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 sentinel node biopsy (SNB) procedure is a multidisciplinary technique, invented to gain prognostic information in different malignant tumors. The aim of the present study was to study the cohort of patients with malignant melanoma, operated with SNB, from the introduction of the technique in Sweden, concerning the prognostic information retrieved and the outcome of the procedures. In Sweden all patients with malignant melanoma are registered at regional Oncological Centers. From these databases ten centers were identified, treating malignant melanoma and performing sentinel node biopsy. Consecutive data concerning tumor characteristics, outcome of the procedure and disease related events during the follow-up time were collected from these ten centers. All cases from the very first in each centre were included. The SNB procedure was performed in 422 patients with a sentinel node (SN) detection rate of 97%, the mean Breslow thickness of the primary tumors was 3.2 mm (median 2.4 mm) and the proportion of ulcerated melanomas 38%. Metastasis in the SN was found in 19% of the patients but there was a wide range in the proportion of SN metastases between the different centers (5-52%). After a follow-up of median 12 months of 361 patients, SN negative patients had better disease-free survival than SN positive (p<0.0001). A false negative rate of 14% was found during the follow-up time. In this study the surgical technique seemed acceptable, but the non-centralized pathology work-up sub-optimal. However, SNB was still found to be a significant prognostic indicator, concerning disease free survival.Acta oncologica (Stockholm, Sweden) 01/2008; 47(8):1519-25. DOI:10.1080/02841860701785533 · 3.71 Impact Factor
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ABSTRACT: The sentinel lymph node (SLN) biopsy in melanoma assesses reliably the status of the regional lymph node basins, provides valuable prognostic information, facilitates early therapeutic lymphadenectomy and identifies patients who are candidates for different adjuvant treatments. The current study was designed to evaluate the feasibility of cytological specimens being placed in PreservCyt as a practical collection methodology for performing evaluation of the SLN status in patients with melanomas. From January 2004 to December 2006, 70 patients with histologically confirmed cutaneous melanoma underwent intraoperative FNA biopsy of the SLN. After identification of the SLN(s), FNA biopsy of the SLN was performed with a 0.6 mm (23 gauge) diameter needle. All the SLNs specimens were examined (using light microscopy 40 x and 200 x) by the same pathologist and cytopathologist, neither of had any knowledge of the medical history of the patient. The histological result of the excised SLN was considered as the final diagnosis. The unsatisfactory rate for TP cytology was 2.17%. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy (OA) for the TP technique were 92.31%, 100%, 100%, 97.06%, and 97.83%, respectively. Using TP cytology, there was greater intensity and distribution of the staining in comparison with immunohistochemistry. The accuracy of TP technique in the evaluation of the SLN status is comparable to those of the histological evaluation, and could be of paramount importance for the preoperative planning of treatment.Surgical Oncology 09/2007; 16(2):121-9. DOI:10.1016/j.suronc.2007.06.002 · 2.37 Impact Factor
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ABSTRACT: Optimal utilization of sentinel node biopsy in the care of cancer patients requires cooperation between the radiologist, surgeon, and the pathologist. Accurate pathologic diagnosis of the sentinel node is central to correct staging, optimal treatment decisions, and precise prognostication of patients with melanoma, breast, colorectal, lung, and gastric cancer. Intraoperative handling, gross dissection, and histologic/immunohistochemical evaluation techniques are all key components of this process. Although not currently part of routine handling, newer molecular techniques may potentially add to the valuable information gained from evaluating sentinel node specimens.The Cancer Journal 01/2015; 21(1):33-8. DOI:10.1097/PPO.0000000000000087 · 3.61 Impact Factor