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.

Figure 1

Three separate tumors of the breast by palpation and imaging, two hard tumors in the CDA and A areas of the right breast and one nonpalpable solid tumor in the C area of the left breast were found.

Figure 2

Magnetic resonance imaging of the breast dense microlobulated masses with irregular margins, 43 × 52 × 37 mm and 17 × 23 × 14 mm, were seen in the CDA and A areas of the right breast, respectively. In the C area of the left breast, a similar characteristic mass, 11 × 20 × 15 mm, was also seen.

Figure 3

Macroscopic cut sections of the tumor A well-defined elastic hard mass, 2.5 × 2 × 1 cm, was excised from the A area of the right breast. Meshwork composed of whitish fibers separating atrophic fatty breast tissue was observed.

Figure 4

Histology of the breast tumor (×40). Many small lymphocytes infiltrated periducts with surrounding dense collagen fibers, accompanied by lymph follicles with germinal centers.

Figure 5

High magnification of the tumor (×400). Small lymphocytes infiltrated between ductal epithelia forming lymphoepithelial lesions.

Figure 6

Lymphocyte markers by immunostaining. Infiltrating lymphocytes consisted more of CD20-positive cells than CD3-positive cells. IgG4-positive lymphocytes were rarely found compared with IgG positive cells.

Figure 7

Autoantibody reacting to the patient's own (a), other DM patient's (b), and non-DM patient's (c) breast tissue. Using the patient's serum as the primary antibody, ductal epithelium showed positive staining at a 1 : 200 dilution.

Figure 8

Antibody absorption test with insulin added to the primary serum at 40 ng/mL (a), 4 μg/mL (b), and 40 μg/mL (c). Staining intensity attenuated corresponding to insulin concentration. At 40 ng/mL, positive staining of ductal epithelia remained, while at 4 μg/mL, staining intensity decreased significantly and almost disappeared at 40 μg/mL.