Thick Cutaneous Melanoma Research Articles

Staging in thick cutaneous malignant melanoma: A sequenced approach

BackgroundPatients with thick cutaneous pT4 malignant melanoma are at high risk for metastatic disease and optimal staging is poorly defined. This study examines the frequency and modality of pre-operative staging to provoke thought on optimal staging. MethodsA retrospective study was performed of patients with clinical T4N0 melanoma diagnosed between 2015-2017. The modality (sentinel lymph node biopsy and/or imaging), timing, and findings of staging investigations were assessed. ResultsOne hundred thirty-six patients with pT4a or pT4b cutaneous melanoma and clinically negative regional lymph nodes were included. Forty patients underwent no staging. Thirty-six patients underwent pre-operative imaging, and of these, regional or distant disease was identified in seven patients (19%). Another 36 patients underwent upfront sentinel lymph node biopsy concurrently with wide local excision. A positive sentinel lymph node biopsy was found in eight (22%) of these patients of which two had regional or distant metastatic disease on post-operative imaging. Of 16 who underwent a sentinel lymph node biopsy after negative pre-operative imaging, three had a positive sentinel lymph node biopsy. ConclusionStaging is non-standardized and underutilized in patients with thick melanoma. With evolving systemic treatment options, a well-defined approach to staging, with consideration for pre-operative imaging in pT4 patients, is essential for high-risk patients.

The Impact of Clinical and Histopathological Factors on Disease Progression and Survival in Thick Cutaneous Melanomas.

Thick cutaneous melanomas (Breslow depth > 4 mm) are locally advanced tumors, generally associated with poor prognosis. Nevertheless, these tumors sometimes display unpredictable behavior. This study aims to analyze clinical and histopathological features that can influence the prognosis of thick melanomas. This is a retrospective study on 94 thick primary cutaneous melanomas diagnosed between 2012 and 2018 that were followed-up for at least five years to assess disease progression and survival. We evaluated the age, gender, tumor location, histological subtype, Breslow depth, Clark level, resection margins, mitotic index, the presence/absence of ulceration, necrosis, regression, microsatellites, neurotropism, lymphovascular invasion, and the pattern of tumor-infiltrating lymphocytes, and their association with disease progression and survival. By conducting univariate analysis, we found that progression-free survival (PFS) was significantly associated with female gender, the superficial spreading melanoma (SSM) subtype, mitotic index, necrosis, microsatellites, and perineural invasion. Overall survival (OS) was significantly associated with female gender, Breslow depth, SSM subtype, necrosis, microsatellites, and perineural invasion. Through multivariate Cox proportional hazards regression, we found that the only factors associated with PFS were Breslow depth, necrosis, microsatellites, and perineural invasion, while the factors associated with OS were Breslow depth, necrosis, microsatellites, and perineural invasion. Certain histopathological features such as Breslow depth, necrosis, microsatellites, and perineural invasion could explain differences in disease evolution. This is one of the first studies to demonstrate an association between necrosis and perineural invasion and outcomes in patients with thick melanomas. By identifying high-risk patients, personalized therapy can be provided for improved prognosis.

Impact of the COVID-19 Pandemic on the Incidence and Thickness of Cutaneous Melanoma in Belgium.

