Evaluation Of Melanoma Research Articles

Precision Oncology in Melanoma: Changing Practices.

Over the last 2 decades, significant progress has been made in our understanding of the genomics, tumor immune microenvironment, and immunogenicity of malignant melanoma. Historically, the prognosis for metastatic melanoma was poor because of limited treatment options. However, after multiple landmark clinical trials displaying the efficacy of combined BRAF/MEK inhibition for BRAF-mutant melanoma and the application of immune checkpoint inhibitors targeting the programmed death-1, cytotoxic T-lymphocyte antigen-4, and lymphocyte activation gene-3 molecules, overall survival rates have dramatically improved. The role of immune checkpoint inhibition has since expanded to the neoadjuvant and adjuvant settings with multiple regimens in routine use. Personalized therapies, including tumor-infiltrating lymphocytes that are extracted from a patient's melanoma and eventually reinfused into the patient, and messenger RNA vaccines used to target neoantigens unique to a patient's tumor, show promise. Improvements in accompanying imaging modalities, particularly within the field of nuclear medicine, have allowed for more accurate staging of disease and assessment of treatment response. Continued growth in the role of nuclear medicine in the evaluation of melanoma, including the incorporation of artificial intelligence into image interpretation and use of radiolabeled tracers allowing for intricate imaging of the tumor immune microenvironment, is expected in the coming years.

Implantation and Evaluation of Melanoma in the Murine Choroid via Optical Coherence Tomography.

Establishing experimental choroidal melanoma models is challenging in terms of the ability to induce tumors at the correct localization. In addition, difficulties in observing posterior choroidal melanoma in vivo limit tumor location and growth evaluation in real-time. The approach described here optimizes techniques for establishing choroidal melanoma in mice via a multi-step sub-choroidal B16LS9 cell injection procedure. To enable precision in injecting into the small dimensions of the mouse uvea, the complete procedure is performed under a microscope. First, a conjunctival peritomy is formed in the dorsal-temporal area of the eye. Then, a tract into the sub-choroidal space is created by inserting a needle through the exposed sclera. This is followed by the insertion of a blunt needle into the tract and the injection of melanoma cells into the choroid. Immediately after injection, noninvasive optical coherence tomography (OCT) imaging is utilized to determine tumor location and progress. Retinal detachment is evaluated as a predictor of tumor site and size. The presented method enables the reproducible induction of choroid-localized melanoma in mice and the live imaging of tumor growth evaluation. As such, it provides a valuable tool for studying intraocular tumors.

Novel Ink - Stained Reflectance Confocal Microscopy Guided Pigmented Skin Lesion Biopsy Technique: Reducing Pathology Sample Bias Through Improved Precision

With skin cancer incidence rate steadily increasing each year, melanoma continues to pose a significant public health problem globally. It is well-known that early detection and prevention of melanoma remains the most important intervention for reducing morbidity and mortality, therefore it is imperative to promote innovation that will advance our ability to diagnose melanoma early. Because prognosis and treatment are dependent on the depth of dermal involvement, definitive diagnosis of melanoma can only be made through histopathologic assessment [1]. Thus, appropriate sampling of tissue is critical for the accurate evaluation of melanoma.

Diagnostic utility of preferentially expressed antigen in melanoma immunohistochemistry in the evaluation of melanomas with a co-existent nevoid melanocytic population: A single-center retrospective cohort study

To the Editor: PRAME (PReferentially expressed Antigen in MElanoma) immunohistochemistry has emerged as a reliable tool for distinguishing benign and malignant melanocytic neoplasms.1-4 Diffuse nuclear immunoreactivity was found in ∼90% of conventional nonspindle cell primary cutaneous melanomas, compared to absent or focal staining in 86% and 13% of conventional nonspitzoid melanocytic nevi, respectively.2

Assessment of 35 Years Longitudinal Observations on Melanoma Patients in a Single Center of Hungary’s Central Region: Effect of Interferon Immunotherapy

