High-grade B-cell lymphomas (HGBCLs) are aggressive blood cancers with a severe disease course, especially when the central nervous system (CNS) is involved. Standard histological examination depends on tissue availability and is currently supplemented with molecular tests, as the status of MYC, BCL2, or BCL6 gene rearrangements is required for proper lymphoma classification. This case report demonstrates the relevance of cerebrospinal fluid (CSF) cell-free DNA testing by integrative next-generation sequencing (NGS) panel. The benefit of this approach resided in tumor genotyping alongside the proof of CNS progression despite MRI negativity, revealing a clonal relationship with the primary tumor lesion. In addition, our strategy allowed us to classify the tumor as DLBCL/HGBL-MYC/BCL2 entity. In clinical practice, such a minimally invasive approach provides a more sensitive tool than standard imaging and cell analyzing techniques, enabling more accurate disease monitoring and relapse prediction in particular cases.
- MeSH
- B-buněčný lymfom genetika patologie diagnóza diagnostické zobrazování MeSH
- cirkulující nádorová DNA genetika MeSH
- difúzní velkobuněčný B-lymfom genetika patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru patologie genetika MeSH
- magnetická rezonanční tomografie * MeSH
- nádorové biomarkery genetika MeSH
- nádory centrálního nervového systému genetika patologie diagnostické zobrazování MeSH
- vysoce účinné nukleotidové sekvenování * MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
VEXAS syndrom je v roce 2020 nově rozpoznaná a popsaná autoinflamatorní choroba. Akronym VEXAS je složen z prvních písmen V = vakuoly, E = E1 enzymy, X = X-chromozom, A = autoinflamatorní, S = somatické. Podstatou onemocnění je získaná somatická patogenní varianta v genu UBA1. Tento gen kóduje enzym E1, který je zodpovědný za regulaci zánětlivých proteinů vazbou na ubikvitin (ubikvitinizace). Kvůli uložení genu na X chromozomu toto onemocnění postihuje muže, a to v jejich druhé polovině života. Choroba má pestré inflamatorní projevy s hematologickými (hyperkoagulace, anémie, trombocytopenie), dermatologickými (Sweetův snydrom) a revmatologickými (perichondritis, artritis) symptomy. Tyto příznaky lze shrnout do pracovní diagnózy „nespecifikovaná systémová autoinflamatorní choroba“ (undifferentiated systemic autoinflammatory disorder – USAID). Průkaz vakuol při cytologickém hodnocení kostní dřeně je pro tuto chorobu charakteristický a definitivní diagnózu potvrzuje průkaz defektu UBA1 genu. V textu popisujeme našeho prvního pacienta s VEXAS syndromem a uvádíme stručný přehled literatury.
The VEXAS syndrome is a recently identified autoinflammatory systemic disease. The acronym VEXAS stands for Vacuoles, E1 enzyme, X linked, Autoinflammatory, Somatic. The disease is due to an acquired somatic mutation of the UBA1 gene, which encodes for the E 1 enzyme, which in turn is responsible for the ubiquitination of proteins. Due to its location on the X chromosome, the disease predominantly affects men in the second half of life. The patients present with a plenty of inflammatory clinical symptoms, often with overlap of hematologic (anemia, thrombocytopenia hypercoagulation), dermatologic (Sweet syndrom), and rheumatologic (artritis, perichondritis) symptoms. These symptoms can be assessed as “undifferentiated systemic autoinflammatory disorder (USAID) ”. Bone marrow smear with the presence of cytoplasmic vacuoles in the bone marrow is characteristic and the mutation of UBA1 gene is proof of this diagnosis. In this article, we report our first clinical case of a VEXAS syndrome and give an overview of the literature, including pathophysiology, clinical symptoms and diagnostics of the disease.
- Klíčová slova
- syndrom VEXAS,
- MeSH
- diferenciální diagnóza MeSH
- genetické nemoci vázané na chromozom X * diagnóza farmakoterapie genetika klasifikace MeSH
- kožní manifestace MeSH
- lidé MeSH
- myelodysplastické syndromy diagnóza klasifikace MeSH
- příznaky a symptomy MeSH
- senioři MeSH
- Sweetův syndrom diagnóza etiologie MeSH
- vakuoly patologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- kazuistiky MeSH
The clinical course of essential thrombocythemia (ET) is complicated with thrombosis which significantly impacts patients' mortality. Studies have identified JAK2V617F mutation as an independent risk factor for thrombosis. Circulating extracellular vesicles (EVs) were evaluated in several studies regarding myeloproliferative neoplasms and thrombosis as potential biomarkers. The present study investigates the relationship between JAK2V617F mutation and EVs levels in 119 ET patients. Our analyses revealed that JAK2V617F-positive patients are at a significantly increased risk of thrombosis within five years before the ET diagnosis (hazard ratio [95% CI]: 11.9 [1.7-83.7], P = 0.013), and that JAK2V617F mutation is an independent risk factor for thrombosis at ET diagnosis or during the follow-up (hazard ratio [95% CI]: 3.56 [1.47-8.62], P = 0.005). ET patients have higher levels of platelet-EVs, erythrocyte-EVs and procoagulant activity of EVs than the healthy population. Absolute and relative counts of platelet-EVs are increased in the presence of JAK2V617F mutation (P = 0.018, P = 0.024, respectively). In conclusion, our results support the role of JAK2V617F mutation in the pathogenesis of thrombosis in essential thrombocythemia through enhancing platelet activation.