(1) Background: COVID-19 had a major impact on cancer diagnostics and treatment. Delays in diagnosis of cutaneous melanoma were particularly feared, given the impact on survival and morbidity that comes with advanced stages. Moreover, its incidence in Belgium has been rapidly increasing in recent decades. This Belgian population-level study quantifies the pandemic effect on the number of melanoma diagnoses and Breslow thickness in 2020 and 2021. (2) Methods: In using an automated algorithm, the number of cutaneous melanoma diagnoses and Breslow thickness were extracted from all pathology protocols from 2017-2021 by the Belgian Cancer Registry. Monthly variations, as well as year-to-year differences, were studied. (3) Results: Annual incidence of cutaneous melanoma fell by 1% in 2020, compared to 2019, mainly due to a diagnostic deficit in March, April, and May 2020. An 8% incidence increase occurred in 2021, primarily reflecting an increase in the number of the thinnest melanomas (≤1 mm). Both the mean and median Breslow thicknesses were higher in spring 2020, resulting from an underrepresentation of thinner tumors. However, no particulars stood out on a full-year basis in either 2020 or 2021. (4) Conclusions: Considering the expected incidence increase, we estimate almost 210 melanoma diagnoses were missed in Belgium in 2020, corresponding to 6% of the expected number. This deficit occurred mainly during the first COVID-19 wave. Despite some rebound, the 2021 total was still 3% short of the expected number, leaving around 325 diagnoses remaining pending in 2020 and 2021, corresponding to a two-year deficit of 4.35%. Fortunately, mainly thin melanomas were missed, without any detectable shift toward thicker tumors later in 2020 and or 2021.

Preoperative assessment of cutaneous melanoma thickness by multispectral dermoscopy.

Preoperative assessment of Breslow thickness by means of sonography and clinical and dermoscopic criteria in white light dermoscopy has been reported, but up until now, the use of multispectral dermoscopy has not been investigated. Aim of this research is to determine whether multispectral dermoscopy and more specifically pigment maps can be used as a predictive marker for Breslow thickness in melanoma. Pigment maps are generated in real time from multispectral dermoscopic images and help to visualize the presence of pigment in a lesion. Multispectral images of 110 melanomas were collected, using a digital handheld multispectral dermatoscope, and assessed independently by five observers for the presence or absence of deep pigment compared with the surrounding skin. According to histopathological examination, the mean Breslow thickness of all 110 melanomas was 1.04 mm (ranging from 0.1 to 14 mm). The group of melanomas where deep pigment was visualized on the multispectral image (n = 78) had a significantly higher Breslow thickness (1.19 mm) than the group where no deep pigment was observed (n = 32, mean Breslow 0.68 mm) (P = 0.025). This study is unique in preoperative assessment of tumour thickness by means of multispectral dermoscopy. Our data indicate that the presence of deep pigment as visualized in digital dermoscopic skin parameter maps identifies a group of thicker melanomas. Further prospective research is needed to validate these pigment maps, generated by multispectral dermoscopy as a measure to predict invasiveness in melanoma.

The TRPA1 Channel Amplifies the Oxidative Stress Signal in Melanoma.

Macrophages (MΦs) and reactive oxygen species (ROS) are implicated in carcinogenesis. The oxidative stress sensor, transient receptor potential ankyrin 1 (TRPA1), activated by ROS, appears to contribute to lung and breast cancer progression. Although TRPA1 expression has been reported in melanoma cell lines, and oxidative stress has been associated with melanocytic transformation, their role in melanoma remains poorly known. Here, we localized MΦs, the final end-product of oxidative stress, 4-hydroxynonenal (4-HNE), and TRPA1 in tissue samples of human common dermal melanocytic nevi, dysplastic nevi, and thin (pT1) and thick (pT4) cutaneous melanomas. The number (amount) of intratumoral and peritumoral M2 MΦs and 4-HNE staining progressively increased with tumor severity, while TRPA1 expression was similar in all samples. Hydrogen peroxide (H2O2) evoked a TRPA1-dependent calcium response in two distinct melanoma cell lines (SK-MEL-28 and WM266-4). Furthermore, H2O2 induced a TRPA1-dependent H2O2 release that was prevented by the TRPA1 antagonist, A967079, or Trpa1 gene silencing (siRNA). ROS release from infiltrating M2 MΦs may target TRPA1-expressing melanoma cells to amplify the oxidative stress signal that affects tumor cell survival and proliferation.

