Sentinel Node Mapping
Sentinel Node Mapping (“The Blue Node”) is the innovative technique first introduced by Dr. Donald L. Morton in 1990 and now considered standard practice for management of clinically localized cutaneous melanoma.
 Current Findings: Metastasis to the regional nodes is the single most important prognostic factor in solid neoplasms. Prior to Dr. Morton’s introduction of intraoperative lymphatic mapping and sentinel lymphadenectomy (LM/SL), the only way to identify nodal metastases was to remove all regional nodes. However, this can cause troublesome postoperative complications and is of no benefit in most patients with clinically normal lymph nodes. LM/SL represents a minimally invasive but highly effective alternative. This surgical sampling technique identifies and examines the first (“sentinel”) lymph node on the drainage pathway from a melanoma on the skin. They found that if this node is free of tumor cells, then the primary melanoma is very unlikely to have spread from its skin site to regional lymph nodes. Patients whose sentinel node contains no evidence of tumor do not need to undergo further lymph node surgery.
Because there are only a few sentinel nodes, they can be cost-effectively scrutinized using highly sensitive immunologic and molecular techniques. LM/SL not only increases the likelihood of detecting nodal micrometastases but also eliminates routine lymphadenectomy in patients who have clinically normal regional nodes. A phase III trial of LM/SL in melanoma, headquartered at JWCI, includes 17 prestigious melanoma centers around the world. Accrual to this trial is now complete at 2001 patients, making it the largest surgical study of melanoma and a prototype for the successful conduct of an international randomized trial. Its results are expected to validate LM/SL for staging clinically localized melanoma and encourage its further application to breast cancer, colon cancer, and other solid tumors that spread via the lymphatics.
Further Investigation: The recent renewal by the National Cancer Institute of follow-up clinical trials will include at least 20 melanoma surgical centers. These trials will determine whether further lymph node surgery is always necessary when the sentinel node contains tumor. Specimens from the clinical trials will be used to develop innovative laboratory technologies for cancer diagnosis and assessment of prognosis. Blood specimens will be monitored for immunological and genetic markers that might be able to predict recurrence of melanoma. Marker-positive patients may be candidates for postoperative biotherapy (interferon), immunotherapy (vaccines) or biochemotherapy. In addition, the investigation will include the innovative use of carbon dye during lymphatic mapping, to confirm identification of the sentinel node and to indicate which part of this node is most likely to contain tumor cells.
Tissue from primary melanomas and regional lymph nodes will be analyzed by histopathological and immunohistochemical techniques. Of particular interest is the immune microenvironment of the sentinel node and how it is related to the preferential growth of tumor in this node. Multiple molecular markers are to be evaluated by quantitative RT-PCR assay (reverse transcriptase-polymerase chain reaction), to improve the sensitivity with which micrometastases can be detected in regional lymph nodes. DNA tumor markers in the primary melanoma and blood will be analyzed, as a means of detecting disease progression and predicting recurrence.
The overall goal of the sentinel node clinical trials is to use melanoma as a model to optimize surgical management of solid neoplasms and better identify candidates for postoperative adjuvant therapy. The concepts underlying the investigations are described in an important study presented by Dr. Morton to the American Surgical Association and scheduled for publication in the Annals of Surgery.
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