In this lecture I will discuss the morphologic subtypes: plasmacytoid, micropapillary, nested and lymphoepithelial-like urothelial carcinoma. An overview of the histology and diagnostic features will be provided along with the salient molecular features. I will review the clinical relevance from the perspective of the treating clinician and examine available outcome data. I will briefly discuss divergent differentiation (squamous, glandular, neuroendocrine) and its can impact on patient prognosis.

Molecular subtypes will be discussed with reference to the TCGA data and the Consensus Molecular Classification of Bladder Cancer. In the lecture, we will explore the morphology and oncogenic features of these molecular subtypes and the clinical impact of the molecular class of an urothelial carcinoma.

I will review targetable molecular alterations that are already in clinical use. Specifically, FGFR tumor status, use of ERBB2 assessment, other antibody drug conjugates, assessment of the mismatch repair status and also PD-L1 tumor status.

Finally we will discuss the topic of hybrid grading in non-muscle invasive bladder cancer and review the evidence for it’s clinical impact.

Throughout, we will discuss the role of the pathologist in ensuring accurate diagnostic interpretation of histology, selection of appropriate tissue for testing and determining the test to be performed, and provision of an integrated report that will enable risk stratification and guide therapeutic decisions.