False-Negative Sentinel Node Biopsy

The concept of the orderly progression of lymph node metastases is exciting and appeals to the surgical frame of mind.The momentum of the practice of lymphatic mapping may cause people to get carried away by their enthusiasm.It is thus important to keep an open eye for developments that may not live up to the expectations, and therefore, the paper from the Italian Melanoma Intergroup in this issue deserves attention.An important purpose of the study of 1313 patients with melanoma was to determine the ability of sentinel node biopsy to identify involved lymph node basins.The false-negative rate was found to be 14.4%; this high rate was obtained despite a meticulous technique and a comprehensive quality control program. 1 High false-negative rates have been reported before but have rarely caused a stir.For patients with melanoma, there has long been consensus on the principal aspects of the technique of lymphatic mapping.The combination of preoperative lymphoscintigraphy and intraoperative use of both blue dye and a gamma ray detection probe provides the best retrieval rate.The sentinel node is identified in close to 100% of patients.The morbidity of the procedure is limited.The tumor status of the sentinel node has proven to be the most important prognostic factor and has been incorporated in the staging system. 2 There is initial evidence that melanoma patients with lymph node metastases have an improved chance of survival if regional node dissection is done early on the basis of sentinel node status. 3 Morton and Cochran, who introduced sentinel node biopsy, initially performed the procedure with routine regional node dissection for confirmation and found an encouraging false-negative rate of 5%. 4 Confirmatory lymph node dissection was quickly abolished, and the false-negative cases were subsequently identified through observation of recurrences in the lymph node basin after a tumor-free sentinel node had been removed.Initially, many investigators looked favorably on the reliability of lymphatic mapping to detect nodal metastases, but the followup duration was too short for all recurrences to manifest.Also, many investigators calculated the rate of false-negative procedures over the entire group of patients or over the group of sentinel node-negative patients.5 This is not correct because one cannot miss an involved node in a patient who does not have involved nodes.Because only approximately 20% of the patients have lymph node metastases, this questionable way of calculating decreases the false-negative rate by a factor of 5. Testori et al. correctly point out that the false-negative rate should be defined as the fraction of the patients with involved nodes that is missed by the procedure and becomes evident later on when the nodes become clinically detectable (Table 1).The false-negative rate is the counterpart of the sensitivity, which is defined as the proportion of node-positive patients (sentinel node-positive patients and patients with recurring disease) that is identified by sentinel node biopsy.Early publications from reputable institutions and cooperative groups around the world showed false-negative rates ranging from 16% to 38% when recalculated to comply with the above recommended definition.5 Even in the interim analysis of the Multicenter Selective Lymphadenectomy Trial I, the false-negative rate is 17.6%.3 These high false-negative rates are reason for concern and reflection.What may be the cause?Testori et al. mention the nuclear medicine physician, the surgeon, and the pathologist as sources of failure, but there are more.It may be that the concept of sequential dissemination does not always apply.We are dealing with a biological system with associated variability.It is conceivable that tumor cells may pass through a sentinel node and lodge in the