BACKGROUNDThe significance of apoptosis and its association with high-grade urothelial carcinoma (HGUC) in urine cytology has yet to be determined. METHODSA computerized search of the study laboratory information system was performed over a 3-year period for all urine cytology specimens processed using the SurePath liquid-based preparation technique. Only those cases with correlating surgical pathology obtained within 6 months after the urine cytologic samples were included in the current study. Cases from ileal conduit samples were excluded. A semiquantitative numerical scoring system (apoptotic index) was used to assess the amount of pyknosis or karyorrhexis, with 0 indicating none, 1 indicating<10 per 10 high-power fields, 2 indicating 10 to 30 per 10 high-power fields, and 3 indicating>30 per 10 high-power fields. Statistical analysis using the Pearson chi-square test was performed. RESULTSA total of 228 cases including 105 benign cases, 79 cases of HGUC, and 44 cases of low-grade urothelial carcinoma (LGUC) diagnosed on follow-up surgical pathology were selected. A score of 0 was observed in 70 benign, 11 HGUC, and 8 LGUC cases; a score of 1 was observed in 31 benign, 21 HGUC, and 23 LGUC cases; a score of 2 was observed in 3 benign, 27 HGUC, and 9 LGUC cases; and a score of 3 was observed in 1 benign, 20 HGUC, and 4 LGUC cases. CONCLUSIONSExcluding ileal conduit urine specimens, the finding of a high apoptotic index (score2) with the presence of pyknosis or karyorrhexis in 10 per 10 high-power fields in the urine cytology appears to be significantly associated with HGUC (P<.05). Cancer Cytopathol 2016;124:546-51. (c) 2016 American Cancer Society. Urinary cytology is a useful, noninvasive and inexpensive test for screening patients with hematuria, or monitoring patients with prior history of urothelial carcinoma. Excluding the ileal conduit specimens, the presence of frequent pyknosis or karyorrhexis in the urine cytology is significantly associated with high-grade urothelial carcinoma. See also Pages 538-9.