Borderline Intermediary Thickness Cutaneous Melanoma: Standard Approach and The New Possibilities for Removal in one Surgical Session

Here we present a case of a 48-year-old female with a melanocytic lesion on the lateral aspect of the right thigh [Figure 1a-1d]. The patient observed a steady growth of the lesion over the last few years and attended our clinic for a dermatological consultation in March 2021. She was otherwise healthy and she reported anamnestic data was unremarkable. On examination of the lateral femoral region of the right thigh, the presence of a single, nodular, hyperpigmented lesion of 1.5cm was noted. The dome shaped lesion was dark brown in colour, smooth and elevated on palpation, and well demarcated from surrounding healthy tissue. Based on the clinical and dermatoscopical findings, a nodular melanoma of intermediate thickness was suspected. Further laboratory workup was conducted and showed no significant deviations from normal paraclinical values. Screening was also negative for tumour spread. All other paraclinical data was unremarkable. Diagnostic work up including CT of the thorax and abdomen detected no metastatic dissemination. The standard two step approaches based on the current AJCC guidelines was employed. The primary excision was performed with 0.5 cm safety margins in all directions [Figure 1e-f]. The elliptical defect was subsequently closed by single interrupted sutures. Histopathological verification confirmed the diagnosis of a nodular malignant melanoma, pT2b N0M0, stage 1B, Clark IV, Breslow thickness of 2mm, without ulceration, with high mitotic activity, well defined lymphocytic stromal reaction and clean resection margins.

Borderline Intermediate Thickness Cutaneous Melanoma Class B: Isn’t it Time for Personalised One Step Surgical Approach as Standard Clinical Behaviour?

We present a 40-year-old female who visited our clinic with a solitary lesion on the posterolateral aspect of the lower left leg (Figure 1a). She noticed a progressive change in the size and shape of the lesion and decided to consult a dermatologist in March 2021. The patient had a history of Hashimoto’s thyroiditis that was well-controlled onlevothyroxine. No other comorbidities were reported and she was otherwise healthy. During the clinical examination a single pigmented patch measuring 2.5 cm in greatest diameter was identified. Morphologically the lesion was asymmetrical with irregular borders and uneven colour. At the centre, an exudative, ulcerated nodule was also noted (Figure1a-f). Clinical and dermatoscopic findings were consistent with the diagnosis of a superficial spreading cutaneous melanoma. Ultrasound diagnostics of the abdominal cavity and retroperitoneal organs showed no signs of tumor spread. Chest radiography was also within normal limits. Laboratory testing showed an elevated uric acid level of 456 μmol/l (reference range 142 - 340 μmol/l), but otherwise all other parameters were normal. Following the recommended American Joint Committee on Cancer (AJCC) guidelines, we performed a primary resection with 0.5 cm margins in all directions. The resected tissue was subsequently sent for histopathological evaluation and confirmed the diagnosis of borderline intermediate thickness malignant melanoma - class B, 4 mm Breslow thickness, Clark IV, (pT4BN0M0) (Figure2a-d). There was high mitotic activity but no spontaneous regression, insignificant lymphocytic stromal reaction and clear resection margins. Post diagnostic workup, including chest and abdominal CT, showed no signs of metastatic dissemination. One week later, the patient was sent to the National Oncology Hospital for re-excision and Sentinel Lymph Node Biopsy (SLNB). The re-excision of additional 2cm from the previous surgical scar was conducted in parallel with removal of the draining sentinel lymph node (Figures 3a & 3d). The closure of the defect after re-excision led to the unfortunate complication of wound dehiscence and failure to close successfully (Figure 3b-c). However, after several sessions of debridement, cleansing, rebandaging and administration of antibiotics, there was visible improvement with subsequent resolution(Figure 3d-f). Since that time, she has been in excellent condition, and no complications have been reported to date.

Does morphology have real impact on local and distant recurrences in head and neck cutaneous melanoma?

