Autoantibody with Cross-Reactivity between Insulin and Ductal Cells May Cause Diabetic Mastopathy: A Case Study

Abstract

Lymphocytic mastopathy or diabetic mastopathy is a benign breast disease characterized by dense fibrosis, lobular atrophy, and aggregates of lymphocytes in a periductal and perilobular distribution. The condition usually affects women with a long history of diabetes mellitus (DM) and also those with autoimmune disorders. While the pathogenesis is unknown, a particular type of class II human leukocyte antigen has been associated with this disease. Herein, we report a case of diabetic mastopathy which clinically and radiologically mimicked primary breast neoplasms. The patient was a 74-year-old woman with a 31-year history of DM type II who presented with multiple firm lumps in bilateral breasts. Findings from mammography, ultrasonography, and magnetic resonance imaging of the breasts revealed an abnormal appearance which suspiciously resembled malignancy. An aspiration cytology specimen showed atypical accumulation of lymphoid cells, leading us to suspect lymphoma. Histology of an excisional biopsy showed the characteristic appearance of lymphocytic mastopathy, which predominantly consisted of B-lymphocytes. Autoantibodies in her serum reacted positively against her ductal epithelium as well as other diabetic and nondiabetic breast ductal cells. An antigen absorption test with insulin revealed attenuating intensity according to insulin concentration. These anti-insulin antibodies produced in the DM patient may cause ductitis because of antigen cross-reactivity.

Mastitis in Autoimmune Diseases: Review of the Literature, Diagnostic Pathway, and Pathophysiological Key Players

“…At least, mammary duct self-antigens may exhibit a cross-reactivity towards other autoantibodies. This mechanism has already been described in a long-lasting Type 2 diabetic patient treated with insulin, in whom anti-insulin autoantibodies cross-reacted with breast ductal epithelium, leading to ductitis and mastitis [30]. This mechanism of cross reactivity could also be involved in the cases of concomitant breast cancer and vasculitis [167,168].…”

“…Miura and coll. described one case of lymphocytic mastopathy in a patient with a 31-year history of Type 2 diabetes [30] and demonstrated the presence of circulating anti-insulin autoantibodies with cross-reactivity towards breast duct epithelium. Such autoantibodies might be linked to the onset of inflammation within the breast tissue and trigger clinical mastitis flares.…”

Diabetic mastopathy in an elderly woman misdiagnosed as breast cancer: A case report and review of the literature

“…In addition, it is also believed that diabetic mastopathy, such as diabetic nephropathy and retinopathy, should be regarded as a chronic complication of diabetes[ 12 ]. Miura et al [ 13 ] reported an elderly female patient whose autoantibodies in serum reacted positively against her ductal epithelium as well as other diabetic and nondiabetic breast ductal cells. The results of the insulin antigen absorption test showed a decreasing insulin concentration with the increasing antigen absorption intensity.…”

Diabetic Mastopathy: An Uncommon Complication of Diabetes Mellitus

“…There are several proposed inflammatory stimuli, including glycosylated native collagen in the breast parenchyma [7], deposition of glycosylated end products that act as neoantigens [6, 11], underlying autoimmune disease [1, 12], antibody cross-reactivity to exogenous insulin [13] or insulin contaminants [14], and altered tissue degradation due to locoregional cytokine imbalances [6, 7]. While debate continues about the inciting stimulus, the remaining pathophysiologic mechanisms are better understood.…”