Atypical squamous cells in exfoliative urinary cytology: clinicopathologic correlates

Presence of atypical squamous cells (ASC) in voided urine is an uncommon finding that may be the harbinger of an underlying malignant process. ASCs in urine may precede a de novo histologic diagnosis of malignancy or be the first sign of a recurrence in the lower urinary tract, or the gynecologic tract (in women). This study analyzed all urine cytology specimens with such diagnoses, with reference to their final histologic outcome. All urine cytology cases (n = 17,446) that included ASCs, evaluated at The Johns Hopkins Hospital between 1989 and 2003 (14 yr), were reviewed for diagnoses. ASCs as defined in this study are keratinizing cells with large and hyperchromatic smudgy nuclei, high N/C ratio, abnormal nuclear or cytoplasmic shapes, and densely orangeophilic cytoplasm. These cases lacked the qualitative and quantitative criteria for malignancy. The final reference outcome was determined by subsequent histologic and clinical follow-up. Of these 17,446 urine specimens, 55 cases (0.3%) from 47 patients had ASCs present. Thirty-two of the 47 patients had adequate follow-up. In 8 of these 32 patients (25%), a diagnosis of squamous-cell carcinoma (SCC) of the urinary bladder or urothelial carcinoma (UC) with squamous differentiation was made on subsequent histologic examination. In two cases (6%) a diagnosis of high-grade cervical SCC was established on subsequent follow-up. Twenty two of 32 cases (69%) remained benign on histologic and prolonged clinical follow-up. We conclude that ASCs in urine are rare (0.3% in this series). An interpretation of ASCs in a urine specimen is made when there is insufficient qualitative/quantitative evidence for a carcinoma diagnosis. ASCs in urine are a clinically valid diagnostic category (31% were later diagnosed with SCC). Most patients with urinary ASCs do not develop malignancy and, therefore, these cells may represent a reactive/inflammatory process most commonly due to vaginal contamination (in women) or exfoliation from the distal urethra (in men). Rarely, ASCs may exfoliate from a uterine cervical SCC and, therefore, a pelvic examination should be considered in such patients.