Nevi - when to refer.

PURPOSE OF REVIEW: Congenital melanocytic nevi (CMN) and acquired nevi are prevalent in pediatric populations, with distinct characteristics and management considerations. This chapter aims to equip pediatricians with knowledge to discern between benign and high-risk nevi, facilitating appropriate referrals and management within primary care settings. Risk factors associated with malignant melanoma (MM) underscore the importance of vigilant monitoring and early referral to dermatology for suspicious lesions. RECENT FINDINGS: Recent findings highlight the variability in CMN presentation and the evolving diagnostic strategies, emphasizing the need for multidisciplinary approaches to optimize patient outcomes. SUMMARY: Management of CMN involves tailored surveillance and intervention strategies, with an emphasis on early identification of high-risk features for MM and neurocutaneous melanosis (NCM). Pediatricians play a crucial role in advocating for sun protection practices and facilitating timely referrals, thereby contributing to the overall well being of pediatric patients with nevi.

[Epidemiological signatures and surveillance bias in cancer]. / Signatures épidémiologiques et biais de surveillance du cancer.

Surveillance bias occurs when variations in cancer incidence are the result of changes in screening or diagnostic practices rather than increases in the true occurrence of cancer. This bias is linked to the issue of overdiagnosis and can be apprehended by looking at epidemiological signatures of cancer. We explain the concept of epidemiological signatures using the examples of melanoma and of lung and prostate cancer. Accounting for surveillance bias is particularly important for assessing the true burden of cancer and for accurately communicating cancer information to the population and decision-makers.

Le biais de surveillance se produit lorsque les variations d'incidence d'un cancer sont le résultat d'un changement dans les pratiques de dépistage ou de diagnostic plutôt que d'une augmentation de la fréquence réelle de ce cancer. Ce biais est lié au concept du surdiagnostic et peut être appréhendé en examinant les signatures épidémiologiques des cancers. Nous expliquons le concept de signature épidémiologique à l'aide des exemples du mélanome et des cancers du poumon et de la prostate. La prise en compte des biais de surveillance est particulièrement importante pour évaluer le fardeau réel du cancer et communiquer avec précision l'information sur le cancer à la population et aux décideurs.

[Epigenetic markers of choroidal melanoma]. / Epigeneticheskie markery melanomy khorioidei.

MicroRNAs (miRNAs) are short non-coding RNAs (18-25 nucleotides in length) that are important participants in the regulation of gene expression. In 2003, their active role in oncogenesis was demonstrated. In 2008, the first report on the isolation of miRNAs from uveal melanoma (UM) tissue was published. Four years later (2012), the presence of miRNAs in the plasma of patients with this category was shown. To date, changes in the expression level of 100 miRNAs in the plasma of cancer patients (with cancer of various localizations) out of the 2654 miRNAs described in mirbase.org have been proven. In the plasma of patients with UM, changes in the expression of only 13 miRNAs have been confirmed. As a rule, studies were conducted in patients at the stage of hematogenous metastasis of UM. PURPOSE: This study analyzed the expression pattern of miRNA-223 and miRNA-126 in patients with localized choroidal melanoma (CM) taking into account biometric parameters in the absence of metastases. MATERIAL AND METHODS: Blood plasma of 84 patients with M0N0 CM aged 35-86 years (mean age 63.4±1.2 years) was investigated. The basis for the diagnosis of CM was the results of ophthalmological examination, optical coherence tomography, and ultrasound scanning. In all cases, the absence of metastases was proven (using computed tomography or magnetic resonance imaging). Control - plasma of 28 volunteers (mean age 62.9±1.42 years, age range 45-78 years), who did not have tumoral, autoimmune, or chronic inflammatory processes. The expression levels of miRNAs circulating in blood plasma were determined by real-time polymerase chain reaction. RESULTS: An increase in the expression levels of miRNA-223 and miRNA-126 in the plasma of all 84 patients with CM was confirmed compared to the control group. Features of the miRNA expression pattern that emerged with changes in the tumor's quantitative parameters were identified. CONCLUSION: Evaluation of the levels of miRNA-223 and miRNA-126 in the blood plasma of patients with CM can be used in clinical practice to clarify the diagnosis of CM, as well as to predict the development of hematogenous metastases.

Melanoma of the external auditory canal: case report and systematic literature review.

