Pigmented Melanoma Research Articles

Uncovering molecular mechanisms for amelanotic/hypopigmented primary cutaneous melanoma.

A portion of approximately 2-20% of cutaneous melanoma (CM) are diagnosed as amelanotic/hypopigmented melanoma (AHM) and represent a challenge for early diagnosis. Since the degree to which somatic mutations and copy number aberrations (CNA) in genes associated with skin-lightening or albinism may contribute to the loss of tumour pigmentation in AHM samples has not yet been addressed, we have investigated loss of function mutations of key pigmentation genes in matched germline and AHM as well as pigmented melanoma (PM) tumour DNA samples. An analysis of clinical and histopathological characteristics together with whole exome sequencing data of 34 fresh frozen primary CM, graded according to the amount of pigmentation present was performed. Together with germline and somatic variant analysis, 30 samples were previously analysed for CNA changes. This study focussed on germline and somatic variants in the coding region of 16 genes known to be associated with albinism/hypopigmentation or variation in human pigmentation in all samples. Chromosomal regions encompassing these 16 genes were examined for DNA copy loss or gain. The finding that red hair related MC1R and TYR R402Q loss of activity gene variant alleles and genotypes are associated with AHM was validated in this study. Germline AHM-related gene variants were enriched in 70% (n=7 of 10) of AHM patients vs 8.3% (n=2 of 24) of PM patients. This surprisingly high frequency of rare germline variants in AHM patients constitutes the "first hit" and confirms that AHM patients are more likely to be albinism allele carriers than patients with PM. Next, in CNA analysis of each tumour sample, 50% (n=4 of 8) AHM samples with a pigmentation gene variant had LOH in the region containing the corresponding gene, and 25% (=2 of 8) had loss-of-heterozygosity (LOH) in chromosomal regions of two AHM-related genes. This study proposes that the likely molecular mechanism for development of amelanogenesis in AHM is carriage of an albinism/hypopigmentation allele followed by LOH of the corresponding gene in the tumour.

Skin Cancer Diagnosis With Multi-Level Classification

Skin cancer arises from the uncontrolled proliferation of abnormal skin cells, primarily triggered by exposure to the harmful ultraviolet (UV) rays of the sun and the utilization of UV tanning beds. This condition poses a heightened risk due to its potential to progress into blood cancer and lead to rapid fatality. Extensive research efforts have been dedicated to advancing the treatment of this perilous ailment. This paper presents a system designed for the examination and diagnosis of pigmented skin lesions and melanoma. The system incorporates a supervised classification algorithm that combines Convolutional Neural Network (CNN) and Deep Neural Network (DNN) architectures with feature extraction techniques. It operates in two distinct stages: the initial stage classifies images into two categories, namely benign or malignant, while the subsequent stage further categorizes the images into one of three classes: basal cell carcinomas, squamous cell carcinomas, or melanoma. Consequently, the comprehensive system addresses four classes, namely benign, basal cell carcinomas, squamous cell carcinomas, and melanoma. This work contributes to the system's design in three significant ways. Firstly, it implements multiple iterations to select the most optimal images, resulting in the highest classification accuracy. Secondly, it employs various statistical methods to identify the most pertinent features, thereby enhancing the classifier's accuracy by focusing on the most informative features for the classification task. Lastly, a two-stage classification approach is implemented, employing two distinct classifiers at different levels within the overall system. Despite the inherent complexity of the real-world problem, the overall system attains a commendable level of classification accuracy. Following rigorous experimentation, the study identifies the top three models. Each approach culminates in a classifier for each stage. The first approach, utilizing a deep learning classifier, achieves an accuracy of 81.82% in the initial cancer discrimination stage and 58.33% in the subsequent stage. The second approach, employing a machine learning classifier, attains an accuracy of 74.63% in the first stage and 64.41% in the second stage. The third approach, utilizing a linear regression classifier, achieves an accuracy of 98% in the first stage and 90% in the second stage. These results underscore the significance of feature selection in influencing model accuracy and suggest the potential for further optimization.

Spatial transcriptomic analysis of amelanotic acral melanoma versus pigmented acral melanoma reveals distinct molecular determinants.

