Atypical urothelial tissue fragments in noninstrumented voided urine specimens are associated with low but significantly higher rates of urothelial neoplasia than benign-appearing urothelial tissue fragments

BACKGROUND The interpretation of urothelial tissue fragments (UTF) in voided urine (VU) specimens is controversial. If UTF contain cytomorphologically atypical cells, the diagnosis often becomes more challenging. The authors previously analyzed the outcome of patients with benign-appearing UTF in 274 noninstrumented VU specimens. In this retrospective study, noninstrumented VU specimens containing UTF with atypical cytomorphological features (AUTF) were evaluated and compared with the previous results. METHODS The Johns Hopkins Hospital electronic pathology database was searched for VU cases containing UTF over a 5-year period. RESULTS A total of 170 noninstrumented VU specimens containing AUTF were identified. Twenty-four specimens had subsequent or coincidental surgical pathology specimens with the following overall rates of neoplasia: high-grade urothelial carcinoma: 8.8% (15 specimens), low-grade urothelial neoplasia: 1.2% (2 specimens), and prostate carcinoma invading the bladder: 0.6% (1 specimen). A total of 49 specimens (28.8%) were diagnosed with urolithiasis on follow-up. Twenty-five cases had follow-up cytology specimens, all of which were negative for malignancy. Of 72 cases without histopathologic, radiologic, or cytopathologic follow-up, 62 (86.1%) had a mean clinical follow-up of 22.5 months and 10 cases did not have clinical follow-up. CONCLUSIONS The presence of AUTF in noninstrumented VU is associated with low rates of urothelial neoplasia but a statistically higher risk of urothelial neoplasia than the presence of BUTF (10.0% vs 4.4%; P<.05). In particular, the rate of high-grade urothelial carcinoma is significantly higher in noninstrumented VU specimens containing AUTF than those containing BUTF (8.8% vs 0.7%; P<.0001). In addition, urolithiasis is associated with AUTF in a substantial percentage of noninstrumented VU specimens.