Cytokeratin 7-and human epidermal growth factor receptor 2-negative Paget disease of the nipple: a case report and review of the literature

Cytokeratin 7 (CK7)- and human epidermal growth factor receptor 2 (HER2)-negative Paget disease is a very rare variant of breast carcinoma, and presents a major diagnostic challenge for pathologists. We report a case of CK7- and HER2-negative Paget disease in a 43-year-old woman. Histological examination of the biopsy specimen revealed neoplastic cells within the epidermis, with abundant pale cytoplasm and large nuclei. In addition, an intermediate-grade ductal carcinoma in situ was found upon a subsequent surgical excision. lmmunohistochemical analysis revealed tumor cells with positive immunoreactivity for GATA3, CAM5.2, estrogen receptor, and progesterone receptor. Negative immunoreactivity was found for CK7, HER2, S-100, CK5/6, GCDFP-15, and neuroendocrine makers. CK7- and HER2-negative Paget disease of the nipple is extremely rare. The importance of recognizing this rare variant of Paget disease lies in avoiding misdiagnosis. Thus, in such cases, GATA3, CAM5.2, estrogen receptor, and progesterone receptor immunohistochemistry will be valuable for the differential diagnosis. Owing to the possibility of small underlying carcinomas, simple mastectomy is a suitable treatment for patients with Paget disease, even if physical examination and ultrasonography reveal no underlying lesion.