The rare entity of bilateral and unilateral neuroendocrine metastases to the breast: a case series and literature review

Abstract

Introduction: Primary neuroendocrine neoplasms (NENs) in the breast are very rare. Until 2011, the prevalence was 0.1% of all breast lesions and 1% of all NENs, whereas metastatic breast NENs represent 1%-2% of all breast tumours. However, it seems that over the last 5 years the diagnostic frequency of breast NENs has increased, probably for more alert specialists and advanced diagnostic tools, leading to a prevalence of 2%-5% of diagnosed breast cancers, mostly in the elderly population. Breast metastases from extramammary malignancies are uncommon and bilateral ones are even more uncommon, with few reported in the literature. We describe four clinical settings of breast metastases from different NENs and the multidisciplinary approach for diagnosis and treatment.

Methods: Four patients were found to have NEN primaries metastasised to the breast. A literature review was conducted to identify similar cases and characterise breast metastases from neuroendocrinal tumors (NETs).

Results: Two patients presented with bilateral breast metastases (one with well-differentiated panNET and another with atypical lung carcinoid) and two had unilateral (one with moderately differentiated lung NET and one with atypical lung carcinoid). There are about 13 cases of NEN breast metastases reported in the English literature. The ileum is the most common primary site, followed by the appendix, duodenum, pancreas and lung.

Conclusion: Breast lesions from extramammary primary often pose a diagnostic challenge, since a breast nodule can be the first and often the only presentation of the disease. However, differentiating between primary and secondary NEN breast lesions is essential, owing to different clinical management and prognosis.

Keywords: bilateral; breast metastases; neuroendocrine; neuroendocrine neoplasms; neuroendocrine tumours.

Figure 1.. Primary small cell neuroendocrine carcinoma of the breast. (A): Neuroendocrine tumour infiltration from sheets of uniform cells with round nuclei; (B): immunohistochemistry for oestrogen receptor shows nuclear reactivity only in non-neoplastic ductal cells while tumour cells are negative; (C): at least for 50% of the population it shows cytoplasmic reactivity for chromogranin and (D): Very high Ki67 proliferative index.

Figure 2.. Breast metastases from pancreatic NET (FNA): Cytopathology could not give information about tumour biological features; the neoplastic elements are uniform and consist of small cells with scant cytoplasm, salt-and-pepper chromatin and micronucleoli and consistent neuroendocrine tumour (A and D: HE 40×; B: Papanicolau 40×; C: Giemsa 100×).

Figure 3.. Breast metastases from pancreatic NET (inset: core biopsy). (A): nests of uniform cells with round nuclei; (B): with high proliferative index of 18% by Ki67; (C): immunohistochemistry for chromogranin A shows diffuse cytoplasmic reactivity in tumour cells and (D) on the other hand, only the lobular structures show positivity for CK7.

Figure 4.. Metastatic breast NET from lung carcinoid. (A): Breast tissue infiltrated in lobular carcinoma fashion; (B): immunohistochemistry for CK7 and for synaptophysin; (C): diffuse cytoplasmic reactivity in tumour cells and (D) with typical pagetoid involvement of the hyperplastic duct.