The overwhelming majority of bladder cancers are transitional cell carcinomas. Albeit mostly monotonous, carcinomas in the bladder may occasionally display a broad spectrum of histological features that should be recognized by pathologists because some of them represent a diagnostic problem and/or lead prognostic implications. Sometimes these features are focal in the context of conventional transitional cell carcinomas, but some others are generalized across the tumor making its recognition a challenge. For practical purposes, the review distributes the morphologic spectrum of changes in architectural and cytological. So, nested and large nested, micropapillary, myxoid stroma, small tubules and adenoma nephrogenic-like, microcystic, verrucous, and diffuse lymphoepithelioma-like, on one hand, and plasmacytoid, signet ring, basaloid-squamous, yolk-sac, trophoblastic, rhabdoid, lipid/lipoblastic, giant, clear, eosinophilic (oncocytoid), and sarcomatoid, on the other, are revisited. Key histological and immunohistochemical features useful in the differential diagnosis are mentioned. In selected cases, molecular data associated with the diagnosis, prognosis, and/or treatment are also included.

A broad spectrum of lesions, including hyperplastic, metaplastic, inflammatory, infectious, and reactive, may mimic cancer all along the urinary tract. This narrative collects most of them from a clinical and pathologic perspective offering urologists and general pathologists their most salient definitory features. Together with classical, well-known, entities such as urothelial papillomas (conventional and inverted), nephrogenic adenoma, polypoid cystitis, fibroepithelial polyp, prostatic-type polyp, verumontanum cyst, xanthogranulomatous inflammation, reactive changes secondary to BCG instillations, schistosomiasis, keratinizing desquamative squamous metaplasia, post-radiation changes, vaginal-type metaplasia, endocervicosis/endometriosis (müllerianosis), malakoplakia, florid von Brunn nest proliferation, cystitis/ureteritis cystica and glandularis, among others, still other cellular proliferations with concerning histological features and poorly understood etiopathogenesis like IgG4-related disease, PEComa, and pseudosarcomatous myofibroblastic proliferations (post-operative spindle cell nodule, inflammatory myofibroblastic tumor), are reviewed. Some of these diagnoses are problematic for urologists, other for pathologists, and still others for both. Interestingly, the right identification of their definitory features will allow their correct diagnoses thus avoiding overtreatment. The literature selected for this review also focuses on the immunohistochemical and/or molecular data useful to delineate prognosis.