Micropapillary urothelial carcinoma: is molecular hair-splitting on target?

Urothelial carcinoma (UC) of the bladder has been well investigated in terms of pathogenesis pathways, natural history and tumor biology. Clinically relevant biomarkers including diagnostic, prognostic and predictive molecular markers have been defined in phenotype and genotype analysis beginning with the Cancer Genome atlas (TCGA) study reported in year 2014 (1). The recent 2016 WHO Classification of Tumors of the Urinary System and Male Genital Organs enumerates several histological variants such as the micropapillary, nested, microcystic, plasmacytoid, lymphoepithelioma-like, lipoid cell, clear cell, sarcomatoid and poorly differentiated types (2). Micropapillary urothelial carcinoma (MPUC), first described by Amin et al. in 1994 has generated considerable interest (3). This aggressive variant of UC has a characteristic morphology, aggressive clinical behavior, high propensity for metastasis to regional lymph nodes and distant organs resulting in shorter survival. Recent analysis of molecular, phenotype and microRNA (miRNA) profiles of this variant define unique features which may assist in early recognition and timely treatment (4).