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Cutaneous melanoma (CM) is an increasingly significant public health concern. Due to alarming mortality rates and escalating incidence, it is crucial to understand its etiology and identify emerging biomarkers for improved diagnosis and treatment strategies. This review aims to provide a comprehensive overview of the multifactorial etiology of CM, underscore the importance of early detection, discuss the molecular mechanisms behind melanoma development and progression, and shed light on the role of the potential biomarkers in diagnosis and treatment. The pathogenesis of CM involves a complex interplay of genetic predispositions and environmental exposures, ultraviolet radiation exposure being the predominant environmental risk factor. The emergence of new biomarkers, such as novel immunohistochemical markers, gene mutation analysis, microRNA, and exosome protein expressions, holds promise for improved early detection, and prognostic and personalized therapeutic strategies.

Diagnosing cutaneous melanoma is usually straightforward based on these malignancies' histopathological and immunohistochemical features. Nevertheless, melanomas can imitate various other neoplasms, sometimes lacking the expression of conventional melanocytic markers and expressing non-melanocytic ones. Furthermore, divergent differentiation is more often encountered in metastatic melanomas and is still poorly described in primary cutaneous melanomas, and little is known about these patients' prognosis and therapeutic approach. Therefore, we reviewed the literature on undifferentiated/dedifferentiated cutaneous melanomas, and we discuss the histological, immunohistochemical, and molecular profiles of undifferentiated/dedifferentiated cutaneous melanomas to understand these peculiar lesions better and improve their diagnostic algorithm. In addition to this, we also discuss how different genetic mutations may influence prognosis and become potential therapeutic targets.

Cutaneous melanoma is one of the most aggressive types of cancer and often proves fatal in metastatic stages. Few treatment options are available, and its global incidence is quickly increasing. In order to gain an improved understanding of the molecular features regarding melanoma progression, we have compared gene and small non-coding RNA expression profiles from cell lines derived from primary melanoma (MelJuSo), lymph node metastasis (MNT-1) and brain metastasis (VMM1), representing distinct stages of malignant progression. Our preliminary results highlighted the aberrant regulation of molecular markers involved in several processes that aid melanoma progression and metastasis development, including extracellular matrix remodeling, migratory potential and angiogenesis. Moreover, bioinformatic analysis revealed potential targets of the microRNAs of interest. Confocal microscopy and immunohistochemistry analysis were used for validation at the protein level. Exploring the molecular landscape of melanoma may contribute to the achievement of future efficient targeted therapy, as well as better prevention, diagnosis and clinical management.

Skin cancer is a common healthcare issue that affects millions of people worldwide. Only a small part of that population is suffering from melanoma and an even smaller proportion has melanoma developed on a pre-existing nevus. This paper illustrates five such cases, diagnosed over an 18-month period, with their histological particular aspects. Among the total number of patients diagnosed and treated in the Department of Plastic and Reconstructive Surgery, University Emergency Hospital, Bucharest, Romania, over approximately one year, of which half for melanoma in general or for benign nevi, only a small fraction had developed melanoma on a common or dysplastic nevus. These patients, as well as those with de novo developed melanoma, are a reason for concern since most of the lesions were diagnosed in a locally advanced stage of the disease. Though efforts are being made to screen and diagnose early, there are still a lot to be done in order to lower the mortality and morbidity rates for this pathology.

Background: Eye and skin share the embryological origin. Both are established risk factors in epidermal skin cancer. There are few reports using iris colour classification scales, most of them analyse colour in general or are too complex to use in daily practice., Objectives: To investigate which iris colour pattern is associated with epidermal skin cancer in a S-E European Caucasian population., Methods: A case-control study was conducted on 480 patients: 229 skin cancers patients and 251 controls (dermatological patients free of skin cancers) admitted in two medical clinics of Dermatology in Bucharest, between October 2011 and May 2014. High-resolution iris photographs were taken for each patient. Three parameters of the iris were analysed individually and in association patterns for each patient: periphery, collaret and freckles., Results: The most frequent iris colour pattern associated with epidermal skin cancer was blue periphery with light brown collaret and freckles present. In terms of individual parameters, the strongest indicators for skin cancer patients were blue periphery and blue collaret., Conclusions: The results of this study sustain the hypothesis that blue periphery with light brown collaret and freckles iris pattern is a reliable phenotypic marker for epidermal skin cancer. The results of this study differ from previous reports in which skin cancer risk was associated with a homogeneous blue iris. We account these differences in the characteristics of the recruited patients (S-E European, skin type II and III). The assessment of iris colour patterns is an easy and inexpensive detection tool in skin cancer risk assessment., (© 2018 European Academy of Dermatology and Venereology.)

Melanomas can exhibit a wide range of unusual morphologies due to the neural crest origin of melanocytes. Several authors have documented variations in size and shape of cells, cytoplasmic features and inclusions, nuclear features and cell architecture. Metastatic melanoma with rhabdomyoblastic differentiation is an extremely rare condition with poor prognosis. Few studies concerning rhabdoid or rhabdomyoblastic differentiation in melanoma are currently available and the current report highlights some of the most important immunohistochemical features of this rare entity. We report on a case of a rhabdomyoblastic metastatic melanoma showing intense positivity for both melanocytic and rhabdoid markers in two cell populations dissociated within the tumor with multiple mismatches in immunomarker expression. Improved recognition of this rare morphological pattern may provide the means for developing new techniques to identify novel therapeutic targets, which would improve the prognostic outlook for these patients.

