Sentinel lymph nodes and breast carcinoma: which micrometastases are clinically significant?

Sentinel lymph node biopsy is changing surgical management of breast cancer and pathologic evaluation of lymph nodes. Although it has long been known that lymph nodes contain occult metastases, pathologists have not generally pursued their identification. Compared with level I-II axillary dissection, the reduced number of sentinel lymph nodes has made additional evaluation more attractive; however, the consequences of increased detection of micrometastases has not been fully explored or appreciated. National data suggest that the composition of traditional TNM stage groupings is changing, with a recent increase in node-positive, stage II breast cancer, most likely the result of increased pathologic scrutiny. Clinical management of this new group of stage II patients is complicated by the lack of a historic prognostic comparison group because many of these patients would have been classified as stage I, node-negative in the past. Early outcome data in sentinel lymph node biopsy suggest no adverse outcome for patients with metastases no larger than 2.0 mm, a finding aligned with the current definition of micrometastasis. When sentinel lymph nodes are sliced at 2.0-mm intervals and totally embedded, the probability of identifying all metastases >2.0 mm is high. Using reasonable sampling strategies, minute metastases have a nearly equal chance of being missed or detected. New staging guidelines have established a lower limit for micrometastases and defined metastases no larger than 0.2 mm as isolated tumor cells or tumor cell clusters; nodes with isolated tumor cells will be classified as node negative (pN0) for stage grouping. Rigorous strategies designed to reliably detect single cells or small cell clusters in sentinel nodes remain time-intensive and cost prohibitive.