BACKGROUND: Relative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings. OBJECTIVE: We performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk using Mendelian randomization, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations. DESIGN, SETTING, AND PARTICIPANTS: Genotypes from nine telomere length-associated variants for 10 784 cases and 20 406 cancer-free controls from six genome-wide association studies (GWAS) of RCC were aggregated into a weighted genetic risk score (GRS) predictive of leukocyte telomere length. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (ORs) relating the GRS and RCC risk were computed in individual GWAS datasets and combined by meta-analysis. RESULTS AND LIMITATIONS: Longer genetically inferred telomere length was associated with an increased risk of RCC (OR=2.07 per predicted kilobase increase, 95% confidence interval [CI]:=1.70-2.53, p<0.0001). As a sensitivity analysis, we excluded two telomere length variants in linkage disequilibrium (R2>0.5) with GWAS-identified RCC risk variants (rs10936599 and rs9420907) from the telomere length GRS; despite this exclusion, a statistically significant association between the GRS and RCC risk persisted (OR=1.73, 95% CI=1.36-2.21, p<0.0001). Exploratory analyses for individual histologic subtypes suggested comparable associations with the telomere length GRS for clear cell (N=5573, OR=1.93, 95% CI=1.50-2.49, p<0.0001), papillary (N=573, OR=1.96, 95% CI=1.01-3.81, p=0.046), and chromophobe RCC (N=203, OR=2.37, 95% CI=0.78-7.17, p=0.13). CONCLUSIONS: Our investigation adds to the growing body of evidence indicating some aspect of longer telomere length is important for RCC risk. PATIENT SUMMARY: Telomeres are segments of DNA at chromosome ends that maintain chromosomal stability. Our study investigated the relationship between genetic variants associated with telomere length and renal cell carcinoma risk. We found evidence suggesting individuals with inherited predisposition to longer telomere length are at increased risk of developing renal cell carcinoma.

• Klíčová slova
• Genetic variants, Mendelian randomization, Renal cell carcinoma, Risk, Telomere length,
• MeSH
• celogenomová asociační studie MeSH
• fenotyp MeSH
• genetická predispozice k nemoci MeSH
• hodnocení rizik MeSH
• homeostáza telomer * MeSH
• jednonukleotidový polymorfismus * MeSH
• karcinom z renálních buněk krev   genetika   patologie   MeSH
• leukocyty chemie   MeSH
• lidé MeSH
• mendelovská randomizace MeSH
• nádory ledvin krev   genetika   patologie   MeSH
• odds ratio MeSH
• rizikové faktory MeSH
• studie případů a kontrol MeSH
• telomery genetika   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, N.I.H., Intramural MeSH

OBJECTIVE: To review the incidence of histologic variants of uterine fibroids of patients in reproductive age and postmenopause. Analysis of potential relations between histological fibroids variants and hormonal activity of the patient. DESIGN: Retrospective analysis. SETTING: Department of Obstetrics and Gynecology, Masaryk University and University Hospital Brno. MATERIAL AND METHODS: Retrospective analysis of 2,397 women who underwent myomectomy or hysterectomy at the Department of Obstetrics and Gynecology, Masaryk University and University Hospital Brno in years 2008-2014. According to input criteria - age of patients between 18-65 years, ultrasound confirmed uterine fibroid. Exclusion criteria was irregular menstrual cycle, hormonal therapy in history or hysterectomy performed for tumors of the small pelvis or for cancer of the uterus or cervix.Group A consisted of 235 patients with regular menstrual cycles, between ages 18-40. Myomectomy was chosen for these patients.Group B consisted of 433 postmenopausal patients between ages 50-65. Laparoscopic and abdominal hysterectomy was performed to these patients. RESULTS: A statistically significant difference was observed in the occurrence of epithelioid type of leiomyoma between women age groups 18-40 and 50-65. In the group of postmenopausal women four malignant forms of leiomyoma were recorded, which were not statistically relevant. CONCLUSION: After evaluating statistical analysis it was found, that there is a statistically significant difference in epithelioid type of uterine leiomyoma. Four patients were detected malignant variant of leiomyoma - leiomyosarcoma in the group of postmenopausal women.