Amelanotic acral melanoma (AAM) is a rare type of acral melanoma that has a poor prognosis. To investigate the transcriptomic differences between AAM and pigmented acral melanoma (PAM). Differences in the spatially resolved transcriptomic profiles of 9 patients with AAM with 29 regions of interest (ROIs) and 11 patients with PAM with 46 ROIs were investigated using S100b and CD3 morphology markers. In S100b+ tumour cell areas, we detected 11 upregulated differentially expressed genes (DEGs; including chaperone/ubiquitin--associated DEGs) and 82 downregulated DEGs (including human leucocyte antigen) in AAMs vs. PAMs. Protein-protein interaction network and pathway analyses revealed significant enrichment of dysregulated translational and nonsense-mediated decay pathways but significant decreases in antigen processing and presentation, interferon signalling and melanin biosynthesis pathways in S100b+ ROIs of AAMs compared with PAMs. In tumour-associated immune cell areas, the numbers of CD8 T cells (P = 0.04) and M1 macrophages (P = 0.01) were significantly decreased, whereas those of monocytes (P = 0.04) and endothelial cells (P = 0.04) were increased in AAMs compared with PAMs. These findings could widen our understanding of the biological differences between AAMs and PAMs, which might result in a different clinical course.

Ultraviolet-Protective Clothing and Sunscreen: Sun-Protection for Healthy Skin

Introduction Prolonged exposure to ultraviolet (UV) radiation from the sun poses numerous risks to the skin, ranging from premature aging to serious health conditions such as skin cancer. UV radiation can penetrate the skin's surface, causing damage to its cells and DNA, which can lead to the formation of wrinkles, sunspots, and other signs of aging. Therefore, consistent and effective sun protection is essential for maintaining the health and vitality of the skin, as well as reducing the risk of sun-related skin damage and diseases. Aim of the study The objective of the study is to conduct a thorough investigation into different aspects of photoprotection and its effects on the skin. This entails assessing the effectiveness and safety of sunscreens, as well as evaluating the impact of sun-protection clothing on skin health. Materials and methods The purpose of this review is to assess the current literature of the effectiveness of the various sun protection measures. The literature was reviewed in the Pubmed, Google Scholar data base. Results Prolonged UV exposure incites photoaging, carcinogenesis, and immunosuppression, amplifying the risk of skin malignancies. Sun-protective clothing, with adequate UPF ratings, emerges as a pivotal element in mitigating UV-induced skin damage, notably reducing the development of pigmented moles and melanoma. Furthermore, effective sunscreen usage, coupled with broad-spectrum protection, is essential in averting UV-induced skin damage and curbing the incidence of skin cancer. These findings emphasize the imperative of comprehensive photoprotection strategies, integrating sunscreen application, sun-protective clothing, and individual risk assessment, to safeguard against solar-induced skin damage and mitigate the prevalence of skin cancer.

Clinical, dermatoscopic and pathomorphological differential diagnosis of pigmented and pigmented melanoma of the skin

Relevance. The study of pigmented melanoma of the skin is an urgent problem today, because this pathology has an aggressive course, frequent localization on the skin, rare occurrence – no more than 2-8% among other malignant neoplasms of the skin, while it is difficult to diagnose clinically, pathohistologically.The purpose of the study: to study the clinical, dermatoscopic and pathomorphological diagnosis of pigmented and pigmented melanoma of the skin. As tasks, the possibilities of diagnosing pigmented and pigmentless melanoma of the skin at the stage of consultation, as well as the features of the use of light microscopy and immunohistochemical examination by pathologists were studied.Material and technical base: Delta Heine 20 dermatoscope, Carl Zeiss Axio Scope A2 light microscope, evaluation of results according to clinical recommendations. As a result of the study, it was revealed that the diagnosis of pigmented, unlike pigmented, melanoma of the skin is difficult due to the lack of characteristic signs. It was concluded that it is advisable to use digital dermatoscopy at the clinical stage; an immunohistochemical examination should be used by a pathologist; if there is doubt about the goodness of the process, an incisional biopsy of the neoplasm with a pathohistological examination is required.

New Approaches to Photodynamic Therapy of Melanomas

SignificanceWe present new approaches to treat both primary cutaneous and ocular melanoma, with potential to reduce metastatic spread ApproachIn mouse models optical clearing combined with dual-photosensitizer PDT is used to treat primary cutaneous xenogafts. Two-photon PDT is used in ocular melanoma of extraocular (conjunctival) or intraocular (uveal) melanoma. Immune effects are investigated in immunocompetent mice using blood biomarkers and by tumor re-challenge. In vitro studies in pigmented and non-pigmented melanoma cells show melanin-mediated photosensitization as a novel mechanism of action of 2-γ PDT. ResultsFull-thickness primary tumor eradication has been achieved: ∼1 and 4 mm in immune deficient and competent mice, respectively. Marked reduction in metastatic tumor burden is observed in the latter. ConclusionsThese studies reopen the possibility of PDT as an effective modality in melanoma.

