More than 97% of neuroendocrine tumors occur in the gastrointerstinal or respiratory system, and primary neuroendocrine carcinoma of the breast is very rare. In a series of 1,845 histopathologically-proven breast cancer, the incidence was about 0.27% (
6).
The diagnosis of primary neuroendocrine carcinoma of the breast can only be made if nonmammary sites are confidently excluded or if an in situ component can be found (
9). There are different histologic subtypes of neuroendocrine carcinomas of the breast reported in the literature (
2-
4). Papotti et al. divided neuroendocrine carcinomas into seven histological types (A-G) (
2). Sapino et al. described five different histological types: solid cohesive, alveolar, small cell, solid papillary, and cellular mucinous (
3). In 2003, the World Health Organization (WHO) recommended differentiation of these tumors into three histologic types: solid, small-cell, and large-cell neuroendocrine carcinoma (
5). There are some features that favor neuroendocrine differentiated carcinoma of the breast and morphologic features should be confirmed immunochemically or by positivity for neuroendocrine markers (
3). NSE, chromogranin, and synaptophysin are widely accepted as neuroendocrine markers, though NSE is relatively non-specific (
4). In our case, the three aforementioned neuroendocrine markers were all positive.
LCNC, one of the subtypes of the 2003 WHO classification of neuroendocrine tumors, shares common features of the neuroendocrine-differentiated tumor described above and also shows more specific cytologic features: large cell size, polygonal shape, low nuclear-cytoplasmic ratio, finely granular eosinophilic cytoplasm, occasionally prominent nucleoli, peripheral palisading, mitosis, and necrosis (
8).
In a clinical setting, neuroendocrine carcinomas usually occur in women around the 7th decade; most patients in the previously reported cases were between 40 and 70 yr old (
2,
4-
6,
9). Our patient was a 27-yr old woman without risk factors of breast cancer and presented with a painful breast mass that had appeared about one year prior. The mass was soft and movable on physical examination. It is an uncommon presentation of breast cancer, considering the patient's age and clinical findings. The prognosis of neuroendocrine-differentiated carcinoma is a subject to debate, probably due to different growth patterns of the subtypes and the low number of cases. In some recent literature, primary neuroendocrine carcinomas of the non-small cell type have shown satisfactory prognosis with adequate surgical excision and adjuvant chemotherapy (
5,
10).
Previously noted mammographic findings of neuroendocrine carcionoma included high-density round masses with spiculated or lobulated margin (
6,
9). Our findings are not significantly different. US findings of our patient were those of gently lobulated, heterogenous, low-echoic mass. In one series of five neuroendocrine carcinomas, most of the lesions demonstrated homogeneous low-echoic masses, though the WHO classification was not used and all of the lesions were of the solid and papillary subtypes (
6). US findings in small-cell carcinoma reported by Mariscal et al. was of a solid, homogeneous, low-echoic mass with a partially ill-defined margin and mild posterior acoustic enhancement (
9). In our case, CT findings are also presented. A chest CT scan was performed as part of a metastastic work-up as well as for evaluation of pulmonary tuberculosis. The lesion appeared as a well-defined, highly-enhancing mass in the left breast.
In summary, we presented imaging findings of a LCNC of the breast. This is the first report describing imaging features of large-cell type neuroendocrine carcinoma and presenting the CT findings of a neuroendocrine-differentiated carcinoma in Korea. This is a rare entity, and description of more cases is necessary to determine the radiologic and clinical features of LCNC.
Kyu Ran Cho, Bo Kyung Seo, Hwan Seok Yong, Aeree Kim,* and Eun-Young Kang
