Answer: Small cell carcinoma of the breast

Histology: The breast is involved by a diffuse proliferation of primitive cells with high nucleus to cytoplasm ratio. On high power examination, mitotic activity is high, and the nuclei mold to each other. Nucleoli are not prominent. Focally, one can appreciate an area of usual ductal carcinoma in situ and invasive ductal carcinoma. Tumor cells demonstrate immunoreactivity for cytokeratin in a punctate perinuclear pattern, typical of neuroendocrine lesions. CD56 and chromogranin were positive and TTF-1 was negative.

Discussion: Malignant lymphoma is a strong consideration when one is dealing with a diffuse small cell malignancy of the breast. However, the nuclei of malignant lymphoma typically have more angulation, and lymphoma would not label for cytokeratins. The alveolar variant of lobular carcinoma would look cytologically similar to this tumor; however, it would not typically show neuroendocrine differentiation and would demonstrate absence of E-cadherin immunoreactivity. This tumor is a high-grade carcinoma derived from ductal epithelium; however, the presence of neuroendocrine differentiation as evidenced both morphologically and immunohistochemically supports diagnosis of small cell carcinoma of the breast.

Small cell carcinomas of the breast occur less frequently than elsewhere in the body, particularly in the lung. The diagnosis of a primary small cell carcinoma of the breast is supported by the absence of small cell carcinoma elsewhere in the body and the presence of DCIS or usual type invasive ductal carcinoma within the same breast. Immunohistochemically, over 50 percent of small cell carcinomas of the breast are immunoreactive for estrogen or progesterone receptors, while the tumors are typically negative for Her-2/neu. These tumors do appear to be responsive to chemotherapy, so the diagnosis is an important one to make.