Background: The incidence of melanoma malignum increases worldwide. Detailed objective analyses from central European region are scarcely available. Objective: To obtain validated data on melanoma distribution and retrospective analysis in the central region of Hungary based on 35 years of experience in a single center. Methods: The authors monitored the clinical course of their patients with melanoma between 1984 and 2018 based on the digitalized documentation of their institute. They analyzed the treated and non-treated cases with the leadership of a dermatologist-pathologist-oncologist. Altogether 867 cases (450 female, 417 male) were examined from the removal of the primary tumor onwards in retrospective way. Results: Distribution of gender, age, tumor stages and body regions by genders were examined. The authors also reviewed the asymptomatic period until tumor progression, morbidity data, the period and effect of the adjuvant low, intermediate and high dose interferon α-2b immunotherapy. Patients with lymph node metastasis who received low or intermediate dose immunotherapy experienced significantly longer tumor-free period than those who got high-dose immunotherapy. In both treated groups, the median value of the asymptomatic months was higher compared to the observation only” group. Conclusion: The results of their long-term follow-up contribute to the accurate evaluation of melanoma and of the interferon therapy in Hungary and in the region.

Impact of the COVID-19 pandemic on staging at presentation of patients with invasive melanoma.

e21579 Background: The COVID-19 pandemic has impacted cancer care beyond the direct implications of viral infection. Delays in presentation and diagnosis may lead to more advanced disease and worse patient outcomes. We evaluated the impact of the pandemic on patients (pts) with melanoma (mel). Methods: A single-institution, retrospective comparison of pts with newly diagnosed invasive mel or metastatic recurrence prior to (pre-cohort, n = 246) and after (post-cohort, n = 246) declaration of the COVID-19 pandemic on March 11, 2020. 492 pts were evaluated between March 1, 2019 and January 12, 2021. Key variables collected included demographics, pathology, stage at diagnosis, surgical management, receipt of adjuvant or systemic therapy, and follow up. Categorical variables were compared using the two-sided Fisher’s exact test, continuous variables were compared using the two-sided Wilcoxon rank sum test, and survival endpoints were evaluated with the Kaplan-Meier method. This study was exempt from review by the IRB. Results: 200 (81.3%) pts presented with early-stage disease and 46 (18.7%) pts presented with metastatic disease in the post-cohort, compared to 209 (85%) and 37 (15%) pts in the pre-cohort, respectively. In the post-cohort there was a significant decrease in stage I pts (28.5% vs 40.7%, p = 0.006), a significant increase in stage III pts (30.5% vs 21.1%, p = 0.023), and a significant increase in pts with metastatic recurrence (7.7% vs 3.3%, p = 0.046) compared to the pre-cohort. There was also a significant increase in pts with brain metastases (BM) in the post-cohort (6.5% vs 1.6%, p = 0.010). For pts with early-stage disease, there was a significant increase in median Breslow depth (2.0 vs 1.4 mm, p = 0.047) and mitotic rate > 1 (78.1% vs 66%, p = 0.008) in the post-cohort. There were trends toward increased ulceration, lymphovascular/perineural invasion, and microsatellite presence. Pts receiving adjuvant therapy in the post-cohort were significantly more likely to receive oral targeted therapy (37.6% vs 27.5%) compared to IV immunotherapy (62.4% vs 72.5%), p = 0.034, perhaps reflecting an attempt to minimize in-person visits. There was not a significant difference between the 2 groups in the type of systemic therapy administered in the metastatic setting. Median progression-free and overall survival were not reached due to a limited number of events in each arm. Conclusions: There was a significant decrease in pts with stage I mel along with a significant increase in pts with stage III mel, metastatic recurrence, and BMs presenting to our institution during the pandemic. Findings are likely related to delays from both the patient (to avoid interaction with the healthcare system - including primary care, dermatology, and oncology) and from the system itself, with some clinics potentially evaluating pts in a limited capacity. These data reaffirm the importance of early detection and evaluation of melanoma.

Melanoma Prevention: Comparison of Different Screening Methods for the Selection of a High Risk Population.

Background: Guidelines recommend limiting melanoma screening in a population with known risk factors, but none indicates methods for efficient recruitment. The purpose of this study is to compare three different methods of recruiting subjects to be screened for melanoma to detect which, if any, is the most efficient. Methods: From 2010 to 2019, subjects were recruited as follows: (1) regular skin examinations (RS), mainly conducted through the Associazione Contro il Melanoma network; (2) occasional melanoma screening (OS), during annual public campaigns; (3) and selective screening (SS), where people were invited to undergo a skin check after filling in a risk evaluation questionnaire, in cases where the assigned outcome was intermediate/high risk. Melanoma risk factors were compared across different screening methods. Generalized Linear Mixed Models were used for multivariable analysis. Results: A total of 2238 subjects (62.7% women) were recruited, median age 44 years (2–85), and 1094 (48.9 %) records were collected through RS, 826 (36.9 %) through OS, and 318 (14.2 %) through SS. A total of 131 suspicious non-melanoma skin cancers were clinically diagnosed, 20 pathologically confirmed, and 2 melanomas detected. SS performed significantly better at selecting subjects with a family history of melanoma and I-II phototypes compared to OS. Conclusions: Prior evaluation of melanoma known risk factors allowed for effective selection of a population to screen at higher risk of developing a melanoma.

