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 hyperplasia

            Papillary hyperplasia

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

            Papilloma-inverted papilloma

            Papillary neoplasm of low malignant potential

            Papillary carcinoma, low-grade

            Papillary carcinoma, high-grade

Invasive neoplasm

            Lamina propria invasion

            Muscolaris propria invasion

Popular terminologies

Flat lesion      

  • Reactive/inflammatory changes
  • Atypia indeterminate for neoplasia
  • Carcinoma in situ

Papillary lesions

  •  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


            Cellular crowding

            “honeycomb” present

            Chromatin normal

            Umbrella cells retained

Papillary neoplasm low malignant potential

            Chromatin coarseness


  Loss of “honeycomb”

            Nuclear shape elongated

            Nuclear enlargement

            Nucleoli indistinct

            Umbrella cells retained

Low grade papillary neoplasm

            Haphazard growth pattern

            Definite increased N/C

            Cellular enlargement


  Uniform granular chromatin

  Nuclear membrane irregularity

            Homogeneous cytoplasm

            Thickened nuclear membranes

            Eccentric nucleus

            Small nucleoli

            Umbrella cells variable

High grade papillary neoplasm

            Large cells, often single


  Very high N/C

  Irregular nuclear outlines

 Nucleoli prominent

 Cytoplasmic differentiation squamous/glandular

 Variable coarse chromatin

 Mitosis frequent

 Umbrella cells absent

Necrotic debrees


Normal cells


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

Reactive changes

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

Low Grade





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).

High Grade






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

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