Trombocytopenie je běžným hematologickým nálezem v denní klinické praxi, je definována poklesem počtu trombocytů pod dolní mez normálního rozmezí. Široké spektrum příčin a různorodost klinického obrazu často představují diagnostickou výzvu. Článek je zaměřen na základní diferenciální diagnostiku trombocytopenie, což je podpořeno dvěma kazuistikami.
Thrombocytopenia is a hematological finding commonly encountered in daily clinical practice; it is defined by a decrease in the number of platelets below the lower limit of the normal range. A broad spectrum of etiologies and variation in clinical presentation often present a diagnostic challenge. The article is focused on the basic differential diagnosis of thrombocytopenia, which is supported by two case reports.
Anemie je běžná hematologická abnormalita, definovaná jako snížení koncentrace hemoglobinu pod dolní hranici normálního rozmezí. V klinické praxi je nejčastější a nejpřínosnější dělení anemií podle středního objemu erytrocytů na normocytární, mikrocytární a makrocytární. Článek je věnován základní diferenciální diagnostice anemií, která je demonstrována na příkladu několika kazuistik.
Anemia is a common hematological abnormality, defined as hemoglobin level under lower limit of normal range. In clinical practice, the most common and most beneficial division of anemia according to the mean cell volume is normocytic, microcytic and macrocytic anemias. The article is devoted to the basic differential diagnosis of anemia, which is demonstrated on the example of several case reports.
Thrombosis is the most common complication in BCR-ABL1 negative myeloproliferative neoplasms (MPN) that significantly impacts patients' mortality. Generally, there is an agreement on risk factors that possibly contribute to the increased risk of thrombosis, including age, history of thrombosis, JAK2V617F mutation, and cardiovascular risk factors. This study retrospectively investigates MPN-related and patient-related variables in relation to the thrombosis occurrence in MPN. Our analyses show that JAK2V617F-mutated patients are at a significantly increased risk of thrombosis within five years before the MPN diagnosis point with a hazard ratio (HR) of 15.49 (p=0.006). In multivariate analyses, independent risk factors for thrombotic complications during the follow-up are history of thrombosis (HR=2.23, p=0.019), age over 60 years at diagnosis (HR=1.56, p=0.037), the presence of JAK2V617F mutation (HR=3.01, p=0.002), and tobacco smoking (HR=1.75, p=0.01). Our results support the multifactorial mechanism of thrombosis in MPN patients, which demands individual and complex management.
- MeSH
- Janus kinasa 2 genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mutace MeSH
- nádory * MeSH
- retrospektivní studie MeSH
- rizikové faktory MeSH
- trombóza * genetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND/AIM: This work aimed to prospectively evaluate the clinical significance of circulating microparticles (MPs) in relation to thrombotic risk factors and thrombotic complications in patients with BCR/ABL1-negative myeloproliferative neoplasms (MPN). PATIENTS AND METHODS: In a cohort of 206 patients with MPN, MPs' procoagulant activity was measured by the Zymuphen functional assay in 429 samples, while platelet- and erythrocyte-MPs were enumerated by flow cytometry in 558 samples. RESULTS: MPN patients had higher MP levels than the control group. The levels of MPs were higher in male patients, smokers, and those who were older than 60 years, and in the presence of JAK2V617F mutation, history of thrombosis, platelets >400×109/l, hematocrit >45%, or leukocytes >10×109/l. Cytoreductive treatment reduced MP levels, with anagrelide being associated with lower MP levels than hydroxyurea. CONCLUSION: The relationship with thrombotic risk factors indicates a possible role of MPs in the complex thrombotic mechanism, though cytoreductive treatment seems to affect this role through reducing MP levels.
- MeSH
- lidé MeSH
- mikropartikule * MeSH
- myeloproliferativní poruchy * farmakoterapie genetika MeSH
- nádory * MeSH
- trombocyty MeSH
- trombóza * etiologie genetika MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
