Metastases from NMMN are rare and account for less than 1% of all mammary malignant neoplasms in clinical series, and up to 5% of autopsies of patients who die as a result of NMMN (1). Such tumors are relatively more common in females. The interval between initial diagnosis of a NMMN and mammary metastases is usually about 2 years—but it can vary from a few weeks to several years. In approximately one-third of the cases, the metastasis in the breast is the first presentation of the NMMN. Usually, there have already been metastases at other sites, or the tumors are detected at various sites synchronously (2,3).

Metastatic foci in breast often present initially as solitary masses (2). Upon disease progression, such tumors can become multiple and bilateral (3). Metastases have been described in the ipsilateral axillary lymph nodes in a substantial proportion of patients with metastases in the breast (2).

Hematopoietic and lymphoid neoplasms involving the breast are sometimes listed under the rubric of breast “metastases,” but they are best regarded as either primary breast neoplasms or as a manifestation of a systemic condition, depending upon the extent of organ involvement. If hematopoietic and lymphoid neoplasms are excluded, the most common NMMNs that secondarily involve the breast include carcinomas of the lung, ovary, stomach, kidney, and cutaneous melanoma. Metastasis from the contralateral breast is a diagnostic consideration when there is bilateral involvement (or history thereof), the histologic appearances of the tumors in the breasts are similar, and there is no evidence of in situ carcinoma in the contralateral breast. In the pediatric population, lymphoma and rhabdomyosarcoma are the most common sources of NMMN in the breast.

On mammography, metastatic tumors tend to present as discrete, solitary, or multiple round masses without spiculation (3). As a result, metastatic tumors cannot be distinguished radiologically from circumscribed primary breast carcinomas, particularly those of the papillary, medullary, or mucinous types. Calcific deposits are uncommon in metastases from NMMN but may occur in metastatic mullerian (tubal, ovarian, or peritoneal) carcinomas (4,5). Ultrasonography typically shows the lesions to be hypoechoic without spiculations (6). Radiologic techniques such as MRI (magnetic resonance imaging) and FDG-PET/CT (fluorodeoxyglucose-positron emission tomography-computed tomography) have also detected metastases in the breast from carcinoma of the thyroid (7), ovary (8), and soft tissue liposarcoma (9). In the latter two instances, the diagnosis of a metastatic NMMN was confirmed by a NCB.

The histopathologic appearance of NMMN in the breast is seldom specifically indicative of the site of origin. A notable exception is pigmented metastatic melanoma, although pigmented melanocytic differentiation can occur in metaplastic mammary carcinoma (10). Melanoma arising in the breast is usually a form of metaplastic carcinoma, and it may therefore express cytokeratin. Noncytokeratin expressing primary melanoma of the breast is neurogenic in origin and cytokeratin-negative. Nonetheless, primary melanocytic lesions of the breast are exceedingly less common than metastatic melanocytic neoplasms.

Among the metastatic carcinomas in the breast that are most likely to be mistaken for a breast primary are those arising in the lung, ovary, mullerian system, and bowel. Included in this group are mucinous, signet ring cell, clear cell, and poorly differentiated non-small cell carcinomas of various organs, as well as malignant melanoma (11). Some types of breast tumors such as small cell, adenoid cystic, and mucoepidermoid carcinomas can occur in other organs, and appropriate clinical workup is prudent in these cases. Metastatic neuroendocrine carcinomas of various organs generally share histologic features with primary mammary carcinoma (12).

Histopathologic evaluation of the limited material obtained in NCB samples is unlikely to provide all of the information that would help to distinguish between a primary and a metastatic tumor. The presence of in situ carcinoma that is histologically similar to the invasive lesion rules out a metastatic NMMN. On the other hand, the absence of in situ carcinoma in association with invasive carcinoma is supportive (but not diagnostic) of metastatic rather than a primary breast carcinoma. Metastatic tumor often surrounds and displaces histologically unremarkable breast glandular parenchyma. This phenomenon is less frequent in primary mammary ductal carcinoma, but it is encountered in invasive lobular carcinoma. The latter typically shows little or no hyperplasia. A peripheral lymphocytic infiltrate and stromal reaction are not unusual at the site of metastatic tumor in the breast as well as in primary breast carcinomas. The finding of more than two grossly evident tumor nodules should lead one to consider metastatic tumor, especially if the histologic pattern is unusual. Lymphovascular tumor emboli may result from metastases in the breast as well as from primary breast carcinomas. Diffuse lymphatic spread of metastatic tumor within the breast can occur, and rarely it produces the clinical appearance of inflammatory carcinoma (13).

An unusual histologic pattern and clinical information about a prior neoplasm are the best clues for identifying a metastatic tumor in the breast. It is important to be sensitive to histopathologic patterns that are not typical for breast carcinoma.