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.

• 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

PURPOSE: Presently, major guidelines do not provide specific recommendations on oncologic surveillance for patients who harbor variant histology (VH) bladder cancer (BCa) at radical cystectomy. We aimed to create a personalized followup scheme that dynamically weighs other cause mortality (OCM) vs the risk of recurrence for VH BCa, and to compare it with a similar one for pure urothelial carcinoma (pUC). MATERIALS AND METHODS: Within a multi-institutional registry, 528 and 1,894 patients with VH BCa and pUC, respectively, were identified. The Weibull regression was used to detect the time points after which the risk of OCM exceeded the risk of recurrence during followup. The risk of OCM over time was stratified based on age and comorbidities, and the risk of recurrence on pathological stage and recurrence site. RESULTS: Individuals with VH had a higher risk of recurrence (recurrence-free survival 30% vs 51% at 10 years, p <0.001) and shorter median time to recurrence (88 vs 123 months, p <0.01) relative to pUC. Among VH, micropapillary variant conferred the greatest risk of recurrence on the abdomen and lungs, and mixed variants carried the greatest risk of metastasizing to bones and other sites compared to pUC. Overall, surveillance should be continued for a longer time for individuals with VH BCa. Notably, patients younger than 60 years with VH and pT0/Ta/T1/N0 at radical cystectomy should continue oncologic surveillance after 10 years vs 6.5 years for pUC individuals. CONCLUSIONS: VH BCa is associated with greater recurrence risk than pUC. A followup scheme that is valid for pUC should not be applied to individuals with VH. Herein, we present a personalized approach for surveillance that may allow an improved shared decision.

• MeSH
• časové faktory MeSH
• cystektomie MeSH
• hodnocení rizik statistika a číselné údaje   MeSH
• karcinom z přechodných buněk diagnóza   mortalita   patologie   terapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru diagnóza   epidemiologie   patologie   MeSH
• močový měchýř patologie   chirurgie   MeSH
• nádory močového měchýře diagnóza   mortalita   patologie   terapie   MeSH
• následné studie MeSH
• pozorné vyčkávání * MeSH
• přežití po terapii bez příznaků nemoci MeSH
• registrace statistika a číselné údaje   MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• senioři MeSH
• staging nádorů MeSH
• věkové faktory MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: The currently available evidence regarding the prognostic and clinical significance of each variant histology subtype of urothelial bladder cancer remains scarce. We assessed the prognostic value of variant histology in patients with urothelial carcinoma of the bladder treated with radical cystectomy. MATERIALS AND METHODS: PubMed®, Web of Science™, Cochrane Library and Scopus® databases were searched for articles published before October 2019 according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. We identified 39 studies comprising 20,544 patients matching our eligibility criteria. RESULTS: Studies were deemed eligible if they compared overall, cancer specific and recurrence-free survival in patients with urothelial carcinoma of the bladder with and without variant histology. Formal meta-analyses were performed for these outcomes. Variant histology was associated with worse cancer specific (pooled HR 1.37, 95% CI 1.24-1.50), overall (pooled HR 1.44, 95% CI 1.26-1.65) and recurrence-free survival (pooled HR 1.32, 95% CI 1.20-1.45). Subgroup analyses demonstrated that "micropapillary" (pooled HR 1.20, 95% CI 1.02-1.41), "plasmacytoid" (pooled HR 2.03, 95% CI 1.17-3.52) and "small cell" variant histology (HR 3.32, 95% CI 1.98-5.59) were also associated with worse overall survival. CONCLUSIONS: Variant histology in patients with urothelial carcinoma of the bladder is associated with increased risks of disease recurrence as well as cancer specific and overall mortality. Variant histology was independently associated with overall survival in the "micropapillary," "plasmacytoid" and "small cell" subgroups. Variant histology should be integrated into prognostic tools to guide risk stratification, treatment planning and patient counseling. However, caution should be exercised in interpreting the conclusions drawn from this study given the limitations, which include the heterogeneity of the population of interest and the retrospective nature of the primary data evaluated.

• MeSH
• cystektomie MeSH
• hodnocení rizik metody   MeSH
• karcinom z přechodných buněk mortalita   patologie   chirurgie   MeSH
• lidé MeSH
• lokální recidiva nádoru diagnóza   epidemiologie   patologie   MeSH
• močový měchýř patologie   chirurgie   MeSH
• nádory močového měchýře mortalita   patologie   chirurgie   MeSH
• přežití po terapii bez příznaků nemoci MeSH
• prognóza MeSH
• urotel patologie   chirurgie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• systematický přehled MeSH

