Atypical Urothelial Cells Indeterminate for Neoplasia

Unfortuntely, as in every other body site, cytologic samples from the urinary tract are not always readily placed into distinct categories. An atypical interpretation is appropriate when morphologic changes exceed those described as benign cellular changes, but lack clear signs of neoplasia (Figs. 2.7, 2.15, 2.33). This is generally encountered when dealing with a sample from a patient with a low grade lesion, especially those called "low malignant potential" (LMP), or in the presence of severe inflammation, calculus disease, or following chemotherapy. Emerging ancillary tests, beyond the scope of this volume, will potentially bring clarity to these frustrating lesions.

Note that "dysplasia" is not included as a diagnostic choice. In the authors' experience, cytologic samples rarely contain cells from a dysplasia unless they have been mechanically dislodged. If they are present, they should be placed in a low or high grade category depending upon individual cell morphology.

Bladder Reactive Atypia
Figure 2.1. Benign Urothelial Cells—bladder washing: The purple fragment is lubricant. Admixed are acute inflammatory cells as well as reactive urothelial cells. Lubricant may be seen in bladder washing and catheterized specimens. (600x)
Bladder Cells Urine

Figure 2.2. Benign Urothelial Cells—catheterized urine: Degeneration may be seen in catheterized urine specimens. In this case, degenerated nuclei are admixed with smaller, hyperchromatic benign urothelial cells. (600x)

Urothelial Cells Urine

Figure 2.3. Benign Urothelial Cells—catheterized urine: A cluster of benign urothelial cells is admixed with a few squamous cells. The urothelial cells exhibit a moderately increased nuclear to cytoplasmic ratio although the nuclei are relatively uniform to slightly irregular in contour. The cells contain a variable chromatin pattern and the cytoplasm is homogeneous (absence of vacuoles). Clusters of benign urothelial cells in catheterized urine specimens should not be mistaken for low or high grade urothelial carcinoma. (600x)

Figure 2.3. Benign Urothelial Cells—catheterized urine: A cluster of benign urothelial cells is admixed with a few squamous cells. The urothelial cells exhibit a moderately increased nuclear to cytoplasmic ratio although the nuclei are relatively uniform to slightly irregular in contour. The cells contain a variable chromatin pattern and the cytoplasm is homogeneous (absence of vacuoles). Clusters of benign urothelial cells in catheterized urine specimens should not be mistaken for low or high grade urothelial carcinoma. (600x)

Carcinoma Cells Urine

Figure 2.4. Benign Urothelial Cells—catheterized urine: In this catheter-ized urine, a large group of benign urothelial cells is present at a low power. At this power, one may be concerned for a low grade urothelial carcinoma. However, such large clusters are often seen in catheterized urine specimens and should not evoke a low grade carcinoma diagnosis. (200x)

Figure 2.4. Benign Urothelial Cells—catheterized urine: In this catheter-ized urine, a large group of benign urothelial cells is present at a low power. At this power, one may be concerned for a low grade urothelial carcinoma. However, such large clusters are often seen in catheterized urine specimens and should not evoke a low grade carcinoma diagnosis. (200x)

Urine Cytology Low Grade Carcinoma

Figure 2.5. Reactive Urothelial Cells—catheterized urine: A large cluster of degenerated, benign, reactive urothelial cells is seen. These cells exhibit low nuclear to cytoplasmic ratios although the nuclei are irregular in contour. The nuclear to cytoplasmic ratio is not increased. Several of the cells show marked hyperchromasia, although degeneration explains this phenomenon. (600x)

Atypical Urothelial Cells Urine

Figure 2.6. Reactive Urothelial Cells—catheterized urine: A cluster of benign, degenerated urothelial cells is seen adjacent to a crystal. The more preserved urothelial cells contain enlarged nuclei that are not hyperchro-matic and may be seen at the edges of the large cluster. For the most part, the nuclei are small and hyperchromatic. (600x)

Figure 2.6. Reactive Urothelial Cells—catheterized urine: A cluster of benign, degenerated urothelial cells is seen adjacent to a crystal. The more preserved urothelial cells contain enlarged nuclei that are not hyperchro-matic and may be seen at the edges of the large cluster. For the most part, the nuclei are small and hyperchromatic. (600x)

