Pathology in Practice

Timothy L. Driver Department of Pathobiology and Diagnostic Investigation and the Diagnostic Center for Population and Animal Health, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824.

Search for other papers by Timothy L. Driver in
Current site
Google Scholar
PubMed
Close
 DVM
and
Cheryl L. Swenson Department of Pathobiology and Diagnostic Investigation and the Diagnostic Center for Population and Animal Health, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824.

Search for other papers by Cheryl L. Swenson in
Current site
Google Scholar
PubMed
Close
 DVM, PhD, DACVP

History

A 12-year-old sexually intact male Labrador Retriever was evaluated at the Michigan State University Veterinary Teaching Hospital because of a 2-week history of left unilateral nasal discharge (varying from mucopurulent discharge to epistaxis) that was unresponsive to treatment with sulfonamide-based antimicrobials. The dog had an episode of hematuria that resolved with antimicrobial treatment approximately 1.5 years earlier.

Clinical and Clinicopathologic Findings

At the hospital, no abnormalities were detected on physical examination. Computed tomography of the nasopharyngeal region revealed a small mass near the left choana that had infiltrated into the nasopharynx. Rhinoscopy was performed to obtain a biopsy specimen of the mass.

Initial clinicopathologic analyses included a CBC, serum biochemical profile, hemostasis profile, and complete urinalysis. For the latter, approximately 6 mL of urine was collected via cystocentesis. Moderate non-regenerative anemia and mild lymphopenia were identified, whereas results of the serum biochemical and hemostasis profiles were unremarkable. However, the urinalysis data were intriguing (Table 1).

Table 1—

Urinalysis data from the initial sample obtained via cystocentesis from a 12-year-old Labrador Retriever that was evaluated because of left unilateral nasal discharge of 2 weeks' duration.

VariableTest resultReference interval1
Urine
   ColorPale yellowYellow
   TransparencySlightly hazyClear
   Specific gravity*1.0231.001–1.060
   pH7.55.5–7.5
   Protein4+Negative to 1+
   Glucose§2+Negative
   Ketones§NegativeNegative
   Heme§TraceNegative
   BilirubinNegativeNegative to 1+
Sediment
   WBCs (No./hpf)5–100–5
   RBCs (No./hpf)15–200–5
   Epithelial cells (No./lpf)NoneNone to few
   Casts (No./lpf)NoneNone
   Crystals (No./lpf)NoneNone
   Bacteria (No./hpf)NoneNone
   Other (No./hpf)Many oval fat bodiesNA

Measured with a refractometer.a

Measured by use of a pH meter.b

Determined via a sulfosalicylic acid test.c

Determined with a urine dipstick.d

Determined by use of a reagent test tablet.e

lpf = Low-power field. NA = Not applicable.

Formulate differential diagnoses from the history, clinical and clinicopathologic findings, and Table 1—then turn the page

Additional Clinicopathologic Data

Microscopic examination of the urine sediment revealed moderate cellularity with low numbers of leukocytes, moderate numbers of erythrocytes, and numerous oval fat bodies. The oval fat bodies were moderately sized and mostly individualized cells that were occasionally seen in small clusters (Figure 1). These cells contained numerous, round, refractile, variably sized, intracytoplasmic vacuoles that had a Maltese cross formation when viewed under polarized light. Because of the presence of oval fat bodies in the sample, additional diagnostic testing was performed. In this initial sample, the total microprotein concentration was 3,080.0 mg/dL and creatinine concentration was 1.3 mg/dL (reference interval,2 53.2 to 475.1 mg/dL); the urine protein-to-creatinine ratio was 2,369.2 (ratio in apparently normal dogs, < 0.5). Also, an initial serum sample was analyzed to determine fractional clearances of various analytes (Table 2). Subsequently, on the same day, a second serum sample was obtained and a second urine specimen was collected via ultrasound-guided cystocentesis for similar analyses (Table 3). In the initial sample, the fractional clearance values for all measured electrolytes and the urine protein-to-creatinine ratio were extremely high, indicative of an almost complete lack of renal function, yet serum biochemical variables were within reference intervals. In the second sample that was submitted for urinalysis, fractional clearance results were apparently normal and glucosuria, proteinuria, and oval fat bodies were not detected.

Table 2—

Fractional clearance values for various biochemical variables determined via analysis of an initial urine sample (collected via cystocentesis) and an initial serum sample obtained from the dog in Table 1.

