Features Of Cutaneous Melanoma Research Articles

Unsupervised Phenotype-Based Clustering of Clinicopathologic Features in Cutaneous Melanoma

Pathogenic phenotypes in cutaneous melanoma have been vastly cataloged, although these classifications lack concordance and are confined to either morphological or molecular contexts. In this study, we perform unsupervised k-medoids clustering as a machine learning technique of 2,978 primary cutaneous melanomas at Mass General Brigham and apply this information to elucidate computer-defined subsets within the clinicopathologic domain. We identified five optimally separated clusters of melanoma that occupied two distinct clinicopathologic subspaces: a lower-grade partition associated with common or dysplastic nevi (i.e., nevus-associated melanomas) and a higher-grade partition lacking precursor lesions (i.e., de novo melanomas). Our model found de novo melanomas to be more mitogenic, more ulcerative, and thicker than nevus-associated melanomas, in addition to harboring previously unreported differences in radial and vertical growth phase status. The utilization of mixed clinicopathologic variables, reflective of actual clinical data contained in surgical pathology reports, has the potential to increase the biological relevance of existing melanoma classification schemes and facilitate the discovery of new genomic subtypes.

The Integrative Analysis Identifies Three Cancer Subtypes and Stemness Features in Cutaneous Melanoma.

Background: With the growing uncovering of drug resistance in melanoma treatment, personalized cancer therapy and cancer stem cells are potential therapeutic targets for this aggressive skin cancer. Methods: Multi-omics data of cutaneous melanoma were obtained from The Cancer Genome Atlas (TCGA) database. Then, these melanoma patients were classified into different subgroups by performing "CancerSubtypes" method. The differences of stemness indices (mRNAsi and mDNAsi) and tumor microenvironment indices (immune score, stromal score, and tumor purity) among subtypes were investigated. Moreover, the Least Absolute Shrinkage and Selection Operator (LASSO) and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) algorithms were performed to identify a cancer cell stemness feature, and the likelihood of immuno/chemotherapeutic response was further explored. Results: Totally, 3 specific subtypes of melanoma with different survival outcomes were identified from TCGA. We found subtype 2 of melanoma with the higher immune score and stromal score and lower mRNAsi and tumor purity score, which has the best survival time than the other subtypes. By performing Kaplan–Meier survival analysis, we found that mRNAsi was significantly associated with the overall survival time of melanomas in subtype 2. Correlation analysis indicated surprising associations between stemness indices and subsets of tumor-infiltrating immune cells. Besides, we developed and validated a prognostic stemness-related genes feature that can divide melanoma patients into high- and low-risk subgroups by applying risk score system. The high-risk group has a significantly shorter survival time than the low-risk subgroup, which is more sensitive to CTLA-4 immune therapy. Finally, 16 compounds were screened out in the Connectivity Map database which may be potential therapeutic drugs for melanomas. Conclusion: Thus, our finding provides a new framework for classification and finds some potential targets for the treatment of melanoma.

Cutaneous melanoma in Argentina: an analysis of its characteristics and regional differences.

PurposeThis study aims to increase the knowledge about the characteristics of cutaneous melanoma in Argentina, their association with the risk of having Breslow ≥1 mm and mortality trends for the period 2002–2017.Patients and methodsDescriptive statistics and regression analyses were done for 10.199 cases within the Argentine Melanoma Registry in the period 2002–2018. Trends in age-standardised mortality rates (ASMR) were analysed using the Join point Regression Model.ResultsCases showed lesions mainly located in males’ trunk (37%) and in females’ lower limbs (29%). The level of invasion was higher in males who also showed higher mortality. Cases from the North West and North East regions showed a major risk of Breslow >1 mm and harboured CM in lower limbs more frequently than in other regions. Nearly, 25% of tumours over 2 mm were in cases aged <50 years and 37.6% in patients ≥50 years. In the North West, North East and Patagonia, the frequency of cases in young people was higher than in older people. In 43% of cases, the melanoma subtype was not specified in the report. The number of superficial spreading melanomas, the most common histology, was nearly twice that of Nodular melanomas the following histology in importance (3,403 and 1,754, respectively). Melanoma mortality rates in all Argentine population increased in the elderly. Lower melanoma mortality rates were observed in the North West. In 2007–2017, ASMR decreased significantly in females (average 1.4% p/year) while it increased nonsignificantly in males (0.4% p/year).The tumours with the worst prognosis were associated with the elderly, males, nodular or acrolentiginous morphologies, residing somewhere other than Centro and Patagonia and with tumors located in the head/neck and legs.ConclusionThe geographical variations found for melanoma characteristics and their mortality in Argentina, makes it imperative that epidemiological research is continued to avoid generalisations and improve future preventive actions.