PURPOSE: We sought to assess the prognostic value of variant histology in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy. MATERIALS AND METHODS: We searched PubMed®, Web of Science™, Cochrane Library and Scopus® databases in May 2019 according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Studies were deemed eligible if they compared overall, cancer specific and recurrence-free survival in patients with upper tract urothelial carcinoma with or without variant histology. Formal meta-analyses were performed for these outcomes. RESULTS: We identified 32 studies with 16,052 patients, including 26 studies with 12,865 patients that were eligible for the meta-analysis. Variant histology was associated with poor outcomes in terms of cancer specific (pooled HR 2.00, 95% CI 1.57 to 2.56), overall (pooled HR 1.76, 95% CI 1.51 to 2.04) and recurrence-free survival (pooled HR 1.64, 95% CI 1.42 to 1.89). Subgroup analyses revealed that micropapillary (pooled HR 3.02, 95% CI 1.71 to 5.34), and squamous and/or glandular variant histologies (pooled HR 1.48, 95% CI 1.14 to 1.92) were also associated with poor cancer specific survival. CONCLUSIONS: Variant histology in patients with upper tract urothelial carcinoma is associated with an increased risk of cancer specific and overall mortality and disease recurrence. Furthermore, variant histology was independently associated with cancer specific survival in the micropapillary, and squamous and/or glandular variant histology subgroups. It may be useful to incorporate variant histology into prognostic tools that help guide patients and physicians in selecting appropriate treatment strategies for upper tract urothelial carcinoma.

• MeSH
• Kaplanův-Meierův odhad MeSH
• karcinom z přechodných buněk mortalita   patologie   chirurgie   MeSH
• klinické rozhodování metody   MeSH
• ledviny patologie   chirurgie   MeSH
• lidé MeSH
• lokální recidiva nádoru diagnóza   prevence a kontrola   MeSH
• nádory ledvin mortalita   patologie   chirurgie   MeSH
• nádory močovodu mortalita   patologie   chirurgie   MeSH
• nefroureterektomie MeSH
• prediktivní hodnota testů MeSH
• přežití po terapii bez příznaků nemoci MeSH
• prognóza MeSH
• studie proveditelnosti MeSH
• ureter patologie   chirurgie   MeSH
• urotel patologie   chirurgie   MeSH
• výběr pacientů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• systematický přehled MeSH

BACKGROUND: The present study tested cancer-specific (CSM) and overall mortality (OM) after partial cystectomy (PC) for variant histology bladder cancer (non-urothelial carcinoma of the urinary bladder UCUB), relative to UCUB and relative to radical cystectomy (RC). MATERIALS AND METHODS: Within the Surveillance, Epidemiology, and End Results registry (2001-2016), we identified patients with stage T1-T2N0M0 non-UCUB and UCUB who had undergone PC or RC. Non-UCUB included adenocarcinoma, squamous carcinoma, neuroendocrine carcinoma, and other histologic subtypes. First, CSM and OM after PC were compared between the non-UCUB and UCUB groups. Second, CSM and OM after PC were compared with RC in the non-UCUB group. Kaplan Meier plots and multivariable Cox regression models were used before and after inverse probability of treatment weighting. RESULTS: Overall, 248 patients (16.3%) treated with PC had had non-UCUB. Of the 248 cases, 115 (46.5%), 50 (20%), 34 (14%), and 49 (19.5%) were adenocarcinoma, squamous carcinoma, neuroendocrine carcinoma, and other histologic subtypes, respectively. The comparison between PC in the non-UCUB and PC in the UCUB group showed higher CSM (hazard ratio, 1.4; P = .03) but the same OM rates (hazard ratio, 1.1; P = .7) in the non-UCUB group. The comparison between PC and RC for the non-UCUB group showed no CSM or OM differences. CONCLUSIONS: PC for non-UCUB was associated with higher CSM compared with PC for UCUB. However, PC instead of RC for select patients with non-UCUB appears not to undermine cancer-control outcomes. Thus, the excess CSM is probably unrelated to cystectomy type but could originate from differences in the tumor biology. These results could act as hypothesis generating for the design of future trials.

• MeSH
• cystektomie metody   statistika a číselné údaje   MeSH
• Kaplanův-Meierův odhad MeSH
• karcinom z přechodných buněk mortalita   patologie   chirurgie   MeSH
• klinické rozhodování MeSH
• lidé středního věku MeSH
• lidé MeSH
• močový měchýř patologie   chirurgie   MeSH
• nádory močového měchýře mortalita   patologie   chirurgie   MeSH
• následné studie MeSH
• program SEER statistika a číselné údaje   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výběr pacientů MeSH
• Check Tag
• 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

BACKGROUND: Female sex in patients treated by radical cystectomy (RC) is associated with more advanced stage and worse survival. However, studies supporting these findings mostly or exclusively relied on urothelial carcinoma of the urinary bladder (UCUB) and did not address non-urothelial variant-histology bladder cancer (VH BCa). We hypothesized that female sex is associated with a more advanced stage and worse survival in VH BCa, similarly to that of UCUB. MATERIALS AND METHODS: Within the SEER database (2004-2016), we identified patients aged ≥18 years, with histologically confirmed VH BCa, and treated with comprehensive RC. Logistic regression addressing the non-organ-confined (NOC) stage, as well as cumulative incidence plots and competing risks regression addressing CSM for females vs. males, were fitted. All analyses were repeated in stage-specific and VH-specific subgroups. RESULTS: Overall, 1623 VH BCa patients treated with RC were identified. Of those, 38% were female. Adenocarcinoma (n = 331, 33%), neuroendocrine tumor (n = 304, 18%), and other VH (n = 317, 37%) were less frequent in females but not squamous cell carcinoma (n = 671, 51%). Across all VH subgroups, female patients had higher NOC rates than males did (68 vs. 58%, p < 0.001), and female sex was an independent predictor of NOC VH BCa (OR = 1.55, p = 0.0001). Overall, five-year cancer-specific mortality (CSM) were 43% for females vs. 34% for males (HR = 1.25, p = 0.02). CONCLUSION: In VH BC patients treated with comprehensive RC, female sex is associated with a more advanced stage. Independently of stage, female sex also predisposes to higher CSM.

