Cases Of Melanoma Research Articles

Melanoma in pregnancy: multidisciplinary treatment management and outcome

Pregnancy-associated melanoma affects both maternal and fetal health. This study aims to demonstrate how a specialized center and a multidisciplinary approach can provide the best outcomes. From January 2006 to September 2023, a bicentric observational study was conducted at the Plastic Surgery Department of Policlinico Umberto I, Sapienza University of Rome, and at the Plastic and Regenerative Surgery Department of the San Gallicano Dermatological Institute IRCCS, Rome, Italy. Out of 6800 melanoma cases, twenty pregnant women were selected: thirteen underwent only wide local excision (WLE), while seven also had sentinel node biopsy (SLNB). All preoperative, operative, and postoperative steps were performed to ensure the safety of mothers and fetuses. Two patients developed metastases, with one fatality from hepatic metastases. The overall survival rate at 5-year follow-up was 86%, and 72% for advanced stages and disease-free patients. No maternal or fetal complications related to surgery were reported. Additionally, early deliveries at 7 and 8 months did not result in neonatal complications. Surgical treatment should be conducted in centers with both surgeons and gynecologists, and special care is necessary for procedures on pregnant women. Based on our experience, pregnancy does not seem to be a negative prognostic factor for melanoma.

The Dutch Early-Stage Melanoma (D-ESMEL) study: a discovery set and validation cohort to predict the absolute risk of distant metastases in stage I/II cutaneous melanoma.

Early-stage cutaneous melanoma patients generally have a favorable prognosis, yet a significant proportion of metastatic melanoma cases arise from this group, highlighting the need for improved risk stratification using novel prognostic biomarkers. The Dutch Early-Stage Melanoma (D-ESMEL) study introduces a robust, population-based methodology to develop an absolute risk prediction model for stage I/II melanoma, incorporating clinical, imaging, and multi-omics data to identify patients at increased risk for distant metastases. Utilizing the Netherlands Cancer Registry and Dutch Nationwide Pathology Databank, we collected primary tumor samples from early-stage melanoma patients, with and without distant metastases during follow-up. Our study design includes a discovery set of metastatic cases and matched controls to identify novel prognostic factors, followed by a validation cohort using a nested case-control design to validate these factors and to build a risk prediction model. Tissue sections underwent Hematoxylin & Eosin (H&E) staining, RNA sequencing (RNAseq), DNA sequencing (DNAseq), immunohistochemistry (IHC), and multiplex immunofluorescence (MxIF).The discovery set included 442 primary melanoma samples (221 case-control sets), with 46% stage I and 54% stage II melanomas. The median time to distant metastasis was 3.4years, while controls had a median follow-up time of 9.8years. The validation cohort included 154 cases and 154 controls from a random population-based selection of 5,815 patients. Our approach enabled the collection of a large number of early-stage melanoma samples from population-based databases with extensive follow-up and a sufficient number of metastatic events. This methodology in prognostic cancer research holds the potential to impact clinical decision-making through absolute risk prediction.

Utilization of primary tumor samples for cancer neoantigen discovery

BackgroundThe use of tumor-infiltrating T lymphocytes (TIL) that recognize cancer neoantigens has led to lasting remissions in metastatic melanoma and certain cases of metastatic epithelial cancer. For the treatment of...

A rare and challenging case of amelanotic subungual melanoma from Syria

A rare and challenging case of amelanotic subungual melanoma from Syria

Declining Clinical Utility of Tools for Predicting Sentinel Lymph Node Biopsy Status: A Single Institution Experience from 2000 to 2021.

