Minimal metastatic disease in sentinel lymph nodes in breast carcinoma: some modest proposals to refine criteria for "isolated tumor cells"

Abstract

Axillary lymph node status is one of the most important prognostic factors in breast carcinoma. The weight of cumulative evidence suggests that the development of the sentinel lymph node (SLN) biopsy procedure has not only allowed for accurate lymph node-staging but has also helped avoid the morbidity of a full axillary dissection in those patients who are unlikely to have metastatic tumor in that location. The detection of metastases in SLNs is facilitated by the, now relatively routine, enhanced histopathologic examination via step-sectioning and immunohistochemistry. In clinical terms, the finding of a metastatic deposit that measures between 0.2 and 2 mm, that is, "micrometastasis" in a SLN is largely noncontroversial; however, the presence of smaller metastatic foci detected either by routine hematoxylin and eosin stain or by cytokeratin immunostain [<0.2 mm, ie, so-called "isolated tumor cells (ITCs)"] has remained problematic since the advent of the SLN biopsy. In this communication, attention is drawn to the broad morphologic range of metastatic disease in SLN that may be placed in the category of so-called ITC. To facilitate the reproducible classification of the various strata of minimal metastasis in sentinel lymph nodes, we recommend the following: (1) the term "isolated tumor cell" (note singular form) be restricted to cases that show the presence of only a single tumor cell. (2) In situations where there are multiple isolated single cells and/or cell cluster(s) present and each cluster measures<0.2 mm, the term "submicroscopic metastasis" be adopted and an actual count of tumor cells present may be given. (3) Restrict the use of the term micrometastasis to cases wherein the largest metastatic focus is larger than 0.2 mm but smaller than 2.0 mm.