem poškození člověka depozity M-IgM, mezi něž patří i popsaný případ.
Waldenström’s macroglobulinaemia (WM) is a low-grade B-cell lymphoproliferative disorder characterised by an immunoglobulin IgM monoclonal gammopathy and bone marrow infiltration by lymphoplasmacytic lymphoma. Clinical features may be related to the overall disease burden, such as anaemia, thrombocytopenia, and constitutional inflammatory symptoms, or may be directly attributable to the IgM paraprotein. The concentration of monoclonal IgM can vary widely in WM. There is no direct relationship between the concentration of monoclonal immunoglobulin IgM and bone marrow infiltration. The spectrum of monoclonal immunoglobulin IgM-related disorders is large because of the diversity of involved organs and pathogenic mechanisms. Lesions commonly result from the deposition of all or part of the M-IgM as aggregates, amorphous, crystalline, microtubular, or fibrillar forms. Other mechanisms include autoantibody activity against a tissue antigen, formation of immune complexes, and complement activation. In addition, even a small B-cell clone may absorb biologically active molecules or induce cytokine secretion. In our case report, we describe a female patient with monoclonal IgM and lambda liver deposition and we discuss the frequency and variety of disorders caused by deposition of monoclonal IgM and free light chain.
- Klíčová slova
- imunokomplexy,
- MeSH
- amyloid imunologie klasifikace MeSH
- amyloidóza diagnóza imunologie klasifikace patologie MeSH
- hepatomegalie etiologie imunologie MeSH
- imunoglobulin M imunologie krev škodlivé účinky MeSH
- krevní nemoci diagnóza etiologie krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- Waldenströmova makroglobulinemie * diagnostické zobrazování diagnóza imunologie patologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- práce podpořená grantem MeSH
Pyogenní granulom (lobulární kapilární hemangiom) se vyznačuje rychle rostoucí lézí podobnou moruši, která může být přisedlá nebo stopkatá. Krvácení, i při lehkém doteku (traumatu), je obvykle jeho prvním klinickým projevem. Na rozdíl od infantilního hemangiomu se může vyskytovat v každém věkovém období včetně dospělosti. Uvádíme kazuistiku 4leté dívky s pyogenním granulomem (PG) levé tváře, který matka pozorovala 3 měsíce po ukončení léčby akutní lymfoblastické leukemie (ALL). V celkové anestezii byla provedena exstirpace parciálně stopkatého PG současně s excizí jeho spodiny. Histologický nález prokázal fokálně prokrvácený lobulární kapilární hemangiom.
Pyogenic granuloma (lobular capillary hemangioma) is characterized by a rapidly growing mulberry-like lesion that may be sessile or pedunculated. Bleeding even with light touch (trauma) is usually its first clinical manifestation. Unlike infantile haemangioma, it can occur at any age, including adulthood. We present a case report of a 4-year-old girl with pyogenic granuloma (PG) of the left cheek, observed by her mother 3 months after treatment for acute lymphoblastic leukemia (ALL). Under general anesthesia, extirpation of the partially pedunculated PG was performed simultaneously with excision of its base. Histological findings showed a focally hemorrhaged lobar capillary hemangioma.
Difuzní velkobuněčný B-lymfom (diffuse large B-cell lymphoma – DLBCL) je nejčastějším typem maligního lymfomu v České republice. Tento zastřešující termín ve skutečnosti reprezentuje velmi heterogenní skupinu agresivních nádorů s různorodou biologií, pestrými klinickými projevy, u nichž je standardem terapie koncept imunoterapie zacílené proti antigenu CD20 nádorových buněk. Kombinace monoklonální protilátky rituximabu s chemoterapií historicky ukázala zásadní přínos mechanizmů cytotoxické imunity nemocného. Tento terapeutický koncept, který historicky vedl k vyléčení u téměř 2/3 nemocných, narazil na své limity. Výzkum alternativních postupů imunoterapie vedl k zavedení generačně nové úspěšné skupiny léčiv zacílené proti antigenu CD19 s různým mechanizmem účinku, od prostého působení protilátky (tafasitamab) přes podání konjugátu protilátky a toxinu (antibody-drug conjugate – ADC; loncastuximab-tesirine) po tvorbu sofistikovaných chimerických konstruktů CAR-T lymfocytů axicabtagene ciloleucel, tisagenlecleucel a lisocabtagene maraucel. Review má za cíl shrnout poznatky pokročilého medicínského výzkumu nových molekul, jejich sekvence a kombinace s přesahem do léčebné praxe v podmínkách České republiky.
