Distinguishing Breast Carcinoma from Müllerian Serous Carcinoma with Mammaglobin and Mesothelin

Differentiation of Müllerian serous carcinoma from metastatic breast carcinoma is a challenging and frequent diagnostic dilemma, particularly in the setting of a pelvic mass or peritoneal carcinomatosis. Precise classification is important as it impacts treatment and prognosis. Antibodies exist that assist with this differential but they are often limited by low sensitivity or specificity. This study evaluated the utility of mesothelin and mammaglobin antibodies in differentiating breast carcinoma (particularly those with a papillary morphology) from Müllerian serous carcinomas. Formalin-fixed, paraffin-embedded archival tissue from 21 breast carcinomas (10 micropapillary, 11 usual type ductal carcinomas) and 20 serous carcinomas (12 ovarian and 8 uterine) in addition to 6 cases of metastatic breast cancer to the ovary (5 cases) and cervix (1 case) were evaluated for the pattern and intensity of reactivity to antibodies to mesothelin, mammaglobin, and GCDFP-15. None of the breast carcinomas stained for mesothelin, whereas 8/12 and 3/8 ovarian and uterine serous carcinomas were positive; however, 7 of these had less than 10% positivity. Mammaglobin was negative in all serous carcinomas. When compared with GCDFP-15, mammaglobin was more frequently and diffusely expressed in breast carcinomas (GCDFP-15 positivity in 8/21 and mammaglobin positivity in 14/21). This study indicates that the addition of mammaglobin to immunohistochemical panels is useful in distinguishing metastatic breast carcinoma from a new primary ovarian or uterine malignancy. Mesothelin is extremely specific in this scenario but can be technically challenging to interpret due to the common patchy, focal staining.