Islet Amyloid in Whole Pancreas Transplants for Type 1 Diabetes Mellitus (DM): Possible Role of Type 2 DM for Graft Failure.

Long-term results with whole pancreas (WPTx) and islet transplantation (IT) continue to be suboptimal. Graft failure with undetectable C-peptide level is attributed to graft sclerosis (chronic rejection), recurrence of Type 1 diabetes mellitus (DM), or insufficient islet mass. In contrast, graft failure with measurable C-peptide has overlapping clinical features with Type 2 DM (suggesting persistent but insufficient ß cell function), but is poorly understood. In general, the morphological substrate for islet failure is unclear because grafted islets are not routinely evaluated. We present two patients with graft failure at 5 and 8 years after successful WPTx for Type 1 DM, presenting with preserved C-peptide levels. On histopathology, the islets had preserved both α and ß cell populations but also prominent accumulation of islet amyloid (IA), the morphological hallmark of Type 2 DM. IA previously reported in IT, represents fibrillary aggregates of islet amyloid polypeptide, a hormone normally cosecreted with insulin. Accumulation of IA correlates quantitatively with the development of hyperglycemia and is known to cause ß cell dysfunction and loss. Accumulation of IA and development of Type 2 DM should be considered and studied as a potential cause of long-term islet failure in IT and WPTx.

Multiple non-metastatic gastrointestinal stromal tumors. Differential features.

INTRODUCTION: gastrointestinal stromal tumors (GISTs) are specific, generally KIT (CD117)-positive, mesenchymal tumors of the digestive tract displaying KIT or PDGFRA gene mutations. Clinically, they tend to present as solitary tumors of the intestinal wall; more rarely, multiple tumors may occur in one or more organs. OBJECTIVE: to review the morphological, immunohistochemical and molecular features of multiple, non-metastatic forms of GIST. SOURCES: review of the literature on Medline, and authors own experience. CONCLUSIONS: multiples GISTs may occur in three different contexts: as spontaneous lesions (in both adults and children); due to familial GIST syndrome (autosomal dominant inheritance); or in association with specific syndromes (e.g. Carney s triad, Carney-Stratakis syndrome, type I neurofibromatosis). Outside these contexts, the existence of multiple GISTs is deemed to be the result of tumor metastasis, and therefore indicative of advanced-stage disease. Clinicians need to be aware of these variants, whose prognosis and treatment differ.