Clinicopathologic data-based sentinel lymph node (SLN) prediction models are used to select patients with melanoma for sentinel lymph node biopsy (SLNB). However, the temporal performance of these models is unknown. Therefore, we investigated whether the performance and clinical utility of the Melanoma Institute of Australia, Memorial Sloan Kettering Cancer Center, and Friedman et al. models changed over time. Primary cutaneous melanoma cases that underwent SLNB at a single tertiary-care cancer center from 2000 to 2021 were identified from a prospectively maintained database. Calibration plots were generated. Values for estimated risks of SLN positivity and area under the receiver operator curve (AUC) were calculated. Clinical utility was assessed at thresholds between 5 and 10% using decision curve analysis. In total, 2977 SLNB cases were included. The estimated risk of SLN positivity and AUCs were similar across periods for all models. However, calibration decreased over time for all models, with progressive underprediction of SLN positivity. Clinical utility also declined over time; in the most recent period investigated (2018-2021), no model offered clinical utility at risk thresholds ≤ 8%, and only the Friedman model provided clinical utility at risk thresholds of 9-10%. The calibration and clinical utility of three predominant models for SLN prediction declined over time. There is a need to periodically reassess the performance of SLN prognostic tools as they are applied to contemporary cohorts. Future studies are needed to determine whether findings are generalizable outside of this study cohort.

A Rare Case of Episcleral Melanoma with GNAQ Mutation Arising from Nevus of Ota.

A Rare Case of Episcleral Melanoma with GNAQ Mutation Arising from Nevus of Ota.

Evidence of 18 F-FDG Utility in Rare Case of Metastatic Anal Melanoma With Prolonged Survival.

A 43-year-old woman presented with an anorectal mass at which time excision was performed, and biopsy revealed anorectal mucosal melanoma (AM), anal subtype. Postexcision, 18 F-FDG PET/CT identified residual melanoma, confirmed on biopsy. Recurrence was monitored every 3 months using 18 F-FDG, which identified a perirectal lymph node 2.5 years later positive for metastatic melanoma. Given the rarity of AM and often delayed diagnosis, patients often present with metastases, resulting in poor prognosis. This unique case of metastatic AM with prolonged survival of 7 years to date supports the implementation of 18 F-FDG in the diagnostics and monitoring of AM.

Primary Melanoma of the Palatine Tonsil in an Adult Filipino Patient: A Case Report

ABSTRACT Objectives: To discuss a case of primary melanoma of the palatine tonsil in a 57-year-old man presented with a dark, pigmented tonsillar mass initially managed as a case of arterio-venous malformation, and review the literature on its presentation, diagnosis, management and outcomes. Methods: Design: Case Report Setting: Tertiary Government Training Hospital Patient: One Results: A 57-year-old man presented with a pigmented, bluish-black mass (7.2 cm) on the right tonsillar area with dysphagia and odynophagia. A CT scan interpretation considered large tonsillar malignancy, right with infiltrations of the soft palate, lingual tonsils and pre-epiglottic space. The initial impression was an arteriovenous malformation and preoperative arterial embolization was followed by a tonsillectomy. The final biopsy result was mucosal melanoma. Refusing further treatment, he expired nine months later in the emergency room, after presenting with decreasing sensorium and desaturations, jaundice and abdominal distension. Conclusion: To the best of our knowledge, this is the first reported case of tonsillar melanoma in the Philippines. Primary tonsillar melanoma is rare but its diagnosis is still possible (although it is usually diagnosed in advanced stages). Despite improvement in surgical techniques and adjuvant therapies, its prognosis remains poor. Regular oral cavity screening may help in early detection.

Melanomas on the dorsum of the hand are extremely rare: A series of seven cases with clinical and dermatoscopic images.

Melanomas on the dorsum of the hand are exceedingly rare, with limited documentation in medical literature. This report presents seven cases of dorsal hand and finger melanomas, encompassing patients from Australia, New Zealand and Turkey, predominantly women with a mean age of 53 years. The majority were invasive, with a mean Breslow thickness of 1.1 mm and none were of lentigo maligna subtype. The rarity of dorsal hand melanomas prompts speculation into potential protective factors unique to this site, challenging existing knowledge on melanoma aetiology and sun exposure.

Primary melanoma of the urinary tract: a clinicopathological study of cases and literature review

AimPrimary malignant melanomas in the bladder or urethra are exceedingly rare. Diagnosing these tumours presents substantial challenges due to their close resemblance in gross appearance and histology to urothelial carcinomas.MethodsA...

Trends in Cutaneous Melanoma in Nova Scotia With a Focus on 2007 to 2019.

