The recently published 2016 World Health Organization (WHO) Classification of Tumors of the Urinary System and Male Genital Organs stems from the accumulated knowledge and data collected during the last 12 years, since the previous edition of the WHO “blue book” 2004. The major changes in prostate pathology include the introduction of a novel grading system for prostate cancer (Grade Groups/International Society of Urological Pathology (ISUP) grades 1–5), the recognition of intraductal carcinoma as a new entity, and the terminological changes regarding the neuroendocrine prostatic neoplasms. In bladder and urothelial tract, within the spectrum of flat and non-invasive lesions, a newly introduced term “urothelial proliferation of uncertain malignant potential” replaced the term “urothelial hyperplasia”, and the term “urothelial dysplasia” was better defined. A category of “invasive urothelial carcinoma with divergent differentiation” was introduced for tumors showing a component of “usual type” urothelial carcinoma combined with other morphologies. A new WHO/ISUP renal tumor grading system was recommended (Grade 1–4). The definition of renal papillary adenoma was modified and expanded to include papillary neoplasms measuring up to 1.5 cm.

Several new epithelial renal tumors were recognized as new entities including:

hereditary leiomyomatosis and renal cell carcinoma (RCC) syndrome–associated RCC, succinate dehydrogenase–deficient RCC, tubulocystic RCC, acquired cystic disease–associated RCC, and clear cell papillary RCC. In testis pathology, intratubular proliferations of testicular germ cell tumors were renamed as “germ cell neoplasia in-situ” (GCNIS), and the testicular neoplasms were divided into two main groups: derived from or unrelated to GCNIS. A major change in penile pathology was the introduction of a new classification of penile squamous cell carcinoma, based on the presence of human papillomavirus (HPV), which characterizes penile tumor subtypes as HPV-related or non-HPV-related. A similar distinction was introduced for the preneoplastic penile intraepithelial precursor lesion (PeIN) into non-HPV related (differentiated PeIN) and HPV-related types (undifferentiated PeIN). In this review, we provide a summary and highlight the changes in the genitourinary pathology introduced by the 2016 WHO blue book, and we also discuss some recent developments that may impact the practice of genitourinary pathology in the near future (AU)