Diagnostic workout of glandular malignant lesions of the bladder according to the 5th WHO classification

Glandular lesions involving the bladder are less common than conventional urothelial carcinoma, and they are often diagnostically challenging diseases, carrying different clinical outcomes. As a group, they encompass both primary and secondary neoplasms, with sometimes overlapping morphological features. In this scenario, proper clinical information is important, in that secondary involvement of the bladder may occur by direct extension or lymphatic/hematogenous spread from carcinomas at other sites, comprising prostate, colon, cervix, breast, and lung. According to the 5th edition of the WHO Classification of urological tumors, glandular morphology is a major hallmark of the following entities: urothelial carcinoma with glandular differentiation, adenocarcinoma, NOS, urachal carcinoma, and tumors of Mullerian type. The distinction among these entities, and between primary and secondary tumors, heavily relies on their biological and immunophenotypical features. This article will review glandular neoplasms of the bladder, highlighting their main immunophenotypical markers. Furthermore, molecular data associated with their pathogenesis, prognosis, and treatment will be described. The aim of this study is to provide a practical and comprehensive up-to-date overview of this complex topic.