Pigmented Mammary Paget Disease and Pigmented Epidermotropic Metastases From Breast Carcinoma

Abstract

Pigmented mammary Paget disease is a rare clinicopathologic variant of mammary Paget disease. It has been described in female and male patients with intraductal mammary carcinoma extending to the epidermis of the nipple and areola through a lactiferous duct. Pigmented cutaneous metastases from breast carcinoma are uncommon variants of epidermotropic metastatic breast carcinoma. All these lesions may mimic malignant melanoma clinically and histopathologically. From a histopathologic point of view, involvement of the dermoepidermal junction by neoplastic cells of the mammary carcinoma seems to be a prerequisite for development of the clinical pigmentation. We report three examples of pigmented mammary Paget disease and six cases of pigmented epidermotropic metastases from breast carcinoma, which were studied from both the histopathologic and immunohistochemical points of view. Two cases of pigmented mammary Paget disease and all cases of pigmented epidermotropic metastatic breast carcinoma showed the proliferation of dendritic melanocytes arranged as solitary units along the dermoepidermal junction and intermingled with the neoplastic cells of the mammary carcinoma in the superficial dermis. In one case of pigmented mammary Paget disease, there was abundant melanin within the cytoplasm of the Paget cells, but an increased number of melanocytes could not be demonstrated. Local production of melanocytic chemotactic factor by neoplastic cells of the mammary carcinoma when they reach the dermoepidermal junction has been postulated as the cause of the melanocytic proliferation and clinical hyperpigmentation of these epidermotropic breast carcinomas. Another possibility is the phagocytosis or transfer of melanin from melanocytes to the intraepidermal neoplastic cells of the breast carcinoma. Pigmented mammary Paget disease and pigmented epidermotropic metastatic breast carcinoma should be differentiated from melanoma clinical and histopathologically.

Quiz Correct answer to the quiz. check your diagnosis Pigmented paget’s disease of the nipple

“…The areola, as a region rich in melanocytes, shows visible effects of that stimulation. However, similar lesions were also observed in extramammary epidermotropic metastases of breast carcinoma [7] and even in other types of carcinomas [7,[13][14][15][16]. Some authors suggest that the hyperpigmentation may be caused by pigment blockage of melanocytes that have been stimulated to grow and, after that, chemoattracted by cancer cells.…”

“…There are several hypotheses trying to explain its origin. The first one involves stimulation of melanocytes by growth factors that are produced by cancer cells [1,7,11,12]. The areola, as a region rich in melanocytes, shows visible effects of that stimulation.…”

“…Some authors suggest that the hyperpigmentation may be caused by pigment blockage of melanocytes that have been stimulated to grow and, after that, chemoattracted by cancer cells. During migration they are blocked and transfer melanin to other epithelial cells [7,17]. Other authors suggest that the epithelial cells of cancer phagocytose melanin from the melanocytes, which causes hyperpigmentation [1,7,11,18].…”

“…Differential diagnosis of this rare entity might be challenging and mainly includes pigmented epidermotropic metastases of breast carcinoma and malignant melanoma [7]. Epidermotropic metastases of breast carcinoma might rarely be pigmented [15].…”

“…It manifests clinically as a pigmented lesion of the nipple, which is caused by accumulation of melanin [1,4,6]. Hyperpigmentation is associated with proliferation of dendritic melanocytes or with accumulation of melanin within the cytoplasm of Paget cells, keratinocytes or melanophages [7,8].…”