Significance, cytomorphology of decoy cells in polyomavirus-associated nephropathy: Review of clinical, histopathological, and virological correlates with commentary

Human polyomaviruses (PyV) are ubiquitous, remaining predominantly inactive hence asymptomatic in the healthy, immunocompetent population. BK and JC PyV potentially infect pan-urinary tract epithelial cells. With reactivation, PyV disrupt cell cycling mechanisms, facilitating viral replication leading to cell necrosis, exfoliation, and, infrequently, carcinogenesis. Exfoliated PyV-infected cells pose diagnostic pitfalls, hence they are termed “decoy cells” as they may mimic high-grade urothelial carcinoma cells. BK polyomavirus-associated-nephropathy (BKVAN) is an inflammatory disease causing interstitial fibrosis with tubular atrophy in renal transplant recipients, increasing risk of graft loss. BKVAN is confirmed by renal biopsy, and managed by immunosuppression modulation. As voided urine may provide pan-reno-urinary tract sampling, cytopathology may serve a critical diagnostic purpose coupled with decoy cell quantification and indirect BK PyV load gauging. Thus, identification of decoy cells and differentiation from high-grade urothelial carcinoma cells, and degenerated, benign urothelial cells, is clinically essential. PyV virology and pathobiology in the context of renal transplantation, immuno-suppression and BKVAN, and, decoy cell cytomorphology and cytopreparation with commentary are highlighted. Decoy cell overall characteristics: variable degeneration; cytomegaly; comet-like shapes; angular cytoplasmic extensions; eccentric, polar nuclear placements; moderate anisocytosis; typically single cells with high N:C ratios. Cytoplasmic features: moderate-abundance; granular, blue-gray monochromatism. Nuclear features: karyomegaly; haphazardly-scattered chromatin densities; smudged, homogeneous, basophilic ground glass masses displacing chromatin alongside inner periphery of regular, symmetrical nuclear envelopes. Background features: granular cellular debris; inflammatory cells; intact and lyzed erythrocytes. Decoy cells lack coarse chromatin as in high-grade urothelial carcinoma cells. Benign urothelial cells exhibit low N:C ratios with fine chromatin distribution and euchromasia.