Клиническая характеристика больных меланомой кожи различных возрастных групп

Клиническая характеристика больных меланомой кожи различных возрастных групп

Features of cutaneous melanoma using dynamic optical coherence tomography: A case report and review of the literature

Features of cutaneous melanoma using dynamic optical coherence tomography: A case report and review of the literature

Weighted correlation network and differential expression analyses identify candidate genes associated with BRAF gene in melanoma

BackgroundPrimary cutaneous malignant melanoma is a cancer of the pigment cells of the skin, some of which are accompanied by BRAF mutation. Melanoma incidence and mortality rates have been rising around the world. As the current knowledge about pathogenesis, clinical and genetic features of cutaneous melanoma is not very clear, we aim to use bioinformatics to identify the potential key genes involved in the expression and mutation status of BRAF.MethodsFirstly, we used UCSC public hub datasets of melanoma (Lin et al., Cancer Res 68(3):664, 2008) to perform weighted genes co-expression network analysis (WGCNA) and differentially expressed genes analysis (DEGs), respectively. Secondly, overlapping genes between significant gene modules and DEGs were screened and validated at transcriptional levels and overall survival in TCGA and GTEx datasets. Lastly, the functional enrichment analysis was accomplished to find biological functions on the web-server database.ResultsWe performed weighted correlation network and differential expression analyses, using gene expression data in melanoma samples. We identified 20 genes whose expression was correlated with the mutation status of BRAF. For further validation, three of these genes (CYR61, DUSP1, and RNASE4) were found to have similar expression patterns in skin tumors from TCGA compared with normal skin samples from GTEx. We also found that weak expression of these three genes was associated with worse overall survival in the TCGA data. These three genes were involved in the nucleic acid metabolic process.ConclusionIn this study, CYR61, DUSP1, and RNASE4 were identified as potential genes of interest for future molecular studies in melanoma, which would improve our understanding of its causes and underlying molecular events. These candidate genes may provide a promising avenue of future research for therapeutic targets in melanoma.

Optical coherence tomography imaging of melanoma skin cancer

No consensus guidelines exist on the use of optical coherence tomography (OCT) for diagnosis of cutaneous melanoma. The objectives of this review are to provide a descriptive review of the literature on characteristics of cutaneous melanomas seen on high-definition OCT (HD-OCT), speckle variance OCT (SV-OCT), and conventional OCT and to compare their diagnostic ability with that of histopathology. A review of PubMed and Google Scholar identified all available literature on OCT in melanoma skin cancer that included all in vivo and ex vivo studies on human or human tissues and excluded all studies on non-human subjects or animal studies. Two hundred nine abstracts were considered for evaluation, 31 abstracts were selected for manuscript review, and 14 abstracts were included that met all criteria. Diagnoses of MIS and MM using HD-OCT and SV-OCT were consistently reported to correlate with histopathology. However, accuracy of diagnosis using conventional OCT varied. Most authors agreed that it was difficult to differentiate MM from benign nevi using conventional OCT. HD-OCT, SV-OCT, and conventional OCT show promise for visualizing cutaneous melanoma. The use of OCT in diagnosis of melanoma is rarely reported in the literature. There is a need to increase and standardize reporting of OCT for diagnosis of cutaneous melanoma.

