Comparison of metastatic neuroendocrine neoplasms to the breast and primary invasive mammary carcinomas with neuroendocrine differentiation

Abstract

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. Metastases to the breast are unusual, comprising less than 1% of all malignant neoplasms of the breast. [1][2][3][4][5] The majority of the metastatic lesions originate from the contralateral breast or hematopoietic malignancies. 1,2,5 Stomach, kidney, ovary, lung, and skin are the other common primary sites. [1][2][3][4][5] Metastatic neuroendocrine neoplasms to the breast are rare and comprise only 1-2% of all metastatic tumors to the breast. To the best of our knowledge, less than 50 cases have been described to date, primarily in the form of isolated case reports and rare case series. Metastatic neuroendocrine neoplasms to the breast may show considerable morphologic overlap with in situ ...

Cytomorphology of metastatic pituitary carcinoma to the bone

“…Because the frequency of metastatic pituitary carcinoma to multiple bones is much less than metastatic neuroendocrine tumor of lung and breast, the metastatic neuroendocrine tumor should be excluded. The tumor cells were immunonegative for CK7, TTF‐1, and GATA‐3, a pattern that is not supportive of either lung or breast adenocarcinoma or neuroendocrine tumor . Consequently, additional immunostains were needed.…”

“…The tumor cells were immunonegative for CK7, TTF-1, and GATA-3, a pattern that is not supportive of either lung or breast adenocarcinoma or neuroendocrine tumor. 17,18 Consequently, additional immunostains were needed.…”

Primary lung carcinoid metastatic to the breast

“…The histopathologic and immunohistochemical distinction is crucial for distinguishing metastatic neuroendocrine neoplasm to the breast from invasive mammary carcinoma as appropriate clinical management can differ. Histologically, nearly all metastatic neuroendocrine tumors to the breast are strongly and diffusely positive for neuroendocrine markers, synaptophysin and chromogranin [7]. In addition, a neuroendocrine metastasis will be estrogen receptor negative and GATA3 negative.…”

“…In addition, a neuroendocrine metastasis will be estrogen receptor negative and GATA3 negative. Breast neuroendocrine metastasis from a lung primary is commonly thyroid transcription factor-1 positive, as opposed to negative in a primary breast carcinoma [7]. The median survival for metastatic atypical pulmonary carcinoid is 3.3 years, with a 5-year survival rate at a dismal 24% [6].…”

Appendiceal neuroendocrine tumour presenting as bilateral ovarian and breast metastasis

“…The main markers that are useful are: [14][15][16][17][18][19][20] • ER/PR, Mamaglobin, GATA 3 for mammary origin • TTF1 for pulmonary origin…”