Immunostain Update: Diagnosis of Metastatic Breast Carcinoma, Emphasizing the Distinction from Gynecologic Cancers

Up to one third of patients with breast cancer will show evidence of metastatic spread over their course of disease. Common sites of metastasis in breast cancer, in addition to axillary and supraclavicular lymph nodes, include bone, liver, lung, pleura (with associated pleural effusion), brain, skin, gynecologic organs, and GI tract, although any anatomic site can be the potential target. Most metastatic lesions occur after the diagnosis of breast cancer has been established, typically within the first 5-10 years. However, some metastases may take 20 to 30 years to manifest. Furthermore, breast cancer can first present as a metastatic lesion. In addition, breast cancer patients have an increased risk of developing a second primary cancer, this occurring in about 12% of affected women. In particular, women with mutations in BRCA1 or BRCA2 gene have an increased lifetime risk for breast, ovarian, tubal and peritoneal cancer. Therefore, pathologists often face the challenging task to confirm the diagnosis of a clinically suspicious metastatic breast cancer, to evaluate the possibility of breast origin in the workup for a metastatic tumor of unknown primary, or to distinguish a metastatic breast lesion from a new second primary carcinoma. Correct distinction in the latter scenario is critical not only for the different treatment the patient will receive but also for the different prognostic implication the diagnosis will confer. With distant metastasis, breast cancer is essentially incurable.