Melanoma represents a significant public health challenge in Canada, contributing to the deaths of over 1000 individuals each year. Prince Edward Island and Nova Scotia were previously noted to have the highest incidence rates of melanoma in Canada. Data from patients diagnosed with or dying from melanoma was extracted from the Nova Scotia Cancer Registry. TNM stage was available for cases diagnosed 2007 to 2017. Incidence (1992-2019) and mortality (1992-2021) rates were examined using Join Point Trend Analysis Software. Between 2007 and 2019, 2450 cases of in situ and 4063 cases of invasive melanoma were documented, of which 52.8% were male. The largest number of cases was from the 60- to 79-year age group. The most common site in females was upper limbs (in situ) and lower limbs (invasive), and for males, face, and neck (in situ), and trunk (invasive). The majority of invasive cases (71.5%) were diagnosed at stage I. Invasive melanoma incidence has been increasing by 2.7% per year since 1992, while in situ disease has increased at a greater rate (4.9% per year). The current estimate of 92% for 5 years of net survival has not changed appreciably over the same period. Survival for late-stage melanoma has shown a modest improvement for patients diagnosed over the period. With increasing rates of melanoma in Nova Scotia, there is a need for informed education, directed at the public and physicians, around pigmented skin lesions. This would allow the patient to detect atypical melanocytic lesions at an early stage. Sun safety practices in Nova Scotia should continue to be encouraged.

Active Learning with Particle Swarm Optimization for Enhanced Skin Cancer Classification Utilizing Deep CNN Models.

Skin cancer is a critical global health issue, with millions of non-melanoma and melanoma cases diagnosed annually. Early detection is essential to improving patient outcomes, yet traditional deep learning models for skin cancer classification are often limited by the need for large, annotated datasets and extensive computational resources. The aim of this study is to address these limitations by proposing an efficient skin cancer classification framework that integrates active learning (AL) with particle swarm optimization (PSO). The AL framework selectively identifies the most informative unlabeled instances for expert annotation, minimizing labeling costs while optimizing classifier performance. PSO, a nature-inspired metaheuristic algorithm, enhances the selection process within AL, ensuring the most relevant data points are chosen. This method was applied to train multiple Convolutional Neural Network (CNN) models on the HAM10000 skin lesion dataset. Experimental results demonstrate that the proposed AL-PSO approach significantly improves classification accuracy, with the Least Confidence strategy achieving approximately 89.4% accuracy while using only 40% of the labeled training data. This represents a substantial improvement over traditional approaches in terms of both accuracy and efficiency. The findings indicate that the integration of AL and PSO can accelerate the adoption of AI in clinical settings for skin cancer detection. The code for this study is publicly available at ( https://github.com/Sayantani-31/AL-PSO ).

Abstract A042: Desmosome mutations in the microenvironment regulate melanoma proliferation

Abstract Desmosomes are transmembrane protein complexes critical for cell-cell adhesion in epithelial tissues and other cell types. In skin cancers like melanoma, epithelial cells called keratinocytes are the predominant cells in the primary melanoma microenvironment, yet it remains largely unknown whether this cell type is subject to genetic alterations during melanoma development and its role in early melanoma progression. In this study, using an integrative analysis of tumor mutations and protein biophysical interactions, we identify a high frequency of genetic alterations in desmosome-related genes in human cancers, with the highest occurrences in cutaneous melanoma. Notably, over 70% of cutaneous melanoma cases exhibit mutations in desmosome genes and desmosome gene mutations are associated with lowered expression of the desmosome complex in melanoma. Using spatial transcriptomics and immunohistochemistry analyses, we find that the decrease in desmosome gene expression predominantly occurs in keratinocytes within the tumor microenvironment rather than in the melanoma cells themselves. To study the functional significance of this alteration in melanoma development, we used a human melanoma/keratinocyte co-culture system using primary melanoma cell lines. Our studies show that knockdown of desmosome genes in keratinocytes markedly increased proliferation of adjacent melanoma cells in melanoma/keratinocyte co-cultures. Additionally, melanoma cell proliferation is enhanced when exposed to media preconditioned by desmosome-deficient keratinocytes. These observations suggest that the gradual accumulation of mutations in desmosome genes within neighboring keratinocytes may create a conducive environment that primes melanoma cells for neoplastic transformation. This study underscores the critical role of genetic alterations in the tumor microenvironment in melanoma progression and highlights the potential for targeting desmosome-related pathways in therapeutic strategies against melanoma. Citation Format: Mohita Tagore. Desmosome mutations in the microenvironment regulate melanoma proliferation [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr A042.