Introduction. The term “local recurrence” is usually understood as regrowth of a tumor after surgical treatment. The regrowth appears within 3–5 cm from postoperative cicatrix. The causes for such prolonged tumor growth or recurrence of patients with cutaneous melanoma are nonradical surgical treatment as well as satellite or transit metastases that were not removed in-block with primary tumor. A great number of clinical researches, aimed at examination of melanoma, its patterns, anatomical criteria and features of clinical course, gave an opportunity to separate satellite or transit metastases into an independent group. Such metastases are realized inside or subdermally, up to 2 cm or more than 2 cm from the primary tumor, yet, not reaching the location of the first regional barrier.The aim of the study is to define influence of the main prognostic factors such as tumor thickness according to Breslow, the level of invasion according to Clark and the presence of ulceration on the frequency of local recurrence with cutaneous melanoma of head and neck.Materials and methods. The research involved 174 patients with cutaneous melanoma of head and neck (1995–2014). According to our index of contraction of a skin flap (median 30 %) the true borders of resection were clearly defined within all the patients. Thereby, 3 groups were identified with the following resection margin: 1.0 cm, where followed-up treatment results were analyzed.Results. Progression-free survival didn’t correlate with the size of surgical resection margins. The survival rates were the best with the lowest resection margin under 0.5 cm (77.3 %) and the worst with the highest resection margin more then 1.0 cm (38.7 %). That means that the treatment results don’t depend on the width increase of tumor resection margin.Conclusions. We consider that clear surgical margins for any thickness of cutaneous melanoma of head and neck should be as follows: 4 mm – 0.72 mm (p = 0.016). In our work, the influence of the main prognostic factors, such as tumor thickness according to Breslow, level of invasion according to Clark and ulceration on the frequency of head and neck cutaneous melanoma local recurrences had no impact.

Germline variants are associated with increased primary melanoma tumor thickness at diagnosis.

Germline genetic variants have been identified, which predispose individuals and families to develop melanoma. Tumor thickness is the strongest predictor of outcome for clinically localized primary melanoma patients. We sought to determine whether there is a heritable genetic contribution to variation in tumor thickness. If confirmed, this will justify the search for specific genetic variants influencing tumor thickness.To address this, we estimated the proportion of variation in tumor thickness attributable to genome-wide genetic variation (variant-based heritability) using unrelated patients with measured primary cutaneous melanoma thickness. As a secondary analysis, we conducted a genome-wide association study (GWAS) of tumor thickness.The analyses utilized 10 604 individuals with primary cutaneous melanoma drawn from nine GWAS datasets from eight cohorts recruited from the general population, primary care and melanoma treatment centers. Following quality control and filtering to unrelated individuals with study phenotypes, 8125 patients were used in the primary analysis to test whether tumor thickness is heritable. An expanded set of 8505 individuals (47.6% female) were analyzed for the secondary GWAS meta-analysis. Analyses were adjusted for participant age, sex, cohort and ancestry.We found that 26.6% (SE 11.9%, P = 0.0128) of variation in tumor thickness is attributable to genome-wide genetic variation. While requiring replication, a chromosome 11 locus was associated (P < 5 × 10−8) with tumor thickness. Our work indicates that sufficiently large datasets will enable the discovery of genetic variants associated with greater tumor thickness, and this will lead to the identification of host biological processes influencing melanoma growth and invasion.

The accuracy of elastographic strain ratio and ultrasound thickness in the differentiation of thin and thick cutaneous melanoma.