• Publikační typ
• časopisecké články 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 compare the accuracy in detecting variant histologies (VH) at transurethral resection of bladder (TURB) and radical cystectomy (RC) specimen among tertiary referral centres, in order to investigate potential reasons of discrepancies from the pathological point of view. PATIENTS AND METHODS: Clinical and histopathological data of TURB specimen and subsequent cystectomy specimen of 3,445 RC candidate patients have been retrospectively collected from 24 tertiary referral centres between 1980 and 2021. VH considered in the analysis were pure squamous cell carcinoma, urothelial carcinoma with squamous differentiation, pure adenocarcinoma, urothelial carcinoma with glandular differentiation, micropapillary bladder cancer (BCa), neuroendocrine BCa, and other variants. The degree of agreement between TURB and RC concerning the identification of VH was expressed as concordance, classified according to Cohen's kappa coefficient. RESULTS: A VH was reported in 17% of TURB specimens, 45% of which were not confirmed in RC. The lowest concordance rate was reported for micropapillary BCa with 11 out of 18 (61%) centres reporting no agreement, whereas neuroendocrine BCa achieved the highest concordance rate with only 3 centres (17%) reporting no agreement. Our results shows that even among centres with the advantage of a referent uropathologist the micropapillary variant is characterized by scarce accuracy between TURB and RC. Differences in TURB specimen acquisition by the urologist and in sampling methods among different centres are the main limitations of the study. CONCLUSIONS: Accuracy of TURB in detecting VH is poor for certain VH, in particular for micropapillary BCa, with evident variation among centres. Novel diagnostic tools are required to better identify these VH and drive patients toward a personalized treatment.

• MeSH
• cystektomie metody   MeSH
• karcinom z přechodných buněk * patologie   MeSH
• lidé MeSH
• močový měchýř patologie   MeSH
• nádory močového měchýře * diagnóza   farmakoterapie   chirurgie   MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: To evaluate variant histologies (VHs) for disease-specific survival (DSS) in patients with invasive urothelial bladder cancer (BCa) undergoing radical cystectomy (RC). MATERIALS AND METHODS: We analysed a multi-institutional cohort of 1082 patients treated with upfront RC for cT1-4aN0M0 urothelial BCa at eight centres. Univariable and multivariable Cox' regression analyses were used to assess the effect of different VHs on DSS in overall cohort and three stage-based analyses. The stages were defined as 'organ-confined' (≤pT2N0), 'locally advanced' (pT3-4N0) and 'node-positive' (pTanyN1-3). RESULTS: Overall, 784 patients (72.5%) had pure urothelial carcinoma (UC), while the remaining 298 (27.5%) harboured a VH. Squamous differentiation was the most common VH, observed in 166 patients (15.3%), followed by micropapillary (40 patients [3.7%]), sarcomatoid (29 patients [2.7%]), glandular (18 patients [1.7%]), lymphoepithelioma-like (14 patients [1.3%]), small-cell (13 patients [1.2%]), clear-cell (eight patients [0.7%]), nested (seven patients [0.6%]) and plasmacytoid VH (three patients [0.3%]). The median follow-up was 2.3 years. Overall, 534 (49.4%) disease-related deaths occurred. In uni- and multivariable analyses, plasmacytoid and small-cell VHs were associated with worse DSS in the overall cohort (both P = 0.04). In univariable analyses, sarcomatoid VH was significantly associated with worse DSS, while lymphoepithelioma-like VH had favourable DSS compared to pure UC. Clear-cell (P = 0.015) and small-cell (P = 0.011) VH were associated with worse DSS in the organ-confined and node-positive cohorts, respectively. CONCLUSIONS: More than 25% of patients harboured a VH at time of RC. Compared to pure UC, clear-cell, plasmacytoid, small-cell and sarcomatoid VHs were associated with worse DSS, while lymphoepithelioma-like VH was characterized by a DSS benefit. Accurate pathological diagnosis of VHs may ensure tailored counselling to identify patients who require more intensive management.

• MeSH
• cystektomie MeSH
• karcinom z přechodných buněk * patologie   MeSH
• lidé MeSH
• nádory močového měchýře * patologie   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• Creutzfeldtova-Jakobova nemoc diagnóza   genetika   MeSH
• elektroencefalografie metody   MeSH
• encefalopatie bovinní spongioformní MeSH
• histologické techniky MeSH
• incidence MeSH
• nemoci mozku diagnóza   MeSH