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Unfortuntely, as in every other body site, cytologic samples from the urinary tract are not always readily placed into distinct categories.
Herpes virus infection cytology: the presence of large multinucleated cells, with ground glass type of chromatin, marginal condensation of chromatin, as well as large eosinophilic intranuclear inclusions (Cowdry type A) are typical findings of Herpes simplex virus or varicella zoster virus cytopathic effects.
An atypical interpretation is appropriate when morphologic changes exceed those described as benign cellular changes, but lack clear signs of neoplasia (Figs.
In the authors' experience, cytologic samples rarely contain cells from a dysplasia unless they have been mechanically dislodged. Benign Urothelial Cells—catheterized urine: Degeneration may be seen in catheterized urine specimens. Benign Urothelial Cells—catheterized urine: A cluster of benign urothelial cells is admixed with a few squamous cells. Benign Urothelial Cells—catheterized urine: In this catheter-ized urine, a large group of benign urothelial cells is present at a low power. Reactive Urothelial Cells—catheterized urine: A large cluster of degenerated, benign, reactive urothelial cells is seen. Reactive Urothelial Cells—catheterized urine: A cluster of benign, degenerated urothelial cells is seen adjacent to a crystal. Atypical Urothelial Cells—catheterized urine: Two large clusters of atypical urothelial cells are seen. Normal Umbrella Cells—bladder washing: Instrumentation will usually produce tissue fragments.
Normal Cells: Bladder washing can produce sheets of normal urothelial cells as well as single umbrella cells.
Normal Urothelial Cells—bladder washing: A fragment of basal urothelial cells is surrounded by single umbrella cells.
Lubricant—bladder washing: A fragment of lubricant is admixed with benign urothelial cells. Reactive Urothelial Cells—bladder washing: Sheets of epithelial cells may be misinterpreted as neoplastic. Reactive Urothelial Cells—bladder washing: These urothelial cells show slightly increased nuclear to cytoplasmic ratios and variably sized nuclei. Reactive Urothelial Cells—bladder washing: Numerous neutrophils, benign squamous cells and reactive urothelial cells are present. Atypical Urothelial Cells Indeterminate for Neoplasia— renal pelvic brushing: This fragment of urothelial cells was originally considered atypical without all the features of a low grade neoplasm. Reactive Urothelial Cells—catheterized urine: These superficial reactive urothelial cells show homogeneous cytoplasm and mildly hyperchromatic nuclei.
Reactive Urothelial Cells—bladder washing: Degenerated slightly atypical urothelial cells are seen.
Polyoma Virus—voided urine: If this is a rare cell in the specimen, then one can presume a viral infection. Polyoma Virus—voided urine: An infected cell displays overall cell enlargement, high NC ratio, and ground glass nucleus with marginated chromatin. Herpes Simplex Infection—voided urine: A cell with herpetic viral inclusions is seen in the center field admixed with blood, benign urothelial cells and acute inflammation.

Herpes Simplex Infection—urethral brushing: Intranuclear inclusions, multinucleation and nuclear molding typify Herpes infection anywhere in the body. Cytomegalovirus Infected Urothelial Cells—voided urine: In urines, viral cytopathic effect is characteristically similar to CMV infections in other body sites.
Human Papillomavirus Infection—bladder washing: Koilo-cytes, the hallmark of HPV infection, can be found rarely in urologic specimens.
Renal Tubular Epithelial Cells—voided urine: As their name implies, these cells derive from the lining cells of the renal tubules. Tubular Cast—voided urine: Renal tubular epithelial cells have usually degenerated by the time they are recovered in voided urine. Assorted Casts—voided urine: Types of casts can be important clinical information and should be mentioned in addition to any epithelial atypia. Red Cell Casts—voided urine: Fragmented red blood cells are arranged in a cylinder with relatively parallel sides.
Non-viral Inclusions—voided urine: Red opaque inclusions in large degenerated spheres are not to be confused with virus infected cells.
Non-viral Inclusions—voided urine: Red inclusions within degenerated cells are frequently seen in voided urines and are of no apparent clinical significance. Benign Crystals—bladder washing: Numerous crystals are seen in this bladder washing specimen.
Atypical Cells, Short of Neoplastic—bladder washing: When cytologic criteria fall between reactive and neoplastic, an indeterminate category is prudent.
If they are present, they should be placed in a low or high grade category depending upon individual cell morphology.
In this case, degenerated nuclei are admixed with smaller, hyperchromatic benign urothelial cells.
The urothelial cells exhibit a moderately increased nuclear to cytoplasmic ratio although the nuclei are relatively uniform to slightly irregular in contour.
These cells exhibit low nuclear to cytoplasmic ratios although the nuclei are irregular in contour. The more preserved urothelial cells contain enlarged nuclei that are not hyperchro-matic and may be seen at the edges of the large cluster. The cells exhibit an increased nuclear to cytoplasmic ratio although the nuclei are not markedly hyper-chromatic.
The distinct cellular outlines, frothy cytoplasm and relatively round, uniform nuclei testify to their benign nature.
This illustration displays the smaller nuclei of the basal cells in comparison with the larger nuclei of umbrella cells surrounding the tissue fragment. Note the smaller nuclei of the basal cells when compared with the umbrella cells which also feature prominent nucleoli.
The cells are admixed with acute inflammatory cells and show either marked nuclear hyperchromasia and degeneration or a prominent nucleolus. Note the low nuclear to cytoplasmic ratio, acute inflammation and bacteria in the background. The cells exhibit only mildly increased nuclear to cytoplasmic ratios and many of the cells contain abundant cytoplasm.

However, nuclear changes could be degeration in a cell from a high grade carcinoma and warrant careful follow-up.
The herpetic cell exhibits a mul-tilobated nucleus and a relatively low nuclear to cytoplasmic ratio. Compare these enlarged nuclei with distinct intranuclear inclusions and perinuclear clearing with the nuclear changes produced by polyoma virus infection. They may originate from genital contamination in voided urines obtained from female patients. They mimic macrophages because of their degenerated, often eccentric, nucleus and foamy cytoplasm. This cast has preserved the morphology without any degeneration, much like a fossil preserves features of long dead creatures.
Clinical management usually includes repeat voided urines, followed by bladder washing and biopsy if atypical cells persist. The first picture, with the Cowdry inclusion could easily be confused with a CMV cytopathic effect. The cells contain a variable chromatin pattern and the cytoplasm is homogeneous (absence of vacuoles). However, such large clusters are often seen in catheterized urine specimens and should not evoke a low grade carcinoma diagnosis.
Note that the boundaries of this tissue fragment are not smooth (compare with low grade papillary lesion in Figure 3.7). Other areas of the same sample had more atypical cells reflecting the lesion, a Papillary Urothelial Neoplasm of Low Malignant Potential. This patient was male, the specimen was obtained by bladder washing, and the lesion was biopsy proven to be a bladder condyloma. The urine also contained numerous leukocytes and some red cells.Careful examination of the penis of the patient failed to reveal any lesion, but he refused cystoscopy. Emerging ancillary tests, beyond the scope of this volume, will potentially bring clarity to these frustrating lesions. Clusters of benign urothelial cells in catheterized urine specimens should not be mistaken for low or high grade urothelial carcinoma. Several of the cells show marked hyperchromasia, although degeneration explains this phenomenon. Nuclear overlap may be seen in catheterized specimens and in this case, the nuclei vary in size, although for the most part are round in shape. They are a frequent finding in voided urines, especially in the presense of inflammation and in older patients. This is probably a HSV-2 infection of the urinary tract epithelium in an immunocompromised patient.

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