Femtosecond pulsed laser photodynamic therapy activates melanin and eradicates malignant melanoma

Photodynamic therapy (PDT) relies on a series of photophysical and photochemical reactions leading to cell death. While effective for various cancers, PDT has been less successful in treating pigmented melanoma due to high light absorption by melanin. Here, this limitation is addressed by 2-photon excitation of the photosensitizer (2p-PDT) using ~100 fs pulses of near-infrared laser light. A critical role of melanin in enabling rather than hindering 2p-PDT is elucidated using pigmented and non-pigmented murine melanoma clonal cell lines in vitro. The photocytotoxicities were compared between a clinical photosensitizer (Visudyne) and a porphyrin dimer (Oxdime) with ~600-fold higher σ2p value. Unexpectedly, while the 1p-PDT responses are similar in both cell lines, 2p activation is much more effective in killing pigmented than non-pigmented cells, suggesting a dominant role of melanin 2p-PDT. The potential for clinical translational is demonstrated in a conjunctival melanoma model in vivo, where complete eradication of small tumors was achieved. This work elucidates the melanin contribution in multi-photon PDT enabling significant advancement of light-based treatments that have previously been considered unsuitable in pigmented tumors.

Dermatoscopic patterns of cutaneous metastases: A multicentre cross-sectional study of the International Dermoscopy Society.

The detection of cutaneous metastases (CMs) from various primary tumours represents a diagnostic challenge. Our aim was to evaluate the general characteristics and dermatoscopic features of CMs from different primary tumours. Retrospective, multicentre, descriptive, cross-sectional study of biopsy-proven CMs. We included 583 patients (247 females, median age: 64 years, 25%-75% percentiles: 54-74 years) with 632 CMs, of which 52.2% (n = 330) were local, and 26.7% (n = 169) were distant. The most common primary tumours were melanomas (n = 474) and breast cancer (n = 59). Most non-melanoma CMs were non-pigmented (n = 151, 95.6%). Of 169 distant metastases, 54 (32.0%) appeared on the head and neck region. On dermatoscopy, pigmented melanoma metastases were frequently structureless blue (63.6%, n = 201), while amelanotic metastases were typified by linear serpentine vessels and a white structureless pattern. No significant difference was found between amelanotic melanoma metastases and CMs of other primary tumours. The head and neck area is a common site for distant CMs. Our study confirms that most pigmented melanoma metastasis are structureless blue on dermatoscopy and may mimic blue nevi. Amelanotic metastases are typified by linear serpentine vessels and a white structureless pattern, regardless of the primary tumour.

The use of the results of multiplex analysis of the morphological substrate of the tumor in the differential diagnosis of pigmented and non-pigmented superficial melanomas of the skin using the example of two clinical observations

The use of the results of multiplex analysis of the morphological substrate of the tumor in the differential diagnosis of pigmented and non-pigmented superficial melanomas of the skin using the example of two clinical observations

Melanogenesis Is Directly Affected by Metabolites of Melatonin in Human Melanoma Cells.

Melatonin (N-acetyl-5-methoxytryptamine, MEL), its kynurenic (N1-acetyl-N2-formyl-5-methoxykynurenine, AFMK) and indolic derivatives (6-hydroxymelatonin, 6(OH)MEL and 5-methoxytryptamine, 5-MT) are endogenously produced in human epidermis. Melatonin, produced by the pineal gland, brain and peripheral organs, displays a diversity of physiological functions including anti-inflammatory, immunomodulatory, and anti-tumor capacities. Herein, we assessed their regulatory effect on melanogenesis using amelanotic (A375, Sk-Mel-28) and highly pigmented (MNT-1, melanotic) human melanoma cell lines. We discovered that subjected compounds decrease the downstream pathway of melanin synthesis by causing a significant drop of cyclic adenosine monophosphate (cAMP) level, the microphthalmia-associated transcription factor (MITF) and resultant collapse of tyrosinase (TYR) activity, and melanin content comparatively to N-phenylthiourea (PTU, a positive control). We observed a reduction in pigment in melanosomes visualized by the transmission electron microscopy. Finally, we assessed the role of G-protein-coupled seven-transmembrane-domain receptors. Obtained results revealed that nonselective MT1 and MT2 receptor antagonist (luzindole) or selective MT2 receptor antagonist (4-P-PDOT) did not affect dysregulation of the melanin pathway indicating a receptor-independent mechanism. Our findings, together with the current state of the art, provide a convenient experimental model to study the complex relationship between metabolites of melatonin and the control of pigmentation serving as a future and rationale strategy for targeted therapies of melanoma-affected patients.

