Primary neuroendocrine carcinoma of the breast is a rare entity, comprising <1% of breast carcinomas. Described here is the case of a 78-year-old woman who developed an invasive tumor in the left breast measuring 2.0 cm x 1.5 cm x 1.2 cm. The tumor was composed of only endocrine elements in the invasive part. It infiltrated in a nested fashion with no tubular formation. Intraductal components were present both inside and outside of the invasive portion. Almost all carcinoma cells consisting of invasive and intraductal parts were positive for synaptophysin and neuron-specific enolase. According to the World Health Organization classification 2012, this tumor was subclassified as neuroendocrine tumor, well-differentiated. Among the subgroup, this tumor was relatively high-grade because it was grade 3 tumor with a few mitotic figures. Vascular and lymphatic permeation and lymph node metastases were noted. In the lymph nodes, the morphology of the tumor was similar to the primary site. No distant metastasis and no relapse was seen for one year after surgery. The prognosis of neuroendocrine carcinomas is thought to be worse than invasive mammary carcinomas, not otherwise specified. Therefore, immunohistochemistry for neuroendocrine markers is important in the routine practice to prevent overlooking neuroendocrine carcinomas.
Although some invasive ductal carcinomas of the breast show areas of neuroendocrine differentiation, primary neuroendocrine carcinoma of the breast is a rare entity, comprising <1% of breast carcinomas. In 2003, the World Health Organization (WHO) recognized this category and defined mammary neuroendocrine carcinoma as expression of neuroendocrine markers in more than 50% of tumor cells. In 2012, WHO revised the category and divided neuroendocrine carcinomas into three subtypes: neuroendocrine tumor, well-differentiated; neuroendocrine carcinoma, poorly differentiated/small cell carcinoma; and invasive breast carcinoma with neuroendocrine differentiation [
A 78-year-old woman was referred to NTT Medical Center Tokyo with a mass in the left breast that was detected by mammography during breast cancer screening. Levels of tumor markers such as carcoinembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) were found to be normal (2.5 ng/mL and 6.9 U/mL, resp.). Computer tomography showed a well-circumscribed mass (1.5 × 0.9 cm) and a swollen lymph node (1.0 × 0.8 cm). No other tumors were detected in any other organs. Aspiration cytology was performed and the mass was diagnosed as a carcinoma. The patient was subsequently admitted to the Medical Center for surgery. She underwent a partial mastectomy and level I lymphadenectomy without sentinel lymph node identification.
Anastrozole was administered postoperatively. The serum tumor marker NSE showed no remarkable change for one year after surgery. No tumoral mass was seen on the computer tomography images.
The surgical specimen (15.5 × 12.0 × 4.0 cm) contained a grayish-white tumor measuring 2.0 × 1.5 × 1.2 cm with a well-demarcated border.
The tumor was an invasive carcinoma with a minor intraductal component. The invasive component was composed of carcinoma cells displaying nested pattern of growth with no tubular formation (Figure
(a) Nested pattern of growth is shown. A mitotic figure can be observed. (H&E, 40×). (b) Intraductal component (H&E, 40×).
Immunohistochemical staining was positive for synaptophysin (Figures
(a) Almost all the cells are positive for synaptophysin (40×). (b) Intraductal component (40×).
In 2012, WHO divided carcinomas with neuroendocrine features into three categories:
The neuroendocrine markers synaptophysin and neuron-specific enolase were found to be positive in almost all the tumor cells. Immunohistochemical positivity to CK7 and ER supports the diagnosis of primary breast tumor, and the presence of an intraductal component with peripheral p63-positive myoepithelial cells is also strong evidence of the breast as the tissue of origin.
Majority of the tumors under the category of neuroendocrine tumor, well-differentiated, are known to be of low or intermediate grade [
The prognosis of neuroendocrine carcinoma is thought to be worse than invasive mammary carcinoma, not otherwise specified [
This report describes a neuroendocrine tumor, well-differentiated, that shows relatively high-grade morphological and biological features. It is recommended to differentiate neuroendocrine carcinomas from other invasive mammary carcinomas by routinely using immunohistochemistry when solid, alveolar, or nested pattern of growth is prominent because the former is thought to show worse prognosis [
The authors declare that they have no conflict of interests.