Polyomavirus-cystitis associated with in situ and invasive urothelial carcinoma in a heart transplant recipient: evidence suggesting sequential progression/evolution from infection to carcinoma.

Abstract

T is increasing concern about the potential association between polyomavirus (PV) and renourinary tract carcinomas, particularly in kidney transplant recipients. We present the case of a 65-year-old African American woman, 6 years after cardiac transplantation, who presented with a large bladder mass on cystoscopy after experiencing gross hematuria. Urine cytology demonstrated decoy cells— typical of PV infection. Biopsy and cystectomy specimen examination revealed a diffuse PV cystitis and concurrent in situ and invasive high-grade urothelial carcinoma with micropapillary features, involving perivesical fat and metastatic to 2 regional lymph nodes (pT3aN2Mx). Areas of cystitis, demonstrating typical PV viral cytopathic changes, stained positive for both viral early gene region large tumor antigen (LT-Ag) and viral late gene region capsid protein 1 (VP1) (Figure 1A, B). Focal p53 positivity in scattered cells was noted in inflamed urothelium, whereas p16 was mostly negative (Figure 1C, D). Viral cytopathic features and VP1 expression were lost in areas with malignant transformation (Figure 1F, J). Large tumor antigen, p16, and p53 were expressed diffusely in the in situ and invasive tumor cells (Figure 1E, G, H, I, K, and L). Bcl-2 was negative in inflamed urothelium and in situ carcinoma and focally positive in invasive carcinoma. Ki-67 positivity ranged from 19% in cystitis to more than 80% in the in situ and invasive carcinoma. Primary carcinoma and metastases demonstrated identical immunoprofiles. Urinary bladder control tissues from 5 nontransplant patients were negative for LT-Ag, VP1, p53, bcl-2, and p16. The posttransplantation immunosuppressive regimen included prednisone, mycophenolate mofetil, and tacrolimus. The patient