Primary Nasosinus Melanoma: A Case Report

Naso-sinusal mucosal melanoma is a highly aggressive but uncommon tumor. It is often diagnosed late, making treatment complex (surgery and/or radiotherapy---), with a generally poor prognosis. The absence of an established etiological factor and a specific clinical appearance make diagnosis difficult at an early stage. This tumor frequently affects women, with a predilection for the 6th decade of life. In this articl, we report a new case of nasosinus melanoma.

MET amplification correlates with poor prognosis and immunotherapy response as a subtype of melanoma: a multicenter retrospective study

BackgroundMesenchymal epithelial transition factor (MET) variant is an independent prognostic factor for worse prognosis in patients with lung cancer or gastroesophageal adenocarcinoma. MET gene variants can be regarded as a subtype of melanoma but there is a lack of studies regarding the frequency of MET genetic alterations and the efficacy of immunotherapy in melanoma patients. The purpose of this study is to explore potential therapeutic strategies for melanoma subtypes with MET alterations.MethodsA total of 1751 malignant melanomas were analyzed to illustrate the landscape of MET mutations. We collected 55 melanoma cases from multicenter for a retrospective cohort from 2010 to 2023. We analyzed the impact of MET amplification on the efficacy of immunotherapy in the retrospective cohort after propensity score matching (PSM) and a pancancer cohort. CIBERSORT was used to evaluate the immune infiltration.ResultsThere were no instances of MET 14 exon skipping, and only instances of MET amplification were found in the 1751 melanomas and our retrospective cohort. Cox proportional hazards model analysis showed that MET amplification (P = 0.006) was significantly associated with poorer overall survival (OS) in patients who received immunotherapy as the first-line treatment. Compared with patients with MET amplification, patients in the negative control (NC) group had a significantly better OS (P = 0.022) after PSM. Analysis of 1661 pancancer cases with the MSK-IMPACT assay showed that patients receiving immunotherapy in the MET amplification group had a trend toward worse OS than those without MET amplification (P = 0.025).ConclusionsThis database analysis showed that the main type of MET mutation is amplification in malignant melanoma. MET-amplified solid tumors might be considered for targeted therapy, as MET amplification can be regarded as a risk factor affecting the prognosis of patients with tumors treated with immunotherapy.

Tumor Upstaging in Invasive Melanoma is Associated with Changes in Clinical Management and Worse Prognosis

BackgroundThe clinical implications and prognostic outcomes associated with tumor upstaging in invasive melanoma have not been well established. ObjectiveTo determine the frequency of tumor upstaging in invasive melanoma, identify risk factors, and assess its impact on clinical management and outcomes. MethodsA retrospective study using data from a statewide Surveillance Endpoints and End Results -affiliated cancer registry between 2014 and 2018 was performed. Multivariable hazard models were used to determine factors associated with upstaging, and overall/melanoma-specific mortality. ResultsOf 4,391 cases of invasive melanoma, 9.4% were upstaged. Significant risk factors on univariate analysis included older age, male sex, non-White race, head/neck location, larger clinical size, incisional and/or punch biopsy method, and increasing time between biopsy and surgical excision. Significant risk factors on multivariable analysis included head/neck location and higher pathologic T stage. Tumor upstaging dictated a change in clinical management in over half of cases, however, only 37.4% fulfilled the recommendation for additional treatment. Upstaged melanomas experienced higher overall (36.0% versus 19.5%; p<0.001) and melanoma-specific (9.0% versus 2.9%; p<0.001) mortality compared to non-upstaged tumors. LimitationsSingle-center retrospective study. ConclusionsTumor upstaging in invasive melanoma is associated with worse survival outcomes, possibly due to shortfalls in clinical management.

Genetic Characteristics of Cutaneous, Acral, and Mucosal Melanoma in Japan.