Abstract CT150: A first-in-human phase I study of the OX40 agonist GSK3174998 (GSK998) +/- pembrolizumab in patients (Pts) with selected advanced solid tumors (ENGAGE-1)

Abstract Background: OX40 is a costimulatory receptor transiently expressed on the surface of activated T cells and some innate immune cells (e.g. NK cells). OX40 agonists have been shown to increase antitumor immunity and improve tumor-free survival in preclinical models, demonstrating increased efficacy when given in combination with a PD-1 inhibitor. GSK998 is a humanized IgG1 agonistic OX40 monoclonal antibody. Methods: ENGAGE-1 (NCT02528357) is a Phase 1 dose escalation study evaluating safety, PK, PD, and clinical activity of GSK998 (0.003-10 mg/kg IV Q3W) alone (Part 1) and in combination with pembrolizumab 200 mg IV Q3W (Part 2) in pts with previously treated advanced solid tumors: non-small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck, renal cell carcinoma, melanoma (MEL), bladder cancer, soft tissue sarcoma (STS), triple-negative breast cancer, and MSI-high colorectal carcinoma. Dose escalation used a continuous reassessment method and 4-week DLT period. Results: A total of 138 pts were enrolled (45 Part 1, 96 Part 2; 3 crossed over from Part 1). Two DLTs occurred in Part 2 only (G3 non-malignant pleural effusion 0.03 mg/kg; G1 myocarditis 10 mg/kg); MTD was not established. Most common (≥10%) treatment-related AEs (mostly G1-2) were diarrhea, fatigue (Part 1) and fatigue, nausea (Part 2). GSK998 demonstrated target engagement in the periphery as evidenced by PK and receptor occupancy (RO); a dose of 0.3 mg/kg was the threshold for linear PK & peripheral RO saturation over the 3-wk dose interval and was selected for further clinical evaluation in MEL, STS, and NSCLC in Part 2 expansion. Clinical responses and SD ≥24 weeks were observed in both PD-1/L1 naïve and experienced pts: Part 1 (1 PR, 1 SD; both 0.3 mg/kg) and Part 2 (2 CR, 7 PR, 9 SD; 0.01-3 mg/kg); Part 2 clinical responses were not correlated with baseline tumor PD-L1 expression levels; including one MEL pt with PD-L1 TPS=0 who progressed on prior CTLA-4/PD-1 treatment and had a CR (>18mo). Overall, peripheral and tumor expression of OX40 was low (<2% total cells in tumor were OX40 +ve). MultiOmyxTM data from tumor biopsies suggested increased NK/decreased Treg involvement in some responders. Conclusions: GSK998 +/- pembrolizumab was well tolerated, with evidence of target engagement; monotherapy clinical activity was limited. While combination responses may not be significantly greater than expected for pembrolizumab alone, responses were observed in some PD-1/L1 experienced pts and some with low PD-L1 expression. Given the low OX40 expression observed and preclinical evidence that increased expression improves activity of OX40 agonism, ongoing clinical evaluation of GSK998 will assess whether concurrent immune-stimulation or immunogenic cell death impacts OX40 expression and increases the efficacy of this agent. Combinations with TLR4 and ICOS agonists and an anti-BCMA antibody-drug conjugate are ongoing. Citation Format: Sophie Postel-Vinay, Vincent K. Lam, Willeke Ros, Todd M. Bauer, Aaron R. Hansen, Daniel C. Cho, F. Stephen Hodi, Jan H.M. Schellens, Jennifer K. Litton, Sandrine Aspeslagh, Karen A. Autio, Frans L. Opdam, Meredith McKean, Neeta Somaiah, Stephane Champiat, Mehmet Altan, Anna Spreafico, Osama Rahma, Elaine M. Paul, Christoph M. Ahlers, Helen Zhou, Herbert Struemper, Shelby A. Gorman, Maura Watmuff, Kaitlin M. Yablonski, Niranjan Yanamandra, Michael J. Chisamore, Emmett V. Schmidt, Axel Hoos, Aurélien Marabelle, Jeffrey S. Weber, John V. Heymach. A first-in-human phase I study of the OX40 agonist GSK3174998 (GSK998) +/- pembrolizumab in patients (Pts) with selected advanced solid tumors (ENGAGE-1) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT150.