Histopathologic abundance of pigmentation correlates with disease-specific survival in malignant melanoma but is not independent of current AJCC pT stage.

The increasing number of melanoma patients makes it necessary to develop best possible strategies for prognosis assessment in order to recommend appropriate therapy and follow-up. The prognostic significance of tumor cell pigmentation has not been fully elucidated. Hematoxylin and eosin (H&E)-stained sections of 775 melanomas diagnosed between 2012 and 2015 were independently assessed for melanin pigment abundance by two investigators, and the impact on melanoma-specific survival was calculated. Unpigmented melanomas (n = 99) had a melanoma-specific survival of 67.7%, melanomas with moderate pigmentation (n = 384) had a melanoma-specific survival of 85.9%, and strongly pigmented melanomas (n = 292) had a melanoma-specific survival of 91.4% (p < .001). In an analysis of melanoma-specific survival adjusted for pT stage and pigmentation, we found a nonsignificant impact of pigmentation abundance with a hazard ratio of 1.277 (p = .74). The study presented here provides evidence in a German cohort that patients with pigmented melanomas have a more favorable prognosis than those diagnosed with nonpigmented melanomas. Moreover, the abundance of pigmentation already seems to provide a first prognostic estimate. However, it does not appear to provide significant additional value for prognostic assessment according to the AJCC 2017 pT classification.

Primary pigmented malignant melanoma of the bladder treated with radical urethrocystectomy and adjuvant therapy

Primary malignant melanoma of the urinary tract is a rare entity with less than 50 cases reported worldwide. The following case concerns a 64-year-old woman whom we first saw in our emergency room due to gross haematuria. As part of the subsequent diagnostic investigation, we detected a primary malignant melanoma of the bladder and the urethra. The patient was treated with radical urethrocystectomy including pelvic lymphadenectomy and an ileum conduit. This was followed by a year of adjuvant therapy using checkpoint inhibitors.

Collagen Hydrolysate Effects on Photodynamic Efficiency of Gallium (III) Phthalocyanine on Pigmented Melanoma Cells.

The conjugation of photosensitizer with collagen seems to be a very promising approach for innovative topical photodynamic therapy (PDT). The study aims to evaluate the effects of bovine collagen hydrolysate (Clg) on the properties of gallium (III) phthalocyanine (GaPc) on pigmented melanoma. The interaction of GaPc with Clg to form a conjugate (GaPc-Clg) showed a reduction of the intensive absorption Q-band (681 nm) with a blue shift of the maximum (678 nm) and a loss of shape of the UV-band (354 nm). The fluorescence of GaPc, with a strong emission peak at 694 nm was blue shifted due to the conjugation which lower intensity owing to reduce quantum yield (0.012 vs. 0.23, GaPc). The photo- and dark cytotoxicity of GaPc, Glg and GaPc-Clg on pigmented melanoma cells (SH-4) and two normal cell lines (BJ and HaCaT) showed a slight decrease of cytotoxicity for a conjugate, with low selectivity index (0.71 vs. 1.49 for GaPc). The present study suggests that the ability of collagen hydrolysate to form gels minimizes the high dark toxicity of GaPc. Collagen used for conjugation of a photosensitizer might be an essential step in advanced topical PDT.

Melanin Stacking Differences in Pigmented and Non-Pigmented Melanomas: Quantitative Differentiation between Pigmented and Non-Pigmented Melanomas Based on Light-Scattering Properties.