• Klíčová slova
• histological type, postmenopause., reproductive age, uterine fibroid,
• MeSH
• dospělí MeSH
• hysterektomie MeSH
• laparoskopie MeSH
• leiomyom patologie   chirurgie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádory dělohy patologie   chirurgie   MeSH
• postmenopauza MeSH
• retrospektivní studie MeSH
• senioři MeSH
• věkové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE OF REVIEW: The most common prostatic cancers (PCa) are acinary adenocarcinomas. Histological subtypes have been variably defined. The purpose of this review is to discuss unusual histological patterns and subtypes of acinar adenocarcinoma, as well as other types of PCa and their prognostic and therapeutic relevance. RECENT FINDINGS: The new term 'subtype' for morphologically defined tumor entities replaced the term 'variant' in the new 2022 classification of the WHO to allow for clear terminological distinction from genetic variants. The 2022 WHO classification mentions prostatic intraepithelial neoplasia (PIN)-like carcinoma, signet-cell-like adenocarcinoma, sarcomatoid carcinoma and pleomorphic-giant-cell adenocarcinoma of the prostate as true subtypes of acinary PCa. Other forms of acinary PCa are termed unusual histological patterns and include atrophic, foamy-cell, microcystic, pseudohyperplastic and mucinous patterns. Nonacinar forms of prostate cancer include other glandular PCa, the ductal adenocarcinoma and the treatment-associated neuroendocrine carcinoma, and nonglandular PCa, the adenosquamous carcinoma, the squamous cell carcinoma and the adenoid cystic (basal cell) carcinoma of the prostate. SUMMARY: True subtypes of acinary PCa and other forms of glandular and nonglandular PCa show relevant differences in prognosis and treatment approach compared with classic acinary PCa. The relevance of unusual histological patterns mainly lies in their deceptive benign appearance and the need for pathologists to know about these entities for accurate and timely diagnosis.

• MeSH
• adenokarcinom * patologie   MeSH
• lidé MeSH
• nádory prostaty * patologie   terapie   MeSH
• prostata patologie   MeSH
• prostatická intraepiteliální neoplazie * patologie   MeSH
• spinocelulární karcinom * patologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Large-scale genome-wide association studies (GWAS) have likely uncovered all common variants at the GWAS significance level. Additional variants within the suggestive range (0.0001> P > 5×10(-8)) are, however, still of interest for identifying causal associations. This analysis aimed to apply novel variant prioritization approaches to identify additional lung cancer variants that may not reach the GWAS level. Effects were combined across studies with a total of 33456 controls and 6756 adenocarcinoma (AC; 13 studies), 5061 squamous cell carcinoma (SCC; 12 studies) and 2216 small cell lung cancer cases (9 studies). Based on prior information such as variant physical properties and functional significance, we applied stratified false discovery rates, hierarchical modeling and Bayesian false discovery probabilities for variant prioritization. We conducted a fine mapping analysis as validation of our methods by examining top-ranking novel variants in six independent populations with a total of 3128 cases and 2966 controls. Three novel loci in the suggestive range were identified based on our Bayesian framework analyses: KCNIP4 at 4p15.2 (rs6448050, P = 4.6×10(-7)) and MTMR2 at 11q21 (rs10501831, P = 3.1×10(-6)) with SCC, as well as GAREM at 18q12.1 (rs11662168, P = 3.4×10(-7)) with AC. Use of our prioritization methods validated two of the top three loci associated with SCC (P = 1.05×10(-4) for KCNIP4, represented by rs9799795) and AC (P = 2.16×10(-4) for GAREM, represented by rs3786309) in the independent fine mapping populations. This study highlights the utility of using prior functional data for sequence variants in prioritization analyses to search for robust signals in the suggestive range.

