Diabetic mastopathy (DMP) is an uncommon benign fibrotic disease of the breast in patients with a history of long-standing diabetic mellitus (DM). It was first described as a breast lump consisting of fibrous tissue and lymphocytic infiltration in 12 patients with type I DM [1]. Since its first description, DMP has been widely recognized as a complication of type I DM. However, some recent reports have demonstrated that DMP can also be associated with type II DM [2,3]. One of the earliest studies of DMP reported the imaging findings of DMP in 36 patients with long-standing type I DM and cataloged some helpful imaging findings, such as radiodense glandular tissue, strong acoustic shadowing in ultrasonography (US), and firm resistance to needle motion during the fine-needle aspiration (FNA) procedure [4]. Subsequent studies have reported similar findings, including heterogeneously dense breast parenchyma, dense glandular tissue or asymmetry in mammograms, and irregular hypoechoic solid lesions with posterior acoustic shadowing in US. However, those studies had limited generalizability due to the small number of cases available [2,5].

DMP often presents as a palpable mass, but it may also be asymptomatic and is sometimes found incidentally during screening mammography or US. The imaging features are often suspicious for malignancy, meaning that biopsy is necessary. FNA is the least invasive option for the diagnosis of breast lesions, but it frequently provides inadequate specimens, which is why core needle biopsy (CNB) is the preferred method for diagnosing potentially malignant breast lesions [4,6,7]. To the best of our knowledge, no research has analyzed the imaging findings of DMP based on the Breast Imaging Reporting and Data System (BI-RADS), and to our knowledge, no studies have evaluated the role of image-guided biopsy in the diagnosis of DMP.

Therefore, the purpose of this study was to evaluate the imaging features of DMP and the role of image-guided biopsy in its diagnosis.

This retrospective review of images and medical records was approved by the Institutional Review Board of our institution, and the requirement for informed patient consent was waived. The pathology database of our institution-a tertiary medical center-was searched for cases with the keyword ‘diabetic mastopathy’ between 2004 and 2014. A total of 19 patients who underwent both imaging studies and biopsy at our institution were ultimately included in our study.

The etiology and pathophysiology of DMP have not been adequately explained, and only hypotheses have been proposed. According to one hypothesis, hyperglycemia is the key etiology of DMP. Glycosylation is accelerated in hyperglycemia, and excessive levels of glycosylated end products induce an autoimmune response, causing lymphocytic infiltration and fibrosis. According to this theory, the severity and duration of hyperglycemia is an important predictive risk factor for DMP [8-13]. Another theory explains DMP as breast involvement of systemic autoimmune disease, based on the similarity of histological features observed in DMP lesions and lymphoepithelial lesions from Hashimoto thyroiditis or Sjögren syndrome [14]. Others have proposed that exogenous insulin itself, its delivery mechanism, or contaminants therein trigger an immune reaction that consequently results in DMP [9,15]. In the past, when studies of DMP were far more limited, DMP was thought to be a breast disease that specifically occurred in type I DM patients using exogenous insulin [15]. However, DMP has also been found in type II DM patients. In fact, this study, although there were five patients with DM of unknown type, included more type II DM patients (n=11) than type I DM patients (n=3). This epidemiological trend may reflect the increased prevalence of long-standing type II DM, due to its increased incidence and the prolonged survival period of type II DM patients.

The mammographic findings of DMP in our study, which were mostly negative findings in dense breast parenchyma, were consistent with those reported in previous studies [5,9]. In contrast, the US findings of DMP, which are discussed further below, were usually suspicious for malignancy. The presence of conflicting results between mammography and US may be helpful in diagnosing DMP.

The US findings varied from case to case, but the most typical US findings observed for DMP were an irregularly shaped, heterogeneous echoic mass with posterior shadowing, which was also consistent with previous studies [5]. These US findings, which were observed in the majority of DMP lesions, corresponded to a diagnosis of BI-RADS category 4, meaning that the biopsy was necessary to exclude malignant tumors from the differential diagnosis.

