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ABSTRACT & COMMENTARY
Synopsis: Histopathological features of ulceration and lymphovascular invasion were found to predict the presence of metastatic melanoma in a series of 105 patients with resected sentinel nodes. Even more important, however, was the thickness of the primary lesion. Histological features may improve predictive power, but absence of these negative factors does not exclude the possibility of nodal spread, and sentinel node dissection is recommended for all patients with primary lesions of 1 mm or greater.
Source: Nguyen CL, et al. Am J Surg. 2001;181:8-11.
The role for sentinel node mapping remains to be established in the management of melanoma. The purpose of the current study from the Medical University of South Carolina was to determine whether certain primary histopathological features of resected melanoma would predict sentinel lymph node status. This information might be used to identify those patients with primary melanoma for whom lymphatic mapping and sentinel lymphadenectomy would be of no benefit.
One hundred twelve patients underwent sentinel node biopsy between May 1995 and August 1999, and sentinel nodes were identified in 105 (94%). Routine histology and immunohistochemistry (to detect HMB-45 and S-100 antigens) were performed on all resected nodes. Of the 7 patients who had undetected sentinel nodes, 3 went on to have formal lymph node dissections, and no evidence for disease was found in any of these 3 patients. Of the 105 sentinel nodes, metastatic melanoma was discovered in 21 (20%). Eighteen of the 21 patients with positive sentinel nodes underwent subsequent lymph node dissections, and additional positive nodes were found in only 3 (17%). Of the 84 patients with negative sentinel nodes, 2 subsequently returned with lymphadenopathy at 7 and 18 months after sentinel lymphadenectomy, indicating at least a 2.4% false-negative rate. Multivariate analysis revealed that tumor thickness greater than 1.5 mm (P = .01), ulceration (P < .01), and lymphovascular invasion (P = .05) predicted the presence of micrometastases. Other prognostic factors that have proven relevant in the Clark melanoma classification system,1 such as a high mitotic rate, the presence of regression, and the absence of tumor-infiltrating lymphocytes were found to have no individual predictive value for occult lymph node involvement. Likewise, clinical factors such as gender and melanoma location were analyzed separately by univariate regression and were found to lack significance.
Thus, Nguyen and colleagues concluded that the presence of these unfavorable histological characteristics (ulceration and lymphovascular invasion) may identify a group of patients with thin melanomas who would benefit from sentinel lymphadenectomy.
COMMENT by William B. Ershler, MD
In this series of patients with melanoma, sentinel nodes were positive in 20%, and the most important factor was the depth of the primary melanoma. None of the patients with melanomas less than 1 mm were positive, whereas more than 50% of those with thickness greater than 3 mm were positive. In addition to thickness, certain histological features, including ulceration and lymphovascular invasion predicted sentinel node positivity. Thus, tumor thickness of greater than 1.5 mm and the presence of ulceration and lymphovascular invasion were highly predictive of sentinel node involvement. However, in a small number of patients, sentinel nodes were present in patients with primary tumor thickness of 1.1 mm, and in 2 of these cases, there were no unfavorable histological features. Thus, a conservative approach would be to proceed with the sentinel node sampling in all patients with tumor thickness of 1 mm or more.
An interesting feature of this study was that of the 18 patients with sentinel node positivity that went on to have regional lymphadenectomy, only 3 were found to have additional nodes positive. This is not different from other published reports and may indicate a step-like progression of regional metastases that may be of clinical relevance.2,3 It is possible that resection of sentinel nodes will have the same effect as more extensive lymphadenectomy with regard to the relevant issues of disease-free and overall survival. However, this conclusion should not be drawn from the current or previous reports but awaits a randomized, controlled clinical trial. In the meantime, it would seem prudent to perform sentinel lymph node dissection in all patients with primary tumors of 1 mm or more, and lymphadenectomy in those with sentinel node positivity.
1. Clark WH, et al. J Natl Cancer Inst. 1989;81: 1893-1904.
2. Morton DL, et al. Arch Surg. 1992;127:392-399.
3. Krag DN, et al. Arch Surg. 1995;130:654-660.