Answer: Carcinoma in situ

Histology: Most of the urothelium in this case is denuded. Examination of the cells that are still present show scattered cells with enlarged hyperchromatic nuclei. These cells are 4 to 5 times the size of stromal lymphocytes. Whereas some of the cells show prominent nucleoli, others show dense hyperchromatic nuclei.

Discussion: Flat urothelial carcinoma in situ (CIS) typically shows discohesive cells. On occasion, this cellular discohesion can become so prominent as to leave only a few residual clinging CIS cells present, with the rest of malignant cells shed off into the urine. The diagnosis of CIS is characterized by the presence of cells with large irregular hyperchromatic nuclei, regardless of how many cells are present or whether the cells occupy the entire thickness of the urothelium. We have recently demonstrated that if one looks at the nuclear size of the largest CIS cells present, they are 5 times the size of lymphocytes, which can always be found in the stroma (1). In contrast, normal urothelium is only 2 times the size of lymphocytes. Reactive urothelial atypia consists of nuclei which are also enlarged, yet nuclei are very uniform and are vesicular with a central prominent nucleolus. Furthermore, with reactive urothelial atypia, one would anticipate seeing more inflammatory cells within the urothelium. Denudation can occur with benign processes, typically associated with tissue removed by cautery (2). Consequently, with a cold cup biopsy without cautery, the presence of denudation is more worrisome for potential CIS. Careful examination of the tissue should be performed looking for scattered malignant cells. The distinction between dysplasia and CIS is one of gradation. Dysplasia lacks the discohesive cells seen with CIS and does not result in a clinging pattern of atypical cells resting on the basement membrane as seen in the current case.