Melanoma of the external auditory canal (EAC) is particularly rare and poorly understood, with limited available data on management and survival. This systematic review aims to analyze existing data and provide insights into the management and prognosis the beginning of EAC melanoma. It is conducted using Pubmed and Scopus databases from the beginning to July 2023 and it follows the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines. Searches are performed using the search string "(melanoma) AND (external auditory canal)".The review includes a total of 30 patients diagnosed with EAC melanoma, supplemented by an additional case from the authors' clinical experience. The role of Breslow thickness as a determining factor for the choice of surgery remains inconclusive due to limited available data. Sentinel lymph node biopsy and adjuvant therapy are sparingly employed, indicating the need for standardized guidelines. Patients in the study demonstrate a 50% overall survival rate at 5 years.EAC Melanoma is a rare and aggressive malignancy with limited therapeutic guidelines. Surgical interventions, including wide local excision and lateral temporal bone resection, are the primary treatment options for patients without distant metastases.

Novel liquid biopsy CNV biomarkers in malignant melanoma.

Malignant melanoma (MM) is known for its abundance of genetic alterations and a tendency for rapid metastasizing. Identification of novel plasma biomarkers may enhance non-invasive diagnostics and disease monitoring. Initially, we examined copy number variations (CNV) in CDK genes (CDKN2A, CDKN2B, CDK4) using MLPA (gDNA) and ddPCR (ctDNA) analysis. Subsequently, low-coverage whole genome sequencing (lcWGS) was used to identify the most common CNV in plasma samples, followed by ddPCR verification of chosen biomarkers. CNV alterations in CDK genes were identified in 33.3% of FFPE samples (Clark IV, V only). Detection of the same genes in MM plasma showed no significance, neither compared to healthy plasmas nor between pre- versus post-surgery plasma. Sequencing data showed the most common CNV occurring in 6q27, 4p16.1, 10p15.3, 10q22.3, 13q34, 18q23, 20q11.21-q13.12 and 22q13.33. CNV in four chosen genes (KIF25, E2F1, DIP2C and TFG) were verified by ddPCR using 2 models of interpretation. Model 1 was concordant with lcWGS results in 54% of samples, for model 2 it was 46%. Although CDK genes have not been proven to be suitable CNV liquid biopsy biomarkers, lcWGS defined the most frequently affected chromosomal regions by CNV. Among chosen genes, DIP2C demonstrated a potential for further analysis.

Identifying Patients At Risk for Melanoma in an Aesthetic Practice.

In the United States, melanoma skin cancer deaths are expected to rise by 4.4% in 2023, reaching 7990. Early detection through visual screening can save lives, but the US Preventive Services Task Force cites insufficient evidence to recommend universal skin screening for all adults. For this reason, the risk for melanoma may be overlooked outside of dermatology settings, leading to delayed diagnoses and poor survival rates. Our project aimed to address this issue by increasing the identification of at-risk individuals visiting a medical aesthetic practice in the Midwest. The literature regarding melanoma risk stratification outside of dermatology settings is deficient. A search yielding 336 articles produced 8 articles for review. Five suggested melanoma risk screenings in general practice are feasible and/or can lead to early detection. Using the Plan-Do-Study-Act model, we executed our project from February through April 2023. Patients visiting the medical aesthetic practice completed a Self-Assessment Melanoma Risk Score questionnaire. We assessed the completed questionnaires and offered visual cancer screenings or dermatology referrals to patients identified as at-risk. A total of 211 patients participated, and 26% (n = 55) were identified as at-risk. This intervention improved the quality of care by identifying patients at risk for melanoma. Future steps include adapting the Self-Assessment of Melanoma Risk Score questionnaire to a new electronic medical record system, incorporating the questionnaire as part of the initial intake and annual patient documentation, and improving patient education and follow-up.

NCCN Guidelines® Insights: Melanoma: Cutaneous, Version 2.2024.

The NCCN Guidelines for Cutaneous Melanoma (termed Melanoma: Cutaneous) provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients. These NCCN Guidelines Insights focus on the update to neoadjuvant systemic therapy options and summarize the new clinical data evaluated by the NCCN panel for the recommended therapies in Version 2.2024 of the NCCN Guidelines for Cutaneous Melanoma.

Primary mucosal malignant melanoma (PMMM) of nasal cavity: A report of two cases.

ABSTRACT: Primary mucosal malignant melanoma of the nasal cavity is a rare tumor with aggressive behavior and a dismal prognosis. An extremely rare tumor that accounts for 0.7% to 1% of all melanomas in Caucasian populations and between 4% and 8% of malignant tumors of the nasal cavity and paranasal sinuses. Taking into account the rarity, it is important to note that malignant melanoma should be considered when making a differential diagnosis of tumors of the nose and paranasal sinuses. Two cases of primary malignant melanoma of the nasal cavity both arising in females, one in a 60-year-old and the other in a 64-year-old, both of whom presented with nasal obstruction and brief symptomatic epistaxis are being presented here. The diagnosis being confirmed by a histopathological examination along with an immunohistochemical analysis by using S100 and HMB45.

