Metastatic Urothelial Carcinoma from Transplanted Kidney with Complete Response to an Immune Checkpoint Inhibitor.

Abstract

Background

Donor-derived malignancy is a rare complication in patients who undergo organ transplant. Approaches to treatment have largely been individualized based on clinical circumstances given the lack of evidence-based guidelines, with therapeutic options ranging from discontinuation of immunosuppression and transplantectomy to the addition of chemotherapy or radiotherapy. Case Presentation. Herein, we describe a 60-year-old woman with metastatic donor-derived upper tract urothelial carcinoma (UTUC) discovered nine years postrenal transplant. Molecular diagnostic studies using polymerase chain reaction amplification of short tandem repeat alleles and HLA tissue typing proved that the urothelial carcinoma originated from donor tissue. She achieved sustained complete remission with transplant nephroureterectomy, retroperitoneal lymphadenectomy, immunosuppression withdrawal, and immunotherapy with pembrolizumab. Routine radiologic surveillance has demonstrated 15-month progression-free survival to date off pembrolizumab, and she is now under consideration for retransplantation.

Conclusions

Immunotherapy using checkpoint inhibitors can serve as a novel treatment option for patients in the clinical predicament of having a solid organ transplant and simultaneous metastatic malignancy. In this report, we also discuss the oncogenic potential of BK virus, the use of checkpoint inhibitors in urothelial carcinoma, and the feasibility of retransplant for this patient population.

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Citation

Published Version (Please cite this version)

10.1155/2020/8881841

Publication Info

Chiang, Ryan S, Ashton A Connor, Brant A Inman, Wen-Chi Foo, David N Howell, John F Madden, Matthew J Ellis, Aparna S Rege, et al. (2020). Metastatic Urothelial Carcinoma from Transplanted Kidney with Complete Response to an Immune Checkpoint Inhibitor. Case reports in urology, 2020. p. 8881841. 10.1155/2020/8881841 Retrieved from https://hdl.handle.net/10161/24263.

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Scholars@Duke

Howell

David Noble Howell

Professor of Pathology

A major focus of both my clinical practice and investigative work is the diagnosis and treatment of disorders affecting solid-organ transplant recipients, particularly infectious complications. For the past 15 years, I have served as the primary pathologist for one of the largest lung transplant programs in the world; in the process contributing to over 20 peer-reviewed publications on complications of lung transplantation, including infections, gastroesophageal reflux, tumors, and antibody-mediated rejection; and writing a major book chapter on the subject (Howell DN and Palmer SM, Pathology of the Lung Transplant. 2006. In: Lynch JP, Ross D, eds. Lung and Heart-Lung Transplantation. Marcel Dekker, Inc., New York, pp. 683-722). I have also been the primary pathologist for Duke's renal and liver transplant programs, authoring or co-authoring a wide variety of journal articles and a book chapter in these areas (e.g., Plumb et al., Transplantation 2006;82:1224-1224; Snyder et al., Am. J. Respir. Crit. Care Med. 2010;181:1391-1396).

A second major area of interest is the pathogenesis of renal glomerular diseases. In collaboration with members of the Division of Nephrology at Duke, I have helped assemble and characterize a large registry of patients with familial focal segmental glomerulosclerosis (FFSGS)(Conlon et al., Kidney Int. 1999;56:1863-1871). Analysis of one of the families in this registry led to the discovery at Duke, in the laboratory of Dr. Michelle Winn, of mutations in the TRPC6 cation channel as a cause of FFSGS (Winn et al., Genomics 1999;58:113-120; Winn et al., Science 2005;308:1801-1804). We are continuing to collect data on additional families with focal segmental glomerulosclerosis. In addition, I have served as principle consultative pathologist for several investigators working in animal models of renal disease and transplantation (e.g., Crowley et al., Hypertension 2010;55:99-108).

Finally, I have devoted considerable time and energy to applications of correlative microscopy to diagnostic pathology, with particular emphasis electron microscopy. I am currently President of the Society for Ultrastructural Pathology, an international organization that promotes the use of ultrastructural examination in both diagnostic pathology and clinical and basic research. Much of my published work in this area involves the role of electron microscopy in the diagnosis of renal diseases (e.g., Howell et al., Ultrastruct. Pathol. 2003;17:295-312; Pavlisko and Howell, Ultrastruct. Pathol., in press), but I have also written extensively, with my colleague Dr. Sara Miller, on the ultrastructural diagnosis of infectious disorders, contributing, among other things, to the first description of a new polyomavirus-induced skin disorder, trichodysplasia spinulosa (Haycox et al., J. Investig. Dermatol. Symp. Proc. 1999;4:268-271).

Ellis

Matthew Jay Ellis

Professor of Medicine
Harrison

Michael Roger Harrison

Associate Professor of Medicine

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