Umbrella Cells Bladder

Figure 2.7. Atypical Urothelial Cells—catheterized urine: Two large clusters of atypical urothelial cells are seen. The cells exhibit an increased nuclear to cytoplasmic ratio although the nuclei are not markedly hyper-chromatic. The cytoplasm is granular and there is an absence of cytoplasmic homogeneity. 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. (600x)

Figure 2.7. Atypical Urothelial Cells—catheterized urine: Two large clusters of atypical urothelial cells are seen. The cells exhibit an increased nuclear to cytoplasmic ratio although the nuclei are not markedly hyper-chromatic. The cytoplasm is granular and there is an absence of cytoplasmic homogeneity. 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. (600x)

Figure 2.8. Normal Umbrella Cells—bladder washing: Instrumentation will usually produce tissue fragments. The distinct cellular outlines, frothy cytoplasm and relatively round, uniform nuclei testify to their benign nature. (600x)

Cytopathic Effect Rounding Cells

Figure 2.9. Normal Cells: Bladder washing can produce sheets of normal urothelial cells as well as single umbrella cells. This illustration displays the smaller nuclei of the basal cells in comparison with the larger nuclei of umbrella cells surrounding the tissue fragment. Note that the boundaries of this tissue fragment are not smooth (compare with low grade papillary lesion in Figure 3.7). (400x)

Figure 2.9. Normal Cells: Bladder washing can produce sheets of normal urothelial cells as well as single umbrella cells. This illustration displays the smaller nuclei of the basal cells in comparison with the larger nuclei of umbrella cells surrounding the tissue fragment. Note that the boundaries of this tissue fragment are not smooth (compare with low grade papillary lesion in Figure 3.7). (400x)

Papillary Urothelial Umbrella Cells
Figure 2.10. Normal Urothelial Cells—bladder washing: A fragment of basal urothelial cells is surrounded by single umbrella cells. Note the smaller nuclei of the basal cells when compared with the umbrella cells which also feature prominent nucleoli. (600x)
Normal Urothelial Cells
Figure 2.11. Lubricant—bladder washing: A fragment of lubricant is admixed with benign urothelial cells. (600x)
Neoplasia Nucleoli

Figure 2.12. Reactive Urothelial Cells—bladder washing: Sheets of epithelial cells may be misinterpreted as neoplastic. Careful examination of nuclear criteria, such as pale chromatin, prominent nucleoli, low NC ratios, and a background of acute inflammation, contributes to the interpretation of reactive/inflammatory cellular changes. (200x)

Figure 2.12. Reactive Urothelial Cells—bladder washing: Sheets of epithelial cells may be misinterpreted as neoplastic. Careful examination of nuclear criteria, such as pale chromatin, prominent nucleoli, low NC ratios, and a background of acute inflammation, contributes to the interpretation of reactive/inflammatory cellular changes. (200x)

Typical Urothelial Cells Images Urine

Figure 2.13. Reactive Urothelial Cells—bladder washing: These urothelial cells show slightly increased nuclear to cytoplasmic ratios and variably sized nuclei. The cytoplasm is homogeneous and only mildly atypical.

Reactive Squamous Cells
Figure 2.14. Reactive Urothelial Cells—bladder washing: Numerous neutrophils, benign squamous cells and reactive urothelial cells are present. Several of the cells show degeneration and nuclear hyperchromasia. The nuclear to cytoplasmic ratio of the cells is not significantly increased. (600x)
Atypical Urothelial Cells

Figure 2.15. 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. Note the high NC ratios, variable nuclear shapes, and hyperchromasia. Other areas of the same sample had more atypical cells reflecting the lesion, a Papillary Urothelial Neoplasm of Low Malignant Potential. See Figure 3.2. (600x)

Malignant Urothelial Cells
Figure 2.16. Reactive Urothelial Cells—bladder washing: A cluster of reactive urothelial cells is seen. The cells are admixed with acute inflammatory cells and show either marked nuclear hyperchromasia and degeneration or a prominent nucleolus. (600x)
Figure 2.17. Reactive Urothelial Cells—catheterized urine: These superficial reactive urothelial cells show homogeneous cytoplasm and mildly hyperchromatic nuclei. Note the low nuclear to cytoplasmic ratio, acute inflammation and bacteria in the background. (600x)
What Are Degenerated Urothelial Cells
Figure 2.18. Reactive Urothelial Cells—bladder washing: Degenerated reactive urothelial cells are seen. These cells exhibit nuclear membrane irregularities and nuclear hyperchromasia. These cells also have a large amount of cytoplasm, indicative of their benign nature. (600x)
Bladder Reactive Atypia

