She underwent a segmental resection of the ileum, along with a total abdominal hysterectomy, bilateral salphingo-ophorectomy, and intraoperative needle biopsies of the liver masses. Histological examination revealed a large carcinoid in the ileum with metastasis to regional lymph nodes. The tumor was present as nests and sheets of uniform cells with focal gland formation (figure ​(figure1A).1A). Cells contained modest amount of eosinophilic cytoplasm and monotonous appearing nuclei with vesicular nucleoli (figure ​(figure1B).1B). Focal areas of mucosal ulceration, as well as extensive perineural and vascular invasion were present. Metastatic deposits of carcinoid tumor were also found in both ovaries and in the liver.

A 24-hour urine specimen revealed predictably high levels of 5-HIAA (5 Hydroxy Indole Acetic acid) at 45.2 (reference range 0.5–9 mg/24 hours). The patient was followed regularly with 24-hour urine 5-HIAA levels and CT scans of abdomen and chest. Two years post diagnosis; mild progression of her liver disease was noted. The patient was initiated on subcutaneous octreotide (Sandostatin) at a dose of 50 mg/m² twice daily.

She remained stable for three and one half years, when she discovered a lump in her left breast. Clinical examination revealed a firm mobile mass in the breast suspicious for tumor. Mammograms were significant for an irregular, marginated mass of 2.2 × 2.0 cm in the upper inner quadrant of the left breast. An ultrasound confirmed these findings, revealing a hypoechoic, irregularly marginated mass highly suspicious for malignancy. The patient underwent lumpectomy of the breast mass for a definitive diagnosis. The gross specimen had a tan grey firm nodule of 2.5 × 1.5 × 1.5 cm with smooth borders within otherwise unremarkable fatty tissue. Histological examination revealed a 2.5 cm nodule containing infiltrating cords and nests of cells morphologically similar to her original ileal carcinoid tumor. The larger nests demonstrated an acinar pattern with rosette formation. The cells contained round to oval nuclei with a fine reticular chromatin pattern (Figure ​(Figure2A2A and ​and2B).2B). Necrosis was absent and mitoses were rare. Focally margins were positive for tumor. A partial mastectomy was performed to remove residual tumor. The patient received adjuvant radiation therapy to the affected breast. She has had no recurrences and has had stable liver disease (metastatic carcinoid) for 5 years following her breast surgery.

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 [4,14,15]. 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 [6,7,13,19]. 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.