Characteristics and clinical significance of histological variants of bladder cancer

Abstract

In the past 10 years evidence for the clinical relevance of variant histology in urinary bladder cancer has been increasing. This increase has resulted in new classifications of urothelial cancers by the WHO in 2016, highlighting the importance of an accurate morphological description of pathological specimens for the therapeutic management of patients with bladder cancer. The rising awareness of the importance of an accurate pathological report manifests itself in the increasing prevalence of reporting of variant histology in daily practice. Histological variants can generally be divided into urothelial and nonurothelial. Urothelial variants often have similar features that also have specific morphological phenotypes, whereas nonurothelial variants have independent features. Overall, histological variants follow a more aggressive clinical course than conventional urothelial carcinoma, but conclusive data on their effect on survival are currently lacking. The clinical relevance of variant histology can manifest at three different levels: diagnostic, as identification is challenging and misinterpretation is not uncommon; prognostic, for patient risk stratification and outcome estimation; and therapeutic, as particular variants could be responsive to specific treatment strategies. An accurate morphological description of histological variants is necessary for patient consultation and therapy planning. Moreover, the association of variant histology with specific mutation patterns promises to be helpful in discovering targeted therapeutic approaches based on specific molecular pathways.

Variants and new entities of bladder cancer

“…Current literature provides increasingly valuable data on the clinical significance and therapy‐related issues concerning urothelial carcinoma with variant histology compared to conventional urothelial carcinoma. In general, variant urothelial carcinoma is considered an aggressive feature as it worsens overall survival due to a higher rate of upstaging after surgery . Gofrit et al .…”

Impact of adjuvant chemotherapy in patients with adverse features and variant histology at radical cystectomy for muscle‐invasive carcinoma of the bladder: Does histologic subtype matter?

“…However, the management of patients who have urothelial carcinoma with variant histology is complex and more challenging. Moreover, the impact of variant histology on outcomes of treatment vary for those with and without muscle‐invasive disease …”

“…For pure squamous cell carcinoma, there is a predilection for immediate surgical resection, because this histologic subtype generally is associated with a poor response to chemotherapy . For micropapillary differentiated urothelial carcinoma, there is no consensus regarding the optimal treatment . In 2014, a study investigating the effect of adjuvant chemotherapy (AC) revealed a higher tumor recurrence rate but a similar cancer‐specific survival rate compared with pure urothelial carcinoma …”

Radical Cystectomy in Pathological T4a and T4b Bladder Cancer Patients: Is There Any Space for Sub Stratification?

“…Sixth, the presence of histological variants and its effect on survival outcomes was not tested in this cohort as it was not available for the whole cohort. We recognize the importance of this parameter [25] and the potential bias introduced by excluding this parameter from the analyses. Seventh, no data regarding the presence of macroscopic residual disease after surgery was included in the database.…”