A 72-year-old man with a previous diagnosis of prostate cancer (Gleason score 3+3) treated by radiation, seeds and Casodex complained recently of urinary frequency. The patient went to see an urologist because of the worsen symptoms. A urine sample was colected for urine cytology.

On voided urine specimen, there are clusters of cells with high nuclear/cytoplasmic ratio, variable nuclear size, nuclear hyperchromasia and prominent eosinophilic nucleoli (Figures 1-2). Immunoreactivity for prostatic acid phosphatase (PAP) is positive (Figure 3) within the cells of concern.

The differential diagnosis considerations included:

• Renal cell carcinoma
• Prostatic carcinoma
• Urothelial carcinoma

Renal cell carcinoma: Renal cell carcinoma is rarely first diagnosed in urine specimens, and, unfortunately, by the time diagnostic cells appear in the urine, the disease is usually far advanced. The diagnostic cells may be very degenerated, usually appear singly, and vary from sparse to abundant. The cells typically have nuclei that range from small, uniform, and bland to large and bizarre, depending on the grade of the tumor. Nucleoli can range from inconspicuous to enormous. However, the most characteristic nuclei have fine pale chromatin and single-cherry-red macronucleoli.

Prostatic carcinoma: The most characteristic cytologic feature of prostatic carcinoma is the presence of prominent nucleoli in relatively uniform malignant glandular cells. When these cells are found in urine, the disease is usually advanced. Poorly differentiated prostate cancers may be difficult to distinguish from poorly differentiated urothelial carcinoma. In such cases, the use of anti-prostatic acid phosphatase (PAP) immunostain is helpful in the diagnostic workup. More recently, the development and application of uPM3 molecular urine test may be an important adjunct to current methods for the detection of early prostate cancer as well (See PM3).

Urothelial carcinoma: Bladder cancer is more commonin men than women, in whites than blacks, and is rare before 40 years of age. Low-grade urothelial carcinomas are difficult or impossible to diagnose cytologically but are seldom fatal. CIS and high-grade invasive cancer are the dangerous lesions, and they can usually be readily detected cytologically. High nuclear/cytoplasmic ratios, irregular nuclear membranes, dense and homogenous cytoplasm, nucleoli usually small or invisible are key features in the diagnosis of low-grade urothelial carcinoma. The cells of high-grade urothelial carcinoma have enlarged nuclei, with high nuclear/cytoplasmic ratios; irregular nuclear membranes; coarse, dark chromatin; macronucleoli; and the cytoplasm is frequently vacuolated.

Few clusters of highly atypical cells suspicious for prostatic adenocarcinoma.

Clinical history provided and positive immunoreactivity to anti-prostatic acid phosphatase immunohistochemistry support this cytologic impression.

1. Fradet Y, Saad F, Aprikian A, et al. uPM3, a new molecular urine test for the detection of prostate cancer.Urology. 2004;64(2):311-316.
2. DeMay RM. Practical principles of cytopathology. ASCP Press, Chicago, 1999.