Diffuse large B-cell lymphoma (DLBCL) is the most common type of malignant lymphoma in the Czech Republic. It represents a very heterogeneous group of aggressive tumors with diverse biology, and varied clinical manifestations. The standard of therapy is based on immunotherapy targeted against the CD20 antigen of the tumor cells. The combination of the monoclonal antibody rituximab with chemotherapy has historically demonstrated a major benefit of cytotoxic immunity mechanisms in patients. This therapeutic concept, which has historically led to cure in nearly two-thirds of patients, has encountered its limits. Research into alternative immunotherapy approaches has led to the introduction of a generationally successful new class of drugs targeting the CD19 antigen with different mechanisms of action ranging from simple antibody action (tafasitamab) to antibody-drug conjugate (ADC) administration (loncastuximab-tesirine), to the formation of sophisticated CAR-T lymphocyte chimeric constructs (axicabtagene ciloleucel, tisagenlecleucel and lisocabtagene maraleucel). The review aims to summarize the findings of advanced medical research of new molecules, their sequences, and combinations with implications for therapeutic practice in the Czech Republic.
- MeSH
- antigeny CD19 účinky léků MeSH
- imunoblastický velkobuněčný lymfom * farmakoterapie MeSH
- imunoterapie metody MeSH
- lidé MeSH
- monoklonální protilátky farmakologie terapeutické užití MeSH
- protokoly antitumorózní kombinované chemoterapie MeSH
- randomizované kontrolované studie jako téma MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
BACKGROUND: Lower gastrointestinal (GI) graft versus host disease (GVHD) represents a severe complication in allogeneic hematopoietic stem cell transplant (HSCT) recipients with high rates of transplant-related mortality. Deregulated innate immunity reactions are the features of its pathogenesis. Cellular senescence has been considered a program of the innate immunity. We focused on lower GI GVHD from the perspective of cellular senescence. OBJECTIVE: We analyzed the impact of p16INK4a expression, a hallmark of cellular senescence, in intestinal biopsies of patients with lower GI GVHD symptoms and NFKB1 gene polymorphisms (rs3774937 C/T and rs3774959 A/G) on HSCT outcome. STUDY DESIGN: Fifty-two single-center patients who presented with symptoms of lower GI GVHD were analyzed in a retrospective manner. Two SNPs located in the NFKB1 gene regions (rs3774937 C/T and rs3774959 A/G) were genotyped from the peripheral blood samples collected before the start of the conditioning. All patients underwent proctosigmoidoscopy with biopsy of the mucosa. The expression of p16INK4a was analyzed in normal intestinal crypts and stroma. RESULTS: Fifty-two patients (50% male) received HSCT for hematological diseases (acute leukemias in 67%) and developed lower GI symptoms. Patients with p16INK4a expression in the intestinal stroma were in lower risk of developing histological grade 3-4 aGVHD (RR 0.18 [95% CI 0.05-0.65]; p = 0.009). The multivariate linear regression confirmed the independent effect of p16INK4a expression on time of the lower GI aGVHD symptoms onset (Coef. 38.9 [95% CI 12.7-65.1]; p = 0.005). The NFKB1 rs3774937 CC and TT/TC genotype were present in 40 and 80% of patients with p16INK4a expression, respectively (p = 0.04). The rs3774959 AA and GG/AG genotype were present among 43 and 82% of patients with p16INK4a expression, respectively (p = 0.02). Expression of p16INK4a was associated with no clinical variable but NFKB1 genotype. CONCLUSIONS: Our results address possible new mechanisms that may lead to better understanding of HSCT-related immune complications. Cellular senescence may bring novel approaches in GVHD diagnostics and therapy.
