Three Dimensional Cell Groups with Disordered Nuclei and Cellular Discohesion Are Associated with High Sensitivity and Specificity in the Cystoscopic Urine Diagnosis of Low Grade Urothelial Neoplasia
Kona Williams, Phillip Williams, Shahidul Islam, Celia Marginean, Harman Sekhon, Eric C Belanger, Kien T Mai. Ottawa Hospital and the University of Ottawa, Ottawa, ON, Canada
Background: A review of cystoscopic urine obtained before the resection of low grade urothelial carcinoma (LGUC) frequently revealed the presence of three dimensional cell groups with disordered nuclei and cellular discohesion (3D-DD). The purpose of this study is to determine the clinical significance of this finding.
Design: 936 consecutive cystoscopic urine specimens were reviewed and divided into 5 groups. Groups 1 (80 specimens) and 2 (20 specimens) included patients with biopsy-proven LGUC collected during follow-up periods of 0-6 months and 6 months to 2 years, respectively. Group 3 (300 specimens) included urine from patients with hematuria and insignificant cystoscopic findings. Group 4 (6 specimens) consisted of patients with a history of urinary stones. Group 5 (530 specimens) included patients with a history of LGUC but no evidence of cystoscopic recurrence.
Results: Specimens with scant cellularity accounted for 20% of the specimens in Group 1, likely associated with technical problems from collection. Tumors with increased cell adhesion or a small exophytic component may also contribute to poor specimen collection. 3D-DD was present in most cases with mild cytologic atypia, and in all cases with papillary stromal fragments. 3D-DD was often associated with increased cellularity and an abundance of single cells. Assuming a 20% inadequate sampling rate over the five specimen groups, 3D-DD was associated with a 72% sensitivity, 96% specificity, 90% positive predictive value (PPV) and 89% negative predictive value (NPV). Two or 3-dimensional cell groups with ordered nuclei and/or cellular non-discohesion were often associated with Groups 3 and 4. Interestingly, 3D-DD was present in a significant number of cases that showed initial concurrent negative findings, but were associated with LGUC in follow-up cystoscopies. In both instances (negative cystoscopies or LGUC), 3D-DD was morphologically similar. Also, 3D-DD was present in 8% of Group 5 specimens, likely representing a possible LGUC or urothelial dysplasia not cystoscopically detectable and with low neoplastic progression.
Conclusions: Our study demonstrated the high specificity and sensitivity of 3D-DD for LGUC. These findings are consistent with the decreased cell adhesion and disordered nuclear arrangement of low grade urothelial neoplasia. Future studies with larger case numbers and longer follow-up periods are necessary to confirm our observations.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 101, Tuesday Afternoon