Presence Of Histological Variant Research Articles

The Impact of Second Opinion Expert Pathology Review in Patient Management at the Time of Transurethral Resection of the Bladder

Background and objectivePathological features in non–muscle-invasive bladder cancer specimens are pivotal in determining correct patients’ therapeutic management. Sparse data exist regarding the importance of second opinion performed by an expert uropathologist. This study aimed to assess the importance of a second opinion by an expert uropathologist in the management of bladder cancer. MethodsThe study relied on 272 bladder cancer specimens from 231 patients seeking a pathology second opinion after transurethral resection of the bladder for a clinical suspicion of bladder cancer, relapse, or second-look procedure. Pathology second opinion was offered by an experienced fellowship-trained uropathologist. Discrepancies were recorded considering primary tumor staging, the presence of muscularis propria, and the presence of histological variants. Cases were categorized as no significant discordance, major discordance without management change, and major discordance with management change according to the European Urology Association (EAU) guidelines. Key findings and limitationsAmong 272 second opinion cases, 39% (108/272) had major discordance and 28% (75/272) had major discordance with change in management according to the EAU guidelines. Upstaging and downstaging were reported in 66 (24%) patients. Improper identification of the presence of muscularis propria was found in 46 (17%) cases, of which 11 (4%) were deemed clinically relevant. Differences regarding the presence of histological variants were diagnosed in 40 cases (15%), resulting in eight (3%) changes in clinical management. In ten specimens (4%), multiple clinically relevant discrepancies were found. Conclusions and clinical implicationsThe second opinion evaluation changed the clinical management in 25% of the cases. These results support the importance of specimen review by an expert uropathologist as a major driver in the correct bladder cancer management. Patient summaryWe investigated the importance of a second opinion performed by an expert uropathologist in the management of bladder cancer. We found that 25% had their treatment plan changed due to the revised pathological report.

Combined use of immunohistochemical markers of basal and luminal subtypes in urothelial carcinoma of the bladder: Association with clinicopathological features and outcomes

OBJECTIVES:Whole genome expression profiles allow the stratification of bladder urothelial carcinoma into basal and luminal subtypes which differ in histological patterns and clinical behavior. Morpho-molecular studies have resulted in the discovery of immunohistochemical markers that might enable discrimination between these two major phenotypes of urothelial carcinoma.METHODS:We used two combinations of immunohistochemical markers, i.e., cytokeratin (CK) 5 with CK20 and CK5 with GATA3, to distinguish subtypes, and investigated their association with clinicopathological features, presence of histological variants, and outcomes. Upon searching for tumor heterogeneity, we compared the findings of primary tumors with their matched lymph node metastases. We collected data from 183 patients who underwent cystectomy for high-grade muscle-invasive urothelial carcinoma, and representative areas from the tumors and from 76 lymph node metastasis were organized in tissue microarrays.RESULTS:Basal immunohistochemical subtype (CK5 positive and CK20 negative, or CK5 positive and GATA3 negative) was associated with the squamous variant. The luminal immunohistochemical subtype (CK5 negative and CK20 positive, or CK5 negative and GATA3 positive) was associated with micropapillary and plasmacytoid variants. Remarkably, only moderate agreement was found between the immunohistochemical subtypes identified in bladder tumors and their lymph node metastasis. No significant difference in survival was observed when using either combination of the markers.CONCLUSION:This study demonstrates that these three routinely used immunohistochemical markers could be used to stratify urothelial carcinomas of the bladder into basal and luminal subtypes, which are associated with several differences in clinicopathological features.

The Impact of Histological Variant on Oncological Outcomes in Patients With Urothelial Carcinoma of the Bladder Treated With Radical Cystectomy.

Bladder cancer with histological variant (HV) has different morphological features from usual urothelial carcinoma (UC). The aim of this study was to evaluate the oncological outcomes of HV in patients with bladder cancer. We retrospectively evaluated data from 102 patients with UC of the bladder treated with radical cystectomy between 1998 and 2017. Pathological findings including HV were assigned by one dedicated pathologist. Recurrence-free survival (RFS) and cancer-specific survival (CSS) and overall survival (OS) were estimated by Cox regression models. In total, 26 patients (25.5%) had HV, and the most common variant was squamous differentiation, followed by glandular differentiation and a mixed variant consisted of squamous and glandular differentiation. The presence of HV was associated with RFS and CSS (p=0.018, p=0.036, respectively). HV has more aggressive tumor biological features compared to those with pure UC. The presence of HV was associated with poor survival.

