Prediction of metastatic melanoma in nonsentinel nodes and clinical outcome based on the primary melanoma and the sentinel node

Abstract

Lymphatic mapping and sentinel node biopsy are well-established techniques for staging and managing patients with melanoma, breast cancer and other malignancies that spread initially to the regional lymph nodes. Identification of tumor in the sentinel node is the most precise staging technique currently available. The sentinel node is the site of metastatic melanoma in approximately 20% of melanoma patients and if tumor is present in the sentinel node it is customary to perform a complete dissection of the lymph nodes of the affected nodal basin. This may be overtreatment for some patients as tumor is identified in the nonsentinel nodes of only one-third of sentinel node-positive melanoma patients treated by completion lymphadenectomy. If it were possible accurately to identify the minority of patients with tumor in the nonsentinel nodes, the patients most likely to benefit from lymphadenectomy, the remaining patients could be spared a potentially morbid operation that is unlikely to confer clinical advantage. In 90 patients with a melanoma-positive sentinel node, who subsequently had a completion lymphadenectomy, we evaluated and compared the capacity of characteristics of the primary melanoma and of the sentinel node to predict individuals likely to have tumor in nonsentinel nodes. We assessed the Breslow thickness of the primary, the amount of tumor in the sentinel node (relative tumor area) and, as an index of immune modulation of the sentinel node, the density of dendritic leukocytes in the nodal paracortex. The relative area of tumor in the sentinel node and Breslow thickness of the primary melanoma most accurately predicted the presence of tumor in the nonsentinel nodes (P ¼ 0.0001 in both cases-Wilcoxon rank sums). The presence of melanoma in the nonsentinel nodes was also predicted by the density of dendritic leukocytes in the paracortex (P ¼ 0.008-Wilcoxon rank sums). These three observations assessed alone and in combination predict the presence of tumor in the nonsentinel nodes with high accuracy. The same characteristics also significantly correlated with tumor recurrence (tumor burden, P ¼ 0.0001, Breslow, P ¼ 0.0001 and dendritic cell density, P ¼ 0.0007) and death from melanoma (tumor burden, P ¼ 0.0001, Breslow, P ¼ 0.0001 and dendritic cell density, P ¼ 0. Keywords: melanoma; sentinel node; tumor burden; immune suppression; tumor recurrence; melanoma deathThe techniques of lymphatic mapping and sentinel node biopsy were developed to improve the management of patients with high-risk (thick and deep) primary melanoma with a high potential for metastases, but no clinical evidence of metastatic spread.

Clinico-pathologic features of primary melanoma and sentinel lymph node predictive for non-sentinel lymph node involvement and overall survival in melanoma patients: A single centre observational cohort study

“…Our aim was to identify variables easy to measure and reproducible to combine at the hope to identify clinically useful predictors of NSLN involvement and significant on OS. For that reason, we did not include in our analysis the SLN tumour burden, even if many studies have found the size of the metastatic deposits in the SLN to be predictive of NSLN involvement [7], [9], [10] and [11]. Also recently, Cadili et al [21] confirmed the prognostic relevance of SLN total tumour size on both NSLN involvement and disease course in a large melanoma patient cohort.…”

“…In our experience, the number of positive SLNs was not associated to an increasing NSLN involvement, whilst the prognostic relevance of Starz classification was ascertained in univariate but not confirmed in multivariate logistic regression analysis. The predictive value of Breslow thickness on NSLN involvement has been found in some previous papers, but not confirmed by others [10], [13], [14], [15], [20], [31] and [33]; the same happens for ulceration, thus confirming a great deal of variability which limits the drawing of definite conclusions. Some studies suggested also to consider the association of two or more variables.…”

“…However, CLND carries significant morbidity [5] and [6] and there is no consensus on the benefit of a completion dissection in melanoma patients. In fact reports in the literature showed that only from 14 to 28% [7], [8], [9], [10] and [11] of positive patients will harbour further disease in the affected basin. Theoretically, only patients with involvement of additional, non-sentinel lymph nodes (NSLN) in the CLND specimen should benefit from a CLND.…”

Long-Term Protective Effect of Mature DC-LAMP+ Dendritic Cell Accumulation in Sentinel Lymph Nodes Containing Micrometastatic Melanoma

“…They observed that the SLNs were more affected than the non-SLNs and suggested that there may be a direct effect of tumor or tumor-associated factors on DC maturation and function. They also showed that a higher frequency of DCs in SLNs was correlated with reduced likelihood of recurrence and death from melanoma (34). The marker they used in that study (S100) identifies DCs at different stages of maturation, including mature DCs.…”

“…In melanomas, it was suggested that invasion of lymph nodes by tumor cells results in suppression of lymph node functions with alterations in immune cell ratio and activity (20,25,33). Cochran et al reported that the paracortex of lymph nodes with melanoma metastases contained decreased numbers of DCs (33,34) that were phenotypically less mature as compared with DCs in nonmetastatic lymph nodes (33). They observed that the SLNs were more affected than the non-SLNs and suggested that there may be a direct effect of tumor or tumor-associated factors on DC maturation and function.…”