Detecting ‘decoy cells’ by phase-contrast microscopy

Sir,

A recent paper by Fogazzi et al. [1] shows how decoy cells can be identified not only by Papanicolau stain on fixed urine or by immunocytochemistry, but also by phase-contrast microscopy without any stain.

BK Polyomavirus is a double-stranded DNA virus belonging to the Papovavirus family, and infects up to 90% of the general population. After primary infection, generally occurring in childhood without evident symptoms, the virus can remain latent in the urinary tract. Reactivation can be enhanced by immunosuppressive conditions, leading to overt clinical disease [2]. The most important clinical manifestations are haemorragic cystitis in bone marrow transplantation, ureteral stenosis and interstitial nephropathy in kidney transplant recipients [3].

BK virus nephropathy (BKN) has been identified as a frequent complication affecting renal transplantation recipients, possibly associated with the degree of immunosuppression, and leading to allograft dysfunction in ~50% of patients [4,5].

Histopathology is the gold standard test for diagnosis. Surrogate markers, such as detection of Polyomavirus-inclusion bearing cells (decoy cells) in the urine [6] and quantification of BK virus DNA in the plasma by polymerase chain reaction (PCR), have been used for diagnosis and management of polyomavirus BKN [7]. The presence of decoy cells in the urine is a 100% sensitive sign of elevated BK virus replication in the urogenital tract, but the positive predictive value for BKN may be <20%. Decoy cells are not exclusive to the BK virus. If PCR for BK virus is negative in urine specimens with presumed decoy cells, this does not exclude the presence of other viruses such as JC virus [8], and certain adenoviruses (e.g. type 11). Detection of BK virus DNA in plasma suggests significant allograft involvement (sensitivity 100%, specificity 88%) [5].

We confirm the results of the authors, reporting the case of a 61-year-old man, who received a kidney transplant in July 2002 from a cadaveric donor. In October 2002, his serum creatinine was 2.0 mg/dl, which then progressively increased up to 6.0 mg/dl in June 2003, while the patient was treated with tacrolimus and mycophenolate mofetil.

The urinalysis by phase-contrast microscopy showed ~2 decoy cells/high-power field, at x400 (tubular and uroepithelial cells with enlarged nuclei and a gelatinous appearance) (Figure 1).



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Fig. 1. Tubular (A) and transitional (B) cells with enlarged nuclei and gelatinous appearance (decoy cells) in a renal transplant patient (phase-contrast microscopy, x400).

 
Quantitative PCR for BK virus DNA in the plasma (>4 x 105 genome copies/250 ml) and in the urine (4 x 105 genome copies/250 ml) was positive [9]. Biopsy of the graft showed a focal tubulitis; the immunocytochemical analysis showed many tubular cells were positive for the SV 40 antigen, specific for BK virus. So we made a diagnosis of BK polyomavirus-associated tubulitis.

In conclusion, it is possible to detect the presence of decoy cells on spot-morning urine sediment analysis by phase-contrast microscopy. This is important as it means that the nephrologist can screen patients for BKN with this simple and feasible test.

The key point remains the clinical suspicion that must be signalled, as in this case, from the clinicians to the laboratory.

Conflict of interest statement. None declared.

Massimo Gai, Giorgina B. Piccoli, Daria Motta, Roberta Giraudi, Danila Gabrielli, Marina Messina, Alberto Jeantet, Giuseppe P. Segoloni and Giacomo Lanfranco

University of Torino A.S.O. San Giovanni Battista Torino Italy Email: massimogai{at}katamail.com

References

  1. Fogazzi GB, Cantù M, Saglimbeni L. ‘Decoy cells’ in the urine due to polyomavirus BK infection: easily seen by phase-contrast microscopy. Nephrol Dial Transplant 2001; 16: 1496–1498[Free Full Text]
  2. Major E.O. Human polyomaviruses. In: Knipe D, Howley P, Griffin D et al. Fields Virology. Vol. 2, 4th Edn. Lippincott Williams, Philadelphia; 2001: 2175–2196
  3. Hirsch HH, Knowles W, Dickenmann M et al. Prospective study of polyomavirs type BK replication and nephropathy in renal-transplant recipients. N Engl J Med 2002; 347: 488–496[Abstract/Free Full Text]
  4. Randhawa PS, Vats A, Zygmunt D et al. Quantitation of viral DNA in renal allograft tissue from patients with BK virus nephropathy. Transplantation 2002; 74: 485–488[ISI][Medline]
  5. Hirsch HH. Polyomavirus BK nephropathy: a (re-)emerging complication in renal transplantation. Am J Transplant 2002; 2: 25–30[CrossRef][ISI][Medline]
  6. Mayr M, Nickeleit V, Hirsch HH, Dickenmann M, Mihatsch MJ, Steiger J. Polyomavirus BK nephropathy in a kidney transplant recipient: critical issues of diagnosis and management. Am J Kidney Dis 2001; 38: E13
  7. Limaye AP, Jerome K, Kuhr C et al. Quantitation of BK virus load in serum for the diagnosis of BK virus-associated nephropathy in renal transplant recipients. J Infect Dis 2001; 183: 1669–1672[CrossRef][ISI][Medline]
  8. Baksh FK, Finkelstein SD, Swalsky PA et al. Molecular genotyping of BK and JC viruses in human polyomavirus-associated interstitial nephritis after renal transplantation. Am J Kidney Dis 2001; 38: 354–365[ISI][Medline]
  9. Merlino C, Bergallo M, Gribaudo G et al. Polyomavirus BK DNA quantification assay to evaluate viral load in renal transplant recipients. J Clin Virol 2003; 28: 265–274[CrossRef][ISI][Medline]




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