Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Graft dysfunction in pancreas and islet transplantation: morphological aspects Cinthia B. Drachenberg and John C. Papadimitriou Introduction b-Cell replacement is the treatment of choice in a subset of patients with diabetes mellitus. Insulin inde- pendence can be achieved through two procedures: whole pancreas transplantation (WPnTx) or islet trans- plantation. Successful b-cell replacement immediately improves the quality-of-life for the diabetic patient [1]. Furthermore, there is evidence that maintaining nor- moglycemia leads to objective improvement of second- ary diabetic lesions that were previously considered irreversible [2]. The beneficial impact of pancreas transplantation on secondary complications of diabetes mellitus has been reviewed recently by Gremizzi et al. [3  ]. It is worth emphasizing that reversal of well established diabetic lesions can be only achieved with long-term normoglycemia. Specifically, reversal of Kimmelstiel–Wilson nodules in diabetes nephropathy was appreciated only in patients with WPnTx function- ing at least10 years [2]. Although the first pancreas transplant was performed in 1966, achievement of acceptable results with WPnTx has been slow, mostly due to a series of technical and immunological difficulties [4]. Since the 1990s, results in this area have continuously improved and WPnTx is currently considered as a standard treatment for selected patients in whom the surgical and immunosuppression risks are outweighed by the morbidity and mortality associated with their disease [5]. Long-term follow-up of a cohort of 1000 patients receiving simultaneous pancreas and kidney (SPK) transplantation showed that at 1, 10 and 20 years, patient and pancreas graft survival were 97, 80 and 58%, and 88, 63 and 36%, respectively [6] The first series of successful islet transplantation were reported in 2000, with achievement of excellent short- term results (1 year insulin independence in 70 – 90% of patients) [7]. Long-term results have been, however, disappointing with return to insulin therapy within 5 years for most patients [8]. Despite the loss of insulin independence over time, most patients with islet Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland, USA Correspondence to Dr Cinthia B. Drachenberg, MD, Department of Pathology, University of Maryland Hospital, 22 South Greene Street, NBW49, Baltimore, MD 21201, USA E-mail: cdrac001@umaryland.edu Current Opinion in Organ Transplantation 2011, 16:106–109 Purpose of review b-Cell replacement in the form of whole pancreas transplantation (WPnTx) or islet transplantation has the goal of providing long-term insulin independence to diabetic patients that may require these types of interventions, with the minimum of iatrogenic side-effects and complications. In search of these ambitious and only partially achieved objectives, continuous advances are made in the field. Recent findings A concerted effort has been made in recent years to categorize the morphological features of allograft rejection in WPnTx. This has followed the general attempts to standardize histopathological and other diagnostic modalities in solid organ transplantation in general. Issues related to antibody-mediated rejection have taken center stage due to their perceived dramatic effects on both short and long-term graft survival. Another issue that diminishes the extent of success with WPnTx is the high incidence of posttransplant diabetes mellitus (PTDM). Understanding the mechanisms involved in this process is important for the development of potential therapeutic interventions and for its prevention. Summary This review will summarize the current understanding on the morphological features of antibody-mediated rejection in WPnTx, the main morphological and clinical aspects of PTDM, including recurrent autoimmune diabetes mellitus, and will briefly discuss histopathological data available on islet transplantation. Keywords antibody-mediated allograft rejection, Banff grading schema, islet transplantation, pancreas transplantation, post transplant diabetes mellitus Curr Opin Organ Transplant 16:106–109 ß 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins 1087-2418 1087-2418 ß 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI:10.1097/MOT.0b013e3283424f44