The 20 non-transplant tumours were all negative for PV T-Ag on IH.
The patients with transplant-associated urothelial carcinoma are summarised in . Of the eight patients with tissue available for review and staining, the mean age at diagnosis was 58 years and male/female ratio was 2
6. Two patients (7 and 8) were transplanted since the first case of BKV nephropathy was diagnosed in Oxford in 2000. Both patients showed post-transplant reactivation of BKV, one diagnosed on renal biopsy and the other on urine cytology.
Patients with post-renal transplant urothelial carcinoma (UC) of the bladder
One of eight urothelial carcinomas in transplant recipients (patient 7) showed strong nuclear staining for PV T-Ag in virtually all tumour cells, with negative staining in adjacent non-neoplastic urothelium (). Typical intranuclear inclusions were not seen on H&E sections and there was no lymphocytic response to the PV-positive tumour cells, even following reduced immunosuppression for 6 weeks after diagnosis and before cystectomy.
Figure 1 Tumour tissue from patient 7, showing high-grade invasive urothelial carcinoma (A), with focal squamous differentiation (B). High power (C) reveals no evidence of typical viral inclusions on H&E stain. Immunohistochemistry for PV T-Ag is negative (more ...)
Patient 7 is a 40-year-old woman, who received a renal transplant in 2001. Her initial immunosuppression was ciclosporin, azathioprine and prednisolone. However, she suffered three early rejections: a Banff 97 type IA rejection at day 7 post-transplantation, treated with 3 days of pulse methylprednisolone; a Banff 97 type III rejection at 13 days post-transplantation, treated with antithymocyte globulin and a Banff 97 type IB rejection, diagnosed at 27 days post-transplantation. The latter was treated with a second 3-day course of pulse methylprednisolone, followed by switch of ciclosporin and azathioprine to tacrolimus and MMF. No urine cytology to detect PV reactivation was performed, but PVN was diagnosed retrospectively using IH for PV T-Ag in a renal biopsy performed for graft dysfunction at 2 years post-transplantation (). This showed a minor non-specific infiltrate with no viral inclusions apparent on the H&E stain. Her bladder tumour was diagnosed 4 years post-transplantation and was treated with radical cystectomy, bilateral native nephrectomy and hysterectomy. Her renal allograft shows good functioning 6 years post-transplantation (serum creatinine 137μ
Figure 2 Renal biopsy 2 years post-transplantation from patient 7, showing a minor non-specific inflammatory cell infiltrate on H&E (A). Immunohistochemistry for PV T-Ag (B) shows staining of tubular epithelial cell nuclei, confirming a diagnosis of PVN. (more ...)
Patient 8 is a 65-year-old woman, transplanted in 2004. She developed BKV reactivation 5 months post-transplantation, diagnosed on urine cytology, but did not have biopsy-proven BKV nephropathy. She developed graft dysfunction 2.5 years post-transplantation, biopsy showing chronic damage with active rejection. Urine cytology at this time showed large numbers of atypical cells distributed singly, which were initially interpreted as decoy cells, indicative of BKV infection (). However, in the third urine specimen (3 months after the first), aggregates of atypical cells were present, suggesting high-grade urothelial carcinoma (). Urothelial carcinoma in situ was confirmed on biopsy () and this was negative for PV T-Ag.
Urine cytology in patient 8 initially suggested BKV infection (A) but a sample 3 months later was more in keeping with urothelial carcinoma (B), confirmed as carcinoma in situ on biopsy (C).