Evaluation of Melanoma (SK-MEL-2) Cell Growth between Three-Dimensional (3D) and Two-Dimensional (2D) Cell Cultures with Fourier Transform Infrared (FTIR) Microspectroscopy.

Fourier transform infrared (FTIR) microspectroscopy was used to evaluate the growth of human melanoma cells (SK-MEL-2) in two-dimensional (2D) versus three-dimensional (3D) spheroid culture systems. FTIR microspectroscopy, coupled with multivariate analysis, could be used to monitor the variability of spheroid morphologies prepared from different cell densities. The characteristic shift in absorbance bands of the 2D cells were different from the spectra of cells from 3D spheroids. FTIR microspectroscopy can also be used to monitor cell death similar to fluorescence cell staining in 3D spheroids. A change in the secondary structure of protein was observed in cells from the 3D spheroid versus the 2D culture system. FTIR microspectroscopy can detect specific alterations in the biological components inside the spheroid, which cannot be detected using fluorescence cell death staining. In the cells from 3D spheroids, the respective lipid, DNA, and RNA region content represent specific markers directly proportional to the spheroid size and central area of necrotic cell death, which can be confirmed using unsupervised PCA and hierarchical cluster analysis. FTIR microspectroscopy could be used as an alternative tool for spheroid cell culture discrimination, and validation of the usual biochemical technique.

EV20-mediated delivery of cytotoxic auristatin MMAF exhibits potent therapeutic efficacy in cutaneous melanoma

Cutaneous melanoma is one of the cancers with the fastest rising incidence and in its advanced metastatic form is a highly lethal disease. Despite the recent approval of several new drugs, the 5-year overall survival rate for advanced cutaneous melanoma is still below 20% and therefore, the development of novel treatments remains a primary need. Antibody-Drug Conjugates are an emerging novel class of anticancer agents, whose preclinical and clinical development has recently seen a remarkable increase in different tumors, including melanoma. Here, we have coupled the anti-HER-3 internalizing antibody EV20 to the cytotoxic drug monomethyl auristatin F (MMAF) to form a novel antibody-drug conjugate (EV20/MMAF). In a panel of human melanoma cell lines, this novel ADC shows a powerful, specific and target-dependent cell killing activity, independently of BRAF status. Efficacy studies demonstrated that a single administration of EV20/MMAF leads to a long-lasting tumor growth inhibition. Remarkably, the effect of this novel ADC was superior to the BRAF inhibitor vemurafenib in preventing kidney, liver and lung melanoma metastases. Overall, these results highlight EV20/MMAF as a novel ADC with promising therapeutic efficacy, warranting extensive pre-clinical evaluation in melanoma with high levels of HER-3 expression.

Utility of whole-body (head-to-toe) PET/CT in the evaluation of melanoma and sarcoma patients.

The aim of this study was to assess the added benefit of whole-body (head-to-toes) PET/CT versus routine 'eyes-to-thighs' PET/CT of melanoma and sarcoma patients. We performed a retrospective review of consecutive whole-body PET/CT scans from January 2006 through December 2010 in patients with melanoma or sarcoma. PET abnormalities in the brain, distal thighs, and legs were recorded and clinical significance was assessed on the basis of pathology, imaging studies, and clinical follow-up. Patients with known primary lesions distal to the proximal femora were excluded as these patients would routinely undergo 'head-to-toe' PET/CT. We reviewed reports from 352 PET/CT examinations in 194 patients with melanoma and 75 PET/CT examinations in 44 patients with sarcoma. Melanoma: 13 patients had brain metastases on PET. In five of these patients, lesions were unknown, but all were in the setting of other metastatic disease. Twenty-seven patients had lower extremity metastases, all in the setting of other metastatic disease. No lower extremity metastases were found in the remaining 167 patients. Sarcoma: one patient had an isolated, unexpected brain metastasis. Six patients had leg metastases, but none were isolated. No lower extremity metastases were found in the remaining 38 patients. In patients with melanoma and sarcoma, inclusion of entire lower extremities adds little additional clinical value as detection of isolated, unexpected metastasis is rare. Brain imaging may add value as the presence of brain metastases alters clinical management. Overall, in patients with melanoma or sarcoma, whole-brain PET/CT imaging may be of value, but routine inclusion of the entire lower extremities adds little additional value.