Cutaneous melanoma is the most deadly of skin neoplasms. Few studies have investigated the role of elastography characteristics so the ability of elastography in the differentiation of thin and thick cutaneous melanoma is still narrow. To investigate the accuracy of elastography in differentiating thin and thick melanoma, by measuring strain ratio (SR) between the lesion and adjacent dermis and hypodermis. We investigated by ultrasound and elastography 52 melanoma lesions in 49 patients. The receiver operating characteristic (ROC) curve method was used to investigate the accuracy of ultrasound and elastographic measurement of SR to surrounding tissue, in the differentiation of thin and thick melanomas. The histopathological measurement of lesions depth called Breslow index was the golden standard test. Areas under the curve (AUC) showed low accuracy for SR to hypodermis in distinguishing between thin melanomas and others (AUC = 0.739, 95% confidence interval [CI] = 0.508-0.970]) with a cut-off value of 0.950, being the only statistically significant result in matter of elastographic measurements. Highly statistically significant results were obtained for B-mode ultrasound depth measurements of the lesion, with an AUC = 0.970 (95% CI = 0.927-1.0) in discriminating thin melanomas of others and 0.951 (95% CI = 0.869-1.0) in discriminating thick melanomas of other types. Despite the appearance that SR may correlate with the depth of the lesion, elastography, by measuring the SRs to dermis and hypodermis, does not have enough accuracy in distinguishing thin and thick melanoma.

Verification of new method for automatic thickness measurement of melanocytic skin tumours by high frequency ultrasound

Histological thickness of cutaneous melanoma (CM), known as the Breslow index (pT), represents the most important prognostic factor. The objective of this study is to evaluate the reliability of automatic algorithm based on B-scan image processing of 22 MHz ultrasound (US) for measuring the thickness of CM and melanocytic nevi (MN). The thickness of CM (n = 54) and MN (n = 91) has been measured manually (mT) and automatically (aT) using an algorithm based on B-scan image processing of 22 MHz US. All melanocytic skin tumours (MST) were surgically excised and their histological thicknesses (pT) according to Breslow were evaluated. The investigated parameters were expressed as medians with interquartile range (IQR) because of their asymmetric distribution, Spearman’s correlation coefficient was determined as well. An agreement between values of mT/aT and mT/pT was evaluated by using the Bland-Altman plots. We found a good agreement of aT and mT with the moderate bias of 0.08 mm and relatively small range (95 % CI –0.01 to 0.18) in CM, accordingly 0.03 mm (95 % CI 0.00 to 0.07 mm) regarding MN. The medians of mT/pT in cases of CM and MN were 0.96 mm (IQR: 0.65-1.52) / 0.97 (IQR: 0.66-1.62) and 0.51 mm (IQR: 0.37-0.67) / 0.69 mm (IQR: 0.46-1.01) respectively. The parameters of the thickness correlated better in CM (r = 0.86) than in MN (r = 0.64) cases. The difference between manual (mT) and automatic (aT) measurements while evaluating the thickness of MST was non-significant. Therefore, automatic algorithm based on B-scan image processing of 22 MHz US is a reliable tool for measuring the thickness of MST by less experienced operators.

Differences in the diagnosis of primary cutaneous melanoma in the public and private healthcare systems in Joinville, Santa Catarina State, Brazil

Background:Cutaneous melanoma accounts for up to 80% of deaths caused by skin cancer. Diagnostic suspicion and access to medical care and early intervention in suspected cases is vital to the patient’s prognosis. Objectives:To compare demographic and histopathological characteristics of primary cutaneous melanoma diagnosed in the public healthcare system (Sistema Único de Saúde SUS) and the private system in Joinville, Santa Catarina State, Brazil. Methods:This cross-sectional retrospective study analyzed primary cutaneous melanoma cases recorded from 2003 to 2014 in the resident population of Joinville. Ethical approval was obtained from the local Research Ethics Committee. Results:893 cases of primary cutaneous melanoma were identified. Patients in the private system were mostly younger, while there were more elderly patients in the public healthcare system (p <0.001). There was no statistically significant association between type of care (public/private) and gender or presence of multiple primary cutaneous melanomas. Histological diagnosis of superficial spreading melanoma was more common in patients treated in private healthcare, while nodular melanoma was more frequent in patients in the public healthcare system (p <0.001). Mean Breslow depth in patients treated in private healthcare was 1.35mm, compared to 2.72mm in the public system (p <0.001). Study limitations:This was a retrospective study using secondary databases. Conclusions:thin cutaneous melanoma (in situ cutaneous melanoma and Breslow T1) showed the strongest association with the private healthcare system, while thick cutaneous melanoma was more frequent in the public system (Breslow category T3 and T4) (p <0.001).

