A 10-month-old female presented with a history of blood spotting in urine for one day. The clinical diagnosis was bladder mass with blood spotting in urine. The tissue obtained from catheterized urine specimen was white-red clump of mass. At gross description, the specimen represented irregular tan tissue fragment measuring 0.7 cm x 0.2 cm x 0.1 cm. The entire material was submitted.

Sections revealed an extensive purulent material admixed with many epithelial fragments with papillary configuration (fig 6.1). Nuclei displayed marked atypia (fig 6.2) and some mitotic figures were present (fig 6.3).

The differential diagnosis considerations included:

• Noninfectious inflammatory disorders of the urinary bladder
• Infectious disorders of the urinary bladder
• Papillary urothelial carcinoma
• Ovarian papillary carcinoma

Papillary serous ovarian adenocarcinoma: Metastatic papillary serous ovarian adenocarcinoma to the bladder in washings shows high cellularity and predominantly tissue fragments and papillary-like clusters composed of large cells with multivacuolated cytoplasm, large pleomorphic nuclei, and prominent nucleoli. Multinucleation may be present along with rare psammoma bodies and debris.

Severe reactive changes in Urothelium

The cytologic characteristics of “atypia of unknown significance” are subjective and interpreted differently by different pathologists. The final histologic diagnosis may range from reactive changes (“reactive urothelial cell changes”) to dysplasia (“urothelial cell atypia”).

The significance of the diagnoses of “reactive atypia” and “atypia of unknown significance” in patient management is questionable. Patients with these entities do not have adverse clinical outcomes. In contrast, patients with urothelial dysplasia of the bladder have an increased risk of developing carcinoma in situ and urothelial carcinoma.

In urine cytology reports, the term reactive atypia should be avoided: instead, reactive urothelial cell changes, which indicates no neoplastic significance, should be used.

Cells are slightly enlarged with a slight enlarged nucleus, bland chromatin, prominent nucleolus, and a vacuolated cytoplasm.

Often there is a history of instrumentation, lithiasis, intravesical therapy, or chronic inflammation. Cellular changes are proportional to the magnitude and duration of the underlying nonneoplastic disorder.

Most of the cases with a cytologic diagnosis of “atypia of unknown significance” fall in the “reactive” category and few in the “atypical” category.

Table 4 compares cytology of papillary urothelial carcinoma grade 1, 2 and 3 (WHO, 1973) and reactive urothelial cell changes.

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