Carcinoids are slow growing neoplasms derived from enterochromaffin cells and are thus neuroendocrine in nature. They arise most commonly in the gastrointestinal or respiratory tract [12
]. Carcinoid syndrome occurs in approximately 5% of patients with intestinal carcinoids and manifests as episodes of diarrhea, abdominal pain, and flushing [13
]. They typically occur in the presence of hepatic metastasis because the liver can no longer metabolize the polypeptides (including serotonin and substance P) produced by the tumor cells. This phenomenon is only observed in intestinal carcinoids due to the venous drainage of this organ system. When the primary tumor is extraintestinal, carcinoid syndrome may be produced without hepatic metastasis [8
Carcinoid tumors are now considered at the well-differentiated end of the spectrum of neuroendocrine carcinomas. By definition, typical carcinoids have a bland morphology, lack necrosis, and have less 2 mitoses per 10 high power fields. However, carcinoids are malignant neoplasms and retain the capacity to metastasize. Morphological features of neuroendocrine carcinomas do not predict their metastatic potential [7
]. Common sites of metastasis are to the lungs, liver, and the peritoneum. Metastases are least likely to involve bone, skin, and brain [12
The first case of metastatic breast carcinoid appeared in the literature in 1957 and was an autopsy finding [4
]. In a review of literature by Rubio et al
, the ileum was found to be the most common primary site for metastatic breast carcinoid. The appendix, duodenum, pancreas, lungs, and ovaries were other primary sites, occurring with equal frequency in their review [8
]. Metastatic breast carcinoids may present clinically as single or multiple well-circumscribed lesions, with a firm consistency. In several published reports, they were clinically interpreted as fibroadenomas, or uncommonly as medullary or mucinous of ductal carcinoma [4
]. In a review by Fishman et al
, 8 of 13 (61.5%) patients with metastatic breast carcinoid were initially considered to have primary breast carcinoma and were subjected to mastectomies [16
]. The diagnosis of metastatic breast carcinoid was made after review of the histology of the mastectomy specimen after it was discovered that the patient had a primary carcinoid at a different site. In our patient, clinical suspicion of metastatic carcinoid was high, although a primary breast carcinoma was also in the differential diagnosis. Misdiagnosis of breast carcinoid as primary ductal carcinoma has also been reported even with a prior history of carcinoid tumor at a different site in the patient [16
]. Organoid nests of cells with rosette-like structures can mimic the pattern of solid or cribriform DCIS (ductal carcinoma in-situ).
Argentaffin and argyrophil stains are usually positive in carcinoid tumors of the small bowel, whereas "primary" carcinoid tumors of the breast demonstrate only argyrophilic granules [12
]. Recently, the very existence of primary breast carcinoids has been discredited [7
]. Carcinoid tumors metastatic to the breast can show estrogen receptor positivity creating problems in differential diagnosis with a primary ductal carcinoma of the breast [18
]. Clinically, there are no reliable criteria to distinguish metastatic breast carcinoid from primary breast carcinoid. In-situ ductal carcinoma may be the only absolute proof of primary nature of breast carcinoma [4
]. Immunohistochemical and ultra structural analysis can be extremely useful in the accurate recognition of neuroendocrine nature of these tumors. These include synaptophysin, chromogranin A and B, and neuron specific enolase (NSE). More recent immunostains include prohormone convertase (PC3), CDX-2, and peptidylglycine a-amidating monooxygenase (PGM).
A modified radical mastectomy was performed in the majority of cases reported in the literature, as the clinical diagnosis was that of a primary breast carcinoma. Lumpectomy has been performed in only a few cases [6
]. Large series of such tumors are lacking in the literature and we cannot recommend a more specific management approach. Large series of such tumors are lacking in the literature and we cannot recommend a more specific management approach, however, axillary lymph node dissection may not be necessary. Estrogen receptors may be positive in carcinoid tumors, however, none have been reported positive in metastatic breast carcinoids to our knowledge. HER-2/neu may be positive and has been described in at least one report of metastatic carcinoid to the breast [7
]. Role of chemotherapy and radiotherapy is also unclear.
In conclusion, metastatic carcinoid tumors to the breast can mimic primary breast carcinoma. In patients with a breast mass and a known history of carcinoid tumor, one should have a high index of suspicion for metastatic disease. A lumpectomy should be offered to these patients rather than modified radical mastectomy as first line therapy.