Intraepithelial lesions of urinary bladder: morphologic considerations.

Urological pathologists representing the World Health Organization and the International Society of Urological Pathology have reached a new consensus on the definitions of flat, non-invasive lesions of the urothelium. Lesions are classified as: (1) carcinoma in situ (CIS); (2) dysplasia; (3) atypia of unknown significance; and (4) reactive atypia. These terms are intended to describe a histological spectrum of architectural and cytological abnormalities ranging from the unequivocally malignant (CIS) through the probably neoplastic (dysplasia) to the benign (atypia). The biological potential of these lesions in individual patients cannot be accurately predicted, although the degree of risk for an adverse outcome is very likely to be proportional to the degree of architectural and cytological anaplasia. It is likely that each phenotype has two biological potentials: dynamic and effete. It should be emphasized that most of our knowledge concerning these lesions in humans has been obtained from studies of groups of patients who have already developed a papillary or nodular, invasive or non-invasive urothelial carcinoma, as descriptions of primary CIS, dysplasia, and atypia are uncommon. Future knowledge in this area might be enhanced by attention to the following: better definitions of terms and more accurate application of words such as bladder cancer, early lesion, tumor progression, precursor, and premalignant; increased understanding of the biological processes underlying phenotypic changes; development of models (probably computer-based) with the capacity to factor in the complexities of human carcinogenesis in an ongoing fashion, as new information becomes available.