Characterization of micrometastatic disease in melanoma sentinel lymph nodes by enhanced pathology: recommendations for standardizing pathologic analysis.
ABSTRACT Lymphatic mapping and sentinel lymph node (SLN) biopsy are widely used as a staging technique for patients with cutaneous malignant melanoma who are at risk for metastases. SLN status has been shown to be a strong predictor of prognosis, and a variety of techniques have been used to identify minimal metastatic disease in SLNs. However, there is no validated consensus method for the optimal histologic analysis of SLNs harvested from melanoma patients. This study was conducted: 1) to assess the yield of metastatic melanoma detected in SLNs deemed negative by initial routine pathologic analysis (RPA) by subjecting them (after review of the original slides) to enhanced pathologic analysis (EPA) that included complete step-sectioning and immunohistochemistry (IHC); 2) to characterize the distribution of metastatic melanoma deposits within the SLNs; 3) to determine a preferred method of pathologic analysis applicable to daily practice; and 4) to attempt to assess the clinical significance of disease detected by EPA. A total of 105 SLNs were harvested from 49 patients who underwent successful SLN biopsy procedures during the period of study. Ten SLNs from 10 patients were positive on initial RPA and were not analyzed further. Ninety-five SLNs from the remaining 39 patients were reviewed and processed with additional hematoxylin and eosin, S-100 protein, and HMB-45 stains at 50-microm intervals for 20 levels or until the SLN tissue was exhausted. A single pathologist reviewed all sections without knowledge of the results of the other stains. Overall, metastatic melanoma was discovered in SLNs from 20 of the 39 patients: SLNs from 6 patients were found to have melanoma on review of the original hematoxylin and eosin slides, and SLNs from 14 patients were positive only after EPA. Twenty-one individual positive SLNs from these 14 patients were detected by EPA; of these, 10 positive SLNs were identified solely by IHC, representing 12% of the patient cohort and 10% of all SLNs studied by EPA. Detection rates were significantly associated with the staining method and the number of levels performed (P < 0.01). S-100 protein staining resulted in the highest yield of SLN positivity (86%), followed by HMB-45 (81%) and hematoxylin and eosin (52%). No single method detected all of the micrometastases. A detailed topographic mapping of metastatic deposits in SLNs was carried out. When using all three staining techniques, all 20 levels were required to identify 100% of the micrometastases; 95% of positive SLNs were identified with 17 levels, 90% with 15 levels, 75% with 10 levels, and 42% with 3 levels. Projected rates of detection for various different sectioning strategies were determined, with alteration of either the number of levels examined, the interval between the levels, or both. Detection of SLN positivity can be increased to 71% by performing three levels at 250-mum intervals, each level being composed of a set of three sections stained with hematoxylin and eosin, S-100 protein, and HMB-45, respectively. Therefore, this is the methodology we propose for the study of SLNs in melanoma patients. After a median follow-up of 87 months (range, 9-134 months), patients with EPA-detected disease and those with negative SLNs by EPA demonstrated improved recurrence-free and disease-specific survival compared with patients with RPA-detected disease in SLNs. Sampling error introduced by variations in pathologic processing should be addressed by standardization of pathologic methods, and the clinical significance of minimal SLN disease should be addressed in prospective studies of homogeneously staged patients.
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ABSTRACT: The objectives of this article are to assess the completeness of the data collected on site-specific factors (SSFs) as a part of Collaborative Stage (CS) version 2 and the impact of the transition from the American Joint Committee on Cancer's (AJCC) 6th to 7th edition guidelines on stage distribution. Incidence data for melanomas of the skin from 18 Surveillance, Epidemiology, and End Results (SEER) registries (SEER-18) were analyzed. Percentages of unknown cases for 7 SSFs were examined, along with staging trends from 2004 to 2010 and differences in AJCC 6th and 7th edition stage distributions for 2010 cases. Fewer than 10% of cases were coded as unknown for SSFs 1 (measured thickness), 2 (ulceration), and 3 (lymph node metastasis). For the remaining SSFs, 36-81% of cases were coded as unknown. Stage distributions were relatively consistent across time and between the AJCC 6th and 7th editions, with the exception of stage IA and stage INOS (not otherwise specified), for which a shift in cases was observed between the AJCC 6th and 7th edition guidelines fOR 2010 cases. A shift of cases out of stage IA and into stage INOS was observed between the AJCC 6th and 7th edition guidelines for 2010 cases. This was attributed to the high number of cases coded as unknown for SSF7 (primary tumor mitotic count/rate). The percentage of cases coded as unknown varied by SSF. Data completeness presents an issue for SSFs introduced in CS version 2. Cancer 2014;120(23 suppl):3807-14. © 2014 American Cancer Society. © 2014 American Cancer Society.Cancer 12/2014; 120 Suppl 23:3807-14. DOI:10.1002/cncr.29050 · 5.20 Impact Factor
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ABSTRACT: Sentinel lymph node (SLN) status currently represents the single most important prognostic factor in clinically localized melanoma and is widely used in patients with melanoma at significant risk for nodal micrometastasis. Although several studies have looked at the rates and implications of inaccuracies in the histopathologic diagnosis of melanocytic lesions, accuracy in the histologic interpretation of the SLN in melanoma has not been addressed. The goal of this study was to determine the rates of discordance in the histopathologic evaluation of the SLN and the potential clinical impact on patients referred to a comprehensive melanoma center.Annals of Surgical Oncology 05/2014; 21(11). DOI:10.1245/s10434-014-3773-8 · 3.94 Impact Factor