VariableSerumUrineFractional clearance* (%)
AppearanceNormalPale yellowNA
Sodium (mmol/L)145 (143–149)15196.3 (< 1)3
Potassium (mmol/L)4.1 (3.4–5.2)4.396.8 (< 20)3
Chloride (mmol/L)109 (107–116)11496.2 (< 1)3
Calcium (mg/dL)10 (9.4–10.9)8.578.5 (0.0–0.4)4
Phosphorus (mg/dL)4.0 (2.1–4.6)4.194.6 (< 39)3
Creatinine (mg/dL)1.2 (0.7–2.0)1.3NA

Values in parentheses represent the reference interval for that variable.

Fractional clearance was calculated by use of the following formula: ([analyte concentration in urine/analyte concentration in serum] × [creatinine concentration in serum/creatinine concentration in urine]) × 100.

These intervals are approximations, and values should be interpreted relative to corresponding serum values. Marked variation has been detected within individuals.

NA = Not applicable.

Table 3—

Fractional clearance values for various biochemical variables determined via analysis of a second urine sample (collected via ultrasound-guided cystocentesis) and a second serum sample obtained from the dog in Table 1.

VariableSerumUrine
AppearanceSlight hemolysisPale yellow
Sodium (mmol/L)150132
Potassium (mmol/L)3.934.4
Chloride (mmol/L)111129
Calcium (mg/dL)9.61.7
Phosphorus (mg/dL)4.035.5
Creatinine (mg/dL)0.862.3

In the second urine sample, high glucose and protein concentrations and oval fat bodies were not detected.

See Table 2 for applicable reference intervals and key.

Figure 1—
Figure 1—

Photomicrographs of unstained urine sediment from the initial sample collected via cystocentesis from a 12-year-old Labrador Retriever. A—Image obtained via routine light microscopy. Notice the presence of oval fat bodies that contain numerous, round, refractile, variably sized, intracytoplasmic vacuoles. B—Image obtained via polarized light microscopy. The oval fat bodies had a Maltese cross appearance when viewed under polarized light. In both panels, bar = 20 μm.

Citation: Journal of the American Veterinary Medical Association 236, 9; 10.2460/javma.236.9.957

Interpretation

None—the evidence suggested that the initial fluid sample submitted for urinalysis was not urine.

Comments

In samples of urine from humans, oval fat bodies are cells that contain highly refractile lipid droplets. These cells may be either renal tubular epithelial cells that have absorbed lipoproteins containing cholesterol and triglycerides5 or macrophages that have phagocytized lipids or degenerating cells.6 When the incorporated droplets contain large amounts of cholesterol, they appear to have a typical Maltese cross formation when viewed microscopically under polarized light.7 Oval fat bodies are commonly observed in sediments of urine samples collected from humans with acute renal failure.8 Patients with nonselective proteinuria, active glomerulonephritis, or IgA nephropathy frequently have the macrophage form of oval fat bodies,8 whereas patients with nephrotic syndrome and marked proteinuria commonly have the renal tubular epithelial form.8 In addition to urine, oval fat bodies also are found in expressed prostatic secretions from humans with prostatic inflammation.9

In the dog of this report, detection of numerous oval fat bodies that had a Maltese cross pattern under polarized light was suggestive of acute renal failure. The detection of 4+ proteinuria suggested either renal tubular or glomerular protein loss, and the detection of 2+ glucosuria, together with a lack of hyperglycemia, suggested decreased renal tubular reabsorption. However, these findings were incongruent with the dog's history, clinical signs, and results of the initial serum biochemical analyses. Assessments of fractional clearances and determination of the urine protein-to-creatinine ratio in the initial sample collected from the dog via cystocentesis were performed to investigate possible renal tubular damage and further characterize the proteinuria, respectively. A second urine sample was collected for testing to assess repeatability of the initial results. In the initial sample, the fractional clearance values for all measured electrolytes and the urine protein-to-creatinine ratio were extremely elevated, which indicated that the serum and urine electrolyte, protein, and creatinine concentrations were closely similar. This suggested that the dog had an almost complete lack of renal function, yet values of serum biochemical variables were within reference intervals. Therefore, the possibilities of a laboratory error or submission of a sample of fluid other than urine were considered. In the second sample that was submitted for urinalysis, fractional clearance results were apparently normal and glucosuria, proteinuria, and oval fat bodies were not detected. With these additional data, it appeared unlikely that the initial sample was truly urine.

