To the Editor:
We read with great interest the article by Chu et al, “Do all patients with sentinel node metastasis from breast carcinoma need complete axillary node dissection?”1
This paper addresses a topic that is being debated frequently by surgeons who have implemented the sentinel node (SN) procedure in breast cancer patients and who no longer perform an axillary lymph node dissection (ALND) when the SN is negative for metastatic involvement. The question frequently put forward is whether an ALND is necessary when the SN contains no more than a micrometastasis, defined by Chu and coworkers as a metastatic deposit <2 mm in diameter. Before one questions the prognostic significance of a micrometastasis in the SN in relation to the incidence of non-SN axillary metastases, however, one has to clearly define which is an SN and which is a non-SN.
In the paper by Chu et al, SNs are defined as nodes that can be radioactive only, blue only, or both. We find this definition not to be in accordance with the concept that the blue dye and the radioactive tracer will identify the same lymphatic drainage route that is followed by metastatic tumor cells. The fact that nodes that are blue only and/or radioactive only can both be designated as SNs, when both techniques are applied simultaneously in the same patient, is disturbing to us, as we reported earlier. 2,3 The blue dye and the radioactive tracer are expected to follow the same lymphatic drainage route and thus end up in the same node, which is the SN. 4
By the criteria used by Chu et al, an average of 1.8 “SNs” were resected. More than one SN appeared to be positive, up to 5 per patient, but it is not clear in how many patients this was the case.
Furthermore, the size of the sentinel node metastasis was also determined in patients with more than one positive (sentinel?) node and related to the incidence of non-SN metastatic involvement.
We find it unlikely that non-SN metastatic involvement in the axilla can be predicted on the basis of more than one positive node removed with the sentinel node procedure. If more than one SN is positive, it is unclear which one should be used as the “reference” node for correlation with non-SN metastatic involvement. From dynamic lymphoscintigraphic images, we know that there may be more than one first-echelon node in the same patient. However, with increasing tumor load of the first echelon node(s), metastatic cells subsequently progress to second-echelon nodes by alternative routing. The same sequence of events is thought to occur for both the radioactive tracer and the blue dye. 5,6
Therefore, when more than one positive node are called SNs, the additional node may actually be a second-echelon node, especially when additional, less radioactive nodes, are also defined as SNs, which was the case in this study. 1 This distinction may not be of importance when the sole purpose of the SN procedure is to establish node negativity in the axilla. When a study is designed to establish a relationship between SN tumor load and non-SN metastatic involvement, however, the distinction between first- and second-echelon nodes becomes an issue in our view. We therefore propose that SN tumor load can only be correctly correlated with non-SN metastatic involvement, in those patients with one positive SN.
Another point for discussion is the method used by Chu et al to determine the size of the SN metastasis. Not all metastases with a certain diameter have the same size, for the simple reason that metastases do not appear as perfect circles on a histology slide. This means that not all microscopic deposits with a diameter of 2 mm are equal in size. If tumor load in the sentinel node is to be correlated with non-SN metastasis, more objective and exact measurements are required.
We have used a different technique for measuring the size of SN metastases. The size of the metastasis in the SN was determined by digital surface area measurements under the microscope and expressed in square millimeters. We arbitrarily defined micrometastases as those with a surface area ≤1 mm2, which may be considerable smaller than those defined as ≤2 mm in diameter. At least six sections were done of each SN with micrometastatic deposits.
In our patients, all SN procedures were done using both radioactive tracer and blue dye. Nodes were designated as SNs when preoperative lymphoscintigraphy showed focal accumulations in the axilla and when the resected nodes were radioactive, with a residual radioactive count in the axilla less than 10% of the hottest node resected (ex vivo count), before the SN procedure was terminated. The blue dye served to facilitate recognition of the radioactive nodes in the axilla.
Of the 77 patients with a positive SN procedure, only 28% with one positive SN had additional axillary metastases, whereas 65% with more than one positive SN had additional axillary metastases upon ALND. We further examined the correlation between tumor load of the SN and the incidence of non-SN metastases only in the group of patients with one positive SN. We found that 16% (4/25) with metastasis <1 mm2 had non-SN metastasis, regardless of mode of histologic detection and regardless of primary tumor size.
Therefore, the preliminary analysis of our data suggests that, with stricter criteria for the SN that is to be used as the reference node in which the measurement is done, and with more objective measurements of the metastatic size, the involvement of non-SN axillary nodes in patients with micrometastases to the SN is greater than the 6% found by Chu et al (T1 and T2 tumors).
In at least three studies, 7–9 SNs were occasionally found to be negative for metastatic tumor cells, while nodes that were neither radioactive nor blue were grossly involved with tumor metastases. It is thought that the grossly involved nodes are unable to retain either radioactive tracer or blue dye. This phenomena may explain in part the existence of micrometastases in the SN with non-SN being positive upon ALND.
The incidence of non-SN metastasis in patients with micrometastasis in the SN should be investigated in larger series of patients.
Frans D. Rahusen MD
Sybren Meijer MD, PhD
Paul J. van Diest MD, PhD
References
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