The US findings in six of the 19 lesions did not resemble masses (i.e., were not space-occupying lesions in two different dimensions), and we therefore classified them as non-mass lesions. This term is not present in the most recent BI-RADS US lexicon, and no standardized method exists for interpreting this kind of lesion. In clinical practice, however, lesions sometimes cannot be classified as masses since they do not meet the definitive criteria of masses. Non-mass-like enhancement is a well-known category in the breast magnetic resonance imaging lexicon, but this terminology has not been commonly used in breast US. However, after the Japan Association of Breast and Thyroid Sonology termed these lesions non-mass image-forming lesions, the term ‘non-mass’ has started to appear in published studies [16,17]. According to a recently published report regarding the US and histopathological findings of non-mass lesions, five cases of DMP were found among 164 non-mass lesions [18]. The authors classified the US findings of non-mass lesions into four types: type I lesions are non-mass lesions showing multiple duct-like structures arranged in a parallel orientation, type II lesions involve a mottled area that does not present as a discrete mass, type III lesions are non-mass lesions associated with architectural distortion, and type IV lesions are non-mass lesions presenting with posterior acoustic shadowing. The five DMP lesions found in this study all showed a type IV pattern on US, and the positive predictive value of type IV non-mass lesions for malignancy has been reported to be similar to that of BI-RADS category 4B. All of the six non-mass-like DMP lesions found in our study were also associated with posterior shadowing, falling into the category of type IV lesions. If type IV non-mass lesions can be equated to BI-RADS category 4B, the pathologic result of DMP from these lesions can be considered concordant with the imaging findings.

Since it is currently impossible to differentiate between DMP and breast cancer based on imaging studies, pathological examination is necessary in most cases. A sample from the breast lesion can be obtained using several methods, and the least invasive procedure is usually preferable. However, FNA, which is considered to be the least invasive procedure, is not commonly used because it often yields inadequate specimens for the diagnosis of DMP [12]. The results of our study showed that CNB yielded a conclusive diagnosis in approximately half of the cases, as ten of the 18 patients who underwent CNB were diagnosed with DMP. Nonspecific fibrosis was the most common result among the cases of DMP that were not correctly diagnosed by initial CNB. In these cases, as CNB acquires only a small part of the lesion, it may have missed the site of inflammation, which is an important diagnostic clue for pathologists. However, CNB is still a better method for the initial biopsy of suspicious breast lesions than FNA or VAB with regard to reliability, feasibility, and risk.

The role of US-VAB in the diagnosis of DMP has not yet been studied. In our study, eight patients who did not receive a specific diagnosis based on initial CNB findings were pathologically diagnosed with DMP via VAB, meaning that surgical excision was fortunately avoided. When the initial biopsy of a suspicious lesion fails to yield a definitive diagnosis, re-biopsy generally requires a larger amount of breast tissue. We suggest that US-VAB is a useful method in this situation, as it provides a larger specimen while still being less invasive than surgical excision. Surgical excision is not required in cases of DMP, as DMP is a universally benign type of lesion. Furthermore, previous studies have stated that surgical biopsy should not be considered because the recurrence rate of the disease has been reported to be as high as 60% [12,19].

This study had some limitations. First of all, it was a retrospective study, meaning that selection bias was inevitable. Since the study population was obtained by searching our institution’s pathology database, patients with DMP who did not undergo biopsy, presumably due to benign-appearing imaging findings, were missed. In addition, since the sonograms were reviewed retrospectively, unmeasurable interperformer differences may have been present. Many patients had limited clinical information regarding their DM status, since their DM was managed in other clinics. Therefore, the overall incidence of DMP and its relationship with various clinical conditions, such as DM complications, medication, or length of hyperglycemia must be evaluated in other future studies with a more specific cohort of DM patients.

In conclusion, while the majority of DMP lesions showed negative findings or nonspecific focal asymmetry on mammograms, the US features were commonly suspicious for malignancy, corresponding to BI-RADS category 4 and making a pathologic diagnosis necessary. US-CNB is the method of choice for initial biopsy due to its feasibility and reliability. As CNB gives nonspecific results in some cases, assessing the correlation between imaging and pathology plays an important diagnostic role, and an additional biopsy may be required. In the cases included in this study, US-VAB sufficed for a conclusive diagnosis, and surgical excision was therefore avoided.