Abstract 3682: Expression levels of genes in primary melanoma associated with clinically meaningful characteristics

Abstract Melanoma survival appears to be improving; however, between 13-68% of individuals with melanoma diagnosed with Stages II-III ultimately die from their melanoma. Factors influencing melanoma survival include sex, age, clinical stage, lymph node involvement and several primary tumor characteristics, such as Breslow thickness, presence of infiltrating lymphocytes (TILs), mitotic rate and ulceration. Identification of genes whose expression in primary tumors is associated with these key tumor/patient characteristics can shed light on molecular mechanisms of melanoma survival. Here we show results from a gene expression analysis of 32 formalin-fixed, paraffin embedded (FFPE) primary melanomas with extensive clinical annotation. We extracted RNA, and measured the expression of 760 genes selected based on published evidence of association with melanoma initiation or outcome using NanoString. The Cancer Genome Atlas (TCGA) data on primary melanomas was used for validation of nominally significant associations. We identified 5 genes that were significantly associated with the presence of TILs in the combined analysis of both datasets after adjustment for multiple testing using the Benjamini-Hochberg false discovery rate method: IL1R2, PPL, PLA2G3, RASAL1, and SGK2. We also identified two genes significantly associated with lymph node status (PIK3CG and IL2RA), and two genes significantly associated with sex (KDM5C and KDM6A). We found that LEF1 was significantly associated with Breslow thickness and CCNA2 with mitosis. These results demonstrate that genetic expression in primary tumors is associated with clinically meaningful characteristics of cutaneous melanoma. Citation Format: Marianne Berwick, Ivan P. Gorlov, Irene Orlow, Carol Ringelberg, Marc Ernstoff, Joel Parker, Meg Gerstenblith, Cheryl Thompson, Eva Hernando, Klaus Busam, Cecilia Lezcano, Sergio Corrales, Siok Leong, Nancy E. Thomas, Christopher I. Amos. Expression levels of genes in primary melanoma associated with clinically meaningful characteristics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3682.

Characteristic features of cutaneous melanoma in a dermatology referral centre in Tehran, Iran.

The characteristics of cutaneous melanoma in the Middle-Eastern countries is poorly described. Therefore we conducted this study to determine the characteristics of melanoma in Iran. A retrospective, cross sectional study of melanoma patients seen at a tertiary referral centre, Iran, from May 2004 to October 2014. Clinical data included age and gender of the patients at the time of diagnosis, tumour location and tumour size. Histological characteristics included Breslow thickness, Clark level and subtype of tumour. A total of 450 cases of melanoma with a male/female ratio of 1.1:1 were reviewed. The mean age of patients was 57.5 years. The most frequent histological subtypes were acral lentiginous melanoma (30%) and lentigo maligna melanoma (29%). In 215 cases (49%) the tumour was located on the extremities. The second most common site was the face. Tumour invasion was mainly at Clark level III and IV. The mean Breslow thickness was 2.8 mm; 143 (38%) melanomas had a Breslow thickness less than 1 mm (T1) and 86 (23%) were more than 4 mm (T4). This study indicates that clinical and histological features of melanoma in Iranians (who are mainly of skin phototypes 3-4) are different from those observed in Western countries. Further cohort studies are required to evaluate the role of ethnic and environmental risk factors for melanoma in different populations.