Figure 2.19. Reactive Urothelial Cells—bladder washing: Degenerated slightly atypical urothelial cells are seen. The cells exhibit only mildly increased nuclear to cytoplasmic ratios and many of the cells contain abundant cytoplasm. Note that the nuclear size is smaller than the size of intermediate squamous cells. (600x)

Figure 2.19. Reactive Urothelial Cells—bladder washing: Degenerated slightly atypical urothelial cells are seen. The cells exhibit only mildly increased nuclear to cytoplasmic ratios and many of the cells contain abundant cytoplasm. Note that the nuclear size is smaller than the size of intermediate squamous cells. (600x)

Figure 2.20. Polyoma Virus—voided urine: If this is a rare cell in the specimen, then one can presume a viral infection. However, nuclear changes could be degeration in a cell from a high grade carcinoma and warrant careful follow-up. (600x)

Urothelial Cells Urine
Figure 2.21. Polyoma Virus—voided urine: An infected cell displays overall cell enlargement, high NC ratio, and ground glass nucleus with marginated chromatin. Compare the infected cell with the adjacent benign urothelial cell. (600x).
Virus Urine

Figure 2.22. 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. The herpetic cell exhibits a mul-tilobated nucleus and a relatively low nuclear to cytoplasmic ratio. The cytoplasm appears homogeneous. (600x)

Figure 2.22. 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. The herpetic cell exhibits a mul-tilobated nucleus and a relatively low nuclear to cytoplasmic ratio. The cytoplasm appears homogeneous. (600x)

Herpes Viral Nuclear Inclusions
Figure 2.23. Herpes Simplex Infection—urethral brushing: Intranuclear inclusions, multinucleation and nuclear molding typify Herpes infection anywhere in the body. This patient had AIDS, and died of systemic Herpes infection. (400x)
Urinary Cytology Herpes Simpleks Virus

Figure 2.24. Cytomegalovirus Infected Urothelial Cells—voided urine: In urines, viral cytopathic effect is characteristically similar to CMV infections in other body sites. Compare these enlarged nuclei with distinct intranuclear inclusions and perinuclear clearing with the nuclear changes produced by polyoma virus infection. They are distinctly and diagnosti-cally different. (600x)

Figure 2.24. Cytomegalovirus Infected Urothelial Cells—voided urine: In urines, viral cytopathic effect is characteristically similar to CMV infections in other body sites. Compare these enlarged nuclei with distinct intranuclear inclusions and perinuclear clearing with the nuclear changes produced by polyoma virus infection. They are distinctly and diagnosti-cally different. (600x)

Herpes Uretral

Figure 2.25. Human Papillomavirus Infection—bladder washing: Koilo-cytes, the hallmark of HPV infection, can be found rarely in urologic specimens. They may originate from genital contamination in voided urines obtained from female patients. This patient was male, the specimen was obtained by bladder washing, and the lesion was biopsy proven to be a bladder condyloma. (400x)

Figure 2.25. Human Papillomavirus Infection—bladder washing: Koilo-cytes, the hallmark of HPV infection, can be found rarely in urologic specimens. They may originate from genital contamination in voided urines obtained from female patients. This patient was male, the specimen was obtained by bladder washing, and the lesion was biopsy proven to be a bladder condyloma. (400x)

Renal Epithelial Cells Urinalysis

Figure 2.26. Renal Tubular Epithelial Cells—voided urine: As their name implies, these cells derive from the lining cells of the renal tubules. They mimic macrophages because of their degenerated, often eccentric, nucleus and foamy cytoplasm. The larger cell in the bottom of the figure is a normal umbrella cell. (600x)

Figure 2.26. Renal Tubular Epithelial Cells—voided urine: As their name implies, these cells derive from the lining cells of the renal tubules. They mimic macrophages because of their degenerated, often eccentric, nucleus and foamy cytoplasm. The larger cell in the bottom of the figure is a normal umbrella cell. (600x)

Figure 2.27. Tubular Cast—voided urine: Renal tubular epithelial cells have usually degenerated by the time they are recovered in voided urine. This cast has preserved the morphology without any degeneration, much like a fossil preserves features of long dead creatures. (200x)

Fine Granular Casts Urine
Figure 2.28. Assorted Casts—voided urine: Types of casts can be important clinical information and should be mentioned in addition to any epithelial atypia. (200x)