Background: The tracking and identification of errors in the detection and follow-up of melanoma are important because there is huge potential to increase awareness about the most vulnerable aspects of diagnosis and treatment, and to improve both from the perspective of healthcare economics. The present study was designed to identify where errors occur and to propose a minimum set of rules for the routine guidance of any specialist in melanoma management., Methods: This report describes the evaluation of a unique series of 33 cases in which errors applying to many steps in the diagnosis and treatment of melanoma were detected. Cases were collected at two centers in Romania, one public and one private, as part of a process of obtaining patient-requested second opinions., Results: A total of 166 errors were identified across the 33 patients, most of which were treatment errors. The errors fell into six categories: clinical diagnostic errors (36 errors among 30 patients); primary surgical errors (31 errors among 16 patients); pathology errors (24 errors among 17 patients); sentinel lymph node biopsy errors (13 errors among 13 patients); staging errors (17 errors among 13 patients); and treatment or management errors (45 errors among 33 patients)., Conclusions: Based on the present results, we propose that in countries lacking national guidelines, clinicians should adhere to international evidence-based guidelines for the diagnosis and treatment of melanoma., (© 2015 The International Society of Dermatology.)

Ocular melanoma is a rare malignancy found in clinical practice. In this paper, we present a case of highly aggressive ocular melanoma, which was surgically removed at the Department of Ophthalmology and diagnosed at the Department of Pathology, Emergency University Hospital, Bucharest, Romania, using conventional histopathological techniques. Uveal melanoma, a subset of ocular melanoma, has a distinct behavior in comparison to cutaneous melanoma and has a widely divergent prognosis. Approximately half of patients with ocular melanoma will develop metastatic disease, predominantly with hepatic, pulmonary or cerebral location, over a 10 to 15 years period. No systemic therapy was associated with an evident clinical outcome for patients with advanced disease and overall survival rate remains poor.

Ocular melanoma is rare in clinical practice. In this study, we present three cases of ocular melanoma surgically removed in the Department of Ophthalmology of the Emergency University Hospital of Bucharest, Romania, and diagnosed in the Department of Pathology of the same hospital using conventional histopathological techniques and immunohistochemical tests.

In the last decades, the incidence of skin cancer is in continuous growth, but the mortality remains at the same level thanks to the new imaging diagnosis methods and surgical treatment. A real problem regarding differential diagnosis between cutaneous melanoma and non-melanotic skin tumor appear, despite advanced technologies, which have a major impact on treatment management. We reported two cases with clinical and dermoscopic aspects of cutaneous melanoma, sustained by positive lymphoscintigraphy. The histopathological exams established that the skin tumor was a pigmented basal cell carcinoma. In such difficult cases, the accuracy of diagnosis is certified only by the microscopical examination with clinical, treatment and prognosis changes.

The article presents statistical correlations of immune cell parameters investigated in patients diagnosed with skin melanoma stage I. Recent data indicate a suppressed immune response, probably sustained by immune-regulating molecules expressed or shed from the tumor. These molecules block an efficient immune response and thus the tumor develops. All the molecules that are part of the tumor escape mechanisms can be targets for immune-mediated anti-tumor agents. We try to find the significance of some immunohistochemical markers (UCHL1, CD4, CD8) in tumoral inflammatory infiltrate and to establish the statistical correlations between molecular markers and tumor grade and stage. The studied parameters were: CD3+, CD4+, CD8+, CD56+16+ and CD19+. The statistical results were performed with SPSS v. 15.0. We demonstrate that a CD4+ on-going immune response is elicited in the investigated patients. We found a possible compensatory mechanism between T-lymphocytes and NK-cells and also between the antibodies generating cells and the natural cytotoxic cells. We are confident that these statistical correlations between clinical, immunological and immunohistochemical data can be useful in the disease management and personalized immune-therapy.

We report mucosal melanoma of the upper lip in a patient affected by the Laugier-Hunziker disease. Using dermatoscopy, two distinct parts were identified in the same mucosal area: nodular (malignant) and macular (benign). A complete surgical excision was performed and the patient has been free of disease for 16 months.

Cutaneous melanomas has become one of the most discussed and studied tumor because its particular immunologic development but also its increasing rate worldwide in the last decades. Even thought many patients are diagnosed at an early stage, the death rate continues to rise due to the increasing incidence of more advanced lesions. The aim of this study is to detect apoptosis in 30 cases of cutaneous melanomas using the in situ end-labeling technique (TUNEL) who quantify apoptotic cell death at single cell level and tissues.

Cutaneous melanoma is a "perfid", aggressive and hard to be treated malignant tumor in case of delayed diagnosis. However, patients still have a chance to escape progressive disease if the lesion is recognized early, when the surgical approach is curative. Dermoscopy has the important advantage of rapidity and non-invasivity in a field with (still) contradictory algorithms of diagnosis and treatment. The recognition of the elementary dermoscopic lesions enables accurate diagnosis for cutaneous melanoma. In our opinion, dermoscopy appears compulsory in the routine dermatologic examination. In vivo microscopy (dermoscopy) together with histopathology (plus or minus immunohistochemistry) seem, at present, to provide the most reliable diagnosis of melanoma.