Cutaneous melanoma is a cancer with metastatic potential characterized by varying amounts of pigment-producing melanocytes, and it is one of the most aggressive and fatal forms of skin malignancy, with several hundreds of thousands of cases each year. Early detection and therapy can lead to decreased morbidity and decreased cost of therapy. In the clinic, this often translates to annual skin screenings, especially for high-risk patients, and generous use of the ABCDE (asymmetry, border irregularity, color, diameter, evolving) criteria. We have used a new technique termed vibrational optical coherence tomography (VOCT) to non-invasively differentiate between pigmented and non-pigmented melanomas in a pilot study. The VOCT results reported in this study indicate that both pigmented and non-pigmented melanomas have similar characteristics, including new 80, 130, and 250 Hz peaks. Pigmented melanomas have larger 80 Hz peaks and smaller 250 Hz peaks than non-pigmented cancers. The 80 and 250 Hz peaks can be used to quantitative characterize differences between different melanomas. In addition, infrared light penetration depths indicated that melanin in pigmented melanomas has higher packing densities than in non-pigmented lesions. Using machine learning techniques, the sensitivity and specificity of differentiating skin cancers from normal skin are shown to range from about 78% to over 90% in this pilot study. It is proposed that using AI on both lesion histopathology and mechanovibrational peak heights may provide even higher specificity and sensitivity for differentiating the metastatic potential of different melanocytic lesions.

Single-Cell RNA Sequencing Reveals Cellular Heterogeneity in an Acral Amelanotic Melanoma After Immunotherapy Treatment.

Anti-programmed cell death ligand-1 (anti-PD-L1) immunotherapy is often used for advanced urothelial carcinoma and melanoma, including amelanotic melanoma, a relatively rare subtype with little to no pigment in the tumor cells. However, cellular heterogeneity of amelanotic melanoma during or after anti-PD-L1 immunotherapy treatments has not been described. To investigate cellular heterogeneity in acral amelanotic melanoma after immunotherapy exposure. We evaluated subtle visual changes of the melanoma by dermoscopy and performed a pathological examination to analyze the heterogeneity of microscopic morphological and immunohistochemistry changes. The cellular transcriptional heterogeneity and corresponding biological function profiles of the melanoma were determined by single-cell RNA sequencing (scRNA-seq). The dermoscopic examination revealed black globules and scar-like depigmentation areas against a homogeneous red background. Pigmented and amelanotic melanoma cells were observed microscopically. The pigmented cells were large and contained melanin granules expressing Melan-A and HMB45; the amelanotic cells were small and did not express HMB45. Ki-67 immunohistochemical staining revealed that the pigmented melanoma cells had a higher proliferative ability than the amelanotic cells. scRNA-seq identified three cell clusters: amelanotic cell cluster 1, amelanotic cell cluster 2, and pigmented cell cluster. Furthermore, a pseudo-time trajectory analysis showed that amelanotic cell cluster 2 originated from amelanotic cell cluster 1 and transformed into the pigmented melanoma cell cluster. The expression pattern of melanin synthesis-related and lysosome-endosome-related genes in different cell clusters supported the cell cluster transformation results. Also, upregulated expression of cell cycle genes indicated that the pigmented melanoma cells had a high proliferative ability. Coexisting amelanotic and pigmented melanoma cells indicated cellular heterogeneity in an acral amelanotic melanoma from a patient who underwent immunotherapy treatment. Additionally, the pigmented melanoma cells acquired a higher proliferative ability than the amelanotic melanoma cells.

Effect of Aspergilus oryzae-fermented broken rice, brewers’ rice and rice bran on melanogenesis in highly pigmented human melanoma, MNT-1

The food and beauty sectors are developing strategies to establish a link between nutrient consumption and skin health, as nutraceuticals offer a promising treatment option for some skin disorders such as hyperpigmentation and premature ageing. As a result, the consumption of food ingredients and supplements claiming to lower the risk of developing such skin problems is increasing. In this study, anti-tyrosinase potential of Aspergillus oryzae-fermented rice by-product water extracts namely fermented broken rice (FBR), brewers’ rice (FBrR), and rice bran (FRB) was assessed through in vitro study using highly pigmented human melanoma MNT-1 cells. The fermented extracts were evaluated for cytotoxicity, anti-tyrosinase activity using intracellular tyrosinase assay as well as melanin content analysis. Their effect on the gene expression of three melanogenic enzymes: tyrosinase (TYR), tyrosinase-related protein-1 (TRP-1) and tyrosinase-related protein 2 (TRP-2) was also assessed by qPCR analysis. As a result, all extracts at tested concentrations of 50 and 100 µg/mL have a low cytotoxicity effect. Together with the positive control kojic acid, the FBR at both concentrations and the FRB at 50 µg/mL significantly decreased intracellular tyrosinase activity. However, their melanin content was not significantly reduced. The qPCR analysis indicated that FBR at 50 and 100 µg/ mL significantly reduced TYR gene expression by up to 71% and 61%, respectively. On the other hand, FBR (100 µg/mL) increased TRP-1 gene expression, whilst FRB (100 µg/ mL) elevated both TRP-1 and TRP-2 gene expression. The positive control kojic acid significantly reduced TYR, TRP-1 and TRP-2 gene expression. However, FBrR demonstrated no significant effect in any of the analyses. Based on these findings, FBR and FRB at 50 µg/mL possess anti-tyrosinase potential. However, further investigation is needed to dissect deeper mechanisms underlying their potential as functional bioingredients for nutraceutical or cosmeceutical applications.

