**Claudia Manini <sup>1</sup> and José I. López 2,\***


Received: 27 October 2020; Accepted: 7 December 2020; Published: 10 December 2020

**Simple Summary:** The spectrum of architectural and cytological findings in UC is wide, although transitional cell carcinoma, either papillary or flat, low- or high-grade, constitutes the majority of cases in routine practice. Some of these changes are just mere morphological variations, but others must be recognized since they have importance for the patient. The goal of this review is to compile this histological variability giving to the general pathologist a general idea of this morphological spectrum in a few pages. The review also updates the literature focusing specifically on the morphological and immunohistochemical clues useful for the diagnosis and some selected molecular studies with prognostic and/or diagnostic implications.

**Abstract:** 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 architecture and cytology. Thus, 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.

**Keywords:** bladder cancer; diagnosis; differential diagnosis; prognosis; histopathology; immunohistochemistry
