Prepared by J. Andrew Keyoung, MD, Department of Radiology, Stanford University Medical Center, Stanford, CA; Rebecca A. Zuurbier, MD, and Erini Makariou, MD, Betty Lou Ourisman Breast Health Center, Department of Radiology, Georgetown University Hospital, Washington, DC; Theodore N. Tsangaris, MD, Department of Surgical Oncology, The Johns Hopkins Hospital, Johns Hopkins Breast Center, Baltimore, MD; and Norio Azumi, MD, Department of Pathology, Georgetown University Hospital, Washington, DC.

CASE SUMMARY

A 38-year-old woman with a 22-year history of type 1 insulin-dependent diabetes presented with a complaint of a lump in the left breast. Physical examination revealed a palpable nodule in the left breast at the 2 o'clock periareolar region. Diagnostic mammography was performed (Figure 1). Directed ultrasound was then performed (Figure 2). Based upon these findings, the patient underwent ultrasound-guided core breast biopsy (Figure 3).

DIAGNOSIS

Diabetic mastopathy

IMAGING FINDINGS

Diagnostic mammography revealed a heterogenous dense (75% to 80% fibroglandular tissue) breast parenchyma pattern in the left breast without suspicious microcalcifications, masses, or architectural distortions (Figure 1). The directed ultrasound examination at the site of the palpable lump revealed a hypoechoic abnormality with fingerlike projections and intense posterior acoustic shadowing. The lesion measured 4 * 2 * 2 cm. (Figure 2).

PATHOLOGIC FINDINGS

Histologic evaluation revealed a dense stromal fibrosis and some periductal lymphocytic infiltration without any evidence of atypia or malignancy comparable with diabetic mastopathy (Figure 3).

DISCUSSION

Diabetic mastopathy is a benign process found predominantly in patients with type 1 diabetes. These lesions are mainly composed of primarily fibrotic and inflammatory elements. For this reason, terms such as diabetic fibrous breast disease, diabetic fibrous mastopathy, lymphocytic mastitis, and lymphocytic mastopathy have also been used since its first description in 1984 by Soler and Khardori. ¹

The prevalence of diabetic mastopathy has been found to be <1% of benign breast diseases, but prevalence can range from 0.6% to 13% in type 1 diabetics. ^1-3 However, this clinical condition is infrequently encountered since breast examination is not performed routinely in younger diabetic patients. Diabetic mastopathy has been reported in women between the ages of 32.2 and 62 years. ⁴ However, it is also known to occur in men with long-standing diabetes. ⁵

The clinical criteria for diagnosis of diabetic mastopathy includes a long-term (usually >5 years) history of type 1 insulin-dependent diabetes mellitus. The physical examination on presentation is that of hard, irregular, easily movable, discrete, painless breast masses. It can be solitary or multiple, and unilateral or bilateral. ² A patient can also have nonpalpable lesion. ⁶

These patients have been described to have dense fibroglandular tissue at mammography. There have been no reported cases of diabetic mastopathy consisting primarily of adipose tissue or mixed fatty and glandular tissue. Strong acoustical shadowing behind the palpable masses can be seen on sonography. ² Attenuation increases due to the fibrotic nature of the masses. Diabetic mastopathy may mimic malignancy ultrasonographically and may have no significant mammographic manifestation, however. Radiographic and morphologic differential diagnosis for diabetic mastopathy includes invasive lobular carcinoma, simple fibrosis of the breast, fibroadenomas with marked fibrosis, mammary fibromatosis, leiomyomatas, and desmoid tumor. ⁷

Histologically, diabetic mastopathy lesions are composed of dense stromal keloid-like fibrosis containing little or no adipose tissue or cellular material. Furthermore, focal perivascular, periductal, and/or perilobular lymphocytic infiltrations with mature B-cell predominance are commonly seen. Epitheloid fibroblasts in the interlobular stroma are also commonly observed. ^3,8

The pathogenesis of diabetic mastopathy is unknown. Some have postulated that since the currently accepted pathogenesis of type 1 diabetes is of autoimmune etiology, it is likely that diabetic mastopathy is also due to an autoimmune process. ^2,8 Nonenzymatic glycosylation of proteins can lead to metabolic and functional abnormalities with neoantigen, resulting in the autoimmune response. Since fibrous tissue deposition and collagen pro-liferation in the breast are similar to that of other diabetic complications, it is not unlikely that some patients with diabetic mastopathy will have thyroid, eye, and joint involvement due to their long-standing insulin-dependent diabetes.

Diabetic mastopathy has also been described in patients with type 2 diabetes mellitus who had been exposed to exogenous insulin. ⁸ This suggests that the exogenous insulin may be related to its development. This may be due to inflammatory or immunologic reaction to the insulin, the vehicle, or a contaminant in the vehicle.

There have been no reported cases of malignancy arising from diabetic mastopathy to date; there has been one reported case of regression. ⁷ In patients with recurrence, it tends to be in the same location involving more breast tissue than previously seen. ⁷

CONCLUSION

Diabetic mastopathy should be considered in the differential diagnosis of a diabetic patient under-
going a breast biopsy for ultrasonographic findings worrisome for malignancy given the hypoechoic lobulated appearance with finger-like projections. It should also be considered concordant at radiographic-pathologic correlation.