title: Urothelial carcinoma with divergent histologic differentiation (mixed histologic features) predicts the presence of locally advanced bladder cancer when detected at transurethral resection.
abstract: OBJECTIVE
  The histologic classification of bladder tumors remains an important predictor of treatment response and patient outcome, with pure nonurothelial tumors associated with poorer outcome compared with pure urothelial carcinoma (UC). Little, however, is known about the significance of UC with divergent (mixed) histologic features at transurethral resection of bladder tumor (TURBT). This study examined the incidence, pathologic spectrum, and clinical significance of this phenomenon.
  
  
  METHODS
  The histologic patterns of 448 consecutive TURBT and 295 subsequent cystectomy specimens from this subgroup were analyzed. The type of divergent tumor differentiation observed in the mixed histologic type cases was categorized and quantified. Pure non-UC cases were excluded. Various clinicopathologic parameters were compared between the mixed histologic type and pure UC cohorts.
  
  
  RESULTS
  UC with mixed histologic features was identified in 25% of all TURBT specimens and was uniformly (100%) high grade and invasive (99%). The most common mixed histologic components were squamous (40%) and glandular (18%). Eleven percent of cases had multiple mixed histologic types. Compared with the pure high-grade UC, UCs with mixed histologic features were associated with muscle invasion at TURBT (chi-square test, P <0.001) and with extravesical disease at cystectomy (chi-square test, P = 0.0001). The presence of mixed histologic features at TURBT was an independent predictor of extravesical disease in a multivariate logistic model (P = 0.007). However, it was not significant for disease-specific survival in the univariate (P = 0.17) or multivariate (P = 0.68) models.
  
  
  CONCLUSIONS
  The results of our study have shown that the presence of mixed histologic features at TURBT indicates locally aggressive disease. Patients with mixed histologic features might benefit from an aggressive multimodality treatment strategy.
authors.affiliation: Department of Pathology, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Wasco
authors.forename: Stephanie
authors.initials: S
authors.lastname: Daignault
authors.forename: Yingxi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lakshmi Priya
authors.initials: LP
authors.lastname: Kunju
authors.forename: Michael
authors.initials: M
authors.lastname: Kinnaman
authors.forename: Thomas
authors.initials: T
authors.lastname: Braun
authors.forename: Cheryl T
authors.initials: CT
authors.lastname: Lee
authors.forename: Rajal B
authors.initials: RB
authors.lastname: Shah
mesh_terms: D000368:Aged; D002295:Carcinoma, Transitional Cell / Q000473:pathology* / Q000601:surgery*; D015653:Cystectomy; D005260:Female; D006801:Humans; D008297:Male; D011379:Prognosis; D001749:Urinary Bladder Neoplasms / Q000473:pathology* / Q000601:surgery*; D013520:Urologic Surgical Procedures / Q000379:methods