Learning Reflectance Confocal Microscopy of Melanocytic Skin Lesions through Histopathologic Transversal Sections

Histopathologic interpretation of dermoscopic and reflectance confocal microscopy (RCM) features of cutaneous melanoma was timidly carried out using perpendicular histologic sections, which does not mimic the same plane of the image achieved at both techniques (horizontal plane). The aim of this study was to describe the transverse histologic sections research technique and correlate main dermoscopic features characteristic of cutaneous melanoma (atypical network, irregular globules and pseudopods) with RCM and histopathology in perpendicular and transverse sections in order to offer a more precise interpretation of in vivo detectable features. Four melanomas and 2 nevi with different dermoscopic clues have been studied. Lesion areas that showed characteristic dermoscopic features were imaged by dermoscopy and confocal microscopy and directly correlated with histopathology in perpendicular and transverse sections. We presented the possibility to perform transverse sections as a new approach to understand RCM features. Atypical network showed different aspects in the 2 melanomas: in one case it was characterized by pleomorphic malignant melanocytes with tendency to form aggregates, whereas in the other elongated dendritic cells crowded around dermal papillae, some of them forming bridges that resembled the mitochondrial aspect at confocal and histopathology transversal sections. Pigment globules in melanomas and nevi differed for the presence of large atypical cells in the former, and pseudopods showed up as elongated nests protruded toward the periphery of the lesion. Transverse histologic research sections have a consistent dermoscopic and confocal correlate, and it may represent an help in confocal feature interpretation and an advance in improving melanoma diagnosis and knowledge of the biology of melanocytic lesions.

Relationship between BRAF mutations and clinicopathological features in cutaneous melanoma: a meta-analysis

Objective To explore the frequencies of BRAF mutations and the relationship between BRAF mutations and clinicopathological features of cutaneous melanoma (CM).Methods Pubmed,Embase,VIP,CNKI and other databases were utilized to search the relative articles and literatures were screened according to inclusion and excluding criteria and the meta-analysis was conducted by RevmanS.0 software.Results Nine researches about BRAF mutations were enrolled in this study including 1134 patients.BRAF mutation rate of CM was 47.3％.As for patients over 50 years old,the OR of BRAF mutations was 2.30 (95％ CI:1.36-3.91; the OR of BRAF mutations for superficial spreading melanoma (SSM) was 2.11 (95％ CI:1.64-2.71) ; the OR of BRAF mutations for lesions in the trunk was 2.35 (95％ CI:1.71-3.21) ; the OR of BRAF mutations for invasion depth less than 1 mm was 1.56 (95％ CI:1.08-2.25).Conclusion BRAF mutations are more frequent in patients over 50 years old,in SSM and in patients whose lesions locate in the truck and invasion depth less than 1 mm,but have no relationship with sex. Key words: Mutation; Melanoma; Meta-analysis; BRAF

Distinctive Clinical and Histologic Features in Cutaneous Melanoma With Copy Number Gains in 8q24

Cutaneous melanoma may be quite heterogeneous in its clinical, histologic, and molecular features. Yet, the current classification of melanoma is limited to 4 main subtypes on the basis of clinical and histopathologic features and has shown limited impact on clinical management including prognostication and treatment. Advances in our understanding of the driving molecular pathways in melanoma and the importance of the mitogen-activated protein kinase pathway have shown that specific activating mutations in oncogenes may correlate with characteristic clinical and histologic features. We evaluated 40 melanoma cases with gains in MYC at 8q24, and we show that their characteristic features include aggressive clinical course, occurrence in nonchronically sun-damaged skin, amelanotic clinical and histopathologic appearance, a nodular or primary dermal growth pattern by histology, frequent epidermal consumption, and infrequent association with a precursor nevus. The v-raf murine sarcoma viral oncogene homolog B1 (BRAF) and neuroblastoma RAS viral oncogene homolog (NRAS) mutation status was also determined. The presence of these mutations was comparable to frequencies previously reported from nonchronically sun-damaged skin. However, the BRAF mutant cases did not show histopathologic features considered characteristic of BRAF mutant melanoma. Considering these distinct clinical and histopathologic features and the possible role as a theragnostic tool, it may be of value to consider 8q24 status in cutaneous melanoma in addition to the mutation status of BRAF in future studies integrating molecular findings into the classification system for cutaneous melanoma.