Patients poorly recognize lesions of concern that are malignant melanomas: is self-screening the correct advice?

Background: Australia is known for its outdoor culture, with a large percentage of its population engaging in outdoor recreational activities, aquatic, non-aquatic and outdoor occupational activities. However, these outdoor enthusiasts face increased exposure to ultraviolet radiation (UVR), leading to a higher risk of skin cancer, including malignant melanoma (MM). Over the past 40 years, there has been a significant rise in skin cancer rates in Australia, with two out of three Australians expected to develop some form of skin cancer by age 70. Currently, skin cancer examinations are not endorsed in asymptomatic or low-risk individuals in Australia, with only high-risk individuals recommended to undergo regular skin examinations. Notably, the Melanoma Institute Australia suggests that one-half of patients identify MMs themselves, although this claim appears to be based on limited Australian data which may not reflect contemporary practice. Therefore this study sought to determine the percentage of patients who were able to self-identify MMs as lesions of concern when presenting for a skin cancer examination. Methods: Multi-site, cross-sectional study design incorporating a descriptive survey and total body skin cancer screening, including artificial intelligence by a skin cancer doctor. Results: A total of 260 participants with suspect MM lesions were biopsied, with 83 (31.9%) found to be melanomas. Of the true positive MMs only a small percentage of participants (21.7% specificity) correctly had concerns about the suspect lesion being a MM. These MMs were located primarily on the back (44.4%), shoulder (11.1%) and upper leg (11.1%). There was no significant difference in the size between those participants aware of a MM versus those who were not (P = 0.824, 24.6 vs 23.4 mm2). Significantly more males identified lesions of concern that were MMs as compared to females (P = 0.008, 61.1% vs 38.9%, respectively). With regard to true negatives males and females were similar (52.1% vs 47.9%, respectively). With regard to false negatives (n = 65), a greater percentage of males than females did not recognize the MM as a lesion of concern (66.2% vs 33.8%, respectively). Participants were more likely to correctly identify an invasive MM as opposed to an in situ MM (27.3% versus 21.3%). Conclusions: Only a small percentage of participants in this study were able to self-identify either in situ or invasive MM as a lesion of concern with a tendency to identify the more advanced, thicker MMs. Given that MM is associated with a high mortality and cost of treatment, particularly when invasive, the inability of lay persons to identify these cancerous lesions will likely lead to delayed treatment and a possible adverse outcome. We believe the current melanoma screening practices in Australian general practice should be revisited to improve patient outcomes with regard to MM. Additionally, prevention campaigns should include images and primary risk factors for MM.

Beyond the Surface: A Case Report of a Patient with Small Bowel Metastasis and Melanoma History. Diagnosis and Management.

Background: Malignant melanoma (MM) is one of the most prevalent and deadliest forms of skin cancer, resulting from the malignant transformation of melanocytes. It accounts for approximately 1.7% of global cancer diagnoses and is the fifth most common cancer in the US. MM can metastasize to almost any part of the body, with early detection significantly improving prognosis. Case presentation: We report the case of an 81-year-old female with a history of malignant melanoma (primary lesion on the left calf) and various comorbidities. She presented with severe anemia of unknown origin. A CT scan was performed due to her medical history, revealing a circumferential, asymmetrical parietal thickening at the level of a hypogastric ileal loop. The lesion suggested a tumoral substrate. Subsequent colonoscopy showed no metastatic lesions, but surgical intervention confirmed a malignant melanoma ileal metastasis. The patient underwent laparoscopic segmental resection with favorable post-surgery outcomes. Histopathological examination of the resected tissue confirmed the diagnosis of small intestine secondary lesions from the malignant melanoma. Conclusion: This case underscores the necessity of considering metastatic melanoma in patients with a history of MM and vague gastrointestinal symptoms. Early and accurate diagnosis through advanced imaging and endoscopic techniques can significantly improve patient outcomes.

Lumbar Melanoma with Sentinel Lymph Nodes in Multiple Basins - Case Report and Review of the Literature.

