ABSTRACT
Primary colorectal follicular lymphomas are rare indolent lymphoid neoplasms in humans that have not been reported in dogs. We describe 3 cases of primary colorectal follicular lymphoma in dogs with histologic and immunohistochemical features similar to their human counterpart. Initial clinical signs in all dogs included tenesmus, hematochezia, and a palpable rectal mass. Two dogs were castrated males and 1 an intact female, between 9 months and 2 years of age, and of varied breeds. All 3 cases of colorectal follicular lymphoma were characterized by proliferation of follicular germinal centers with no polarity or mantle zone and were composed of centrocytes admixed with fewer centroblasts. By immunohistochemistry, lymphoid cells expressed CD20, BCL2, and BCL6 and lacked expression of CD3, CD5, and cyclin D1. Polymerase chain reaction for rearrangements of the immunoglobulin heavy chain confirmed a monoclonal population in all cases. In 2 of the 3 cases, a solitary nodular colorectal mass was excised and appeared curative; however, the third case had multiple colorectal masses and the animal developed multicentric lymphoma. This case series immunohistochemically characterizes and distinguishes colorectal follicular lymphoma from atypical lymphoid hyperplasia.
Subject(s)
Colorectal Neoplasms/veterinary , Dog Diseases/pathology , Lymphoma, Follicular/veterinary , Animals , Colon/pathology , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/pathology , Dog Diseases/diagnosis , Dogs , Female , Lymphoma, Follicular/diagnosis , Lymphoma, Follicular/pathology , Male , Polymerase Chain Reaction/veterinaryABSTRACT
Type 2 diabetes is a leading cause of morbidity and mortality among noncommunicable diseases, and additional animal models that more closely replicate the pathogenesis of human type 2 diabetes are needed. The goal of this study was to develop a model of type 2 diabetes in guinea pigs, in which diet-induced glucose intolerance precedes ß-cell cytotoxicity, two processes that are crucial to the development of human type 2 diabetes. Guinea pigs developed impaired glucose tolerance after 8 weeks of feeding on a high-fat, high-carbohydrate diet, as determined by oral glucose challenge. Diet-induced glucose intolerance was accompanied by ß-cell hyperplasia, compensatory hyperinsulinemia, and dyslipidemia with hepatocellular steatosis. Streptozotocin (STZ) treatment alone was ineffective at inducing diabetic hyperglycemia in guinea pigs, which failed to develop sustained glucose intolerance or fasting hyperglycemia and returned to euglycemia within 21 days after treatment. However, when high-fat, high-carbohydrate diet-fed guinea pigs were treated with STZ, glucose intolerance and fasting hyperglycemia persisted beyond 21 days post-STZ treatment. Guinea pigs with diet-induced glucose intolerance subsequently treated with STZ demonstrated an insulin-secretory capacity consistent with insulin-independent diabetes. This insulin-independent state was confirmed by response to oral antihyperglycemic drugs, metformin and glipizide, which resolved glucose intolerance and extended survival compared with guinea pigs with uncontrolled diabetes. In this study, we have developed a model of sequential glucose intolerance and ß-cell loss, through high-fat, high-carbohydrate diet and extensive optimization of STZ treatment in the guinea pig, which closely resembles human type 2 diabetes. This model will prove useful in the study of insulin-independent diabetes pathogenesis with or without comorbidities, where the guinea pig serves as a relevant model species.