Carolien H. M. van Deurzen

Purpose: Application of current nodal status classification is complicated in lobular breast carcinoma metastases. The aim of this study was to define the optimal interpretation of the pTNM classification in sentinel node (SN) –positive patients to select patients with limited or with a high risk of non-SN involvement. Patients and Methods: SN metastases of 392 patients with lobular breast carcinoma were reclassified according to interpretations of the European Working Group for Breast Screening Pathology (EWGBSP) and guidelines by Turner et al, and the predictive power for non-SN involvement was assessed. Results: Reclassification according to definitions of EWGBSP and Turner et al resulted in different pN classification in 73 patients (19%). The rate of non-SN involvement in the 40 patients with isolated tumor cells according to Turner et al and with micrometastases according to EWGBSP was 20%, which is comparable to the established rate for micrometastases. The rate of non-SN involvement in the 29 patients with micrometastases according to Turner et al and with macrometastases according to EWGBSP was 48%, which is comparable to the established rate for macrometastases. Therefore, the EWGBSP method to classify SN tumor load better reflected the risk of non-SN involvement than the Turner et al system. Conclusion: Compared with the guidelines by Turner et al, the EWGBSP definitions better reflect SN metastatic tumor load and allow better differentiation between patients with lobular breast carcinoma who have a limited or a high risk of non-SN metastases. Therefore, we suggest using the EWGBSP definitions in these patients to select high-risk patients who may benefit from additional local and/or systemic therapy.

Iatrogenic displacement and mechanical transport of epithelial cells to the sentinel node (SN) has been suggested to result in false-positive findings in breast cancer patients, but little biologic evidence has yet been presented for this hypothesis. As malignant nuclei are larger than benign ones, nuclear morphometry of SN isolated tumor cells (ITC) could provide relevant information with regard to the malignant origin-or-not of epithelial cells in the SN. In patients with primary invasive breast cancer and SN ITC with (N=16) or without (N=45) non-SN involvement, nuclear morphometry was performed on the primary tumor as well as on the ITC in the SN. Nuclear size in the primary tumor was compared with that in the corresponding ITC. Patients with SN micrometastases (N=30) and SN macrometastases (N=30) served as controls. Nuclear size of ITC was significantly smaller compared with nuclear size of the corresponding primary tumor (P<0.0001). In contrast, there were no differences in nuclear size between SN micrometastases and macrometastases on the one hand and their corresponding primary tumors on the other. In addition, a subgroup of cases (10/61, 16%) with benign morphometric features of SN ITC nuclei (small and isomorph) could be discerned that had no non-SN metastases. In conclusion, nuclei of SN ITC are significantly smaller compared with the corresponding primary tumor and are often not associated with non-SN involvement. This supports the hypothesis that some of these deposits could represent benign epithelium or degenerated malignant cells lacking outgrowth potential.

There are many reports on the frequency of non-sentinel lymph node involvement when isolated tumor cells are found in the sentinel node, but results and recommendations for the use of an axillary lymph node dissection differ among studies. This systematic review was conducted to give an overview of this issue and to provide recommendations for the use of an axillary lymph node dissection in these patients. We searched Medline, Embase, and Cochrane databases from January 1, 2002, through November 27, 2007, for articles on patients with invasive breast cancer who had isolated tumor cells in the sentinel lymph node (according to the sixth edition of the Cancer Staging Manual of the American Joint Committee on Cancer) and who also underwent axillary lymph node dissection. Of 411 selected articles, 29 (including 836 patients) were included in this review. These 29 studies were heterogeneous, reporting a wide range of non-sentinel lymph node involvement (defined as the presence of isolated tumor cells or micro- or macrometastases) associated with isolated tumor cells in the sentinel lymph node, with an overall pooled risk for such involvement of 12.3% (95% confidence interval = 9.5% to 15.7%). This pooled risk estimate was marginally higher than the risk of a false-negative sentinel lymph node biopsy examination (ie, 7%-8%) but marginally lower than the risk of non-sentinel lymph node metastases in patients with micrometastases (ie, approximately 20%) who are currently eligible for an axillary lymph node dissection. Because 36 (64%) of the 56 patients with isolated tumor cells in their sentinel lymph node also had non-sentinel lymph node macrometastases, those patients with isolated tumor cells in the sentinel lymph node without other indications for adjuvant systemic therapy might be candidates for axillary lymph node dissection.