• MeSH
• adenokarcinom genetika   patologie   MeSH
• Bayesova věta MeSH
• celogenomová asociační studie MeSH
• genetická predispozice k nemoci MeSH
• lidé MeSH
• nádory plic genetika   patologie   MeSH
• spinocelulární karcinom genetika   patologie   MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

OBJECTIVE: To evaluate the impact of discordant histological diagnoses between transurethral resection of bladder tumour (TURBT) and radical cystectomy (RC) on cancer-specific mortality (CSM) in patients with bladder cancer (BCa). PATIENTS AND METHODS: We relied on a multi-institutional database collecting data of patients with BCa who underwent TURBT and subsequent RC from nine centres between 2000 and 2023. We tested concordance rates between TURBT and RC in detecting urothelial carcinoma of the urinary bladder (UCUB) as well as non-UCUB hystological subtypes, using RC as the reference standard. Concordance was defined as the agreement between a specific histological subtype identified both at TURBT and RC and evaluated according to Cohen's kappa coefficient. Subsequently, survival analyses consisted of Kaplan-Meier plots and multivariable Cox regression (MCR) models addressing CSM according to concordance between TURBT and RC (namely, concordant vs discordant). RESULTS: Overall, 3160 patients were identified. Of these, 2762 (87%) harboured UCUB and 398 (13%) non-UCUB at TURBT vs 2481 (79%) UCUB and 679 (21%) non-UCUB at RC. There were 683 (21.6%) patients with a discordant diagnosis between TURBT and RC. The overall concordance in detecting non-UCUB subtypes was defined as fair concordance (Cohen's kappa coefficient: 0.32). In MCR models, a discordant diagnosis exhibited higher CSM relative to those with a concordant diagnosis (hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.1-1.6; P = 0.002). In a sensitivity analysis including patients with UCUB not exposed to neoadjuvant chemotherapy, this survival disadvantage was even higher (HR 1.5, 95% CI 1.1-1.7; P = 0.04). CONCLUSIONS: A discordant histopathological diagnosis between TURBT and RC is associated with higher CSM rates, particularly in cases initially misdiagnosed as UCUB. However, we also observed a moderate concordance between TURBT and RC in identifying non-UCUB subtypes.

• Klíčová slova
• accuracy, bladder cancer, bladder cancer histology, conconrdance, histological evaluation, histological subtypes, histological variants, radical cystectomy, survival, transurethral resection, turbt,
• Publikační typ
• časopisecké články MeSH

Pathogenic variants in JAG1 are known to cause Alagille syndrome (ALGS), a disorder that primarily affects the liver, lung, kidney, and skeleton. Whereas cardiac symptoms are also frequently observed in ALGS, thoracic aortic aneurysms have only been reported sporadically in postmortem autopsies. We here report two families with segregating JAG1 variants that present with isolated aneurysmal disease, as well as the first histological evaluation of aortic aneurysm tissue of a JAG1 variant carrier. Our observations shed more light on the pathomechanisms behind aneurysm formation in JAG1 variant harboring individuals and underline the importance of cardiovascular imaging in the clinical follow-up of such individuals.

• Klíčová slova
• Alagille syndrome, JAG1, intracranial aneurysm, thoracic aortic aneurysm,
• MeSH
• Alagillův syndrom * genetika   MeSH
• lidé MeSH
• protein jagged-1 genetika   metabolismus   MeSH
• proteiny vázající vápník MeSH
• srdce MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• JAG1 protein, human MeSH Prohlížeč
• protein jagged-1 MeSH
• proteiny vázající vápník MeSH