The impact of histological variants on outcomes after open radical cystectomy for muscle-invasive urothelial bladder cancer: results from a single tertiary referral centre.

To evaluate the impact of histological variants on oncological outcomes of patients with muscle-invasive bladder cancer treated with open radical cystectomy and furthermore to determine any association between survival and each histotype of bladder cancer. Data from 525 consecutive patients with muscle-invasive bladder cancer treated with radical cystectomy between January 2008 and May 2019 were collected retrospectively. The Kaplan-Meier curves and multivariable analysis addressed the role of histological variants in recurrence, cancer-specific and overall mortality between all subgroups. Of 525 patients, 131 (25.0%) showed a histological variant at radical cystectomy. With a median follow-up of 31months, 209 (39.8%) recurrences, 184 (35.0%) cancer-related deaths and 260 (49.5%) overall deaths were reported. The presence of histological variant was associated with advanced tumour stage, the presence of concomitant carcinoma in situ, lymph node metastasis, lymphovascular invasion and positive surgical margins compared to pure urothelial bladder cancer (all p values < .008) and resulted as an independent risk factor for cancer-specific mortality (p = 0.001). Patients with a histological variant were at significantly higher risk for recurrence, cancer-specific mortality and overall mortality (all p values ≤ .001). Micropapillary, sarcomatoid or small cell differentiation was associated with reduced survival. The presence of histological variants at radical cystectomy seems to be weakly associated with reduced survival compared to pure urothelial bladder cancer paired for pathologic stage. The association of histological variants with advanced and biologically aggressive tumours suggests the need for attention on the overall management of these patients, in particular for micropapillary, sarcomatoid and small cell differentiation.

