High grade urothelial carcinoma in kidney transplant patients with a history of BK viremia - Just a coincidence?

INTRODUCTION: Kidney transplant recipients (KTR) have a three-to-four-fold increased risk of developing urothelial carcinoma (UC) compared to the general population. BK polyoma virus (BKV) infection is known to affect approximately 15% of KTR. In vitro models support a potential pathogenic role for BKV in the development of UC. We describe a series of UC in kidney transplant recipients. METHODS: Electronic patient records were searched to identify KTR with UC who had undergone kidney only or simultaneous kidney and pancreas transplantation in a single UK center between 2009 and 2015. Where available, stored pathological samples were retrieved, re-examined and stained for SV40 as a marker of BKV using standard staining protocols for kidney biopsy samples. RESULTS: Fourteen KTR had developed UC post-transplant. Of these, 10 KTR had a history of BKV infection post-transplant. Six of these 10 KTR developed a rare micropapillary tumor subtype of UC which is typically only found in <1% of UC cases. All six micropapillary tumor samples stained positive for SV40, including samples from metastases. Three tumor samples were available from the four KTR with no history of BKV infection and were not micropapillary subtype and were negative for SV40. Three micropapillary tumors from immunocompetent patients were examined as controls and were negative for SV40. CONCLUSIONS: These findings would support a pathogenic role for BK virus in the development of rare micropapillary subtype urothelial tumors in the kidney transplant population.

Translational research will fail without surgical leadership: SCOTRRCC a successful surgeon-led Nationwide translational research infrastructure in renal cancer.

BACKGROUND: High quality human biosamples with associated high quality clinical data are essential for successful translational research. Despite this, the traditional approach is for the surgeon to act as a technician in the tissue collection act. Biomarker research presents multiple challenges and the field is littered with failures. Tissue quality, poor clinical information, small sample numbers and lack of validation cohorts are just a few reasons for failure. It is clear that the surgeon involved in tissue acquisition must be fully engaged in the process of biosampling for a specific condition, as this will negate many of the issues for translational research failure due to an inadequate bioresource. APPROACH: In this Matter for Debate paper, the Scottish Collaboration On Translational Research into Renal Cell Cancer (SCOTRRCC) is discussed as an example of a urological surgery lead bioresource which has resulted in a National collection of renal cancer tissue and blood (from over 900 patients to date), negating all of the traditional issues with biobanks because of close enagagement and acknowledgement of urologists and uropathologists from seven centres around Scotland. SCOTRRCC has leveraged renal cancer research in Scotland resulting in several high impact publications and providing a springboard for future research in this disease in Scotland and beyond. CONCLUSIONS: The SCOTRRCC model presented here can be transferred to other surgical disciplines for success in translational research.

Epstein-Barr virus-positive primary cutaneous follicle centre lymphoma; an age-related phenomenon?

Primary cutaneous follicle centre lymphoma is the most frequently encountered primary cutaneous B cell lymphoma, often presenting in the head and neck region. Treatment is locally directed with surgery and/or radiotherapy. The prognosis is usually excellent with only local recurrences and generally no dissemination to extracutaneous sites. Epstein-Barr virus (EBV) is frequently encountered in lymphoproliferative disorders associated with immunosuppression, typically iatrogenic and congenital, or acquired as a consequence of a human immunodeficiency virus infection. More recently, age-related immune senescence has been proposed as a main driver in the evolution of EBV-positive lymphoproliferative disorders. We report a 50-year-old male presenting with a 2-3-year history of an inflamed eruption centred on the forehead and scalp. Incisional biopsy showed pathological features typical of primary cutaneous follicle centre lymphoma (PCFCL), and in the absence of systemic disease, he was treated with local radical radiotherapy. A cutaneous relapse occurred 10 months after initial diagnosis and 29 months after completing radiotherapy, he presented with a right-sided submandibular lymph node mass. Pathological examination of an excised node showed an EBV-positive diffuse large B cell lymphoma. Retrospective examination of the presenting PCFCL also showed the neoplastic lymphoid cells to be positive for EBV, both by in situ hybridization and on immunohistochemical staining for LMP1. EBV-associated PCFCL is an extremely rare occurrence. We speculate that, in this case, the EBV-positive lymphoma has most likely arisen as a consequence of age-related immune senescence, thereby further expanding the pathological spectrum of age-related EBV-associated B cell lymphoproliferations.