The role of lymph node ultrasound evaluation in melanoma - review of the literature.

Melanoma is an aggressive tumour, resistant to treatment, derived from melanocytes, with an increasing incidence in the last years in the majority of countries. The most important prognostic factor in the initial stages (I/II) is the presence of metastases at the level of lymph nodes. Ultrasound (US) is a non-invasive method, used in the pre- and post-operative node evaluation due to its high availability, the reduced cost and easy reproducibility. The US accuracy is however dependent on operator expertise. The present article proposes a presentation of the US role in the evaluation of lymph nodes in melanoma patients.

5 - Utility of Whole Genome SNP Microarray and Targeted Somatic Mutations in Evaluation of Melanoma, Histologic Mimics of Melanoma, and Glioblastoma

5 - Utility of Whole Genome SNP Microarray and Targeted Somatic Mutations in Evaluation of Melanoma, Histologic Mimics of Melanoma, and Glioblastoma

The Skin Cancer Objective Structured Clinical Examination (SCOSCE): A multi-institutional collaboration to develop and validate a clinical skills assessment for melanoma

Assessing medical students on core skills related to melanoma detection is challenging in the absence of a well-developed instrument. We sought to develop an objective structured clinical examination for the detection and evaluation of melanoma among medical students. This was a prospective cohort analysis of student and objective rater agreement on performance of clinical skills and assessment of differences in performance across 3 schools. Kappa coefficients indicated excellent agreement for 3 of 5 core skills including commenting on the presence of the moulage (k = 0.87, 95% confidence interval 0.77-0.96), obtaining a history for the moulage (k = 0.84, 95% confidence interval 0.74-0.94), and making a clinical impression (k = 0.80, 95% confidence interval 0.68-0.92). There were no differences in performance across schools with respect to 3 of 5 core skills: commenting on the presence of the moulage (P = .15), initiating a history (P = .53), and managing the suspicious lesion (P value range .07-.17). Overall, 54.2% and 44.7% of students commented on the presence of the moulage and achieved maximum performance of core skills, respectively, with no difference in performance across schools. Limitations include overall sample size of students and schools. The Skin Cancer Objective Structured Clinical Examination represents a potentially important instrument to measure students' performance on the optimal step-by-step evaluation of a melanoma.

Immunosuppression is an independent prognostic factor associated with aggressive tumor behavior in cutaneous melanoma

A number of factors other than those identified by the American Joint Committee on Cancer (AJCC) may have prognostic significance in the evaluation of melanoma. We sought to evaluate commonly recorded clinical features potentially associated with aggressive melanoma. We conducted a retrospective case-control study. We included patients given a diagnosis of cutaneous melanoma with at least 5years of follow-up or documented metastases. Patients were divided into nonaggressive and aggressive groups. Univariate and multivariate statistical analyses were performed to evaluate the association of multiple clinical and histologic parameters and metastases. We included 141 patients. Significant prognostic factors in univariate analysis associated with nonaggressive disease included history of dysplastic nevus syndrome and ABCDE criteria. Significant factors in univariate analysis associated with aggressive disease included age and immunosuppression. Only age and immunosuppression remained significant in multivariate analysis when controlled across statistically significant histologic variables from AJCC. The study is retrospective and has a small sample size. Older patients and those with a history of immunosuppression may be at higher risk for aggressive disease and should be closely monitored after an initial diagnosis of melanoma.

The use of elastin immunostain improves the evaluation of melanomas associated with nevi

The use of elastin immunostain improves the evaluation of melanomas associated with nevi

Humoral shift and increased early recurrence with GM-CSF + vaccine versus vaccine alone