Sentinel lymph node biopsy versus observation in thick melanoma: A multicenter propensity score matching study.

The clinical value of sentinel lymph node (SLN) biopsy in thick melanoma patients (Breslow >4 mm) has not been sufficiently studied. The aim of the study is to evaluate whether SLN biopsy increases survival in patients with thick cutaneous melanoma, and, as a secondary objective, to investigate correlations between survival and lymph node status. We included 1,211 consecutive patients with thick melanomas (>4 mm) registered in the participating hospitals' melanoma databases between 1997 and 2015. Median follow-up was 40 months. Of these patients, 752 were matched into pairs by propensity scores based on sex, age, tumor location, histologic features of melanoma, year of diagnosis, hospital and adjuvant interferon therapy. The SLN biopsy vs. observation was associated with better DFS [adjusted hazard ratio (AHR), 0.74; 95% confidence interval (CI) 0.61-0.90); p = 0.002] and OS (AHR, 0.75; 95% CI, 0.60-0.94; p = 0.013) but not MSS (AHR, 0.84; 95% CI, 0.65-1.08; p = 0.165). SLN-negative patients had better 5- and 10-year MSS compared with SLN-positive patients (65.4 vs. 51.9% and 48.3 vs. 38.8%; p = 0.01, respectively). As a conclusion, SLN biopsy was associated with better DFS but not MSS in thick melanoma patients after adjustment for classic prognostic factors. SLN biopsy is useful for stratifying these patients into different prognostic groups.

Excision margins and sentinel lymph node status as prognostic factors in thick melanoma of the head and neck: A retrospective analysis.

Recommended margins for thick cutaneous melanoma (Breslow thickness >4 mm; T4) have decreased over recent decades. Optimal margins and the role of sentinel node biopsy (SNB) in thick head and neck melanoma remain controversial. A single-center review was conducted of patients treated between 2002 and 2012 assessing the impact of excision margins and sentinel lymph node status on locoregional recurrence and melanoma-specific survival (MSS). One hundred eight patients were identified. Median age was 71.1 years and median Breslow thickness was 6.0 mm. Median follow-up was 40 months. Locoregional recurrence occurred in 27% and there was no significant reduction in recurrence with margins ≥2 cm (p = .17). Increasing margins did not improve survival (p = .58). Fifty-nine patients (55%) underwent SNB, of which 27% were positive. There was a trend toward longer survival for patients who were sentinel lymph node-negative (p = .097). Wider margins do not significantly improve locoregional recurrence or MSS. Sentinel lymph node involvement reflects a poor prognosis. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1373-1379, 2016.

Wide versus narrow excision margins for high-risk, primary cutaneous melanomas: long-term follow-up of survival in a randomised trial