MP55-19 IMPACT OF HISTOLOGICAL VARIANTS IN NODE POSITIVE PATIENTS TREATED WITH RADICAL CYSTECTOMY FOR BLADDER CANCER

You have accessJournal of UrologyBladder Cancer: Invasive II (MP55)1 Apr 2020MP55-19 IMPACT OF HISTOLOGICAL VARIANTS IN NODE POSITIVE PATIENTS TREATED WITH RADICAL CYSTECTOMY FOR BLADDER CANCER Marco Bandini*, Emanuele Zaffuto, Simone Scuderi, Andrea Salonia, Roberta Lucianò, Filippo Pederzoli, Stefania Zamboni, Luca Afferi, Burgio Giusy, Marco Moschini, Federico Deho', Roberto Bertini, Alberto Briganti, Francesco Montorsi, Renzo Colombo, Andrea Necchi, and Andrea Gallina Marco Bandini*Marco Bandini* More articles by this author , Emanuele ZaffutoEmanuele Zaffuto More articles by this author , Simone ScuderiSimone Scuderi More articles by this author , Andrea SaloniaAndrea Salonia More articles by this author , Roberta LucianòRoberta Lucianò More articles by this author , Filippo PederzoliFilippo Pederzoli More articles by this author , Stefania ZamboniStefania Zamboni More articles by this author , Luca AfferiLuca Afferi More articles by this author , Burgio GiusyBurgio Giusy More articles by this author , Marco MoschiniMarco Moschini More articles by this author , Federico Deho'Federico Deho' More articles by this author , Roberto BertiniRoberto Bertini More articles by this author , Alberto BrigantiAlberto Briganti More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , Renzo ColomboRenzo Colombo More articles by this author , Andrea NecchiAndrea Necchi More articles by this author , and Andrea GallinaAndrea Gallina More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000924.019AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The prognostic role of histological variants (HV) in bladder cancer (BCa) patients after radical cystectomy (RC) have been previously demonstrated in several studies. Either pure non-urothelial carcinoma (UC) and UC with divergent differentiation are associated with higher cancer specific mortality (CSM) compared to pure UC. We aimed to examine whether the presence of HV may be associated with higher CSM in patients harboring pathological lymph node invasion (LNI) at RC. METHODS: Between 1988 and 2018, we prospectively collected 2209 BCa patients treated with RC and extended pelvic lymph node dissection (ePLND). Inclusion criteria consisted of patients with pathological LNI disease. Histologic specimens after RC were all examined by dedicated uro-pathologists. For this study purpose, the population was grouped in pure UC vs. HV BCa (e.g. pure non-UC or UC with divergent differentiation). The statistical significance of differences in medians and proportions was respectively tested with the Kruskal-Wallis and Chi-square tests between pure UC and HV BCa, for all reported variables. Kaplan-Meier (KM) and Cox regression analysis tested for predictors of CSM. RESULTS: Overall, we identified 545 BCa patients that harbored LNI after RC and ePLND. Of these, 410 (75.2%) and 135 (24.8%) harbored pure UC and HV BCa. No statistically significant differences were found between the two groups in terms of age at RC, gender, pT stage, pN stage, surgical margin status, use of neoadjuvant (p=0.6) and adjuvant chemotherapy (all p>0.2), respectively. At KM analysis, pure TCC and HV BCa exhibited similar (p=0.6) 2yr (35 vs. 39%), 5yr (65 vs. 47%) and 10yr (70 vs. 58%) CSM rates. At multivariable Cox regression analysis, number of positive nodes (HR: 1.04, p=0.003), positive surgical margins (HR: 1.83, p=0.03), pT3 (HR: 3.32, p=0.02), and pT4 (HR: 3.61, p=0.02) stage were associated with higher CSM rates. Adjuvant chemotherapy resulted associated with lower CSM rates (HR: 0.37, p=0.0002). Conversely, HV did not reach independent prediction status (HR: 0.9, p=0.8) for CSM. CONCLUSIONS: Our retrospective, single-institution study demonstrates that survival of LNI patients is unfavorable and mainly influenced by pT stage, positive surgical margins, and burden of lymph node metastases. Conversely, the presence of HV does not impact on CSM. Future studies should investigate the role of HV identification within the lymph node metastases as potential unfavorable prognostic factors in LNI patients. Source of Funding: none © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e845-e846 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Marco Bandini* More articles by this author Emanuele Zaffuto More articles by this author Simone Scuderi More articles by this author Andrea Salonia More articles by this author Roberta Lucianò More articles by this author Filippo Pederzoli More articles by this author Stefania Zamboni More articles by this author Luca Afferi More articles by this author Burgio Giusy More articles by this author Marco Moschini More articles by this author Federico Deho' More articles by this author Roberto Bertini More articles by this author Alberto Briganti More articles by this author Francesco Montorsi More articles by this author Renzo Colombo More articles by this author Andrea Necchi More articles by this author Andrea Gallina More articles by this author Expand All Advertisement PDF downloadLoading ...

Pure but Not Mixed Histologic Variants Are Associated With Poor Survival at Radical Cystectomy in Bladder Cancer Patients.

To evaluate the impact of pure and mixed histologic variant versus pure urothelial carcinoma in nonmetastatic bladder cancer (BCa) patients treated with radical cystectomy (RC). We evaluated data from 1067 patients treated with RC and pelvic lymph node dissection between 1990 and 2013 at a single institution tertiary-care referral center. All specimens were evaluated by dedicated uropathologists. Univariable and multivariable Cox regression analyses tested the impact of the presence of pure and mixed histologic variants versus pure urothelial on recurrence, cancer-specific mortality, and overall mortality after accounting for all available confounders. In total, 201 (19%) and 137 (13%) patients were found with mixed and pure variants at RC, respectively. Mixed preponderant variants were sarcomatoid, lymphoepitelial, squamous, and glandular; small-cell and micropapillary variants were found mostly as pure variants. With a median follow-up of 6.5 years, patients who harbored pure variant were found by multivariable analyses to have lower survival outcomes compared to pure urothelial carcinoma (all P< .01). Conversely, no differences were found between mixed variant versus pure urothelial by multivariable Cox regression analyses predicting recurrence, cancer-specific mortality, and overall mortality (all P>.1). The presence of histologic variants at RC is a common finding, accounting for approximately 30% of specimens. In this setting, the presence of a pure variant but not the presence of mixed variant with urothelial carcinoma is related to a detrimental effect on survival outcomes after RC.