Intreduction: Melanoma is an extremely aggressive form of skin neoplasia, an important stage in the diagnostic and treatment is identifying the dissemination at the lymphatic level. For a more accurate staging, the sentinel lymph node biopsy technique is performed, which in most of the time addresses one, respectively 2 locations, but cases with sentinel nodes in 3 lymphatic basins have rarely been described. Case report: We present a case of melanoma located in the right lumbar region, which from the point of view of histopathological features has a Breslow index of 4.2 mm, classified in the pT4b stage. After the CT evaluation was performed, it was decided that there is indication for performing the sentinel lymph node technique and excision with a margin of safety. Scintigraphy revealed that sentinel lymph nodes were identified in 3 different regions, respectively the right axilla and bilateral inguinal. Conclusions: Melanoma located on the trunk can present different lymphatic routes for the sentinel lymph nodes, unlike that on the limbs where certain patterns are present. Identifying these lymph nodes in cases like this involves a challenge both from a diagnostic and surgical point of view.

Benefits of dermoscopy in primary care.

ABSTRACT: Skin cancer is the most common cancer in the United States, with an estimated 9,500 new diagnoses made each day. Dermoscopy (also called dermatoscopy) is an established clinical approach to improving skin cancer evaluation. However, only 8% to 9% of primary care physicians use it, and no data are available for physician associate/assistant or NP use. This article reports a dermoscopy algorithm that primary care providers can use to increase the detection of skin cancer and reduce unnecessary referrals and biopsies.

Advancing immunotherapy for melanoma: the critical role of single-cell analysis in identifying predictive biomarkers.

Melanoma, a malignant skin cancer arising from melanocytes, exhibits rapid metastasis and a high mortality rate, especially in advanced stages. Current treatment modalities, including surgery, radiation, and immunotherapy, offer limited success, with immunotherapy using immune checkpoint inhibitors (ICIs) being the most promising. However, the high mortality rate underscores the urgent need for robust, non-invasive biomarkers to predict patient response to adjuvant therapies. The immune microenvironment of melanoma comprises various immune cells, which influence tumor growth and immune response. Melanoma cells employ multiple mechanisms for immune escape, including defects in immune recognition and epithelial-mesenchymal transition (EMT), which collectively impact treatment efficacy. Single-cell analysis technologies, such as single-cell RNA sequencing (scRNA-seq), have revolutionized the understanding of tumor heterogeneity and immune microenvironment dynamics. These technologies facilitate the identification of rare cell populations, co-expression patterns, and regulatory networks, offering deep insights into tumor progression, immune response, and therapy resistance. In the realm of biomarker discovery for melanoma, single-cell analysis has demonstrated significant potential. It aids in uncovering cellular composition, gene profiles, and novel markers, thus advancing diagnosis, treatment, and prognosis. Additionally, tumor-associated antibodies and specific genetic and cellular markers identified through single-cell analysis hold promise as predictive biomarkers. Despite these advancements, challenges such as RNA-protein expression discrepancies and tumor heterogeneity persist, necessitating further research. Nonetheless, single-cell analysis remains a powerful tool in elucidating the mechanisms underlying therapy response and resistance, ultimately contributing to the development of personalized melanoma therapies and improved patient outcomes.

Leiomyoma - Ciliary Body Tumor. A Case Report.

AIM: To demonstrate a rare case of ciliary body leiomyoma in our patient Case report: A 72-year-old female reported to our clinic for a preventive examination, upon which we found a dome-shaped grey-brownish mass on the retinal periphery. After completing gonioscopic and ultrasound examinations, we referred the patient to a specialist facility. Due to a finding of suspicious malignant melanoma, we completed the MRI scan and recommended enucleation of the eyeball. A histopathological examination showed a leiomyoma of the ciliary body. CONCLUSION: The aim of this case report is to demonstrate the difficulty of intraocular leiomyoma diagnosis. Only immunohistochemical examination differentiated the tumor from malignant melanoma and determined the diagnosis of ciliary body leiomyoma. Perhaps because of the extreme rarity of this type of tumor, we often neglect to consider a diagnosis of leiomyoma.

The number needed to biopsy for cutaneous melanoma in academic dermatology clinics.

A standard metric for melanoma detection is the number needed to biopsy (NNB). This metric has been used to evaluate practicing dermatologists, dermatology advanced practice professionals, and primary care providers. This metric, however, has rarely been applied to residency clinics. We aimed to determine the NNB at the University of Colorado residency clinics. Moreover, we sought to determine the impact of the coronavirus disease 2019 (COVID-19) pandemic on NNB. This study is a retrospective analysis of biopsies performed from 2016 to 2022 at the Denver Health Medical Center and the Rocky Mountain Regional Veteran Affairs dermatology clinics. Differential diagnosis at the time of biopsy was searched for keywords including melanoma, melanoma in situ, and lentigo maligna. Skin biopsies that included re-excisions were excluded. The NNB was subsequently generated by dividing the number of biopsied lesions with suspected melanoma by the number of histologically confirmed melanomas. The data was further separated by pre-COVID-19 (2016-February 2020), COVID-19 shutdown period (March 2020-July 2020), and post-COVID-19 (March 2020-present). Demographic data, including age, sex, race, and Fitzpatrick type, were collected. There were 2230 biopsies with suspected melanoma in the differential diagnosis at both clinic sites from 2016 to 2022. Of these, 362 were histologically confirmed melanoma. Total NNB was 6.16. The pre-COVID-19 NNB was 5.86, and the post-COVID-19 NNB was 6.91. Residency clinics have NNB similar to published values of practicing dermatologists. Furthermore, within these clinics, the impact of the COVID-19 pandemic was appreciated by a relative, although statistically insignificant, increase in NNB.

