Colonic Carcinoid Metastatic to the Breast Open Access

Metastatic tumors of the breast are uncommon. Such metastases from nonmammary sources are exceedingly rare, accounting for approximately 2% of all breast tumors.1 The published reports of nonmammary tumors that can metastasize to the breast include bronchogenic carcinomas, malignant melanomas, rhabdomyosarcomas, malignant mesotheliomas, thyroid carcinomas, renal cell carcinomas, malignant lymphomas, and gastrointestinal carcinomas.2,3 Malignant neoplasms from gastrointestinal tract organs that have been reported to metastasize to the breast include those from the stomach, pancreas, esophagus, and colon. The majority of these tumors are adenocarcinomas.4 Approximately 23 cases of carcinoid tumors with associated breast metastasis, as distinct from primary carcinoid tumors of the breast, have been reported.5 Distant metastases from carcinoid tumors are usually associated with a poor prognosis and decreased survival. Thus, although both primary and metastatic mammary carcinoid tumors are uncommon, the proper recognition of such lesions is important owing to the different clinical management and prognosis of these patients.

A 53-year-old woman presented to our clinic with a palpable breast lump. The mammogram was noncontributory. A lumpectomy was performed that, on frozen section, showed a neoplastic lesion. Permanent sections showed that the tumor was composed of sheets of small uniform cells divided into lobules by delicate vascular septa. These uniform cells had round “salt-and-pepper” nuclei with inconspicuous nucleoli and a moderate degree of eosinophilic cytoplasm (Figure 1, a and b). Immunohistochemical analysis showed that the lesional cells were strongly positive to the neuroendocrine marker panel of antibodies: chromogranin A (Figure 2, a), neuron-specific enolase, synaptophysin, serotonin, and low-molecular-weight keratin. The lesional cells were negative to staining with antibodies to cytokeratins 7 and 20, estrogen and progesterone receptors, carcinoembryonic antigen, and c-Erb-B2 antibodies. The presence of pleomorphic neurosecretory-type granules within the cytoplasm of the tumor cells by ultrastructural analysis (Figure 2, b) confirmed the neuroendocrine nature of the lesion and strongly suggested the possibility of a metastatic lesion from a midgut carcinoid. A detailed review of her medical records confirmed a right hemicolectomy for an ileal carcinoid (Figure 3, a and b) with lymph node and omental metastases that had been performed elsewhere 10 years earlier. A detailed pathologic analysis of this lesion by light microscopy and histochemical, immunohistochemical (Figure 4, a), and ultrastructural analyses (Figure 4, b) aided in confirming the metastatic nature of the current breast lesion.

A palpable breast mass usually comes under scrutiny for signs suggestive of a primary breast cancer. The possibility of a nonmammary neoplasm should, however, be kept in mind when histologically different lesions are encountered. In children, rhabdomyosarcoma seems to be the most common primary source of a metastatic breast lesion. In adults, however, the most frequent types of tumors that metastasize to the breast are malignant melanomas, lymphomas, and neuroendocrine-like tumors, especially small cell carcinomas and carcinoids.3 

The main problem in the recognition of these lesions lies in differentiating them from primary breast carcinomas. In this context, a history of an extramammary primary tumor is helpful, though it must be remembered that the breast mass, unilateral or bilateral, may be the first manifestation of a clinically occult carcinoid.6,7 The delayed clinical presentation of a metastatic lesion remains a diagnostic challenge. Most such patients present with a palpable mass that may have a benign mammographic appearance. When straightforward histopathologic diagnosis is difficult, ancillary studies such as immunohistochemical studies are necessary for accurate diagnosis. In this regard, when certain histologic features are seen, the diagnosis of metastasis should be considered. Such features include atypical histologic features for a primary breast carcinoma, a well-circumscribed lesion with multiple satellite foci, the absence of an intraductal component, and the frequent presence of many lymphatic emboli.3 

Ancillary studies, including immunohistochemical and ultrastructural analyses, can be extremely useful in the accurate recognition of the neuroendocrine nature of these tumors. The specific cellular localization of serotonin and substance P has been demonstrated in separate populations of tumor cells both in the hepatic and mammary neoplasms in a case of midgut carcinoid with breast metastasis.8 Radionuclide-labeled imaging techniques with 123I-metaiodo-benzylguanidine and 1111n-diethylenetriamine penta-acetic acid pentetreotide have been applied for the localization of these lesions on the basis of isotope uptake by receptors present in these neuroendocrine tumors.5 

Primary carcinoid tumors of the breast are described in both the male breast9 and the female breast.10 The differential diagnosis between primary carcinoid tumors of the breast and carcinoid tumors metastatic to the breast is often controversial in surgical pathology. As in our case, the receptor status for estrogen and progesterone hormones is usually negative for metastatic breast carcinoids.2 However, definitive diagnoses can be achieved only by the correlation of detailed clinical histories and complete pathologic evaluations along with the exclusion of noncontributory factors. The recognition of unusual breast tumors with particular reference to nonmammary metastatic lesions of the breast with delayed intervals of clinical presentation continues to present a diagnostic challenge. Nevertheless, these lesions must be accurately diagnosed to avoid unnecessary mastectomies and to implement appropriate therapies.

We thank Todd Reichert, Michelle Henson, and Karen Slattery for their technical assistance in the production of the illustrations.