Downregulation of DAB2IP results in cell proliferation and invasion and contributes to unfavorable outcomes in bladder cancer

The DOC-2/DAB2 interactive protein (DAB2IP) is a member of the Ras GTPase-activating protein family. It has been shown to be often downregulated and a poor prognostic factor in several human malignancies. In this study, we analyzed the clinicopathological features and outcomes of DAB2IP expression in 135 patients with urothelial carcinoma of the bladder (UCB) treated by radical cystectomy plus bilateral lymph node dissection, and evaluated the effect of DAB2IP knockdown in vitro using the MTT method, colony formation assay, cell cycle assay, and cell migration and invasive assay. We found low expression of DAB2IP was significantly associated with high pathological stage (P = 0.002), high pathological grade (P = 0.02), tumor size more than 3 cm (P = 0.04), and presence of histological variants (P = 0.01). DAB2IP was an independent prognostic factor of disease recurrence (hazard ratio, 2.67; P = 0.034) and cancer-specific survival (hazard ratio, 2.79; P = 0.038). Knockdown of DAB2IP could promote cell proliferation, migration, and invasion. Downregulation of DAB2IP could activate the ERK and Akt pathways and was correlated with the expression of epithelial–mesenchymal transition markers, such as E-cadherin and vimentin. In conclusion, downregulation of DAB2IP is associated with features of biologically aggressive UCB and results in cell proliferation, migration, and invasion of bladder cancer. DAB2IP may serve as a promising biomarker in patients with UCB treated by radical cystectomy and bilateral lymph node dissection.

Upstaging of urothelial cancer at the time of radical cystectomy: factors associated with upstaging and its effect on outcome

What's known on the subject? and What does the study add? The reported discordance between staging on transurethral bladder resection and on radical cystectomy pathology in the literature ranges from 20 to 80%.Correct staging in bladder cancer has direct implications for its management. The upstaging from organ-confined (OC) to non-organ-confined (nOC) disease has been reported in 40% of cases. Lymphovascular invasion (LVI) is a factor known to be associated with poor clinical outcome. Pathological upstaging was observed in our cohort in 40% of cases and most cases (80%) were upstaged from OC to nOC disease. During the study period the frequency of upstaging observed increased. We found LVI (hazard ratio [HR]= 5.07, 95% CI = 3.0-8.3, P < 0.001) and any histological variant variant (HR = 2.77, 95% CI = 1.6-4.8, P < 0.001) to be strong independent predictors of upstaging. Patients with clinical T2 bladder cancer found with upstaging at the time of radical cystectomy had a poorer outcome than patients with no upstaging. Identification of patients at high risk of upstaging at radical cystectomy is key to improving their management and outcome. To analyse the details of bladder cancer (BC) staging in a large combined radical cystectomy (RC) database from two academic centres. To study rate and time trends, as well as risk factors for upstaging, especially clinical factors associated with staging errors after RC. Characteristics of patients undergoing RC at University Health Network, Toronto, Canada (1992-2010) and University of Turku, Turku, Finland (1986-2005) were analysed. Among 602 patients undergoing RC, 306 (51%) had a discordance in clinical and pathological stages. Upstaging occurred in 240 (40%) patients and 192 (32%) patients were upstaged from organ-confined (OC) to non-organ-confined (nOC) disease. During the study period, upstaging became more common in both centres. In multivariate analyses, T2 disease at initial presentation (P= 0.001, odds ratio [OR]= 2.62, 95% confidence interval [CI]: 1.44-4.77), high grade disease (P= 0.01, OR = 2.85, 95% CI: 1.21-6.7), lymphovascular invasion (LVI) (P < 0.001, OR = 5.17, 95% CI: 3.48-7.68), female gender (P= 0.038, OR = 0.6, 95% CI: 0.38-0.97, and histological variants (P < 0.001, OR = 2.77, 95% CI: 1.6-4.8) were associated with a risk of upstaging from OC to nOC disease. Upstaged patients had worse survival rates than patients with correct staging. This was especially significant among patients with carcinoma invading bladder muscle before undergoing RC (16% vs 46% 10-year disease-specific mortality, P < 0.001). Upstaging is a common problem and unfortunately no improvements have been observed during the last two decades. LVI and the presence of histological variants are strong predictors of upstaging at the time of RC. Pathologists should be encouraged to report LVI and any histological variant at the time of TURBT.