LAUSR

Carcinoma in situ (CIS) is difficult to visualize with white light cystoscopy (WLC), whereas blue light cystoscopy (BLC) using photosensitizing agents improves detection rates. We retrospectively reviewed transurethral biopsies of bladder tumors in which both WLC and BLC evaluations were performed (N=135 samples from 79 patients). Biopsies were classified based on the presence/absence of fluorescence under BLC and the final pathological report (CIS/benign/atypical). Forty-one (30%) cases were diagnosed as CIS; of those, 38 (93%) were BLC(+), including 23 that were WLC(-). Conversely, 51 (38%) lesions were BLC(+), but classified as non-CIS. Eleven BLC(+) cases were diagnosed as "atypical." These cases were anonymized and reviewed by 7 pathologists for concordance, and then immunostained for CK20, p53 and Ki67. Immunohistochemistry results were interpreted as consistent with CIS if there was full-thickness staining of CK20, more than 50% p53-positive cells, and over 50% Ki67-positive cells. Review of BLC (+)/atypical cases showed a mean agreement of 79%, and none of the cases showed staining pattern consistent with CIS. Therefore, all 11 cases of BLC(+)/atypical were considered non-CIS for the final analysis. All patients with BLC(+)/atypical lesions had history of intravesical BCG and/or mitomycin. Using final pathology as the reference, sensitivity, specificity and negative predictive value (NPV) of BLC were 93% (CI 80.1%-98.5%), 46% (CI 35.4%-56.3%) and 94% (CI 82.5%-97.8%), respectively. The low specificity of BLC leads to BLC(+) lesions with atypical diagnosis. Morphological classification of these lesions is fairly consistent among different pathologists. Immunohistochemistry for p53/CK20/Ki67 in this setting is only helpful to potentially avoid overcalling CIS.