Metastatic neuroendocrine
neoplasms to the breast may show considerable morphologic overlap with primary mammary
carcinomas, particularly those showing evidence of neuroendocrine differentiation, and may be misdiagnosed as such. Accurate distinction between these two entities is crucial for determination of appropriate clinical management. The histologic and immunohistochemical features of metastatic neuroendocrine
neoplasms to the breast were studied and compared with the features of primary invasive mammary
carcinomas with neuroendocrine differentiation, which served as controls. Of the metastatic neuroendocrine
neoplasms, 15 were well-differentiated
neuroendocrine tumors with
carcinoid tumor-type morphology and 7 were poorly differentiated/high-grade
neuroendocrine carcinomas with small-cell or large-cell neuroendocrine
carcinoma morphology. The majority of the metastatic
neoplasms originated in the lung and gastrointestinal tract. There were histologic similarities between metastatic neuroendocrine
neoplasms and invasive mammary
carcinomas with neuroendocrine differentiation, both of which exhibited neuroendocrine histologic features (nested and trabecular architecture, minimal tubular differentiation, and characteristic nuclear features). Only one case of the invasive mammary
carcinomas with neuroendocrine differentiation was modified Bloom-Richardson grade 1 (largely due to minimal tubular differentiation on most such
tumors), and the invasive mammary
carcinomas with neuroendocrine differentiation were often associated with in situ
carcinoma. Immunohistochemistry was helpful in distinguishing metastatic neuroendocrine
neoplasms from invasive mammary
carcinomas with neuroendocrine differentiation. Whereas the majority of invasive mammary
carcinomas with neuroendocrine differentiation were positive for
estrogen receptor and GATA3, metastatic neuroendocrine
neoplasms were typically negative for
estrogen receptor and GATA3, and metastatic well-differentiated
neuroendocrine tumors often showed immunoreactivity for site-specific markers. Although the histologic and immunohistochemical features of a
breast tumor may raise the suspicion of a metastatic neuroendocrine
neoplasm, the pathologic findings should be interpreted in the context of the clinical history and imaging findings in order to establish an accurate diagnosis.