The association of cytokeratin-only-positive sentinel lymph nodes and subsequent metastases in breast cancer

Introduction: The purpose of this study was to better characterize the clinical significance of cytokeratin immunohistochemistry (IHC)-only-positive lymph node metastases among patients with breast cancer. Methods: We performed a retrospective review of 334 patients who underwent sentinel lymph node (SLN) biopsy from 1 February 1997 through 31 July 2001. SLN biopsies were evaluated using standard hematoxylin and eosin (H&E) techniques. If H&E was negative, cytokeratin IHC was performed. We then evaluated the incidence of subsequent regional and distant metastatic disease. Results: Cytokeratin IHC was performed on 183 sentinel node biopsies from 180 patients comprising a total of 427 sentinel lymph nodes. The procedures included lumpectomy and SLN biopsy (n = 83), mastectomy with SLN biopsy (n = 7), lumpectomy with SLN biopsy and completion axillary dissection (n = 80), and modified radical mastectomy with SLN biopsy and completion axillary dissection (n = 13). Cytokeratin IHC was negative in 175 axillary specimens and positive in 8 (4.4%) from 8 different patients. In these eight specimens, deeper sections with subsequent H&E staining additionally identified micrometastasis in four patients. Three of these 8 patients (37.5%) developed distant metastatic disease compared with 1 of the 172 patients (0.6%) with negative cytokeratin IHC (P < .001). Additionally, one of the cytokeratin-positive patients developed regional nodal metastasis compared with none of the 172 cytokeratin-negative patients. Conclusions: Cytokeratin IHC provides a clinically relevant adjunct to H&E staining for evaluating sentinel lymph nodes in breast cancer. These data suggest that patients with cytokeratin-positive sentinel nodes are at increased risk for development of regional and distant metastatic disease.