Multidisciplinary patient-centered approach to the management of skin cancer.

In recent years, new approaches for optimal patient management of cancer have focused on patient-centered care, with integration of tumour-directed treatment and patient-directed supportive and palliative care throughout the disease journey from prevention through screening, diagnosis, treatment, and follow-up. In 2022, at the International Forum of Dermatology (IFD), a scientific session was entirely dedicated to highlight recent developments on patient-centered approaches in skin cancer. An international panel of different groups of participants involved in a patient's journey on the management of skin cancer presented and discussed challenges and barriers that persist in the field of skin cancer prevention and care pathways. Although primary prevention remains a crucial step in the prevention of melanoma, the different surveys performed during the last 20 years demonstrate that the use of sunscreen increases very slowly. Secondary prevention that includes skin screening and diagnostic measures may benefit from the development of digital tools. To improve adherence, patients need accurate, reliable information about their disease and the treatment options, and this type of content that can also be made available on digital tools. Shared decision-making is a hallmark of a patient-centered approach and requires health care providers who can communicate well to patients and their families, underscoring the pivotal role of health care professionals all through the patient journey. Health care providers have a crucial role in supporting patients through their journey in skin cancer. They will benefit from mobile apps and technologies that have been developed recently to address challenges in skin cancer prevention, detection and care, including those that are primarily directed to the patient. However, more peer-reviewed studies are needed as well as regulations to ensure that apps are accurate, reliable, and up to date.

Reflectance confocal microscopy versus dermoscopy for the diagnosis of cutaneous melanoma: a head-to-head comparative meta-analysis.

This meta-analysis aimed to evaluate the comparative diagnostic performance of reflectance confocal microscopy (RCM) and dermoscopy in detecting cutaneous melanoma patients. An extensive search was conducted in the PubMed and Embase databases to identify available publications up to December 2023. Studies were included if they evaluated the diagnostic performance of RCM and dermoscopy in patients with cutaneous melanoma. The quality of the included studies was assessed using the Quality Assessment of Diagnostic Performance Studies (QUADAS-2) tool. A total of 14 articles involving 2013 patients were included in the meta-analysis. The overall sensitivity of RCM was 0.94 [95% confidence interval (CI), 0.87-0.98], while the overall sensitivity of dermoscopy was 0.84 (95% CI, 0.71-0.95). These results suggested that RCM has a similar level of sensitivity compared with dermoscopy ( P  = 0.15). In contrast, the overall specificity of RCM was 0.76 (95% CI, 0.67-0.85), while the overall specificity of dermoscopy was 0.47 (95% CI, 0.31-0.63). The results indicated that RCM appears to have a higher specificity in comparison to dermoscopy ( P  < 0.01). Our meta-analysis indicates that RCM demonstrates superior specificity and similar sensitivity to dermoscopy in detecting cutaneous melanoma patients. The high heterogeneity, however, may impact the evidence of the current study, further larger sample prospective research is required to confirm these findings.

Diagnostic accuracy of high-frequency ultrasound for cutaneous neoplasms: a narrative review of the literature.

High-frequency ultrasound has been used to visualize depth and vascularization of cutaneous neoplasms, but little has been synthesized as a review for a robust level of evidence about the diagnostic accuracy of high-frequency ultrasound in dermatology. A narrative review of the PubMed database was performed to establish the correlation between ultrasound findings and histopathologic/dermoscopic findings for cutaneous neoplasms. Articles were divided into the following four categories: melanocytic, keratinocytic/epidermal, appendageal, and soft tissue/neural neoplasms. Review of the literature revealed that ultrasound findings and histopathology findings were strongly correlated regarding the depth of a cutaneous neoplasm. Morphological characteristics were correlated primarily in soft tissue/neural neoplasms. Overall, there is a paucity of literature on the correlation between high-frequency ultrasound and histopathology of cutaneous neoplasms. Further studies are needed to investigate this correlation in various dermatologic conditions.