SummaryBackgroundThe necessary margin of excision for cutaneous melanomas greater than 2 mm in thickness is controversial. At a median follow-up of 5 years, findings from our previously published randomised trial of narrow (1 cm) versus wide (3 cm) excision margins in patients with thick cutaneous melanomas showed that narrow margins were associated with an increased frequency of locoregional relapse, but no significant difference in overall survival was apparent. We now report a long-term survival analysis of that trial.MethodsWe did a randomised, open-label multicentre trial in 59 hospitals—57 in the UK, one in Poland, and one in South Africa. Patients with one primary localised cutaneous melanoma greater than 2 mm in Breslow thickness on the trunk or limbs (excluding palms or soles) were randomly assigned (1:1) centrally to receive surgery with either a 1 cm or 3 cm excision margin following an initial surgery. The randomisation lists were generated with random permuted blocks and stratified by centre and extent of initial surgery. The endpoints of this analysis were overall survival and melanoma-specific survival. Analyses were done in the intention-to-treat population. This trial was not registered because it predated mandatory trial registration.FindingsBetween Dec 16, 1992, and May 22, 2001, we randomly assigned 900 patients to surgery with either a 1 cm excision margin (n=453) or a 3 cm excision margin (n=447). At a median follow-up of 8·8 years (106 months [IQR 76–135], 494 patients had died, with 359 of these deaths attributed to melanoma. 194 deaths were attributed to melanoma in the 1 cm group compared with 165 in the 3 cm group (unadjusted hazard ratio [HR] 1·24 [95% CI 1·01–1·53]; p=0·041). Although a higher number of deaths overall occurred in the 1 cm group compared with the 3 cm group (253 vs 241), the difference was not significant (unadjusted HR 1·14 [95% CI 0·96–1·36]; p=0·14). Surgical complications were reported in 35 (8%) patients in the 1 cm excision margin group and 65 (15%) patients in the 3 cm group.InterpretationOur findings suggest that a 1 cm excision margin is inadequate for cutaneous melanoma with Breslow thickness greater than 2 mm on the trunk and limbs. Current guidelines advise a 2 cm margin for melanomas greater than 2 mm in thickness but only a 1 cm margin for thinner melanomas. The adequacy of a 1 cm margin for thinner melanomas with poor prognostic features should be addressed in future randomised studies.FundingCancer Research UK, North Thames National Health Service Executive, Northern and Yorkshire National Health Service Executive, British United Provident Association Foundation, British Association of Plastic Surgeons, the Meirion Thomas Cancer Research Fund, and the National Institute for Health and Research Biomedical Research Centre at The Royal Marsden NHS Foundation Trust.

Value of sentinel lymph node biopsy and adjuvant interferon treatment in thick (>4 mm) cutaneous melanoma: an observational study.

The role of sentinel lymph node biopsy and the benefit of immunotherapy with interferon in thick (>4 mm) melanomas remain uncertain. Our aim was to assess the value of both sentinel lymph node (SLN) biopsy and immunotherapy in the prognosis of thick melanomas. A retrospective study based on a computerized patient database in which patients have been prospectively collected since 2005 was performed. Age, sex, location, Breslow thickness, tumor ulceration, regression, Clark level, tumor infiltrating lymphocytes, tumor mitotic rate, microscopic satellite and vascular invasion were included in the analysis. Disease-free (DFS), disease-specific (DSS) and overall (OS) survivals were evaluated by the Kaplan-Meier method and Cox regression analysis. A series of 141 patients with melanomas thicker than 4 mm were included. Multivariate regression showed a worse prognosis in SLN-positive patients with respect to SLN biopsy-negative patients (DFS, hazard ratio [HR] 2, p = 0.04; DSS, HR 2.2, p = 0.002; OS, HR 2.4, p = 0.02). The observational group was shown to have a worse prognosis than the SLN-positive group but was very similar to the clinically positive group. Immunotherapy with high-dose interferon showed a protective effect (DFS, HR 0.5, p = 0.02; DSS, HR 0.3, p = 0.001; OS, HR 0.3, p = 0.001). Our data indicate that SLN biopsy and adjuvant interferon should be considered for patients with thick melanomas.

NY-ESO-1 expression is associated with primary cutaneous melanoma thickness

NY-ESO-1 expression is associated with primary cutaneous melanoma thickness

Clinicopathological characteristics at primary melanoma diagnosis as risk factors for brain metastasis

