Answer: Infiltrating ductal carcinoma with neuroendocrine (carcinoid-like) morphology

Histology: At low power this appears to be a classic invasive breast carcinoma, as the lesion has a spiculated appearance. The neoplasm consists of nests of tumor cells separated by a desmoplastic stroma. At high power, the cells have neuroendocrine chromatin, characterized by finely dispersed chromatin without prominent nucleoli. The appearances are similar to that of a carcinoid tumor; for example, one of gastrointestinal tract origin. Several features point to the current case being a primary breast lesion. First, there is a focal in situ component, characterized by a rounded collection of neoplastic cells within an elastotic duct. Second, the neoplastic cells are diffusely reactive for estrogen receptor. Third, there is no history of a carcinoid tumor elsewhere in this patient. Fourth, there is focal staining for GCDFP.

Discussion: Small cell carcinoma does occur in the breast; however, these neoplasms feature cells with high mitotic rate and extensive necrosis. Metastatic carcinoid tumor is a critical differential diagnosis in this case. Careful attention to the clinical history and the morphologic and immunohistochemical features described above help eliminate this possibility. Infiltrating lobular carcinoma is excluded by solid nested pattern of the tumor cells, the lack of discohesion, and the lack of signet ring cell morphology.

Neuroendocrine carcinomas of the breast are defined by the WHO as carcinomas containing greater than 50% of cells that express neuroendocrine markers by immunohistochemistry. These comprise a minority of breast carcinomas, likely in the range of 2-5%. Importantly, these should be graded using standard criteria, and the fact that the tumor has carcinoid-like morphology has no prognostic significance. The key point, however, is that metastatic carcinoid tumor to the breast should be excluded. Well-differentiated neuroendocrine carcinomas not infrequently metastasize to the breast. As discussed above, the presence ductal carcinoma in situ, diffuse estrogen receptor immunostaining, and immunostaining for gross cystic disease fluid protein can help establish a primary breast carcinoma.