BACKGROUND/AIM: This study determined whether computed tomography (CT) is an appropriate means by which to differentiate non-invasive and minimally invasive forms of pulmonary adenocarcinoma from the invasive variant. PATIENTS AND METHODS: A total of 64 patients (38 men and 26 women, aged 42-76, mean age 64), who underwent surgery for pulmonary adenocarcinoma and a chest CT no less than 1 month before surgery, were included in the study. Lesions exhibiting ground glass opacity or ground glass opacity with a solid component of 5 mm or smaller, were defined as minimally invasive or non-invasive adenocarcinomas. CT findings were correlated with histopathological examination. RESULTS: Distinguishing minimally invasive and non-invasive adenocarcinoma from invasive adenocarcinoma using CT was achieved with a sensitivity of 77.7%, a specificity of 97.8%, a positive predictive value of 93.3%, and a negative predictive value of 91.8%. CONCLUSION: CT can be useful in assessing the degree of invasiveness of pulmonary adenocarcinoma and is a potential tool for the individualization of treatment.

• Klíčová slova
• Lung, adenocarcinoma, computed tomography, diagnostic imaging, histological type, pulmonary nodule, tumor,
• MeSH
• adenokarcinom plic diagnostické zobrazování   patologie   chirurgie   MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• individualizovaná medicína MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory plic diagnostické zobrazování   patologie   chirurgie   MeSH
• počítačová rentgenová tomografie MeSH
• rentgenový obraz - interpretace počítačová metody   MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Basal cell carcinoma (BCC) recurrences are relatively frequent event in a routine dermatologic practice. One of the most important factor which impacts risk of their development is a histomorphological appearance of tumor. DESIGN: The purpose of our study was to compare histological types of primary and corresponding relapsing BCCs of the skin. MATERIAL AND METHODS: The study included 36 cases of BCC recurrences from 34 patients, 17 women and 17 men. The patients ranged in age from 32 to 97 years, with a mean age of 67.1 years at the time of (the first) recurrence. RESULTS: Both tumor groups generally exhibited the same proportion of indolent and aggressive histological phenotype. In 21 cases (58.4%), we found an identical histological BCC type in primary and subsequent relapsing lesion. In 3 cases (8.3%), primary lesion showed indolent histological features without aggressive--growth component, while recurrent tumor already manifested it. Conversely, in next 3 cases (8.3%) primary tumor exhibited focal infiltrative-growth features and corresponding relapsing lesion did not. Of the remaining 9 cases (25%), histomorphological phenotype was not identical, but it showed the same prognostic histological tumor variant. CONCLUSION: Based on the results of our study it can be assumed that a BCC recurrence is a dynamic histogenetic process, during which the phenotypic transformation and the changes in histomorphological picture of lesions occur, probably as a result of the interactions between cancer cells and re-modulated surrounding stroma.

• MeSH
• bazocelulární karcinom patologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru patologie   MeSH
• nádory kůže patologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

OBJECTIVES: Two cases of an extremely rare paraganglioma-like variant of medullary thyroid carcinoma (MTC) are reported. METHODS: The patients were a 65-year-old male (case 1) and a 14-year-old female (case 2). Unilateral thyroid nodule and homolateral cervical lymphadenopathy was present in case 1; bilateral thyroid nodules were seen in case 2. Fine needle aspiration cytology (FNAC) was performed from thyroid nodules (in both cases) and from a cervical lymph node (in case 1). RESULTS: The cytological smears contained predominantly ovoid to spindled epithelial cells arranged in cohesive three-dimensional clusters with sharp margins; isolated individual cells were seen only rarely. No colloid or other material was present in the background. The tumour cells showed significant nuclear atypia with occasional bizarre and/or binucleated cells. The nuclear chromatin was coarse and granular, sometimes with grooves and intranuclear inclusions. The cytoplasm was inconspicuous. Polygonal or triangular cells, amyloid and azurophillic cytoplasmic granules were absent in both cases. Calcitonin expression was demonstrated in case 2. Histological examination confirmed the paraganglioma variant of MTC in both cases. Mutation of RET proto-oncogene in exon 16 (Met918Thr) - germline in case 2 and somatic in case 1 was detected by sequencing of DNA in both cases. CONCLUSIONS: This is the first description of cytological findings in the paraganglioma-like variant of MTC. Despite its rarity, it can be reliably diagnosed by FNAC if material for immunocytochemistry is obtained.