The precise source of the initial sample that contained oval fat bodies was unknown. The veterinary technician who collected the sample via cystocentesis reported no difficulty during collection. Of the 6 mL of fluid collected, 5 mL was used to obtain sediment for examination. The possibility that the sample was free abdominal fluid was considered; however, no abdominal fluid was evident during ultrasound-guided cystocentesis to collect the second sample for urinalysis. Furthermore, the dog had no other signs or indications of free abdominal fluid. A more likely possibility was that a prostatic or paraprostatic cyst had been aspirated. The dog was 12 years old and sexually intact. At the initial evaluation, a prostate gland examination was not performed because of a large amount of feces in the rectum. Prostatic and paraprostatic cysts are not uncommon (estimated prevalence in adult large-breed dogs, 14%10) and often are associated with benign prostatic hyperplasia or other prostatic disease.11 Cysts may be classified as either retention or paraprostatic cysts. Paraprostatic cysts may be very large (up to 30 cm in diameter12) and usually are attached by a stalk of tissue to the prostate gland.11 Although the cysts may be detected via abdominal palpation, contrast radiography is often necessary to differentiate the urinary bladder from unmineralized cysts.

Oval fat bodies are frequently detected in expressed human prostatic secretions,9 especially when an inflammatory response is present, but to the authors' knowledge, their presence in canine prostatic fluid has not been reported. Cytologically, canine prostatic cyst fluid is characterized by low cellularity with predominantly large, vacuolated, and phagocytic macrophages in a proteinaceous background. These macrophages may have a moth-eaten appearance when flattened because of cytoplasmic vacuoles that overlie the nucleus.13 Canine prostatic secretions contain cholesterol that may be phagocytized by macrophages.11 However, to observe the characteristic Maltese cross pattern associated with oval fat bodies, microscopic examination of unstained cystic fluid under polarized light is required because lipids are dissolved during staining processes.

In the dog of this report, histologic examination of sections of the nasal mass biopsy specimen revealed an infiltrative, densely cellular epithelial neoplasm, which was diagnosed as a nasal transitional cell carcinoma. Because of the presence of a malignant nasal neoplasm and lack of clinical signs indicative of prostatic disease, no further diagnostic testing was pursued.

a.

Reichert TS meter, Reichert Inc, Depew, NY.

b.

IQ Scientific Instruments, San Diego, Calif.

c.

Ricca Chemical Co, Arlington, Tex.

d.

Siemens Labstix, Siemens Healthcare Diagnostics Inc, Tarrytown, NY.

e.

Siemens Ictotest, Siemens Healthcare Diagnostics Inc, Tarrytown, NY.

References

  • 1.

    Osborne CA, Stevens JB. The urinary tract in health: definition of terms and concepts. In: Urinalysis: a compassionate guide to patient care. Shawnee, Kan: Bayer Corp, 1999;111.

    • Search Google Scholar
    • Export Citation
  • 2.

    Braun JP, Lefebvre HP, Watson AD. Creatinine in the dog: a review. Vet Clin Pathol 2003;32:162179.

  • 3.

    Lefebvre HP, Dossin O & Trumel C, et al. Fractional excretion tests: a critical review of methods and applications in domestic animals. Vet Clin Pathol 2008;37:420.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Jacobs RM, Lumsden JH, Taylor JA. Canine and feline reference values. In: Bonagura JD, ed. Kirk's current veterinary therapy XIII. Philadelphia: WB Saunders Co, 2000;12071227.

    • Search Google Scholar
    • Export Citation
  • 5.

    McPherson RA, Ben-Ezra J, Zhao S. Basic examination of urine. In: McPherson RA, Pincus MR, eds. Henry's clinical diagnosis and management by laboratory methods. 21st ed. Philadelphia: WB Saunders Co, 2006;409419.

    • Search Google Scholar
    • Export Citation
  • 6.

    Weller JM. Examination of the urine. In: Weller JM, ed. Fundamentals of nephrology. San Francisco: Harper & Row, 1979;7986.

  • 7.

    Zimmer JG, Dewey R & Waterhouse C, et al. The origin and nature of anisotropic urinary lipids in the nephrotic syndrome. Ann Intern Med 1961;54:205214.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Graber M, Lane B & Lamia R, et al. Bubble cells: renal tubular cells in the urinary sediment with characteristics of viability. J Am Soc Nephrol 1991;1:9991004.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Krieger JM. Prostatitis, epididiymitis and orchitis. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and practice of infectious diseases. 6th ed. Philadelphia: Churchill Livingstone Inc, 2005;13821384.