UHRF1/UBE2L6/UBR4-mediated ubiquitination regulates EZH2 abundance and thereby melanocytic differentiation phenotypes in melanoma

Cellular heterogeneity in cancer is linked to disease progression and therapy response, although mechanisms regulating distinct cellular states within tumors are not well understood. We identified melanin pigment content as a major source of cellular heterogeneity in melanoma and compared RNAseq data from high-pigmented (HPCs) and low-pigmented melanoma cells (LPCs), suggesting EZH2 as a master regulator of these states. EZH2 protein was found to be upregulated in LPCs and inversely correlated with melanin deposition in pigmented patient melanomas. Surprisingly, conventional EZH2 methyltransferase inhibitors, GSK126 and EPZ6438, had no effect on LPC survival, clonogenicity and pigmentation, despite fully inhibiting methyltransferase activity. In contrast, EZH2 silencing by siRNA or degradation by DZNep or MS1943 inhibited growth of LPCs and induced HPCs. As the proteasomal inhibitor MG132 induced EZH2 protein in HPCs, we evaluated ubiquitin pathway proteins in HPC vs LPCs. Biochemical assays and animal studies demonstrated that in LPCs, the E2-conjugating enzyme UBE2L6 depletes EZH2 protein in cooperation with UBR4, an E3 ligase, via ubiquitination at EZH2’s K381 residue, and is downregulated in LPCs by UHRF1-mediated CpG methylation. Targeting UHRF1/UBE2L6/UBR4-mediated regulation of EZH2 offers potential for modulating the activity of this oncoprotein in contexts in which conventional EZH2 methyltransferase inhibitors are ineffective.

Risk factors for the occurrence and development of paraneoplastic ophthalmopathies in dogs and cats

The frequency of oncological diseases in animals is becoming more and more every year. The development of diagnostic studies, the development of new treatment protocols contributes in some cases to improving the prognosis of the disease. However, a big problem is the development of paraneoplastic syndromes in various oncological pathologies, which leads, on the contrary, to a deterioration in the prognosis. There is no specific treatment for paraneoplastic processes – improvement of the condition and disappearance of paraneoplastic manifestations is the result of treatment of the primary tumor. Cancer-associated ophthalmopathies, such as paraneoplastic syndrome, are no exception. In addition to secondary eye pathologies, intraocular neoplasms are also found against the background of oncological processes. Intraocular tumors in animals are relatively rare neoplasms, there are both malignant and benign tumor processes. In dogs, we most often encounter pigmented melanomas, less often with squamous cell carcinoma and sarcomas of an unclear phenotype. In cats, the most common intraocular pathology is melanoma, followed by lymphoma and posttraumatic sarcoma of the orbit of the eye is not uncommon. They can develop in both elderly animals and animals of a younger age group. This article presents the results of studies of risk factors for the occurrence and development of immune-mediated paraneoplastic ophthalmopathies in dogs and cats. The article discusses the possible causes of the development of ophthalmic paraneoplastic pathologies, the etiopathogenesis of which includes a number of factors. The possibilities of innovative diagnostic methods, such as magnetic resonance imaging and computed tomography, complete ophthalmological examination using modern ophthalmological equipment, are considered. And the variants of morphological diagnoses are presented, in which cancer-associated ophthalmopathies most often develop.

