‘Decoy cells’ in the urine due to polyomavirus BK infection: easily seen by phase-contrast microscopy

(Section Editor: G. H. Neild)

Giovanni B. Fogazzi, Mariadele Cantú and Lucia Saglimbeni

Divisione di Nefrologia e Dialisi, Ospedale Maggiore, IRCCS, Milano, Italy

Keywords: ‘decoy cells’; phase-contrast microscopy; polyomavirus BK infection; tubulitis; viral inclusion bodies

Renal allograft recipients are at risk of reactivation of polyomavirus BK (PVBK). When reactivated, the virus proliferates within the nuclei of the cells of the uroepithelium and of renal tubules with a possible severe derangement of the renal function and allograft frequent loss [15].

The most frequent disorder caused by PVBK is a nephropathy characterized by tubular changes often associated with interstitial inflammation and tubulitis, the distinguishing lesion being tubular cells whose nuclei are heavily altered by viral inclusion bodies [15].

The hallmark of the PVBK infection is the presence in the urine of so-called decoy cells, which are infected cells shed into the urine from the renal tubules (especially the distal segments and the collecting ducts) and uroepithelium (especially the superficial layers) [5].

In the experience of some authors, the higher the number of ‘decoy cells’ in the urine, the greater the probability of finding the PVBK nephropathy [2]. In contrast, other investigators have reported that even when the ‘decoy cells’ are ‘abundant’, the positive predictive value is as low as 27% [5], which indicates that ‘decoy cells’ may be present without any clinical disease. Patients at higher risk of developing PVBK nephropathy are those who have ‘decoy cells’ in the urine in association with impaired renal function and repeated episodes of acute rejection, and are under treatment with tacrolimus and/or mycophenolate mofetil [5].

Usually ‘decoy cells’ are identified by Papanicolaou stain on fixed urine that has been either smeared or cytocentrifuged [2,5]. Other techniques are identification of specific PVBK antigens by immunocytochemistry [4,5], or electron microscopy, which shows typical viral particles with a diameter of 45 nm within the nuclear inclusions [25].

By Papanicolaou stain, most ‘decoy cells’ show a much enlarged nucleus, which is occupied by a basophilic inclusion surrounded by chromatin that confers a ground-glass or gelatinous appearance. Sometimes the nuclear inclusion has a vesicular aspect, or it may be surrounded by a halo, and the chromatin may be clumped [2,5]. When ‘decoy cells’ derive from the uroepithelium, the heavily enlarged and altered nuclei as well as the irregular shape of the cell body can mimic the changes observed in neoplastic cells [2,5].

We show here how ‘decoy cells’ can be easily identified by phase-contrast microscopy. The images presented here (Figure 1Go) were observed in October 2000 in the urine of a 31-year-old Italian man (with congenital obstructive uropathy), who in June 1999 had received a kidney from his mother. Four months later, while receiving tacrolimus and mycophenolate mofetil, the patient developed a progressive renal dysfunction, with serum creatinine rising slowly to 4.3 mg/dl. The presence of PVBK was suspected after the finding of many ‘decoy cells’ (more than one per high-power field, at x400) by phase-contrast microscopy, and was later confirmed by the renal biopsy findings (focal acute tubular necrosis, many tubular cells with typical nuclear inclusion bodies, interstitial inflammation, and tubulitis), and by the finding, by polymerase chain reaction, of PVBK DNA in the patient's plasma (courtesy of the Institute of Virology, University of Pavia).



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Fig. 1. (A–C) Examples of tubular cells with enlarged nuclei showing a typical gelatinous or ground-glass appearance. (D) Several cells of this type clustered together in a cast (arrows). In these cells the chromatin can be marginated toward the nuclear membrane, as in (B), upper cell, or clumped in coarse central mass, bottom cell. (E) A cell with a nuclear inclusion body surrounded by a clear halo (‘bird's eye’ appearance) (left), and a cell with an enlarged nucleus, containing a coarse inclusion body. (F) A cell with a nuclear clear halo entrapped in a cast (arrow). (G) A probable superficial transitional cell (diameter 67.5 µm) with an enlarged vesicular nucleus. (H) Two other probable superficial transitional cells (longitudinal diameter 62 µm) with very evident nuclear inclusion bodies (phase-contrast microscopy, original magnification x400).

 
By phase-contrast microscopy, ‘decoy cells’ show the same abnormalities described for stained specimens, namely, enlargement of the nucleus with a ground-glass or vesicular appearance, altered chromatin, enlarged nucleoli, the presence of a halo, and at times also cytoplasmic vacuoles (Figure 1Go). In our experience, these features make ‘decoy cells’ different from tubular cells and transitional cells found in all other conditions. The only exception is represented by cells infected by cytomegalovirus, which frequently show a ‘bird's eye’ appearance, similar to that shown in Figure 1EGo (cell in the left).

Notes

Correspondence and offprint requests to: Giovanni B. Fogazzi, Divisione di Nefrologia e Dialisi, Ospedale Maggiore, IRCCS, Via Commenda 15, I-20122 Milano, Italy. Back

References

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