Clinical and Genomic Considerations for Variant Histology in Bladder Cancer

Urothelial carcinoma demonstrates remarkable plasticity in its ability to differentiate into divergent histologic subtypes in both a pure and mixed form. This review presents the most current data pertaining to bladder cancer with variant histology.

Recognition of bladder cancer variants has increased profoundly in the past two decades with their inclusion in the pathologic guidelines and increased awareness among pathologists and urologists. Most of the available literature consists of small single-institutional studies, but there is compelling evidence to support deviation from the normal urothelial carcinoma management pathways for certain subtypes. While traditionally diagnosed by microscopic appearance, next-generation sequencing and molecular profiling have enabled identification of genomic markers associated with specific variants that exist in tumors lacking classic histologic hallmarks. This genomic information holds promise for predicting response to specific treatments or even in the development of novel targeted therapies. Combining increased awareness of variant histology, its impact on clinical outcomes, and genomic data will result in a more nuanced treatment approach to reduce morbidity and optimize oncologic outcomes for our patients.