Epithelial cells in urine

Different types of epithelial cells can be observed in urine. Some of these are readily identifiable, however it is difficult to distinguish small transitional epithelial cells from WBC and renal tubular epithelial cells from transitional epithelial cells. Thus, all non-squamous cells in urine are considered to be of transitional origin. When we are unsure about the origin of the cells in urine, we can stain a urine sediment with Wright's stain (or Diff-quik) and perform a cytologic examination on the urine sediment.

Epithelial cells are subjectively semi-quantified in urine (usually under low power using the 10x objective) as: none seen, few, moderate, many

Neoplastic cells of renal, urinary or reproductive origin can exfoliate in the urine and a urinalysis is definitely indicated if a tumor in one of these sites is suspected in the animal. Examination of a regular urine sediment preparation can be the first clue to identification of neoplastic cells, however the diagnosis of neoplasia is based on cytologic criteria of malignancy in the cells, which are not easy to discern in these wet preparations. Thus, we recommend that a cytologic analysis of the urine (using a standard hematologic stain, such as Wright's stain) is performed if neoplasia is suspected.

For more information on the types of epithelial cells seen in urine, click on the links in the table below or scroll down.

For a compilation of images, please refer to the urine sediment atlas.


Transitional epithelial cellswbc epi

The urinary tract from the pelvis down the ureters to the bladder and the proximal urethra is lined by transitional epithelial cells. These cells vary in size and shape depending on the location from which they originate, e.g. those from the renal pelvis are more caudate whereas those from the bladder are more round to polygonal and vary in size. These cells naturally slough into the urine in quite low numbers, so none to a few transitional epithelial cells are seen in the urine from healthy animals. Note that this depends on the method of urine collection, since these cells will be sloughed (traumatically) when the bladder is catheterized.

Transitional epithelial cells must be distinguished from WBC, because they both have the same granular appearance. In general, transitional epithelial cells (arrow in above image) are larger and have more irregular borders than WBC (which are uniformly more round, arrowhead in above image).

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Squamous epithelial cells

squamous
epithelial comp

These can be keratinized or non-keratinized.

Non-keratinized squamous epithelial cells originate from the distal urethra, prepuce and/or vagina. They are larger than transitional cells and have small central nuclei. They can be round or have one or more flat border. Keratinized squamous epithelial cells are from the skin or vulva and are large cells with angular borders. They may or may not have nuclei (see upper image to the right). Nuclei are more visible in cells when the urine is stained with Sedi-stain (see central panel on right). If in doubt about the origin of the cells, a Wright's stain (routine hematologic stain) can be performed on a urine sediment and demonstrates the central nuclei and angular borders of squamous epithelial cells (lower panel on right).

Squamous cells are frequently seen as contaminants in voided urine samples and can also contaminate samples collected by catheterization. Urine collected by cystocentesis should not contain any squamous epithelial cells.

Note that although these cells are considered contaminants, large numbers may represent abnormal genitourinary conditions, specifically squamous metaplasia of the prostate in the dog. This occurs secondary to excess estrogen, usually secreted by testicular tumors (particularly Sertoli cell tumors, but this has also been reported with interstitial cell tumors).

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Renal tubular epithelial cells

These are rarely seen in the urine and, as mentioned above, are very difficult to distinguish from transitional epithelial cells. If large numbers of smaller epithelial cells of uniform appearance (size and shape) are observed in the urine, a renal origin for these cells is suspected. Transitional epithelial cells tend to be more variable in size and shape (to some extent). Sloughing of large numbers of renal tubular epithelial cells would indicate renal tubular injury.

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Neoplasia

TCC comp
The upper panel demonstrates large neoplastic epithelial cells in an unstained urine sediment from a dog with a bladder mass. The lower panel demonstrates that these cells display clear cytologic criteria of malignancy in a Wright's stained cytology smear of the urine.

Neoplastic cells, typically those of transitional epithelial origin (transitional cell carcinoma or TCC) may slough into the urine. The presence of these cells can be diagnostic of urinary neoplasia, however they are not always seen in the urine in affected animals (i..e. the lack of these cells in a urinalysis does not rule out neoplasia).

TCC are more common in dogs and frequently originate in the trigone of the urinary bladder, although the prostatic urethra and urethra per se is a common site in male and female dogs, respectively (prostatic urethra TCC often invade the prostate and mimic primary prostatic carcinomas in male dogs). Diagnosis of neoplasia depends upon the identification of cytologic criteria of malignancy in the epithelial cells, e.g. marked variation in nuclear and cell size (called anisokaryosis and anisocytosis, respectively), multiple nucleoli of variable size within one nucleus, multinucleation with intracellular anisokaryosis, macronucleoli. These features are only reliably discernable in cytologic smears (stained with a hematologic stain such as Diff-quik or Wright's stain) and are difficult to impossible to identify with confidence in an unstained preparation of urine (see image on right). Thus, a urine cytology should be performed on animals with suspected tumors.

TCC usually invade the bladder wall and cause hemorrhage. They may also become secondarily inflamed from necrosis or a superimposed bacterial infection. Thus, hematuria and, to a lesser extent, pyuria, can be features of a urinalysis in animals with TCC.

Rarely, other tumors originating in the bladder or kidney (e.g. lymphoma, renal carcinoma) can exfoliate into the urine. Pictured below are images from an unstained and Wright's stained urine sediment from a cat with renal lymphoma. The neoplastic lymphoblasts had exfoliated into the urine and provided the diagnosis in this case.

lymphoma unstained renal lymphoma stained
Unstained urine sediment from a cat demonstrating a large uniform round cell with a high nuclear to cytoplasmic ratio (arrow; a similar cell is observed at the top, the other cells are interpreted as transitional epithelial cells). This was not a normal finding in urine, hence a cytospin smear of the urine was prepared and stained with Wright's stain for cytology. A Wright's stained smear revealed numerous leukocytes (neutrophils, with phagocytized bacterial rods) and moderate numbers of large round cells with round nuclei, small amounts of deep blue cytoplasm and high nuclear to cytoplasmic ratios (arrow). This was diagnostic for lymphoma, which originated from the cat's kidney. This phenomenon is quite rare.

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