Immunohistochemically detected tumor cells in the sentinel lymph nodes of patients with breast carcinoma: Biologic metastasis or procedural artifact?

Sentinel lymph node (SLN) biopsy is a new standard of care for patients with breast carcinoma, and allows enhanced pathologic analysis with serial sections and immunohistochemical (IHC) staining for cytokeratins to be performed on a routine basis. However, the significance of SLN micrometastases detected only by IHC is uncertain. Are these tumor cells truly markers of metastatic potential, or simply evidence of passive displacement by preoperative instrumentation of the tumor site? Here we evaluate whether the pattern of SLN metastasis in breast carcinoma is related to the degree of manipulation at biopsy before surgery, independently of other known predictors. Among 4016 consecutive eligible patients with breast carcinoma registered in a prospective SLN database at Memorial Sloan Kettering Cancer Center, we noted patient/tumor characteristics, pathologic status of the SLN (negative, positive by hematoxylin and eosin [H&E], or positive only on IHC), and method of previous biopsy (none, fine-needle aspiration biopsy [FNAB], core needle biopsy, or surgical biopsy). Multivariate analysis showed that the likelihood of an H&E-positive SLN was significantly associated with lymphovascular invasion, tumor size, tumor type, and tumor location, but not with the method of biopsy. In contrast, the likelihood of finding an SLN positive only on IHC was unassociated with any of the four variables above, but was significantly associated with the method of biopsy. After no previous biopsy, FNAB, core needle biopsy, or surgical biopsy, IHC-positive SLN were present in 1.2%, 3.0%, 3.8%, and 4.6% of patients, respectively (P = 0.002). These data suggest that the frequency of IHC-positive SLN in patients with breast carcinoma 1) is unrelated to conventional predictors of lymph node positivity, 2) is increased after instrumentation of the tumor site, and 3) is increased approximately proportionate to the degree of manipulation. A proportion of IHC-positive SLN were present before biopsy and therefore less likely to be artifactual.