To better identify melanoma patients who are, at the time of primary melanoma diagnosis, at high risk of developing brain metastases, primary melanoma characteristics were examined as risk factors for brain metastasis development. In a study of two patient cohorts, clinicopathological characteristics prospectively collected at primary cutaneous melanoma diagnosis for patients with/without brain metastasis were assessed in univariate and multivariate analyses using data from two prospectively collected databases: the Melanoma Cooperative Group (MCG) (1972-1982) and the Interdisciplinary Melanoma Cooperative Group (IMCG) (2002-2009). Candidate risk factors were evaluated in association with time to brain metastasis using either the log-rank test or Cox proportional hazards regression analysis with/without considering competing risks. Out of 2341 total patients included in the study, 222 (9.5%) developed brain metastases (median follow-up: 98 months). The median time to brain metastases was 30.5 months and the median survival time after brain metastases was 4 months. Increased hazard ratios (HRs) for brain metastasis were found among thicker (logarithmic value in mm) (MCG: HR=1.97, P<0.0001; IMCG: HR=1.31, P=0.018), ulcerated (MCG: HR=1.93, P=0.01; IMCG: HR=3.14, P<0.0001), and advanced-stage (MCG: HR=2.08, P=0.008; IMCG: HR=2.56, P=0.0002) primary melanomas on the basis of multivariate Cox regression analysis assuming the presence of competing risks. Primary cutaneous melanoma thickness, ulceration, and stage were identified and validated as risk factors associated with time to melanoma brain metastasis.

Age-related disparities in use of completion lymphadenectomy for melanoma sentinel lymph node metastasis

BackgroundGuidelines recommend that patients with melanoma metastatic to the sentinel lymph node (SLN) undergo a completion lymphadenectomy (CLND) of the affected lymph node basin. We have previously reported on decreased use of SLN biopsy among elderly patients. We hypothesized that elderly patients with SLN metastases would have lower rates of CLND relative to their younger counterparts. MethodsThe Surveillance, Epidemiology, and End Results database was queried for patients who underwent SLN biopsy for intermediate thickness cutaneous melanoma (Breslow thickness 1.01 mm–4.00 mm) from 2004 to 2008 and were found to have SLN metastasis. Patients were categorized according to age by decade. We then used multivariate logistic regression models to predict receipt of CLND. Additional covariates included sex, race/ethnicity, T stage, tumor histology, tumor location, and ulceration. The likelihood of receiving a CLND was reported as OR with 95% CI; significance was set at P ≤ 0.05. ResultsEntry criteria were met by 765 patients. Of these, 548 (71.6%) patients underwent CLND. On multivariate analysis, patients in the age groups 70–79 y old (OR 0.39, CI 0.20–0.78; P = 0.007) and ≥80 y old (OR 0.27, CI 0.12–0.61; P = 0.001) were less likely to undergo CLND than the youngest age group (1–39 y old). ConclusionsElderly patients with SLN metastasis are less likely to receive CLND than their younger counterparts. A multi-center randomized clinical trial evaluating the potential survival benefit of CLND is ongoing. Further research to assess reasons why the elderly are less likely to receive CLND are needed.

Assessing rural–urban disparities in the use of sentinel lymph node biopsy for melanoma

BackgroundWe hypothesized that patients in urban areas with intermediate thickness cutaneous melanoma would have higher rates of sentinel lymph node biopsy (SLNB) relative to their rural-dwelling counterparts. MethodsThe Surveillance, Epidemiology, and End Results database was queried for patients who underwent surgery for intermediate thickness cutaneous melanoma from 2004–2008. Patients were categorized as coming from urban or rural counties based on a nine-point scale. We used multivariate logistic regression models to predict use of SLNB. Covariates examined included sex, race/ethnicity, age, T stage, tumor histology, tumor location, and ulceration. The likelihood of undergoing SLNB was reported as OR with 95% CI. ResultsOf 8441 patients, 8382 (99.3%) had complete information regarding use of SLNB. On multivariate analysis, patients from rural counties had a decreased likelihood of receiving a SLNB (OR 0.87, CI 0.78–0.97; P = 0.014). Additional factors associated with a decreased likelihood of receiving a SLNB included increasing age, Asian/Hispanic/Unknown race, and head and neck or overlapping primary tumor site. ConclusionsPatients in rural areas are less likely to receive a SLNB for intermediate thickness cutaneous melanoma than their urban-dwelling counterparts.