The Association between the Morphology of Vessels in Primary Cutaneous Melanoma on Dermoscopy, with the Breslow Index, the Presence of Ulceration, and the Dermoscopic Signs of Extensive Regression

Background: Dermoscopy is a noninvasive technique for the diagnosis of cutaneous melanoma that may play a role in the preoperative assessment of melanoma thickness. With this technique, several vascular morphologies have been identified. The objectives of this study are to study the presence and morphology of blood vessels in a series of primary melanomas and to investigate whether they are related to the Breslow index, the presence of ulceration, and extensive dermoscopic regression. Methods: This cross-sectional study included nonacral, nonfacial primary melanomas, with dermoscopic images from four hospitals in Spain. The outcome variables were the Breslow index, the presence of dermoscopic ulceration, and an extensive dermoscopic regression. The explicative variables were the presence of vessels, the predominant vessel in the most raised area of the melanoma, and the presence of polymorphous vessels. To study the association between qualitative variables and the Breslow index, we used the Kruskal-Wallis test or Mann-Whitney U test and between qualitative variables, the χ² test. To study the magnitude of the association, the ORs (95% CI) were calculated. Results: A set of 516 images from melanomas was collected. The presence of vessels was associated with thicker melanomas (p < 0.001). Vessel type was associated with different Breslow indexes (p < 0.001) (arborizing, linear irregular, corkscrew, glomerular, hairpin, and dotted vessels (in decreasing order)). The polymorphous vessels were associated with thicker melanomas (p < 0.001). Linear irregular vessels were associated with ulceration (OR = 10.6, 95% CI 4.9–24.0, p < 0.001) and dotted vessels with the presence of extensive dermoscopic regression (OR = 2.7, 95% CI 1.4–5.2, p = 0.003). The main limitations of this study were the high selection of cases and the difficulty in identifying vessels in pigmented melanomas by dermoscopy. Conclusions: The morphology of blood vessels in cutaneous melanoma on dermoscopy is associated with the Breslow index, the presence of ulceration, and extensive dermoscopic regression.

The Rise of Artificial Intelligence - High Prediction Accuracy in Early Detection of Pigmented Melanoma

The incidence of malignant melanoma is increasing worldwide. If detected early, melanoma is highly treatable, so early detection is vital.Skin cancer early detection has improved significantly in recent decades, for example by the introduction of screening in 2008 and dermoscopy. Nevertheless, in particular visual detection of early melanomas remains challenging because they show many morphological overlaps with nevi. Hence, there continues to be a high medical need to further develop methods for early skin cancer detection in order to be able to reliably diagnosemelanomas at a very early stage.Routine diagnostics for melanoma detection include visual whole body inspection, often supplemented by dermoscopy, which can significantly increase the diagnostic accuracy of experienced dermatologists. A procedure that is additionally offered in some practices and clinics is wholebody photography combined with digital dermoscopy for the early detection of malignant melanoma, especially for monitoring high-risk patients.In recent decades, numerous noninvasive adjunctive diagnostic techniques were developed for the examination of suspicious pigmented moles, that may have the potential to allow improved and, in some cases, automated evaluation of these lesions. First, confocal laser microscopy should be mentioned here, as well as electrical impedance spectroscopy, multiphoton laser tomography, multispectral analysis, Raman spectroscopy or optical coherence tomography. These diagnostic techniques usually focus on high sensitivity to avoid malignant melanoma being overlooked. However, this usually implies lower specificity, which may lead to unnecessary excision of benign lesions in screening. Also, some of the procedures are time-consuming and costly, which also limits their applicability in skin cancer screening. In the near future, the use of artificial intelligence might change skin cancer diagnostics in many ways. The most promising approach may be the analysis of routine macroscopic and dermoscopic images by artificial intelligence.For the classification of pigmented skin lesions based on macroscopic and dermoscopic images, artificial intelligence, especially in form of neural networks, has achieved comparable diagnostic accuracies to dermatologists under experimental conditions in numerous studies. In particular, it achieved high accuracies in the binary melanoma/nevus classification task, but it also performed comparably well to dermatologists in multiclass differentiation of various skin diseases. However, proof of the basic applicability and utility of such systems in clinical practice is still pending. Prerequisites that remain to be established to enable translation of such diagnostic systems into dermatological routine are means that allow users to comprehend the system's decisions as well as a uniformly high performance of the algorithms on image data from other hospitals and practices.At present, hints are accumulating that computer-aided diagnosis systems could provide their greatest benefit as assistance systems, since studies indicate that a combination of human and machine achieves the best results. Diagnostic systems based on artificial intelligence are capable of detecting morphological characteristics quickly, quantitatively, objectively and reproducibly, and could thus provide a more objective analytical basis - in addition to medical experience.