    • Search Google Scholar
    • Export Citation
  • 10.

    Black GM, Ling GV & Nyland TG, et al. Prevalence of prostatic cysts in adult, large-breed dogs. J Am Anim Hosp Assoc 1998;34:177180.

  • 11.

    Smith J. Canine prostatic disease: a review of anatomy, pathology, diagnosis, and treatment. Theriogenology 2008;70:375383.

  • 12.

    Foster RA. Male reproductive system. In: McGavin MD, Zachary JF, eds. Pathologic basis of veterinary disease. 4th ed. St Louis: Mosby Elsevier, 2007;13171348.

    • Search Google Scholar
    • Export Citation
  • 13.

    Borjesson D. Urinary tract. In: Raskin RE, Meyer DJ, eds. Atlas of canine and feline cytology. Philadelphia: WB Saunders Co, 2001;253260.

    • Search Google Scholar
    • Export Citation
  • Figure 1—

    Photomicrographs of unstained urine sediment from the initial sample collected via cystocentesis from a 12-year-old Labrador Retriever. A—Image obtained via routine light microscopy. Notice the presence of oval fat bodies that contain numerous, round, refractile, variably sized, intracytoplasmic vacuoles. B—Image obtained via polarized light microscopy. The oval fat bodies had a Maltese cross appearance when viewed under polarized light. In both panels, bar = 20 μm.

  • 1.

    Osborne CA, Stevens JB. The urinary tract in health: definition of terms and concepts. In: Urinalysis: a compassionate guide to patient care. Shawnee, Kan: Bayer Corp, 1999;111.

    • Search Google Scholar
    • Export Citation
  • 2.

    Braun JP, Lefebvre HP, Watson AD. Creatinine in the dog: a review. Vet Clin Pathol 2003;32:162179.

  • 3.

    Lefebvre HP, Dossin O & Trumel C, et al. Fractional excretion tests: a critical review of methods and applications in domestic animals. Vet Clin Pathol 2008;37:420.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Jacobs RM, Lumsden JH, Taylor JA. Canine and feline reference values. In: Bonagura JD, ed. Kirk's current veterinary therapy XIII. Philadelphia: WB Saunders Co, 2000;12071227.

    • Search Google Scholar
    • Export Citation
  • 5.

    McPherson RA, Ben-Ezra J, Zhao S. Basic examination of urine. In: McPherson RA, Pincus MR, eds. Henry's clinical diagnosis and management by laboratory methods. 21st ed. Philadelphia: WB Saunders Co, 2006;409419.

    • Search Google Scholar
    • Export Citation
  • 6.

    Weller JM. Examination of the urine. In: Weller JM, ed. Fundamentals of nephrology. San Francisco: Harper & Row, 1979;7986.

  • 7.

    Zimmer JG, Dewey R & Waterhouse C, et al. The origin and nature of anisotropic urinary lipids in the nephrotic syndrome. Ann Intern Med 1961;54:205214.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Graber M, Lane B & Lamia R, et al. Bubble cells: renal tubular cells in the urinary sediment with characteristics of viability. J Am Soc Nephrol 1991;1:9991004.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Krieger JM. Prostatitis, epididiymitis and orchitis. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and practice of infectious diseases. 6th ed. Philadelphia: Churchill Livingstone Inc, 2005;13821384.

    • Search Google Scholar
    • Export Citation
  • 10.

    Black GM, Ling GV & Nyland TG, et al. Prevalence of prostatic cysts in adult, large-breed dogs. J Am Anim Hosp Assoc 1998;34:177180.

  • 11.

    Smith J. Canine prostatic disease: a review of anatomy, pathology, diagnosis, and treatment. Theriogenology 2008;70:375383.

  • 12.

    Foster RA. Male reproductive system. In: McGavin MD, Zachary JF, eds. Pathologic basis of veterinary disease. 4th ed. St Louis: Mosby Elsevier, 2007;13171348.

    • Search Google Scholar
    • Export Citation
  • 13.

    Borjesson D. Urinary tract. In: Raskin RE, Meyer DJ, eds. Atlas of canine and feline cytology. Philadelphia: WB Saunders Co, 2001;253260.

    • Search Google Scholar
    • Export Citation

Advertisement