Answer: Urothelial carcinoma in situ

Histology:

Discussion: Urothelial carcinoma in situ (CIS) is defined as a flat noninvasive urothelial neoplasm composed of “high-grade” malignant cells. The term CIS without qualifiers replaces the old term “Flat CIS”. Papillary non invasive carcinoma are to be termed as such. CIS is not graded (by definition high grade). Presence of cytologically malignant cells regardless of their quantity in a flat lesion qualifies for CIS. A full thickness mucosal involvement is not required and Pagetoid presence of malignant cells is likewise sufficient for the diagnosis. Umbrella cell layer can be retained. Although CIS can display a spectrum of nuclear atypia and size, a practical rule of thumb that we have found to be helpful is to observe a nuclear size that is five folds that of stromal lymphocytes in lesions that qualifies as CIS. In comparison, nuclei of normal urothelial cells are approximately twice the size of stromal lymphocytes. The nuclear enlargement and hyperchromasia in CIS should be appreciable using the 10X objective. Cellular dyscohesiveness, nuclear pleomorphism and atypical mitotic figures can also be helpful features. Immunostaining for CK20, p53 (full thickness) and CD44 (absence of staining) can help achieve the diagnosis of CIS.

CIS lesions are frequently multifocal and involve areas other than bladder base. Lesions with architecture of papillary hyperplasia and cytologic feature of CIS are referred to by some authors as “CIS with early papillary formations” and thought to represent a morphologic transition into non invasive high grade papillary urothelial carcinoma and should be managed as CIS. Cystoscopic findings in CIS range from unremarkable mucosa to the presence of erythema or edema. Urine cytology is an important diagnostic tool. The presence of CIS in association with a superficial bladder cancer significantly increases the risk for recurrence and progression. Multifocality is associated with worse outcome. Furthermore, CIS refractory to two or more courses of intravesical BCG/chemotherapy carries a higher risk for developing muscle invasive disease hence the aggressive treatment option of radical cystectomy could be considered in such patients. CIS involvement of prostatic urethra is associated with resistance to intravesical therapy and could also lead to a radical cystoprostatectomy consideration when not eradicated. When staging cystoprosattectomy specimens obtained for invasive disease, CIS extension into prostatic glands and rarely into seminal vesicle without invasion of prostatic stroma is not equated with extravesical extesion and does not in and by itself affect patient outcome.