Figure 2.29. Red Cell Casts—voided urine: Fragmented red blood cells are arranged in a cylinder with relatively parallel sides. (400x)

Urothelial Red Inclusions

Figure 2.30. Non-viral Inclusions—voided urine: Red opaque inclusions in large degenerated spheres are not to be confused with virus infected cells. The exact origin of these inclusions is not known. They do not correlate with any disease process. They are a frequent finding in voided urines, especially in the presense of inflammation and in older patients. (600x)

Figure 2.30. Non-viral Inclusions—voided urine: Red opaque inclusions in large degenerated spheres are not to be confused with virus infected cells. The exact origin of these inclusions is not known. They do not correlate with any disease process. They are a frequent finding in voided urines, especially in the presense of inflammation and in older patients. (600x)

Urothelial Cytology
Figure 2.31. Non-viral Inclusions—voided urine: Red inclusions within degenerated cells are frequently seen in voided urines and are of no apparent clinical significance. They usually accompany acute inflammation. (600x)
Degeneration Cells
Figure 2.32. Benign Crystals—bladder washing: Numerous crystals are seen in this bladder washing specimen. The crystals range in size and shape and few benign urothelial cells are observed. (600x)

Figure 2.33. Atypical Cells, Short of Neoplastic—bladder washing: When cytologic criteria fall between reactive and neoplastic, an indeterminate category is prudent. Clinical management usually includes repeat voided urines, followed by bladder washing and biopsy if atypical cells persist. (400x)

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Responses

  • aino alen
    What diagnosis do i use for benign reactive urothelium?
    6 years ago
  • Tiblets Abraham
    What are rare degenerated atypical urothelial cells?
    6 years ago
  • quintilia
    What are reactive urothelial cells?
    6 years ago
  • ANGEL
    How serious are urothelial clusters with low grade urothelial neoplasia?
    5 years ago
  • dora
    What are atypical urothelial cellls?
    5 years ago
  • Tesfalem
    What are reactive urotheial cellscom?
    5 years ago
  • noora
    What are clusters of urothelial cells with atypical?
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  • senay
    Can atypical cells be present urine?
    5 years ago
  • jay
    WHAT IS UROTHELIAL INFLAMMATORY CELLS?
    5 years ago
  • timoteo
    What are atypical and neoplastic cells in urine?
    5 years ago
  • Sayid Samuel
    What is urothelial cell with marked atypia?
    4 years ago
  • anette
    Can a rare cluster of atypical urothelial cells be a benign tumor?
    3 years ago
  • santo
    Why umbrella shaped shaped cell in urothelium have more nuclei?
    2 years ago
  • Merimas
    What are urothelial fragments?
    2 years ago
  • Ugo
    What is the reason for atypical cells in urine sample?
    2 years ago
  • eric
    What does rare cluster atypical dysplastic urothelial cells mean?
    2 years ago
  • Rikki
    What are clusters of highly atypical urothelia cells?
    2 years ago
  • steven
    What areRARE ATYPICAL UROTHELIAL CELLS?
    2 years ago
  • rosamunda
    What causes urothelial cells reactive atypia, favor reactive in males?
    1 year ago
  • mari hassi
    What do we mean by rare atypical degenerating cells in a urine sample?
    1 year ago
  • brendan
    What does rare urothelial cells and crystals mean?
    1 year ago
  • carolyn
    What does atypical aggregates of urothelial cells with mildly enlarged nuclei mean?
    1 year ago
  • jo
    What do atypical urotherial cell clusters in urine indicate?
    1 year ago
  • arianna russo
    What are atypical uretheoal cells?
    1 year ago
  • dennis herrmann
    What is significance of otypicals cells in urinalysis?
    1 year ago
  • Sinikka
    What does highly atypical urothelial cells indicate?
    1 year ago
  • sigismond
    Does rare atypical transitional cells mean few?
    1 year ago
  • hanna-mari
    What is atypical ureothelium?
    1 year ago
  • jessica
    What is alypical urothelial cell?
    10 months ago
  • Daisy
    What does atypical urothelial cells mean with favor reactive process?
    9 months ago
  • Kate
    WHAT ARE DEGENERATIVE UROTHELIAL CELLS A SYMPTOM OF?
    5 months ago
  • juuso
    What does atypical urothelial cells marked acute inflammation and bacteria present mean?
    2 months ago

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