Structural Correlations Between Dermoscopic Features of Cutaneous Melanomas and Histopathology Using Transverse Sections

Interpretation of dermoscopic features of cutaneous melanoma is based on histologic description of perpendicular sections of the lesions that does not reflect the overview achieved by epiluminescence. We describe the utilization of transverse sections as a tool to define the histopathology of features that are the dermoscopic hallmarks of cutaneous melanoma. From a collection of 23 pigmented lesions with the dermoscopic diagnosis of cutaneous melanoma submitted for surgical excision we selected, from each specimen, one dermoscopic feature (black dots and globules, brown dots, blues dots and globules, depigmentation, broadened network, radial streams or pseudopods) that was sampled with a 4-mm punch (specimen) to obtain perpendicular and transverse sections. Using this strategy, it was possible to correlate the histopathology of all features that are often used as criteria for diagnostic dermoscopy. The black dots were pigmented neoplastic cells at the dermal-epidermal junction (DEJ) and within the epidermis in heavily pigmented columns. Similar findings were seen in brown dots, however there was slightly less pigment. No statistical difference was observed between brown dots and black dots regarding size, area and number of atypical cellnests. Blue dots correlated to melanophages, surrounding the superficial vascular plexus. Depigmentation was characterized by intense fibrosis of the papillary dermis. The pigmented network showed atypical pigmented or non-pigmented melanocytes at the DEJ and epidermis as well as heavily pigmented keratinocytes in the basal cell layer. The radial streaming and pseudopods had neoplastic cells in nests, a stratified growth pattern arranged in centrifugal linear extensions, resembling a arborescent branching. The results represented herein, are an important tool for understanding histopathological alterations responsible for dermoscopic features and for improving the efficacy of this diagnostic method.

New prognostic factors and developing therapy of cutaneous melanoma

The multiple molecular alterations underlying the neoplastic process and clinical characteristics of cutaneous melanoma are currently under intensive investigation. Recent studies have demonstrated that the levels of melanoma-associated proteins in tumor tissue or in patient serum can serve as new markers to predict disease outcome. Similarly, the expression of thousands of genes in melanoma tumors can be surveyed simultaneously using DNA arrays, allowing molecular profiling of individual tumors, which gives the possibility of classifying melanomas based on their biological diversity. Large clinical studies have also identified multiple prognostic factors, such as tumor ulceration, and led to development of a new, more precise melanoma staging system, which emphasizes the biological characteristics of the primary disease. These new findings may have an important role in earlier measurement of the clinical response and provide a basis for tailored melanoma therapy, the development of which will also be discussed in this review.

An immunological aspect of melanoma and its potential application in adjuvant therapy

In an attempt to understand some of the natural immunological characteristics of cutaneous melanoma so that we can plan justifiable immunotherapeutic approaches, 23 patients were studied. The autologous leukocyte migration inhibition assay was utilized to assess in vitro their tumor-specific cellular immunity. This assay was specifically used because when presensitized lymphocytes are exposed to the same antigen, they release lymphokines which inhibit the natural migration of the leukocytes. All the patients were staged pathologically according to the TNM system. Twelve of them had regional metastasis, i.e., stage III, and underwent regional lymphadenectomy. The other 11 had distant metastases, i.e., stage IV disease, and all their gross tumors were resected. These 23 patients were the source of tumor material and peripheral blood. Fresh autologous leukocytes were obtained for the assays, from each patient, on the day of surgery and prior to the administration of the preoperative medications. These were tested in vitro, on the same day, with freshly prepared autologous tumor extracts as the source of autologous tumor antigens. The results revealed that the preoperative leukocytes of patients with stage III melanoma expressed hypersensitivity to their tumors, with significant inhibition of their leukocyte migration, compared to those with distant metastases who expressed no such sensitivity, P = 0.012. Such hypersensitized lymphocytes may be capable of producing more efficient lymphokine activated killer (LAK) cells for an effective adjuvant adoptive immunotherapy.