Metastatic melanoma presenting as an isolated breast tumor: a study of 20 cases with emphasis on several primary mimickers.

CONTEXT: The mammary gland can be a site of metastasis in patients with malignant melanoma, which is easily recognized microscopically if clinical information is available. Nonetheless, metastatic melanoma presenting as an isolated mammary tumor can be more challenging to diagnose because it can simulate a primary breast carcinoma clinically and morphologically. OBJECTIVE: To review metastatic melanoma to the breast, presenting as primary breast carcinomas clinically and morphologically. DESIGN: The authors report 20 cases of metastatic melanoma clinically presenting as breast tumors. Cases with widespread metastatic presentation were excluded. RESULTS: Epithelioid and spindle cell tumors predominated, suggesting mammary ductal, papillary, or sarcomatoid carcinoma. Most cases (16 of 20) were submitted for consultation or second opinion owing to their unusual presentation in the breast, or to perform predictive/prognostic immunohistochemical assays. Seven cases had a remarkable phenotypic spectrum expanding the differential diagnosis to large cell lymphoma, leiomyosarcoma, medullary carcinoma, malignant schwannoma, and liposarcoma. Tumor cells were negative for cytokeratin stains and positive for S100 protein, HMB-45, and Melan-A. Negative staining was also observed for epithelial membrane antigen, CD45, desmin, estrogen and progesterone receptors, and human epidermal growth factor receptor 2. CONCLUSIONS: Metastatic melanoma may simulate a broad spectrum of primary breast malignancies. Although the application of a simple panel of antibodies assists in rendering the correct interpretation, lesions presenting as isolated breast tumors may introduce a significant diagnostic difficulty, especially when there is inadequate patient history and/or limited biopsy material. Further challenges are introduced by the extraordinary phenotypic plasticity of metastatic melanoma. Awareness of this pattern variance is essential to avoid inappropriate treatment, especially in cases simulating a "triple negative," poorly differentiated carcinoma of the breast.