Spectrum of Imaging Findings in Paget’s Disease of the Breast—A Pictorial Review

Mammography plays an important role in the diagnosis and management of Paget’s disease; however, it has its own limitations and may be normal in some cases (Fig. 2). The common mammographic findings are skin thickening in the nipple areolar region (Fig. 3), asymmetric density (Fig. 4), nipple retraction or a discrete mass. The mass may be sub-areolar or distant from the nipple-areolar region. Other findings include malignant pleomorphic calcifications (Figs. 5 and 6) that may or may not be associated with skin thickening or architectural distortion. The role of mammography in Paget’s disease is not only in detection of an underlying mass or DCIS, but also in follow-up of patients undergoing conservative breast surgery so that recurrence can be ruled out. Various studies have evaluated the role of mammography in Paget’s disease. In a study by Gunhan-Bilgen et al. [10], 15 % of cases had a negative mammogram while Ikeda et al. concluded that 50 % cases with typical clinical features of Paget’s disease had negative mammography findings [11]. Morrogh et al. found that 65 % patients with a negative mammogram had an underlying unifocal cancer [12]. Muttarak et al. [13] studied the clinical, imaging and pathological findings in 16 cases of Paget’s disease and found a high degree of invasive carcinoma as most of their patients presented late and had positive mammographic findings.

Ultrasound is used not only to confirm the mammography findings in a case of Paget’s disease, but also when the mammogram is negative. The findings on ultrasound include heterogeneous hypoechoic areas in breast parenchyma, presence of a discrete mass or dilated ducts. Microcalcifications are not appreciated on ultrasound. Sometimes, there may be an area of DCIS with pleomorphic calcification on mammogram with an underlying mass, which is better appreciated on ultrasound (Figs. 7a and b and 8a and b). In some cases, however, even when there is pleomorphic calcification with nipple areolar thickening on mammogram, ultrasound findings can be non-specific and may show only skin thickening in the nipple areolar region (Fig. 9a, b and c).

With advances in technology and use of dedicated breast coils, magnetic resonance imaging (MRI) is increasingly being used for evaluation of clinically suspected cases of Paget’s disease (Figs. 10a–e and 11a and b). It is a highly sensitive modality and can be used in cases where both mammography and ultrasound findings are negative.

At times there is a diagnostic dilemma in a case of chronic mastitis presenting with a thickening and palpable mass in the nipple areolar region, where imaging helps in making a diagnosis (Figs. 12 and 13) and helps in deciding management.

In a case report by Amano et al. [14], MRI accurately depicted underlying DCIS in a patient without a palpable mass or any positive mammography findings.

The findings on MRI include thickening and enhancement of nipple-areolar complex, an underlying mass, enhancing DCIS or a combination of these findings. Enhancement patterns of the normal nipple-areolar complex are variable, including absent, mild or intense enhancement [7]. However, on comparing the two sides, asymmetric enhancement is noted in the nipple-areolar region with the involved region showing irregular, discoid or irregular enhancement in the case of Paget’s disease [15]. Nipple involvement may also be seen even when there is no clinical suspicion of Paget’s disease [16]. If there is no mass in the sub-areolar region, the entire breast has to be examined to detect any mass that is away from the nipple-areolar region, as the management in such cases is based on imaging findings. Echevarria et al. [17] discussed the effectiveness of MRI in detecting occult breast cancer associated with Paget’s disease of the nipple-areolar complex, while Peters et al. [18] discussed the role of MRI as a problem-solving tool in patients with a normal mammogram and no clinically palpable mass. Frei et al. [19] evaluated pre-operative mammography and MRI findings in nine biopsy proven cases of Paget’s disease and concluded that Paget’s disease of breast with underlying DCIS can be effectively diagnosed by MRI. Though Paget’s disease is predominantly a clinical diagnosis, negative mammography cannot reliably exclude underlying malignancy. Both clinical and imaging findings are complementary to each in order to make a diagnosis [20].

The treatment of Paget’s disease has been controversial and depends upon the origin of Paget cells. If the epidermotropic theory is believed, then there is an invasive component in the breast and the treatment of choice is mastectomy. The intraepidermal transformation theory, however, says that Paget’s cells form de novo in nipple epithelium, and hence, the treatment of choice in cases confined to the nipple areolar region is resection of nipple-areolar complex followed by local irradiation, making the role of mastectomy controversial.

Earlier, the treatment was mastectomy with or without axillary dissection. In one of the earliest studies by Joseph and Robinson in 1981, involvement of axillary lymph nodes was described as an important prognostic factor, and modified radical mastectomy was recommended in this group of patients [21]. There may be recurrence or distant metastasis in patients with axillary lymph node involvement (Fig. 14). Kothari et al. studied 70 patients of Paget’s disease and found that since it is often associated with underlying malignancy, cone excision of nipple would result in incomplete excision in 75 % cases [22]. Dixon et al. reported high recurrence rates (40 %) in cases treated with local excision where there was an in-situ component along the nipple region [23]. In cases of Paget’s disease of the nipple with DCIS or invasive cancer away from the nipple areolar region, complete resection of disease and the nipple areolar complex is needed, followed by radiotherapy [24]. Dalburg et al. did not find any difference in survival rates in patients of Paget’s disease who underwent breast conservative surgery or mastectomy [25]. Therefore, in a histopathology proven case of Paget’s disease of the nipple, a pre-operative MRI of the breast should be performed to know the exact nature and extent of disease, especially when breast conservative surgery is contemplated as the treatment.