Advances in surgical treatment of melanoma.

Malignant melanoma is fatal in one-fifth of the patients who are diagnosed with the disease. It is a solid tumor cancer that spreads primarily through lymph nodes, making it amenable to surgical treatment. Surgical interventions for melanoma that have developed over the years include diagnostic biopsy, wide excision, lymph node staging, and treatment of local and visceral metastases. Lymphatic mapping and sentinel lymph node biopsy are two important surgical approaches that are gaining favor over more traditional nodal staging. The use of reverse transcriptase-polymerase chain reaction (RT-PCR) to diagnose submicroscopic disease shows promise for staging patients at the earliest possible time. Multicenter, randomized clinical trials such as the Sunbelt Melanoma Trial are vital in answering the question of how best to treat early metastatic melanoma.

Factors that predict the presence of sentinel lymph node metastasis in patients with melanoma.

BACKGROUND: This analysis was performed to identify prognostic factors that are predictive of sentinel lymph node (SLN) metastasis in melanoma. METHODS: Analysis was performed of a multi-institutional, prospective, randomized trial of SLN biopsy for melanoma. Eligibility criteria included age 18 to 70 years, Breslow thickness of 1.0 mm or more, and clinically negative regional lymph nodes. SLNs were evaluated by serial sectioning and immunohistochemistry for S100. Univariate chi-square and multivariate logistic regression analyses were performed to assess factors predictive of the presence of a positive SLN. Probability values of less than.05 were considered significant. RESULTS: SLNs were identified in 99.7% of patients. A total of 1058 patients were evaluated; 961 patients had complete data and were included in the statistical analysis. SLNs were positive for tumor in 208 of 961 patients (22%). Breslow thickness, Clark level, ulceration, and patient age were factors that were found to be independently predictive of the presence of SLN metastasis. CONCLUSIONS: Increasing Breslow thickness, Clark level of more than III, the presence of ulceration, and patient age of 60 years or less are the most important independent prognostic factors associated with the finding of positive SLN in patients with melanoma.

Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of nonsentinel nodes following completion lymphadenectomy for melanoma.

INTRODUCTION: Most melanoma patients with sentinel lymph nodes (SLN) that are histologically positive for metastasis have no additional positive lymph nodes found upon completion lymph node dissection (CLND). Therefore, it has been suggested that CLND may not be required for all patients with positive SLN. This study was undertaken to determine the frequency with which nonsentinel nodes contain melanoma cells detected by RT-PCR. METHODS: Negative control lymph nodes were obtained from patients with breast and colon cancer. Positive control lymph nodes contained histologic evidence of melanoma. Nonsentinel nodes were harvested from melanoma patients undergoing CLND for a positive SLN. RT-PCR analysis for melanoma markers tyrosinase, gp100, MART-1, and MAGE-3 was performed, with Southern blot detection. The RT-PCR test was considered positive for the presence of melanoma cells if tyrosinase and at least one other marker were detected above background levels. RESULTS: RT-PCR analysis detected the presence of melanoma cells in 0/100 (0%) of negative control lymph nodes and 28/29 (97%) of positive control lymph nodes. A total of 117 histologically negative nonsentinel nodes from 13 patients who underwent CLND for positive SLN were evaluated. RT-PCR analysis was positive in 18/117 histologically negative nonsentinel nodes (15%) from 7/13 patients (54%). CONCLUSION: RT-PCR analysis suggests that when the SLN contains histologic evidence of melanoma, the remaining nodes in that basin are at risk for metastatic disease, despite the fact that these nonsentinel nodes are infrequently histologically positive.

Sentinel lymph node biopsy for melanoma: how many radioactive nodes should be removed?

BACKGROUND: Sentinel lymph node (SLN) biopsy has become a standard method of staging patients with cutaneous melanoma. Sentinel lymph node biopsy usually is performed by intradermal injection of a vital blue dye (isosulfan blue) plus radioactive colloid (technetium sulfur colloid) around the site of the tumor. Intraoperative gamma probe detection has been shown to improve the rate of SLN identification compared to the use of blue dye alone. However, multiple sentinel nodes often are detected using the gamma probe. It is not clear whether these additional lymph nodes represent true sentinel nodes, or second-echelon lymph nodes that have received radiocolloid particles that have passed through the true sentinel node. This analysis was performed to determine the frequency with which these less radioactive lymph nodes contain metastatic disease when the most radioactive, or "hottest," node does not. MATERIALS AND METHODS: In the Sunbelt Melanoma Trial, 1184 patients with cutaneous melanoma of Breslow thickness 1.0 mm or more had sentinel lymph nodes identified. Sentinel lymph node biopsy was performed by injection of technetium sulfur colloid plus isosulfan blue dye in 99% of cases. Intraoperative determination of the degree of radioactivity of sentinel nodes (ex vivo) was measured, as well as the degree of blue dye staining. RESULTS: Sentinel nodes were identified in 1373 nodal basins in 1184 patients. A total of 288 of 1184 patients (24.3%) were found to have sentinel node metastases detected by histology or immunohistochemistry. Nodal metastases were detected in 306 nodal basins in these 288 patients. There were 175 nodal basins from 170 patients in which at least one positive sentinel node was found and more than one sentinel node was harvested. Blue dye staining was found in 86.3% of the histologically positive sentinel nodes and 66.4% of the negative sentinel nodes. In 40 of 306 positive nodal basins (13.1%), the most radioactive sentinel node was negative for tumor when another, less radioactive, sentinel node was positive for tumor. In 20 of 40 cases (50%), the less radioactive positive sentinel node contained 50% or less of the radioactive count of the hottest lymph node. The cervical lymph node basin was associated with an increased likelihood of finding a positive sentinel node other than the hottest node. CONCLUSIONS: If only the most radioactive sentinel node in each basin had been removed, 13.1% of the nodal basins with positive sentinel nodes would have been missed. It is recommended that all blue lymph nodes and all nodes that measure 10% or higher of the ex vivo radioactive count of the hottest sentinel node should be harvested for optimal detection of nodal metastases.