Prognostic Significance of Isolated HMB45 or Melan A Positive Cells in Melanoma Sentinel Lymph Nodes

Department of Dermatology, Skin Cancer Center Hannover, Hannover Medical School, Hannover, Germany.
American Journal of Surgical Pathology (Impact Factor: 5.15). 09/2007; 31(8):1175-80. DOI: 10.1097/PAS.0b013e3180341ebc
Source: PubMed


The detection of micrometastases (defined as groups of malignant cells) in the sentinel lymph node (SLN) is an important prognostic tool in melanoma. The use of immunohistochemistry with melanocytic markers such as HMB45 and Melan A increases the detection rate of micrometastases but there are also cases with isolated immunohistochemically positive cells (IPC). To determine the prognostic significance of isolated HMB45 and/or Melan A positive cells in melanoma SLN, we compared the clinical course of 47 patients with IPC to 308 patients with negative SLN and to 122 patients with micrometastases. The mean follow-up was 38.1 months. By Kaplan-Meier analyses, relapse free survival and overall survival of patients with IPC were similar to SLN negative patients, whereas patients with micrometastases had a significantly worse relapse free survival and overall survival. In the 47 patients with IPC, 6 relapses (12.8%) and 3 melanoma-related death (6.4%) occurred, in the SLN negative patients 36 relapses (11.7%) and 17 melanoma-related deaths (5.5%), in the patients with micrometastases 46 relapses (37.7%) and 29 melanoma-related deaths (23.8%). Prognosis of patients with IPC in SLN did not correlate with type of positive staining (HMB45, Melan A, or both), capsular involvement, number of cells, presence of cytologic atypias of IPC, or tumor penetrative depth. In conclusion, with short-term follow-up IPC in melanoma SLN are without prognostic significance.

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    • "Like their stem cell counterparts in normal tissue, tumor-initiating cells are capable to self-renew [10] by asymmetric cell division resulting in the formation of a tumor-initiating cell and differentiated progeny which have lost the tumor-initiating potential of the mother cell [11]. In malignant melanomas this progeny is characterized by either the melanoma antigens HMB45 and MART-1 [12], the microphthalmia-associated transcription factor (MITF) or the melanin synthesis controlling enzyme tyrosinase (TYR). However, besides asymmetric cell division, label-retention and colony-formation as well as a high cellular plasticity are determinants of stem-like cells. "
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    PLoS ONE 05/2014; 9(5):e92596. DOI:10.1371/journal.pone.0092596 · 3.23 Impact Factor
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    • "Lymph nodes were cut parallel to the longest axis into slices about 1 mm thickness and embedded in paraffin blocks. Four sections (3 μm thick) of each slice were produced with a microtome: the first one was stained with haematoxylin-eosin, and the subsequent for the immuno-hystochemistry with S100, HMB45 and MART1 antibodies [9,10]. "
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    ABSTRACT: Complete lymph node dissection (CLND) is the gold standard treatment for patients with a positive sentinel lymph node (SLN) biopsy. Considering the morbidity associated with CLND it is important to identify histological features of the primary tumor and/or of SLN metastasis that could help to spare from CLND a subset of patients who have a very low risk of non-SLN metastasis. The objective of this study is to identify patients with a very low risk to develop non-SLNs recurrences and to limit unnecessary CLND. A retrospective long-term study of 80 melanoma patients with positive SLN, undergone CLND, was assessed to define the risk of additional metastasis in the regional nodal basin, on the basis of intranodal distribution of metastatic cells, using the micro-morphometric analysis (Starz classification). This study demonstrates that among the demographic and pathologic features of primary melanoma and of SLN only the Starz classification shows prognostic significance for non-SLN status (p<0.0001). This parameter was also significantly associated with disease-free survival rate (p<0.0013). The Starz classification can help to identify, among SLN positive patients, those who can have a real benefit from CLND. From the clinical point of view this easy and reliable method could lead to a significant reduction of unnecessary CLND in association with a substantial decrease in morbidity. The study results indicate that most of S1 subgroup patients might be safely spared from completion lymphatic node dissection. Furthermore, our experience demonstrated that Starz classification of SLN is a safe predictive index for patient stratification and treatment planning.
    Journal of Experimental & Clinical Cancer Research 08/2013; 32(1):47. DOI:10.1186/1756-9966-32-47 · 4.43 Impact Factor
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    • "Thus, we focus our analysis on this characteristic. There is considerable debate as to how to stratify SLN tumour burden; Satzger et al (2007) found that isolated immunohistochemically positive tumour cells are without prognostic significance and DFS of these patients did not differ from that of SLN-negative patients, an observation that is supported in a broader sense by Van Akkooi et al (2006). In their study, no patient with an SLN tumour load of o0.1 mm had additional non- SLN positivity upon CLND, and 5-year overall survival was 100%. "
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    ABSTRACT: Twenty per cent of sentinel lymph node (SLN)-positive melanoma patients have positive non-SLN lymph nodes in completion lymph node dissection (CLND). We investigated SLN tumour load, non-sentinel positivity and disease-free survival (DFS) to assess whether certain patients could be spared CLND. Sentinel lymph node biopsy was performed on 392 patients between 1999 and 2005. Median observation period was 38.8 months. Sentinel lymph node tumour load did not predict non-SLN positivity: 30.8% of patients with SLN macrometastases (> or =2 mm) and 16.4% with micrometastases (< or =2 mm) had non-SLN positivity (P=0.09). Tumour recurrences after positive SLNs were more than twice as frequent for SLN macrometastases (51.3%) than for micrometastases (24.6%) (P=0.005). For patients with SLN micrometastases, the DFS analysis was worse (P=0.003) when comparing those with positive non-SLNs (60% recurrences) to those without (17.6% recurrences). This difference did not translate into significant differences in DFS: patients with SLN micrometastasis, either with (P=0.022) or without additional positive non-SLNs (P<0.0001), fared worse than patients with tumour-free SLNs. The 2-mm cutoff for SLN tumour load accurately predicts differences in DFS. Non-SLN positivity in CLND, however, cannot be predicted. Therefore, contrary to other studies, no recommendations concerning discontinuation of CLND based on SLN tumour load can be deduced.
    British Journal of Cancer 06/2008; 98(12):1922-8. DOI:10.1038/sj.bjc.6604407 · 4.84 Impact Factor
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