Atypical Renal Tubular Cell Clusters in Voided Urine of Renal Transplant Patients Predict Graft Dysfunction: A Clinicopathologic Study.
Ramneesh Bhatnagar, Cinthia Drachenberg, Dino delMar, Paul N Staats. University of Maryland Medical Center, Baltimore
Background: We recently reported clusters of atypical cells in voided urine cytology in a significant minority of renal transplant patients (Arch Pathol Lab Med. 2010;134:1362). The three-dimensional, cohesive clusters, which occur only in transplant patients, are composed of cells with a high N-C ratio; round, hyperchromatic, eccentrically placed nucleus; prominent central nucleolus; and granular cytoplasm. The clusters could potentially be confused with urothelial, renal, or prostatic carcinoma. The cells show RCC+, CK 7+, p63- immunophenotype, consistent with renal tubular origin. The findings are transient, being absent in later urine cytology specimens from the same patient, but the clinical significance has not been examined.
Design: The voided urine cytology specimens for 100 renal transplant patients excluding polyoma virus infection were reviewed in our previous study. Clinical data was reviewed for these patients over a period of two years. Specifically, biopsy-proven acute graft rejection and episodes of significantly increased creatinine were noted.
Results: Of the 18 patients who exhibited atypical cell clusters; clinical follow-up was available in 17. Two (12%) patients had a concurrent biopsy showing acute rejection; 8 (47%) others developed biopsy-proven acute rejection in a mean of 3.8 months and maximum of 6 months, and another 5 (29%) developed other evidence of graft dysfunction (15 (88%) in total). Of the 82 patients without clusters, eighteen were lost for follow-up leaving 64 for evaluation; 2 developed biopsy-proven acute rejection and 2 developed other evidence of graft dysfunction (4 (6%) total). The presence of atypical renal tubular clusters had a sensitivity of 83% and specificity of 90% in predicting biopsy-proven acute cellular rejection, with a positive predictive value of 59% and negative predictive value of 97%. For evidence of graft dysfunction more broadly, the sensitivity was 79%, specificity 97%, PPV 88%, and NPV 94%.
Conclusions: A majority of renal transplant patients with atypical renal tubular cell clusters in voided urine developed acute rejection, and nearly all showed evidence of graft dysfunction in the months following identification of the abnormal cytology; findings which occurred very rarely in transplant patients without renal cell clusters. While further study is necessary to confirm these results, these findings preceded subsequent graft dysfunction and are likely associated with graft injury such as rejection.
Tuesday, March 1, 2011 8:00 AM
Platform Session: Section F, Tuesday Morning