[Diagnosis and treatment of urothelial carcinoma of the bladder with divergent histology].

The diagnosis "urothelial carcinoma with divergent histology (UC-DH)" subsumes urothelial carcinomas that have additional histological features beyond conventional UC (not-otherwise specified, NOS). These include UCs with additional squamous, glandular, trophoblastic, or Müllerian differentiation. Histological subtypes (STs) of UC, such as micropapillary, nested, plasmacytoid, sarcomatoid, lymphoepithelial, and others, must be distinguished from these. Histogenetically, both UCs with divergent histology and the histological UC STs arise from preexisting urothelium. In general, detection of UC-DH/ST is associated with unfavorable and aggressive biology, and the majority of patients are directed to early radical cystectomy. In the case of muscle-invasive UC-DH/ST there is uncertainty as to whether and which neoadjuvant therapy should be performed. The available data on organ-preserving intravesical therapy in patients with non-muscle-invasive UC-DH/ST are still limited and poorly validated. Sarcomatoid, plasmacytoid, and micropapillary UC-DH/STs seem to have less favorable oncological outcomes. In any case, clean, deep resection and sufficient imaging of local staging using multiparametric MRI is required in all patients with UC-DH/ST for individual and risk-adapted treatment planning. Muscle-invasive UC-DH/ST should be treated in the same manner as pure UC, i.e., with neoadjuvant chemotherapy followed by radical cystectomy. Only micropapillary UC seems to respond worse to chemotherapy than pure UC. Also in metastatic UC-DH/ST do the same treatment algorithms apply as in pure UC. In order to recognize UC-DH/ST clinically, a comprehensive histopathological evaluation with reporting of the percentage of each histological component is necessary. Early immunohistochemical or molecular pathological evaluation is also recommended, as particularly the micropapillary variant shows targetable alterations.