Urothelial lesions with inverted growth patterns: histogenesis, molecular genetic findings, differential diagnosis and clinical management

Inverted lesions of the urinary bladder comprise a spectrum of changes ranging from von Brunn's nests to inverted urothelial carcinoma. Differentiating these lesions is important because their proper clinical management and their expected clinical outcomes are distinctly different. In this article, we review the spectrum of inverted urothelial lesions of the bladder, including current morphological criteria, key differential diagnosis, molecular genetic findings and histogenesis. We have refined the diagnostic criteria for various bladder lesions with inverted growth patterns. A number of well-recognized urothelial lesions with inverted morphology occur in the urinary bladder. Some are so common that they are considered normal variants of urothelium, whereas others are rare. It is important for the surgical pathologist to recognize these lesions and their overlapping morphological features, because in some cases establishing an accurate diagnosis is challenging. In this article, we review the spectrum of inverted urothelial lesions of the bladder. Emphasis is placed on differential diagnosis, molecular genetic findings, morphology and histogenesis.