Urinary Tract Cytology
The urothelium is a unique mucosa, specialized for the urinary tract for its ability to expand and contract, and as a barrier against the toxic urine. This stratified epithelium is morphologically intermediate between cuboidal and squamous, hence its hold name, “transitional”.
The surface cells have abundant cytoplasm, the luminal surface of which may appear thickened. The nuclei of these superficial cells, also called “umbrella cells” may have prominent nucleoli and may be multinucleated.
Squamous epithelium can occur as a result of metaplasia or as a congenital area, especially within the trigone of women. The distal portion of the penile urethra is lined by squamous epithelium. In female, vaginal contamination during a voided urine collection can be a source of benign or atypical squamous and glandular epithelium.
The WHO/ISUP Consesus classification
May include cases formerly diagnosed as “mild dysplasia”
Flat lesion with atypia
Reactive (inflammatory) atypia
Atypia of unknown significance
Dysplasia (low-grade intraurothelial neoplasia)
Carcinoma in situ (high-grade intraurothelial neoplasia)
Papillary neoplasm of low malignant potential
Papillary carcinoma, low-grade
Papillary carcinoma, high-grade
Lamina propria invasion
Muscolaris propria invasion
- Reactive/inflammatory changes
- Atypia indeterminate for neoplasia
- Carcinoma in situ
- Normal cells clusters in voided urine – Papilloma
- Normal cells/Slightly atypical cells clusters – Papillary neoplasm low malignant potential
- Slightly atypical /Mildly atypical cells cluster – Low grade papillary neoplasm
- Highly atypical cell cluster – High grade papillary neoplasm
Since the morphologic changes in the lowest grade lesions are essentially identical to normal urothelium, the sensitivity of cytology for the accurate disgnosis of these tumors is low. However, the risk tha a low-grade lesion may progress to invasive carcinoma is minimal, reducing the negative consequences of a false negative.
High grade lesions fortunately are easily recognized and reliably diagnosed so that immediate histologic confirmation and treatment can proceed.
Progressive cytologic changes in the grading of urothelial lesions
Umbrella cells retained
Papillary neoplasm low malignant potential
Loss of “honeycomb”
Nuclear shape elongated
Umbrella cells retained
Low grade papillary neoplasm
Haphazard growth pattern
Definite increased N/C
Uniform granular chromatin
Nuclear membrane irregularity
Thickened nuclear membranes
Umbrella cells variable
High grade papillary neoplasm
Large cells, often single
Very high N/C
Irregular nuclear outlines
Cytoplasmic differentiation squamous/glandular
Variable coarse chromatin
Umbrella cells absent
A) voided urine – low nuclear/cytoplasmic ratio
B) voided urine – note the thickened unilateral aspect of the cytoplasmic borders
C) voided urine – large rond nuclei with prominent nucleoli and vescicular cytoplasm
D) voided urine – marked hypercromasia in isolated cells
E) voided urine – low nuclear/cytoplasmic ratio altough the nuclei are irregular in contour
F) voided urine – Numerous acute inflammatory cells are seen in the background
G-L) voided urine – The cellular changes of low-grade lesions are minimal (I), one of the difficulties in diagnosing these tumors. Architetural crowding (G,H,L) with minimal nuclear atypia (I) are the most robust features Pseudopapillary cluster of neoplastic cells showing an hobnail appaerance at the edge and absence of umbrella cells. The cells have an increased nuclear/cytoplasmic ratio, hyperchromatic nuclei and homogeneous cytoplasm (L).
M-Q) voided urine -The cells exhibit high nuclear cytoplasmic ratios (M, P), nuclear hypercromasia and nuclear membrane irregularities (O). The nuclear membrane appears thick in some instances (O, Q). Often degeneration may limit interpretation of high grade urothelial carcinomas (N).
Carcinoma in Situ
R-S) voided urine – Carcinoma in situ cells are isolated with a vary high nuclear cytoplasmic ratios, coarse & clumped chromatin. Sometimes with prominent-multiple macronucleoli
T-U) voided urine – metastases from clear cell renal carcinoma. papillary aggregates with clear cytoplasm(T), prominent nucleoli and abundant finely microvacuolized cytoplasm(U).
V-Z) voided urine – Keratinizing squamous cell carcinoma metastases from uterine cervix. Malignant squamous cells are admixed with degenerated debris, have an elongated appearance and the cytoplasm is keratinazed
Cytologic Detection of Urothelial Lesions – Essentials in Cytopatology Series – Dorothy Rosenthal, Stephen S. Raab