- MeSH
- gastrointestinální nemoci * etiologie MeSH
- inhibitor p16 cyklin-dependentní kinasy * genetika MeSH
- jednonukleotidový polymorfismus MeSH
- lidé MeSH
- nemoc štěpu proti hostiteli * genetika metabolismus MeSH
- NF-kappa B - podjednotka p50 * genetika MeSH
- retrospektivní studie MeSH
- stárnutí buněk genetika MeSH
- transplantace hematopoetických kmenových buněk * škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Amyloidosis is a rare metabolic disorder primarily brought on by misfolding of an autologous protein, which causes its local or systemic deposition in an aberrant fibrillar form. It is quite rare for pulmonary tissue to be impacted by amyloidosis; of the three forms it can take when involving pulmonary tissue, nodular pulmonary amyloidosis is the most uncommon. Nodular pulmonary amyloidosis rarely induces clinical symptoms, and most often, it is discovered accidentally during an autopsy or via imaging techniques. Only one case of nodular pulmonary amyloidosis, which manifested as a spontaneous pneumothorax, was found in the literature. In terms of more precise subtyping, nodular amyloidosis is typically AL or mixed AL/AH type. No publications on AH-dominant type of nodular amyloidosis were found in the literature. We present a case of an 81 years-old male with nodular pulmonary AH-dominant type amyloidosis who presented with spontaneous pneumothorax. For a deeper understanding of the subject, this study also provides a review of the literature on cases with nodular pulmonary amyloidosis in relation to precise amyloid fibril subtyping. Since it is often a difficult process, accurate amyloid type identification is rarely accomplished. However, this information is very helpful for identifying the underlying disease process (if any) and outlining the subsequent diagnostic and treatment steps. Even so, it is crucial to be aware of this unit and make sure it is taken into consideration when making a differential diagnosis of pulmonary lesions.
- MeSH
- amyloidóza * komplikace diagnóza patologie MeSH
- lidé MeSH
- plíce diagnostické zobrazování patologie MeSH
- plicní nemoci * komplikace diagnóza patologie MeSH
- pneumotorax * diagnóza etiologie MeSH
- senioři nad 80 let MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- Publikační typ
- kazuistiky MeSH
- přehledy MeSH
- Publikační typ
- abstrakt z konference MeSH
Epstein-Barr virus (EBV), defined as a group I carcinogen by the World Health Organization (WHO), is present in the tumour cells of patients with different forms of B-cell lymphoma, including Burkitt lymphoma, Hodgkin lymphoma, post-transplant lymphoproliferative disorders, and, most recently, diffuse large B-cell lymphoma (DLBCL). Understanding how EBV contributes to the development of these different types of B-cell lymphoma has not only provided fundamental insights into the underlying mechanisms of viral oncogenesis, but has also highlighted potential new therapeutic opportunities. In this review, we describe the effects of EBV infection in normal B-cells and we address the germinal centre model of infection and how this can lead to lymphoma in some instances. We then explore the recent reclassification of EBV+ DLBCL as an established entity in the WHO fifth edition and ICC 2022 classifications, emphasising the unique nature of this entity. To that end, we also explore the unique genetic background of this entity and briefly discuss the potential role of the tumour microenvironment in lymphomagenesis and disease progression. Despite the recent progress in elucidating the mechanisms of this malignancy, much work remains to be done to improve patient stratification, treatment strategies, and outcomes.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The presence of wild-type RAS alleles, as determined by genotyping codons 12, 13, 59, 61, 117, and 146, is a prerequisite for personalized anti-EGFR treatment of metastatic colorectal cancer (mCRC) patients. Here we describe analytical validation of in-house developed massively parallel sequencing technology (MPS) in comparison to the in vitro diagnostics (IVD) certified qPCR method. DNA extracted from FFPE samples from CRC patients (n=703) and reference standards (n=33) were tested for KRAS and NRAS mutations in 6 codons of exons 2, 3, and 4 using deep amplicon sequencing (DAS) on a MiSeq benchtop sequencer (Illumina). Two different amplicon lengths and two different library preparation methods (long-RAS and short-RAS) were tested in order to evaluate their impact on DAS performance. In parallel, identical tumor DNA was tested by the following IVD assays: therascreen KRAS RGQ PCR Kit (Qiagen), cobas® KRAS Mutation Test (Roche Diagnostics), and SNaPshot assay (Thermo Fisher Scientific). Both DAS assays detected all the mutations present in reference standards and external quality control samples, except for the artificially generated KRAS codon 146 mutation. The DAS assays performed sufficient analytical specificity and sensitivity (≥0.95). The use of shorter amplicons prolonged the preparation steps but significantly improved the sequencing success rate of FFPE-derived DNA. RAS mutation frequencies in the Czech CRC patients were similar to previous reports, although rare mutations were also detected. DAS with short amplicons is a good strategy for routine assessment of somatic mutations in low-quality FFPE-derived DNA.
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
