Solid neuroendocrine carcinomas of the breast: metastases or primary tumors?

Abstract

Neuroendocrine breast carcinomas are rare but may represent either metastatic or primary lesions. So far, clinical and preoperative histopathological examinations do not distinguish properly between a primary or metastatic breast tumor. Due to any possible consequences following an appropriate treatment, markers which may be helpful for such a distinguishment are needed. We addressed this study in order to evaluate the immunohistochemical expression of GCDFP-15 and mammaglobin in a subset of pure neuroendocrine breast carcinomas (n = 9) and compared the expression profile with a cohort of non-mammary neuroendocrine tumors (n = 99). We observed in our study that solid neuroendocrine breast carcinomas are characterized by the expression of estrogen and progesterone receptors as well as GCDFP-15 and/or mammaglobin. GCDFP-15 was expressed in 6 out of 9 cases, mammaglobin was positive in 4 out of 9 tumors. In contrast, neuroendocrine tumors of the non-mammary cohort expressed neither GCDFP-15 nor mammaglobin. We conclude that mammaglobin and GCDFP-15 as markers of epithelial breast origin may work as a new and reliable diagnostic tool to distinguish primary endocrine tumors of the breast from a metastatic neuroendocrine disease. This is of utmost importance, especially for surgical management.

Diagnostic utility of mammaglobin and GCDFP-15 in the identification of primary neuroendocrine carcinomas of the breast

“…Table 1 summarizes the immunohistochemical profile for the expression of estrogen receptor (ER), progesterone receptor (PR), HER2, mammaglobin, and GCDFP-15 in tumor specimens from NEBC patients. Our findings largely recapitulate those presented by Richter-Ehrenstein et al [7]. All NEBC expressed high levels of estrogen and progesterone receptors.…”

“…In three patients, both markers were negative. Remarkably, they did not find any expression of mammaglobin or GCFFP-15 in immunohistochemical evaluation of chromogranin A/synaptophysin-positive non-mammary neuroendocrine tumors [7]. confirm the primary nature of these endocrine tumors, we recently tested the hypothesis that mammaglobin stating can help, in combination with GCDFP-15 (a sensitive and specific marker of breast carcinoma), to establish the correct diagnosis of breast carcinomas [9].…”

“…It was intriguing that HER2 2+ staining (but absence of gene amplification) was found in the sole NEBC that was negative for both markers. Richter-Ehrenstein et al similarly reported that HER2 overexpression was found in only one NEBC, which was negative for both markers [7]. Although the very small number of cases obviously limits the relevance of the correlation between HER2 positivity and mammaglobin/GCDFP-15 double-negative NEBC patients, additional studies with longer follow-up and more cases need to be further pursued to establish whether this "combimarker" (i.e.…”

“…have recently evaluated a new diagnostic tool to distinguish between primary NEBC from a metastatic disease of other sites [7]. Using the immunohistochemical markers for epithelial of breast origin mammaglobin and Gross Cystic Disease Fluid Protein (GCDFP-15), they compared a subset of pure NEBC (n=9) with a cohort of nonmammary neuroendocrine tumors.…”

Primary Neuroendocrine Tumor of Breast: Report of a Rare Case with Review of Literature

“…In the Breast imaging study could not differentiated the primary from metastatic NETs [3]. In clinical examination primarily focus on ruling out breast metastasis from small cell carcinoma of the lung, the gastrointestinal tract, pancreas, and the cervix.…”