3013 Background: Vaccines are currently under evaluation in melanoma, and many vaccine strategies use GM-CSF as an immune adjuvant. There are few randomized data yet available to determine the clinical impact of the addition of GM-CSF to vaccination. We conducted a randomized, prospective trial of an allogeneic melanoma vaccine with or without GM-CSF to determine the immune and clinical effects. Methods: 95 patients were stratified by stage and randomized to Canvaxin vaccine (with bacille Calmette-Guerin [BCG]) or Canvaxin (+BCG) and GM-CSF (200 mcg/m2/d) injected at the vaccine sites after vaccination for 5 days. Antibody titers against a urinary tumor-associated melanoma antigen were measured by ELISA, and DTH skin testing was done using PPD and unadulterated vaccine cells. Results: There was a significant early rise in both IgG and IgM titers in the GM-CSF arm with an early high plateau at about 8 weeks for both. The rise in antibody titer was slower in the non-GM-CSF arm with IgG rising throughout the study period and IgM peaking at 20 weeks. Conversely there was a delay in PPD responsiveness in the GM-CSF arm. PPD conversion percentage surpassed 90% in the non-GM-CSF arm at 6 weeks and peaked at 100% at 12 weeks. In the GM-CSF arm, only 76% converted at 6 weeks and only 87% were ever sensitized. A trend toward diminished DTH response was noted in the GM-CSF arm as early as 4 weeks and became significant at 16 weeks (p=0.01) and when considered throughout the trial. There was a marked increase in early recurrences in the GM-CSF arm leading to a significant survival difference when examined at 2 years (96% versus 72%; log-rank p=0.0017). Conclusions: When given at the site of vaccination, GM-CSF appears to accelerate the onset of a humor immune response while delaying cellular responses. In addition there appears to be evidence of adverse clinical effects in terms of early recurrence and possibly survival. Recent reports of increased myeloid suppressor cells with GM-CSF treatment may provide an immune mechanism for our findings. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration CancerVax

Design and preclinical evaluation of melanoma targeting agents for internal radionuclide therapy

Design and preclinical evaluation of melanoma targeting agents for internal radionuclide therapy

Acne Vulgaris: False-Positive Finding on Integrated 18F-FDG PET/CT in a Patient with Melanoma

WEB This is a Web exclusive article. alignant melanoma was diagnosed in approximately 59,580 patients in the United States in 2005. Appropriate treatment of patients with this tumor depends on accurate staging at presentation. CT has been used in the evaluation of melanoma at high risk of metastasis (i.e., thick, ulcerated primary tumors [stage IIC] or stage III disease). Because the accuracy of CT in the detection of occult metastatic lesions is limited, whole-body 18F-FDG PET has emerged as a complementary imaging technique and is being used with increasing frequency in examinations of patients with advanced melanoma [1, 2]. Although integration of PET and CT findings increases diagnostic accuracy, use of this combination in the detection of distant metastatic lesions is associated with a high falsepositive rate [3]. Awareness of potential diagnostic pitfalls is therefore needed to avoid misinterpretation of integrated PET/CT images that can lead to inaccurate staging. In particular, accurate identification of cutaneous and subcutaneous metastasis of melanoma is important because the lesions may represent new or additional regional or distant metastatic disease. Such findings may influence the overall treatment approach. We report the case of a patient with melanoma lymph node metastasis (American Joint Committee on Cancer stage III) who had 18F-FDG accumulation at the sites of acne vulgaris that might have been misinterpreted as evidence of multiple distant cutaneous or subcutaneous metastatic lesions, potentially altering the pre-PET surgical treatment plan of regional lymph node dissection.

Sentinel lymph node biopsy in thin melanoma patients

We sought to determine the incidence of positive sentinel lymph nodes in thin melanoma (<or=1.0 mm) patients and if subgroups could be identified with a higher risk of occult nodal disease. Patients with <or=1.0 mm lesions treated between 1997 and 2003 were reviewed. Sentinel nodes underwent microscopic analysis including step sectioning and immunohistochemical examination. Some nodes underwent reverse transcriptase-polymerase chain reaction (RT-PCR) evaluation for melanoma markers. Sixty-four of 107 thin melanoma patients underwent sentinel node biopsy (SNB). Mapped patients were more likely to have Clark >or= III and thicker lesions (mean 0.77 mm vs. 0.47 mm), but were not different in regards to age, sex, or lesion location. Eight percent and 58% of sentinel nodes were positive by routine histology and RT-PCR, respectively. Among mapped patients, younger age was the only significant prognostic factor for node positivity. With a median follow-up of 18 months among all patients, one regional recurrence (at 2 years) has been identified. Given the low morbidity of sentinel lymph node biopsy, this procedure should be discussed with selected thin melanoma patients to detect microscopic disease, however PCR positivity by our methods is too commonly seen to be clinically significant in thin melanoma patients and requires additional study.