The presence of nodal metastases and the number of lymph nodes with metastases are among the most important predictors of the outcome for patients with breast cancer. Approximately 20% to 40% of patients with breast cancer and clinically undetectable lymph nodes have pathologic evidence of lymph node metastases. Axillary lymph node (ALN) dissection to pathologically assess node status is not only diagnostic but may be therapeutic as well, although this remains controversial. Unfortunately, women who undergo axillary dissection are at risk for side effects including arm pain, arm edema, and limitation of motion. A sentinel lymph node (SLN) is the first lymph node along the route of lymphatic drainage from a primary breast tumor. Sentinel lymph node biopsy carries lower morbidity and cost than a complete axillary dissection. Dowlatshahi et al. reported a preliminary study assessing the incidence of occult metastases using serial sectioning at 0.25 mm intervals and stains for cytokeratin.
SLNs from 52 patients with invasive breast carcinoma with a mean dimension of only 1.35cm were evaluated microscopically with routine 2mm section intervals and hematoxylin and eosin (H & E) staining. A comparison was then made to the same specimens sectioned serially at 0.25mm intervals and stained immunohistochemically for cytokeratin, following SLN dissection.
Metastases were found in the SLNs of 6 patients (12%) when examined by H & E staining and in 30 patients (58%) when examined by IHC.
Of 24 patients whose metastases were identified by IHC alone, half of them had isolated tumor cells and half of them had clusters of malignant cells.
Since the false positive rate (number of positive findings that are really negative divided by the number of true and false positives) of identifying micrometastases by IHC to cytokeratins alone remains unknown, it is difficult to quantify how many SLN metastases were actually underestimated by routine histologic examination. Many studies have shown that the long term relapse rate for patients with small (<1cm) ALN negative tumors based on traditional staging is <10% and that adjuvant hormonal and chemotherapy are of little utility in this setting. Clinical implications of IHC staining in identifying micrometastases require further clinical investigation with prospective randomized trials.