• MeSH
• fatální výsledek MeSH
• lidé MeSH
• medulární karcinom diagnóza   diagnostické zobrazování   genetika   patologie   MeSH
• mladiství MeSH
• mutace MeSH
• mutační analýza DNA MeSH
• nádory plic sekundární   MeSH
• nádory štítné žlázy diagnóza   diagnostické zobrazování   genetika   patologie   MeSH
• paragangliom diagnóza   diagnostické zobrazování   genetika   patologie   MeSH
• protoonkogen Mas MeSH
• protoonkogenní proteiny c-ret genetika   MeSH
• sekvence nukleotidů MeSH
• senioři MeSH
• tenkojehlová biopsie * MeSH
• ultrasonografie MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• MAS1 protein, human MeSH Prohlížeč
• protoonkogen Mas MeSH
• protoonkogenní proteiny c-ret MeSH

CONTEXT: Urothelial carcinoma can exhibit a wide range of variant morphologies. Many variants present diagnostic challenges and carry clinical implications that inform prognosis and treatment decisions. OBJECTIVE: To provide an overview of the diagnostic, therapeutic, and prognostic significance of histological variants of urothelial carcinoma. EVIDENCE ACQUISITION: A PubMed/MEDLINE-based literature search was conducted using the key terms "urothelial carcinoma", "variant histology", "nested", "micropapillary", "microcystic", "sarcomatoid", "squamous differentiation", "glandular differentiation", "clear cell", "plasmacytoid", "lymphoepithelioma-like carcinoma", "squamous cell carcinoma", "small cell carcinoma", "adenocarcinoma", "radiotherapy", "neoadjuvant chemotherapy", and "adjuvant chemotherapy". EVIDENCE SYNTHESIS: The incidence of variant histology is increasing due to improved recognition. Nonetheless, diagnosis can pose challenges due to sampling limitations and interobserver variability. Although associated with advanced disease at presentation, survival outcomes for most variants do not differ significantly compared with pure urothelial carcinoma of the same stage. Controversy exists regarding optimal management due to the low quality of available evidence. For most cases, radical cystectomy with pelvic lymph node dissection (with neoadjuvant chemotherapy when appropriate) represents the standard of care. Small cell carcinoma and lymphoepithelioma-like carcinoma appear to be particularly chemosensitive. CONCLUSIONS: Accurate identification of variant histological subtypes is an important part of risk stratification, as these variants exhibit aggressive biological behaviour. Variant histology tumours are associated with advanced disease at presentation, which must be considered when counselling patients regarding survival outcomes. Optimal management remains to be defined but in most cases; neoadjuvant chemotherapy and radical cystectomy with pelvic lymph node dissection remains the mainstay of treatment. PATIENT SUMMARY: It is important to recognise histological variants of urothelial carcinoma as they indicate aggressive disease. When compared with patients with pure urothelial carcinoma of the same disease stage, survival does not appear to be significantly worse. In most cases, patients with invasive variant histology should be treated with neoadjuvant chemotherapy and radical cystectomy. Take Home Messages Accurate identification of variant histology is important as it exhibits aggressive biological behaviour and affects treatment. Although associated with advanced disease at presentation, with appropriate treatment, survival outcomes are not significantly different compared with pure urothelial carcinoma of the same stage.

• Klíčová slova
• Adenocarcinoma, Bladder cancer, Clear cell urothelial carcinoma, Lymphoepithelioma-like carcinoma, Microcystic urothelial carcinoma, Micropapillary urothelial carcinoma, Nested urothelial carcinoma, Plasmacytoid urothelial carcinoma, Sarcomatoid urothelial carcinoma, Small cell carcinoma, Squamous cell carcinoma, Variant histology,
• MeSH
• karcinom z přechodných buněk klasifikace   diagnóza   patologie   terapie   MeSH
• lidé MeSH
• prognóza MeSH
• urologické nádory klasifikace   diagnóza   patologie   terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH