Higher Breslow Thickness Research Articles

Median Breslow thickness during, post and pre-COVID-19 lockdown and correlation with socioeconomic factors.

e21574 Background: Access to routine cancer care during COVID-19 pandemic was greatly affected. The impact of this on melanoma care is unknown. Breslow thickness (BT) was seen to decrease and then increase during and post-COVID-19 lockdown in Italy. Here, we aim to study the impact of COVID-19 lockdown on melanoma care in the United States. Methods: Patients diagnosed with cutaneous melanoma (CM) pre (September 15th 2019-March 14th 2020), during (March 15th-June 14th 2020), and post-lockdown (June 15th-December 14th 2020) were retrospectively studied using Metropolitan Detroit Cancer Surveillance System (MDCSS) database. Patients without an identifiable primary lesion, or with ocular, mucosal, or acral melanoma were excluded. Demographic and clinical characteristics were reviewed. The primary endpoint was median BT during and post vs pre-lockdown. Fisher's exact and Kruskal-Wallis tests were performed for categorical and continuous variables, respectively, to compare groups. Interaction in subgroup analyses was assessed using likelihood ratio tests. Linear regression analyses were performed with Box-Cox transformed BT. Cox proportional hazards regression analyses were performed for overall survival. Covariates for multivariable analysis were selected using LASSO-based penalized regression models. Results: 802 patients were included (pre N = 347, during N = 87, post N = 368). Patients diagnosed with CM post-lockdown were younger (age < 50 years pre = 14%, during = 13%, post = 23%). More patients diagnosed pre-lockdown carried government-issued insurance (pre = 48%, during = 39%, post = 38%). No difference (diff) in median BT was seen between periods (median = 0.6mm for pre, during, and pos). Married status was associated with a lower BT vs unmarried (diff = -0.19, 95% CI -0.36 to -0.014, p = 0.034) and higher census tract poverty level was associated with a higher BT (5%-10% diff = 0.17, 95% CI 0.004 to 0.33, p = 0.045; 10%-100% diff = 0.27, 95% CI 0.093 to 0.45, p = 0.003) vs 0-5% poverty on univariable analysis. Male gender was associated with a lower BT on multivariable analysis (diff = -0.12, 95% CI -0.20 to -0.04, p = 0.005) and lower risk of death on univariable analysis (HR = 0.50, 95% CI 0.31 to 0.82, p = 0.006). Conclusions: We found no difference in median BT during and post- vs pre-lockdown. We also identified at-risk populations (female, unmarried, and living in greater poverty areas) who could benefit from proactive melanoma care. Time to surgery from initial diagnosis during and post vs pre-lockdown would be of interest to study further.

Melanoma Detected Through Teledermatology Versus In-Person Visits.

Background: Early detection of melanoma improves survival; however, patients face long wait times to receive dermatology care. Teledermatology (TD) is a promising tool to optimize access to care and has shown promise for the identification of malignancies but has not been well studied for melanoma. We evaluated the utility of TD as a triage tool to allow high-risk lesions of concern to be seen more expeditiously. Methods: Patient sociodemographic factors and histological characteristics of 836 melanomas biopsied between March 2020 and November 2022 in the University of Pittsburgh Medical Center health system were retrospectively evaluated, stratified by initial appointment type of TD versus in-person visit. Results: Patients first seeking care through teledermatology had shorter wait times to initial evaluation (p < 0.001) and eventual biopsy (p < 0.001), and these melanomas had higher Breslow thickness (p < 0.001), were more ulcerated (p = 0.002), invasive (p = 0.001), and of a more aggressive subtype (p = 0.007) than those initially evaluated in-person. TD was also utilized by a higher proportion of younger (p = 0.001) and non-white (p = 0.03) patients who identified their own lesion (p < 0.001). Conclusions: TD may be a strategy to improve melanoma outcomes by providing an accessible avenue of expedited care for high-risk lesions associated with worse clinical prognosticators of disease.

Efficacy of adjuvant therapy in patients (pts) with AJCC v8 stage IIIA cutaneous melanoma.

9518 Background: Pts with resected AJCC v8 stage IIIA melanoma have been under-represented in clinical trials of adjuvant drug therapy. The benefit of adjuvant targeted and immunotherapy in this population is unclear. Methods: In this multicenter, retrospective study, pts with stage IIIA melanoma (AJCC v8) who received adjuvant pembrolizumab or nivolumab (PD1), BRAF/MEK-targeted therapy dabrafenib + trametinib (TT), or no adjuvant treatment (OBS) were included. Recurrence free survival (RFS), distant metastasis free survival (DMFS), and toxicity rates were examined. Results: 613 pts from 34 centers across Australia, Europe and USA were included. The median follow-up was 2.6 yrs (IQR, 1.6-3.4 yrs). Pt characteristics and follow-up were similar across the cohorts (Table). Completion rates of 12-month PD1 and TT therapy were 57.0% and 69.2% respectively. 1-yr RFS was 93.3% (95% CI, 90.3-96.4) in PD1, 100% in TT and 91.3% (95% CI, 88.1-94.7) in OBS cohorts. 2-yr RFS was 79.3% (95% CI, 74.1-84.8) for PD1, 100% for TT and 84.3% (95% CI, 79.9-89.0) in OBS cohorts. 2-yr DMFS was 88.4% (95% CI, 84.3-92.8) in PD1, 100% in TT and 91.1% (95% CI, 87.7-94.7) in OBS cohorts. Risk of recurrence was associated with higher breslow thickness (HR 1.73, 95% CI 1.36-2.20), higher mitotic rate (HR 1.07, 95% CI 1.02-1.12) and neck as the site of nodal metastases (HR 2.71, 95% CI 1.45-5.06) in the overall cohort (p&lt;0.05). Neck nodal metastases were associated with higher risk of recurrence in OBS cohort (HR 3.82, 95% CI 1.91-7.66; p&lt;0.05) but not in the PD1 cohort. Rates of ≥ Grade 3 toxicities were 10.9% with PD1 and 20.0% with TT; discontinuation due to toxicity occurred in 25.0% and 30.0%, respectively. No new safety signals were observed. Rates of unresolved toxicity at last follow-up were 26.9% in PD1 and 7.7% in TT cohorts. Conclusions: In this large international study, adjuvant PD1 or TT did not significantly improve RFS or DMFS compared to OBS in pts with resected stage IIIA melanoma. Prognosis in stage IIIA melanoma is favourable and outcomes after adjuvant therapy in this population needs further study in prospective randomised trials. [Table: see text]

Association of Complex Lymphatic Drainage in Head and Neck Cutaneous Melanoma With Sentinel Lymph Node Biopsy Outcomes

Although sentinel lymph node biopsy (SLNB) is a vital staging tool, its application in head and neck melanoma (HNM) is complicated by a higher false-negative rate (FNR) compared with other regions. This may be due to the complex lymphatic drainage in the head and neck. To compare the accuracy, prognostic value, and long-term outcomes of SLNB in HNM with melanoma from the trunk and limb, focusing on the lymphatic drainage pattern. This cohort observational study at a single UK University cancer center included all patients with primary cutaneous melanoma undergoing SLNB between 2010 to 2020. Data analysis was conducted during December 2022. Primary cutaneous melanoma undergoing SLNB between 2010 to 2020. This cohort study compared the FNR (defined as the ratio between false-negative results and the sum of false-negative and true-positive results) and false omission rate (defined as the ratio between false-negative results and the sum of false-negative and true-negative results) for SLNB stratified by 3 body regions (HNM, limb, and trunk). Kaplan-Meier survival analysis was used to compare recurrence-free survival (RFS) and melanoma-specific survival (MSS). Comparative analysis of detected lymph nodes on lymphoscintigraphy (LSG) and SLNB was performed by quantifying lymphatic drainage patterns by number of nodes and lymph node basins. Multivariable Cox proportional hazards regression identified independent risk factors. Overall, 1080 patients were included (552 [51.1%] men, 528 [48.9%] women; median age at diagnosis 59.8 years), with a median (IQR) follow-up 4.8 (IQR, 2.7-7.2) years. Head and neck melanoma had a higher median age at diagnosis (66.2 years) and higher Breslow thickness (2.2 mm). The FNR was highest in HNM (34.5% vs 14.8% trunk or 10.4% limb, respectively). Similarly, the false omission rate was 7.8% in HNM compared with 5.7% trunk or 3.0% limbs. The MSS was no different (HR, 0.81; 95% CI, 0.43-1.53), but RFS was lower in HNM (HR, 0.55; 95% CI, 0.36-0.85). On LSG, patients with HNM had the highest proportion of multiple hotspots (28.6% with ≥3 hotspots vs 23.2% trunk and 7.2% limbs). The RFS was lower for patients with HNM with 3 or more affected lymph nodes found on LSG than those with fewer than 3 affected lymph nodes (HR, 0.37; 95% CI, 0.18-0.77). Cox regression analysis showed head and neck location to be an independent risk factor for RFS (HR, 1.60; 95% CI, 1.01-2.50), but not for MSS (HR, 0.80; 95% CI, 0.35-1.71). This cohort study found higher rates of complex lymphatic drainage, FNR, and regional recurrence in HNM compared with other body sites on long-term follow-up. We advocate considering surveillance imaging for HNM for high-risk melanomas irrespective of sentinel lymph node status.

Prognosis of polypoid melanoma: a comparative study with non-polypoid melanomas.

Polypoid melanoma is considered an exophytic and frequently non-pigmented variant of nodular melanoma with an adverse prognosis; however, very few studies have been published about it with contradictory results. Therefore, our objective was to determine the prognostic value of this configuration in melanomas. A transversal retrospective study of 724 cases was analyzed according to the main configuration (polypoid vs. non-polypoid) regarding their clinicopathologic characteristics and survival analysis. Of the 724 cases, 35 (4.8%) met the definition of polypoid melanoma; such cases, compared with non-polypoid melanomas, were associated with a high Breslow thickness (7 mm vs. 3 mm), 68.6% had a Breslow >4 mm; showed different clinical stages of presentation, and presented more ulceration (77.1 vs. 51.4%). In the 5-year overall survival (OS) analysis, polypoid melanoma is associated with a lower 5-year OS, together with lymph node metastasis, Breslow thickness, clinical stage, mitoses per mm 2 , vertical growth phase, ulceration, and state of the surgical margins; however, in the multivariate analysis, the factors that remained independent predictors of death were the Breslow thickness groups, the clinical stage, the presence of ulceration, and the state of the surgical margins. Polypoid melanoma was not an independent predictor of OS. We found a prevalence of 4.8% of polypoid melanomas, which showed a worse prognosis than non-polypoid melanomas, explained by a higher proportion of ulcerated cases, greater Breslow thickness, and ulceration. However, polypoid melanoma was not an independent predictor of death.

Non-Coding RNA Investigations in Cutaneous Melanoma: A Step forward in Discovering Novel Biomarkers

Non-Coding RNA Investigations in Cutaneous Melanoma: A Step forward in Discovering Novel Biomarkers

Long-term time trends in incidence, survival, and mortality of malignant melanoma in the United States.

e21599 Background: While there have been newer treatments that were developed in the last decade for metastatic melanoma, there is lack of data that directly looks at survival in melanoma before and after introduction of these new agents. We tried to explore the epidemiology of malignant melanoma including incidence to look at the trends of its incidence, survival and mortality in different groups over the last two decades. Methods: Data was obtained from the Surveillance, Epidemiology, and End Results Program (SEER Research Data, 18 Registries from 2000-2018) and data was cleaned and analyzed in STATA 16. 363,517 records were included in analysis from which baseline characteristics and median were obtained for survival time and survival analysis was done by Cox regression method to compare survival time between different groups. Pearson correlation was calculated to look for association between survival time and Breslow thickness. Results: Mean age group was 55-64 years, with 58% males and 42% females. 95% were White, 0.43% were Black, 0.63% were Asian and 3.79% were other races. 87% were localized, whereas 13% were metastatic. Mean Breslow thickness was 1.27mm (1.26-1.28). Overall median survival time was 62 months for malignant melanoma and 27 months for metastatic malignant melanoma. 42.63% were diagnosed before 2009 and 57.37% were diagnosed from 2009 to 2018. Cumulative incidence rate of melanoma increased from 4.78 to 6.57 per 100,000 persons whereas mortality rate increased from 0.29 to 2.23 per 100,000 persons from years 2000 to 2012 respectively. With contrast to age below 65, patients with age 65 and above had lower survival time (HR 4.78 95% CI 4.71-4.85, p &lt; 0.01). There seemed to be an increase in incidence of melanoma among patients above 65 compared to below 65. When compared to males, females had significantly higher survival time (HR 0.62 95% CI 0.61-0.63, p &lt; 0.01). Similarly, when compared to White population, Black and Asian population had lower survival time (HR 2.27 95% CI 2.11-2.43, p &lt; 0.01 &amp; HR 1.57 95% CI 1.14-1.68, p &gt; 0.01) respectively. Comparing to localized disease, both regional and distant involvement had significantly lower survival time (HR 3.21 95% CI 3.15-3.28, p &lt; 0.01 &amp; HR 11.34 95% CI 11.07-11.61, p &lt; 0.01) respectively. Breslow thickness had a negative correlation with survival months [regression coefficient (R) of -2.21 p &lt; 0.01 (95% CI -2.35 to -2.07)]. Compared to patients who died before 2012, patients who died in 2012 or after had significantly better survival (HR 0.46, 95% CI 0.46-0.47, p &lt; 0.01). Conclusions: Both, the incidence, and mortality of melanoma are rising, with more increase in age above 65 years. There appears to be an improvement in survival among patients who died after 2012, which may be an indirect indicator of the effectiveness of newer therapies. Risk factors for lower survival time were male sex, Black &amp; Asian race, metastatic disease, and higher Breslow thickness.

Enhanced risk of multiple sentinel lymph node basins in truncal and head and neck melanoma

Introduction: Truncal and head and neck melanomas have a greater propensity to drain to multiple lymph node basins (MLNB) compared to extremity melanomas, which drain predominantly to a single lymph node basin (SLNB). The objective of this study was to compare the lymphatic drainage patterns and characteristics of truncal and head and neck melanoma, to assess their clinical usefulness in areas of unpredictable drainage. Methods: A retrospective review of 143 patients with head and neck or truncal melanoma from 2014–2018 treated at a tertiary referral hospital in Melbourne, Australia. Patients scheduled for a wide local excision (WLE) and SeNBx, and those whose initial biopsy results stated melanoma type, cell type and BT, were included. Patients were excluded if they underwent nodal biopsy alone. Results: We identified 95 patients with truncal and 48 with head and neck melanoma. Drainage to MLNB was significantly higher in the truncal melanoma group (36.8%) compared to the head and neck group (10.4%) (P = 0.001). Patients with drainage to MLNB had a higher positive sentinel node biopsy (SeNBx) rate compared to those with SLNB (40.0% verus. 12.6%, P &lt;0.0001). Truncal melanomas that drained to MLNB were associated with a significantly higher Breslow thickness (2.1 versus. 1.5, P = 0.02), ulceration (40.6% vs. 20.7%, P = 0.043) and mitotic rate (3.0 versus. 2.0, P = 0.045) compared to equivalent melanomas that drained to SLNB. Conclusion: Patients with melanomas occurring in the trunk exhibit higher rates of drainage to MLNB compared to melanomas arising in the head and neck. Patients with drainage to MLNB also demonstrate a higher rate of positive SeNBx than those with SLNB drainage. This may represent more aggressive disease pathology or later diagnosis of lesions within these locations, or a lymphatic system that is more facilitatory of spread.

Melanoma in children and adolescents: analysis of susceptibility genes in 123 Italian patients.

A polygenic inheritance involving high, medium and low penetrance genes has been suggested for melanoma susceptibility in adults, but genetic information is scarce for paediatric patients. We aim to analyse the major high and intermediate melanoma risk genes, CDKN2A, CDK4, POT1, MITF and MC1R, in a large multicentre cohort of Italian children and adolescents in order to explore the genetic context of paediatric melanoma and to reveal potential differences in heritability between children and adolescents. One-hundred-twenty-three patients (<21 years) from nine Italian centres were analysed for the CDKN2A, CDK4, POT1, MITF, and MC1R melanoma predisposing genes. The rate of gene variants was compared between sporadic, familial and multiple melanoma patients and between children and adolescents, and their association with clinico-pathological characteristics was evaluated. Most patients carried MC1R variants (67%), while CDKN2A pathogenic variants were found in 9% of the cases, the MITF E318K in 2% of patients and none carried CDK4 or the POT1 S270N pathogenic variant. Sporadic melanoma patients significantly differed from familial and multiple cases for the young age at diagnosis, infrequent red hair colour, low number of nevi, low frequency of CDKN2A pathogenic variants and of the MC1R R160W variant. Melanoma in children (≤12 years) had more frequently spitzoid histotype, were located on the head/neck and upper limbs and had higher Breslow thickness. The MC1R V92M variant was more common in children than in adolescents. CDKN2A common polymorphisms and MC1R variants were associated with a high number of nevi. Our results confirm the scarce involvement of the major high-risk susceptibility genes in paediatric melanoma and suggest the implication of MC1R gene variants especially in the children population.

Effect of changes in Breslow thickness between the initial punch biopsy results and final pathology reports in acral lentiginous melanoma patients

Acral lentiginous melanoma (ALM) is the most common subtype of cutaneous melanoma among Asians; punch biopsy is widely performed for its diagnosis. However, the pathologic parameters evaluated via punch biopsy may not be sufficient for predicting disease prognosis compared to the parameters evaluated via excisional biopsy. We investigated whether changes in Breslow thickness (BT) between initial punch biopsy results and final pathology reports can affect the prognosis of ALM. Pathologic parameters were recorded from specimens acquired through the initial punch biopsy and wide excision. Patients were classified into two groups based on a change in Breslow depth: the BT increased or decreased on comparing the samples from the initial punch biopsy and final wide excision. We compared clinical characteristics, and a Cox regression model was used to identify independent prognostic factors influencing melanoma-specific death (MSD). Changes in BT did not affect MSD (hazard ratio [HR]: 0.55, P = 0.447). In multivariate analysis, a higher BT (> 2 mm) (HR: 9.93, P = 0.046) and nodal metastasis (HR: 5.66, P = 0.041) were significantly associated with an increased MSD risk. The use of punch biopsy did not affect MSD despite the inaccuracy of BT measurement as long as ALM was accurately diagnosed.

Volume tumor impact on melanoma survival assessed using Breslow density

Volume tumor impact on melanoma survival assessed using Breslow density

Is adjuvant treatment for melanoma in clinical practice comparable to trials? The first population-based results.

e21523 Background: Little is known about the outcome of adjuvant therapy in melanoma patients beyond the clinical trial setting. The Dutch Melanoma treatment Registry (DMTR) is a population-based registry, set up in July 2013 to monitor the safety and quality of melanoma care. Since 2019, adjuvant treated melanoma patients have also been registered in the DMTR, following approval and reimbursement of adjuvant treatment in the Netherlands in December 2018. Methods: Analyses were performed on melanoma patients treated with adjuvant anti-PD1 therapy included in the DMTR between 01-07-2018 and 31-12-2019. Descriptive statistics were used to analyze patient-, and treatment characteristics, and death as well as relapse rates. Results: Six hundred and fifty-seven patients treated with adjuvant systemic therapy were included in the DMTR. The majority (94%) of these patients was treated with anti-PD1. Twenty percent of the anti-PD1-treated patients developed grade ≥3 toxicity. Of the 279 patients with a minimum follow-up of one year after start of anti-PD1, 170 (61%) prematurely discontinued therapy. Relapse and death occurred in respectively, 38% and 12% of patients within one year of follow-up. Relapse was significantly more frequent in older patients, with high Breslow thickness and ulcerated melanomas. Conclusions: These data show more frequent premature discontinuation of adjuvant anti-PD1 in daily clinical practice than reported in the registration trials. Moreover, incidence of severe toxicity, relapse and death during adjuvant treatment appears higher in the real-world setting.

Primary cutaneous melanoma of the scalp: Patterns of clinical, histological and epidemiological characteristics in Brazil.

Scalp melanoma is a subgroup of melanomas on the head and neck, historically associated with worst prognosis. Knowledge of the usual presentation of scalp melanoma can help to understand the reasons for the poor outcomes of treatment. This is the first publication to describe the clinical, histopathological and epidemiological profile of patients with scalp melanoma in a Latin American population. A cross-sectional study was performed of all primary cutaneous melanoma seen by the A.C.Camargo Cancer Center between 2008 and 2018, using an electronic health records to access clinical and pathology data. When compared to trunk and limbs, increasing age is expected for patients with scalp melanoma (10.865; CI (95%) = [8.303; 13.427]). Regarding risk of invasion, scalp melanomas have a higher chance to be invasive than in situ (OR = 1.783; CI (95%) = [1.196; 2.657]) and present with higher Breslow thickness (OR = 3.005; CI (95%) = [2.507; 3.601]). Scalp site was significantly associated with male sex (OR = 3.750; CI (95%) = [2.533; 5.554]), perineural invasion (OR = 13.739; CI (95%) = [5.919; 31.895]), ulceration (OR = 2.311; CI (95%) = [1.488; 3.588]), and mitosis (OR = 2.366; CI (95%) = [1.701; 3.292]), when compared to trunk and limbs melanoma. In the present study, head and neck melanomas represented 14.9% of all melanomas, a frequency slightly lower than that described in the literature and the mean age of melanoma on the scalp found was lower than that reported in the literature. These results could be explained by the demographic characteristics of Brazil, which has a population with a lower life expectancy compared to the European and North American population. Scalp melanomas occurred in older men, were diagnosed with greater Breslow thickness and were associated with the presence of perineural invasion, mitosis and ulceration.

Melanoma of the External Auditory Canal: A Review of Seven Cases at a Tertiary Care Referral Center.

Examine the presentation and management characteristics of seven patients with melanoma of the external auditory canal (EAC). Retrospective case series and review of the relevant literature. Records of seven patients from 2003 to 2017 with melanoma of the EAC were reviewed for characteristics of presentation, subsequent management, and outcomes. A thorough review of relevant literature is presented. The median age is 52 years, with four females. The average Breslow depth was 3.6 mm, with five patients having a Clark level IV or greater on presentation. Six patients underwent lateral temporal bone resection, and one patient underwent wide local excision of the cartilaginous canal. Sentinel lymph node biopsy (SLNB) was performed in three patients. Three patients experienced distant recurrence an average of 20 months following primary therapy. Median follow-up was 21 months. At last follow-up, four were free of disease, one had active disease, and two were deceased from melanoma. This is the largest series and the first to report the use of SLNB for patients with EAC melanoma in the peer-reviewed literature. Patients with external auditory canal melanoma present with higher Breslow thickness and stage relative to all external ear melanomas. Management should include wide local excision, which entails lateral temporal bone resection when the bony ear canal is involved. SLNB has a critical role in identifying patients with early metastatic disease. Postoperative radiation therapy should be considered for patients with high-risk features to reduce the risk of locoregional relapse. Chemotherapy, and especially immunotherapy, has an emerging role for this disease. 4 Laryngoscope, 131:165-172, 2021.

The association between serum vitamin D level and risk and prognosis of melanoma: a systematic review and meta-analysis.

Vitamin D has antineoplastic effects, but the synthesis of vitamin D requires ultraviolet radiation, a known risk factor for melanoma. To investigate the correlations between serum vitamin D levels and risk and prognosis of melanoma. A systematic review and meta-analysis were conducted. Online databases were searched on 31 Oct 2018. Twenty-five studies with a total of 11166 patients with melanoma were included. There was no significant difference in serum vitamin D levels between patients with melanoma and controls [standardized mean difference (SMD), -0.185; 95% confidence interval (CI), -0.533 to 0.162]. However, the prevalence of vitamin D deficiency was significantly higher in patients with melanoma than that in controls (odds ratio, 2.115; 95% CI, 1.151-3.885). In terms of prognosis, serum vitamin D levels were significantly higher in melanoma patients with lower Breslow thickness (≦1 vs. >1mm: SMD, 0.243; 95% CI, 0.160-0.327). Moreover, melanoma patients with lower vitamin D levels had a significantly higher mortality rate (hazard ratio, 1.558; 95% CI, 1.258-1.931). Vitamin D deficiency is associated with higher Breslow thickness and mortality in melanoma patients.

Tumor tissue hnRNP M and HSP 90α as potential predictors of disease-specific mortality in patients with early-stage cutaneous head and neck melanoma: A proteomics-based study.

Background: Breslow tumor thickness and mitotic rate are standardly used for risk stratification of patients with malignant melanoma. However, their prognostic value is relatively limited and a need for improved prognostication has been advocated. We aimed to screen the tumor tissue proteome in a search for potentially useful prognostic factors in early-stage cutaneous head and neck melanoma.Methodology and Findings: Proteomic profiles of archival formalin-fixed tissue samples of 31 patients (age 23–90 years) with early-stage head and neck cutaneous malignant melanoma (American Joint Committee on Cancer, AJCC, stage I/II) were determined and expression intensities were compared to those of melanocytic nevi, yielding ratios used in data analysis. Medical charts were retrospectively reviewed to determine time elapsed since diagnosis to disease-specific death or censoring. In a multivariate recursive partitioning analysis (as per AJCC guidelines), higher expression levels of heterogeneous nuclear ribonucleoprotein M (hnRNP M) [n = 18, HR = 1.94 vs. the entire cohort; HR = 5.95 (95%CI 2.43–14.5) for “high” vs. “low” (n = 13)] and of heat shock protein 90 alpha (HSP 90α) [n = 17, HR = 2.09 vs. the entire cohort; HR = 4.59 (95%CI 1.87–11.2) for “high” vs. “low” (n = 14)] were each independently strongly associated with higher mortality (accounting for clinical and standard pathohistological features). Higher Breslow thickness and mitotic rate were associated with higher mortality only when proteomic data were disregarded.Conclusions and Significance: Data suggest that tumor tissue expression of hnRNP M and/or of HSP 90α deserve further investigation and clinical validation as potential novel risk stratification aids in patients with stage I-II cutaneous head and neck malignant melanoma.

Expression of estrogen receptors in Spitz and Reed nevi.

Estrogens play a key role in the skin. They are associated with an increased production of melanin, proliferation of melanocytes, increased skin thickness and increased cutaneous vascularization. Spitz and Reed nevi are acquired melanocytic lesions that generally develop during childhood or adolescence, a period of changes in sex hormones background. Our study project aimed at investigating, through immunohistochemical analysis, the expression levels of ERß receptors and their expression patterns (cytoplasmic or nuclear) in Spitz and Reed nevi. In our study, we collected a total of 86 melanocytic lesions of patients: of these, 16 were common nevi, 23 were Spitz nevi, 18 were Reed nevi and 29 were melanomas. Expression curves for estrogen receptors were constructed using the Kaplan-Meier method and compared using a log-rank test. Statistical analysis was performed using MedCalc® (MedCalc Software, Ostend, Belgium). Immunohistochemical analysis on all histological sections of nevi and melanomas was performed to evaluate the expression levels of of ERß and their expression patterns (cytoplasmic or nuclear). The agreement between the operators was calculated using Fleiss κ values. The correlation between immunoreactivity for the β-estrogen receptor and the sex of patients with Spitz and Reed nevi showed that immunoreactivity was higher in male patients. The correlation between β-estrogen receptor immunoreactivity and patient age for Spitz and Reed nevi showed no statistically significant correlation. Correlation between immunoreactivity for the β-estrogen receptor and histotype: Spitz and Reed nevi showed a high intensity, while in common nevi and in melanomas the immunoreactive was low. The correlation between receptor immunoreactivity for β estrogens and Breslow thickness in melanomas indicated that Breslow thickness of non-immunoreactive melanomas for ERβ was much higher than those showing high immunoreactivity for this receptor. Spitz and Reed nevi express a higher immunoreactivity for estrogens than common nevi and melanomas, especially those with a high Breslow thickness; and immunoreactivity is higher in younger age groups.

Malignant Melanoma Cells and Hair Follicles.

The extension of atypical melanocytes to the hair follicle, also termed melanoma folliculotropism, is poorly evaluated and its role is contradictory. We performed an observational study focusing on anatomical areas rich in follicles, such as the head and neck region. Primary head and neck melanomas diagnosed in the Melanoma Unit, Policlinic Sant'Orsola-Malpighi, University of Bologna were analyzed. Folliculotropism was evaluated with a quantitative and morphologic parameter. Statistical analyses were performed correlating patients' prognosis with folliculotropism and other clinical and histopathologic factors. The study was carried out on a sample of 62 patients. The diffuse distribution (atypical melanocytes present in more than three contiguous follicular units) correlated with scalp localization, nodular subtype, higher Breslow thickness, and a poorer prognosis. We believe that folliculotropism should be further investigated and reported by pathologists during the histologic diagnosis of melanoma.

Immunohistochemical Analysis of BRAF (V600E) Mutation and P16 Expression in Malignant Melanoma in Lagos, Nigeria: A 10-Year Retrospective Study.

Background In Blacks, malignant melanoma (MM) is associated with greater morbidity and mortality compared to Caucasians. MMs with BRAF V600E mutation as well as those with loss of p16 protein expression are associated with aggressive behavior and worse prognosis. Objectives We determined BRAF (V600E) mutation status and loss of p16 expression in MM cases in Lagos, Nigeria, and correlated these with histopathologic parameters and patients' age. Methods Forty-five cases of MM received between January 2005 and December 2014 in the Anatomic and Molecular Pathology Department of Lagos University Teaching Hospital were subjected to immunohistochemical studies to determine BRAF V600E mutation and p16 protein expression. These included cutaneous (n=37), musosal (n=3), and ocular MM (n=2) as well as lymph node metastatases (n=3). Results BRAF (V600E) mutations were detected in 5/45 (11%) while 31/45 (69%) of the cases had loss of p16 expression. No statistically significant association was found between the BRAF (V600E) mutation, loss of p16 expression, and histologic parameters such as histologic variant, Clark level, Breslow thickness, and ulceration. Conclusion BRAF (V600E) mutation was detected only in a small proportion of cases while loss of p16 expression occurred in most cases which also had high Clark level, high Breslow thickness, and ulceration.

ANALYSIS OF EPIDEMIOLOGICAL CHARACTERISTICS OF MELANOMA PATIENTS

Melanoma is malignant disease and the incidence of melanoma has been increasing worldwide, resulting in an important socio-economic problem especially in not well development countries. At the time when the incidence of many tumors is decreasing, melanoma incidence continues to increase. Incidence in Southern Europe is ranging from 1,9/100.00 in Albania across 3,3/100.000 in Bulgaria to 14,5/100.000 in Slovenia and in Serbia 8,5/100.000 for male and 5,9/100.000for female (ASR-W, 2012). In Serbia, during 2007 to 2012, according to Cancer Registry of Central Serbia, there are about 622 new melanoma diagnoses, 320 male and 302 female. During 2012, in Republic of Serbia melanoma was the 10th most common diagnosed cancer and 12th most common cancer caused death, in both, females and males. The aim of this study was to analyzed clinical and epidemiological characteristic of melanoma. Retrospective study, data analysis, all patients referred and treated in two year period in Clinic for Burns, plastic and reconstructive surgery, Clinical Center of Serbia, Belgrade. All data are collected in hospital based registry The analyzed characteristics of interest: sex, age, subtype of melanoma, primary location of melanoma, Breslow thickness and Clark level of invasion, number of mitosis, ulceration, TNM stadium, the presents of microsatellites, metastases, level of Protein S and LDH and decision of future treatment . Decision about future treatment are made according AJCC (re-excision and SLNB – Sentinel Lymph Node Biopsy ) and follow-up of patients after SLNB is still lasting. In two year period, 201 patients were treated in our hospital, all patients in this study were with pathohistologically verified diagnoses of melanoma. The average age of patients was 61, 47 ( 25 - 87). The most common primary location of melanoma was trunk with some differences between sexes. The most common subtype of melanoma was superficial subtype in 69% of patients. Ulceration were present in 22% of all primary melanomas and mitosis in 47, 5% and microsatellites in 3, 5%. Protein S and LDH level were elevated in patients with higher Breslow thickness. According to the AJCC protocol we made a decision about future treatment, re-excision and SLNB. The follow-up after SLNB is still lasting and we are still collecting data. The study showed the correlation between subtype of melanoma, higher Breslow thickness and the level of invasion by Clark, as well as elevated level of protein S and LDH and the presents of ulcerations and mitosis with decision about future treatment according to AJCC protocol.