Acral and mucosal melanomas are more prevalent in Asians than in Caucasians, unlike cutaneous melanomas, which are predominant in Caucasians. Recent studies have suggested that non-Caucasian cutaneous melanomas responded less to immune checkpoint inhibitors, highlighting the need for genetic profiling across ethnicities. This study aimed to elucidate the genetic characteristics of Japanese melanomas, which is an under-researched topic. Single-nucleotide variants, indels, and copy number alterations in 104 Japanese melanoma patients (37 cutaneous, 52 acral, and 15 mucosal) were analyzed using custom panel sequencing. Driver events were detected in 94% of the cases. Among cutaneous melanoma cases, 76% had BRAF mutations, and 8% had NRAS mutations. In acral melanoma, BRAF (9%), NRAS (17%), KRAS (8%), KIT (19%), and NF1 (7%) mutations were detected. Major driver mutations in mucosal melanoma were detected in NRAS, KRAS, NF1, PTEN, GNAQ, and KIT. The median tumor mutational burden across all melanoma types was 4.6 mutations/Mb, with no significant difference between the cutaneous and acral/mucosal types. Of the 21 patients with both primary and metastatic lesions, 11 showed distinct mutations in each. Potentially actionable mutations were detected in 58 patients in addition to BRAF V600E/K mutations in 31. This study highlights distinct genetic abnormalities and actionable alterations in Japanese melanoma patients. This suggests a lower tumor mutational burden in East Asian cutaneous melanoma, which may affect the efficacy of immune checkpoint inhibitors. The heterogeneity of driver mutations across and within individuals highlights the need for personalized treatment approaches.

The first case of primary malignant melanoma of the esophagus to achieve pathologic complete response after preoperative ipilimumab + nivolumab followed by resection.

Primary malignant melanoma of the esophagus is a rare disease with a poor prognosis. Surgical resection is common, but there is no consensus on perioperative treatment. Studies have reported the efficacy of programmed cell death-1 inhibitors (e.g., nivolumab, pembrolizumab) and anti-cytotoxic T-lymphocyte-associated antigen 4 agents (e.g., ipilimumab) in treating malignant melanoma. Here, we present the first case of primary malignant melanoma of the esophagus with lymph node metastases treated with nivolumab and ipilimumab followed by resection, achieving a pathologic complete response. A 75-year-old man presented with dysphagia. Esophagogastroduodenoscopy revealed a black, elevated lesion in the mid-thoracic esophagus. Biopsy confirmed primary malignant melanoma of the esophagus, showing tumor cells with melanin deposition, positive for HBM45 and S-100 staining. Computed tomography showed enlarged lymph nodes in the subclavian and mediastinum regions, suggesting metastases. After two courses of preoperative chemotherapy with ipilimumab and nivolumab, which significantly shrank the tumor, the patient underwent robot-assisted subtotal esophagectomy and 3-field lymph node dissection. Histopathological examination revealed no tumors or lymph node metastases, confirming a pathologic complete response. Given the rarity and poor prognosis of primary malignant melanoma of the esophagus, this case provides valuable insights for treatment strategies.

A unique case of cutaneous melanoma: case report and literature review

A unique case of cutaneous melanoma: case report and literature review

Current Insights into the Role of UV Radiation-Induced Oxidative Stress in Melanoma Pathogenesis.

Cutaneous melanoma accounts for the majority of skin cancer-related deaths, and its incidence increases each year. The growing number of melanoma cases, especially in advanced stages, poses a significant socio-medical challenge throughout the world. Extensive research on melanoma pathogenesis identifies UV radiation as the most important factor in melanocytic transformation. Oxidative effects of UV irradiation exert their influence on melanoma pathogenesis primarily through modification of nucleic acids, proteins, and lipids, further disrupting cellular signaling and cell cycle regulation. Its effects extend beyond melanocytes, leading to immunosuppression in the exposed skin tissue, which consequently creates conditions for immune surveillance evasion and further progression. In this review, we focus on the specific molecular changes observed in the UV-dependent oxidative stress environment and their biological consequences in the course of the disease, which have not been considered in previous reviews on melanoma. Nonetheless, data show that the exact role of oxidative stress in melanoma initiation and progression remains unclear, as it affects cancerous cells differently depending on the specific context. A better understanding of the pathophysiological basis of melanoma development holds promise for identifying potential targets, which could lead to effective melanoma prevention strategies.