Bootcongres

Abstract Introduction BKV is a polyomavirus causing tubulo-interstitial nephritis in 5-10% of renal allografts. Recently, 4 cases of renal allograft carcinomas developing in the context of BKV nephropathy have been reported. Case We present another case of a BKV-induced carcinoma in a 62-year old female with biopsy proven BKV nephropathy (typical histology, anti-SV40 positivity, blood BKV load 6.4e6 copies/ml) 6 months after transplantation. After reduction of immunosuppression and adding leflunomide and later cidofovir, the plasma creatinine stabilized at ~250 μmol/l. The viral load decreased several log steps, but remained at 1000 copies/ml. The patient did well until she presented 4.5 years after transplantation with fever and weight loss. A CT scan showed a mass in the allograft. A biopsy showed adenocarcinoma. No metastases were found and transplantectomy was performed. At microscopy, the nuclei of tumor cells, but not those in the surrounding normal tissue, stained strongly for SV40. The tumor cells also stained positive for CK5/6, CK-HMW CK19, CK7, EMA and E-cadherin, and negative for N-cadherin. This profile proves collecting duct (CD) origin of the tumor. The patient received a 2nd kidney transplant 2.5 years later and is doing well without recurrence of tumor or BK viremia (FU 8 months). In view of the CD origin of the allograft tumor, we retrospectively performed CK-HMW (CD marker) and KI-67 (MIB-1, a proliferation marker) staining of the 6 months allograft biopsy and, remarkably, found exclusive co-localization of these markers with anti-SV40. Conclusion Our findings suggests that BKV preferentially infects CD cells and causes their proliferation, which in smoldering BKV infections may cause tumor formation as in our patient. Agreeing with this, immunohistochemistry was consistent with a CD origin in 3 / 4 BKV-related renal allograft tumors reported earlier, and we found 2 more BKV-induced renal allograft tumors in a series of “usual” CD carcinomas. As BKV related allograft tumors are rare and BKV reactivation after renal transplantation is common, unknown hits in addition to the viral infection must be relevant. Nevertheless, our report underscores the oncogenic potential of the BKV. An interesting pathogenetic observation is that the anti-SV40 antibody that is used to diagnose BKV nephropathy identifies the BKV antigen “L-Tag”, a protein that inactivates nuclear tumor suppressor proteins (e.g. p53 and pRb) and plays a role in BKV replication.