Bladder cancer can be classified histologically as urothelial or non-urothelial. Urothelial cancer has a propensity for divergent differentiation, which has increasingly been recognized in recent years due to heightened awareness and improved immunohistochemistry techniques. Furthermore, the recent World Health Organization classification of urothelial cancers improved clarity on this issue, with its listing of 13 histologic variants of urothelial cancer. The divergent differentiation patterns include, amongst others, squamous, glandular, micropapillary, nested, lymphepithelioma-like, plasmacytoid and sarcomatoid variants of urothelial cancer. Attempts to quantify the amount of divergent differentiation present, such as using the nonconventional differentiation number, have been made recently, which will improve the ability to compare publications from different centres. Genetic-based studies have indicated that the histologic variants of urothelial cancer arise from a common clonal precursor. Mostly, the current evidence suggests that urothelial cancer with divergent differentiation has a worse prognosis when compared with pure urothelial cancer. This article will review the current literature on variant histologies of urothelial cancer, and well as new developments in pure squamous cell carcinoma, small cell carcinoma and adenocarcinoma of the bladder.

• Up staging to muscle invasive disease occurred in 45.9% (n = 592) of 1,291 patients with clinical ≤ T1, including 30.6% of patients with Tis only at transurethral resection.• Of the 3,166 patients with clinically organ confined (OC) tumor stage, 1,357 (42.9%) were up staged to non-organ confined pathologic tumor stage.• Within each clinical stage stratum, patients who were clinically under staged had a higher probability of disease relapse or death from UCB compared to those who were same staged or down staged on pathologic examination ( P < 0.05). CONCLUSIONS• We identified clinical under staging in half of the patients undergoing radical cystectomy for UCB.• Up staging resulted in a higher likelihood of disease progression and eventual death from UCB.• These findings should be considered when utilizing pre-operative risk-adapted strategies for selecting candidates for neoadjuvant chemotherapy. KEYWORDSbladder cancer, survival, radical cystectomy, stage, migration, discrepancy What's known on the subject? and What does the study add?Observations from small retrospective studies have indicated that a considerable number of patients undergoing radical cystectomy for bladder cancer experience a stage migration (either upstaging or downstaging) when comparing clinical and pathological staging. In addition, it is unclear if pathological upstaging is an adverse prognostic feature independent of pathological stage.We report the frequency of upstaging and downstaging using a large, international multicentre cohort of patients undergoing radical cystectomy for bladder cancer without neoadjuvant chemotherapy. Our findings indicate that pathological upstaging is not an independent adverse prognostic feature when considering pathological stage. Study Type -Prognosis (case series) Level of Evidence 4 OBJECTIVE• To compare the clinical and pathologic stage among a large, multi-institutional series of patients undergoing radical and to determine the effect of stage discrepancy on outcomes. PATIENTS AND METHODS• Data was collected from nine centers and 3,393 patients with urothelial carcinoma of the bladder (UCB) treated with radical cystectomy and pelvic lymphadenectomy without neo-adjuvant chemotherapy.• A retrospective cohort design was used to assess the percentage of patients experiencing stage discrepancy and the impact of stage discrepancy on time to disease relapse and time to death from UCB. RESULTS• Clinical under staging occurred in 50% of patients and pathologic down staging occurred in 18% of patients.

were analyzed using the Kaplan-Meier method and Cox regression analysis. RESULTSThe median age of patients was 68 years with a mean (median) follow-up time of 35 (29) months. The 30, 60 and 90-day postoperative mortality rates were 1.3%, 2.6% and 3.2%, respectively. The 5-year overall, recurrencefree and cancer-specific survival was 57%, 48% and 67%, respectively, with a local recurrence rate of 6%. Pathological stage distribution was < pT2N0, n = 498 (23%); pT2N0, n = 365 (17%); pT3N0, n = 463 (21%); pT4N0, n = 170 (8%); and pTxN + , n = 507 (23%). Only 3.1% of patients received neoadjuvant chemotherapy and 19.4% received adjuvant chemotherapy. On multivariate analysis, lower pathological stage, negative surgical margins, receipt of adjuvant chemotherapy, performance of pelvic lymphadenectomy and an absence of smoking were associated with prolonged disease-specific and overall survival.

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