Pigmented mammary Paget disease is a very rare clinicopathologic variant of mammary Paget disease. Because the clinical and histological features of pigmented mammary Paget disease are very similar to those of malignant melanoma, it is very difficult to differentiate and diagnose. Herein, we describe a case of pigmented mammary Paget disease mimicking malignant melanoma.

A 67-year-old Asian woman with a history of breast and thyroid cancers presented with an asymptomatic brownish to black plaque on the left nipple that had been present for 10 years (Fig. 1A). Ten years previously, she had a diagnosis of ductal carcinoma in situ of the left breast and she underwent partial mastectomy with postoperative radiation therapy. She had regular positron emission tomography/computed tomography (PET/CT) scans for recurrence evaluation during the 10-year follow-up period. Her last PET/CT scan follow-up was 2 years ago; however, no evidence of recurrence or metastasis was noted at that time. On dermoscopy, the lesion showed multiple colors, irregular dots/globules, small gray-blue pepper-like granules, and scar-like depigmentation, which strongly suggest malignant melanoma (Fig. 1B). A punch biopsy was performed at the darkest part of the lesion. Hematoxylin and eosin staining showed large neoplastic epithelial cells with pigmentation. Furthermore, a focal neoplastic microinfiltration was seen in the superficial dermis with moderate inflammatory infiltrate (Fig. 2A). On the basis of the clinical and histopathologic findings, the lesion was diagnosed as malignant melanoma. Following this initial biopsy, wide excision with 1 cm margins and sentinel lymph node biopsy were performed. In frozen-section examination, micrometastases were not identified; therefore, a complete lymph node dissection was not performed. Hematoxylin and eosin staining of the excised specimens showed atypical epithelial cells with pale cytoplasm containing hyperchromatic large nuclei. The tumor cells were scattered or formed clusters along and above the basal layer of the epidermis; however, the cells were restricted within the epidermis. Inflammatory cell infiltration, mostly composed of lymphocytes, with some melanophages in the superficial dermis was also seen (Fig. 2B). Immunohistochemical tests showed that the tumor cells were positive for cytokeratin 7 (CK7) (Fig. 2C), epithelial membrane antigen (EMA), and C-erbB2 (Fig. 2D). The cytoplasm of the tumor cells was positive for D-PAS staining. The tumor cells were negative for S-100, HMB-45 (Fig. 2E), and Melan-A staining (Fig. 2F). On the basis of these findings, the diagnosis was revised as pigmented mammary Paget disease. The sentinel lymph node in frozen section was reported negative for micrometastases; however, the final pathologic report with immunohistochemical staining showed metastatic carcinoma in one lymph node (maximal metastasis dimension, 2 mm). The patient was referred to the general surgery department for total mastectomy and total axillary lymphadenectomy. A diagnosis of invasive ductal cancer was concluded after mastectomy, and the patient is currently undergoing chemotherapy.

Paget disease of the breast usually presents as an erythematous patch mimicking nipple eczema. However, Azzopardi and Eusebi1 first described pigmented mammary Paget disease as a pigmentation of breast carcinoma in 1977. Currently, about 35 cases have been reported in the literature2. A possible explanation for the mechanism of hyperpigmentation was that Paget cells might induce the production of melanin from normal melanocytes3.

Because the clinical, dermoscopic, and histologic features are very similar with malignant melanoma, immunohistochemical staining is essential for differentiating pigmented mammary Paget disease from malignant melanoma. The tumor cells show positive staining for CK7, EMA, C-erbB2, and CAM 5.2 but negative for melanoma cell markers such as S-100, Melan-A, and HMB-454. In our case, because the clinical, dermoscopic, and histological features of the patient were consistent with the features of malignant melanoma, we performed a wide excision without immunohistochemical evaluation. Because a misdiagnosis was made owing to a lack of evaluation, an unnecessary excision was performed before total mastectomy.

Although it is very difficult to differentiate Paget cells from melanoma cells on the basis of histologic features, there are some different features between them. Paget cells are situated above the basal keratinocytes with some ductal formation, whereas melanoma cells are located in all layers of the epidermis including the basal layer, with intraepidermal pagetoid spread. Also, Paget cells are not seen freely in the dermis, whereas melanoma cells may be present in the dermis5,6. Nevertheless, as these differences are not often obvious, immunohistochemical staining is necessary.

An intraductal or infiltrating ductal carcinoma of the breast can be seen in association with mammary Paget disease7. In our case, the patient also previously had ductal carcinoma in situ and received partial mastectomy with postoperative radiation therapy. However, although our patient had regular evaluations with biennial PET/CT scan and annual mammography during 10 years, mammary Paget disease has not been detected. A few case reports have documented the efficacy of the detection of extramammary Paget disease by using PET/CT scan; however, there is no report about its usefulness in mammary Paget disease. In our case, PET/CT scan did not detect the lesion although it has been existing for 10 years. Therefore, skin biopsy should be performed in suspicious lesions by using checklists such as the ABCDE criteria.

Because the treatment and prognosis of pigmented mammary Paget disease and malignant melanoma are different, the diagnosis of pigmented lesions of the breast should be decided carefully. In this case, immunohistochemical staining is indispensable for the final diagnosis of pigmented mammary Paget disease.