Melanoma Research最新文献

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but are associated with a range of immune-related adverse events (irAEs). While gastrointestinal irAEs are well-recognized, cholecystitis remains an exceedingly rare and poorly understood complication. We present a rare case of ir-cholecystitis in a patient with melanoma following combination therapy with nivolumab and ipilimumab. The patient developed acute gastrointestinal symptoms and fever shortly after the second dose, leading to hospitalization. Laboratory evaluation and imaging studies confirmed cholecystitis without gallstones, while given the timing, clinical context, and imaging findings, immune-related cholecystitis was suspected. Initial conservative management with intravenous hydration, antibiotics, and bowel rest was insufficient, necessitating corticosteroid therapy, which led to rapid clinical improvement. This case underscores the importance of considering rare irAEs, such as ir-cholecystitis, in patients receiving ICIs - even in the absence of classical symptoms. Due to the scarcity of reported cases and the absence of established treatment guidelines, management remains empirical. Our experience, together with a review of the available literature, supports the potential role of corticosteroids in refractory cases, though further research is needed to guide standardized therapeutic approaches.

MRI is the preferred method for evaluating hepatic metastases from uveal melanoma. This study was aimed to predict the progression of hepatic metastases from uveal melanoma using gadoxetic acid-enhanced MRI findings. This retrospective study included patients (≥18 years) with uveal melanoma who underwent gadoxetic acid-enhanced liver MRI for evaluation of hepatic metastasis between 2010 and 2023 at two tertiary referral centers. Radiologists retrospectively evaluated the baseline MRI findings of the included patients and assessed tumor responses on follow-up studies according to the Response Evaluation Criteria in Solid Tumors version 1.1. Independent prognostic factors for the time to progression of hepatic metastases were identified using Cox proportional regression analysis. A nomogram based on the multivariable analysis was created and internally validated. A total of 65 patients (mean age, 61.5 ± 14.0 years; 36 men and 29 women) were included. Multivariable analysis revealed that the size of the largest tumor [hazard ratio (HR): 1.028, P  = 0.005], precontrast T1 hypointensity (HR: 3.033, P  = 0.016), mild to moderate T2 hyperintensity (HR: 3.680, P  = 0.001), and hepatobiliary phase hypointensity (HR: 3.370, P  = 0.020) were significantly associated with shorter time to progressions of hepatic metastases from uveal melanoma. An internally validated nomogram developed using these MRI findings demonstrated excellent agreement between the predicted probabilities and actual rates of tumor progression, as shown by the calibration plots, with a Harrell's c-index of 0.807. Gadoxetic acid-enhanced MRI findings may be useful in predicting the progression of hepatic metastases from uveal melanoma.

Thrombocytopenia is a well-documented hematologic consequence in patients undergoing percutaneous hepatic perfusion (PHP) to treat hepatic metastases secondary to ocular melanoma. In this case, four sequential PHP procedures resulted in significant thrombocytopenia, reaching 92, 75, 64, and 68% of baseline values. The thrombocytopenia was transient and spontaneously resolved within weeks. During the third procedure, a rotational thromboelastometry analysis was performed. We observed no clinically significant bleeding events, and rotational thromboelastometry analysis demonstrated a modest 11% reduction in maximum clot firmness, indicating preserved hemostatic function. These findings suggest that thrombocytopenia associated with PHP does not necessarily result in clinically relevant bleeding, and prophylactic platelet transfusion may not be warranted. Instead, perioperative coagulation monitoring utilizing viscoelastic hemostatic assays provide a dynamic, real-time assessment of hemostatic integrity, facilitating goal-directed perioperative management and intervention during PHP.

Host genetic ancestry plays an important role in shaping somatic mutation landscapes and may influence therapeutic outcomes as well as the risk of developing treatment-related adverse events. As genetic ancestry has been associated with differential susceptibility to melanoma subtypes, distinct somatic mutation frequencies and variable responses to immune checkpoint inhibitors warrant further investigation. This study investigated the genetic ancestry of a North American melanoma population using banked biospecimens from 744 patients enrolled in the ECOG-ACRIN E1609 phase III clinical trial (stages IIIB, IIIC, M1a, or M1b). Peripheral blood samples were genotyped using the Illumina Infinium Global Screening Array v3.0 + Multi-Disease BeadChip, followed by quality control, integration with reference dataset, and linkage disequilibrium pruning (198 064 single nucleotide polymorphisms). Dimensionality reduction was performed with Uniform Manifold Approximation and Projection analysis, and genetic ancestry was inferred using unsupervised ADMIXTURE models. Most patients (728 of 744; 97.8%) had predominant European (EUR) ancestry, followed by minor representation from admixed American (12 of 744; 1.6%) and East Asian (4 of 744; 0.5%) populations. Moreover, based on ADMIXTURE model (K = 5), 96.9% of participants had an estimated EUR ancestry proportion exceeding 80%. Self-reported race and ethnicity demonstrated strong concordance with genetically inferred ancestry, although a small subset of participants exhibited discordant ancestry components. Participants who self-identified as Hispanic exhibited mixed EUR-Admixed American ancestry components. Most patients represented predominant EUR ancestry, with limited representation of non-EUR populations. Integrating ancestry-informed genomic analyses will enhance understanding of melanoma susceptibility, improve prediction of immune-related adverse events, and support the development of tailored immunotherapy strategies.

Gastric metastasis of melanoma is a rare event associated with poor prognosis and short survival. Patients usually present with gastrointestinal symptoms, and in the absence of a prior history of primary tumor elsewhere, this can pose a diagnostic challenge. Melanoma has an inherent property to show transdifferentiation, which is retained even at the site of metastasis. Osteosarcomatous differentiation in melanoma is extremely uncommon, restricted to isolated case reports in the literature. A 79-year-old male patient, a known case of gastric mucosa-associated lymphoid tissue lymphoma, presented with generalized weakness and dysphagia of 15 days duration. Clinical impression was of lymphoma progression. Upper gastrointestinal endoscopy showed a 4 × 5 cm proliferative growth in the gastric fundus. Biopsy of the lesion was suggestive of melanoma with osteosarcomatous differentiation. It was regarded as metastasis as patient had a history of acral lentiginous melanoma 2 years ago. Patient was, however, willing only for palliative treatment. Patient succumbed to septic shock within 2 months of diagnosis. Herein, we report a case of gastric metastasis of melanoma with osteosarcomatous differentiation and discuss the clinical presentation, radiologic findings, challenges in histopathological diagnosis, and treatment options for this unusual entity.

Paraneoplastic syndromes (PNS), manifestations of systemic effects of a tumor, are rare in patients with melanoma. We describe two cases of patients who presented with rare PNS, fever, and cutaneous melanosis, that resolved after treatment of melanoma. The first patient, a 64-year-old woman, presented with high fever. After diagnostic evaluation, infectious causes were excluded and the patient was diagnosed with metastatic melanoma. The fever was attributed as a PNS. After surgical removal of a large necrotic intramuscular metastasis in her leg, her fever dissolved completely, allowing continuation of immunotherapy. The second patient, a 76-year-old man, presented with a grayish skin pigmentation and dark urine and referred to the gastroenterologist. He was diagnosed with metastatic melanoma and his symptoms were recognized as cutaneous melanosis. After initiation of immunotherapy, the pigmentation gradually faded. This case series show two distinct and rare paraneoplastic phenomena in melanoma. Early recognition and tailored management of PNS is crucial, as these syndromes may obscure underlying malignancy or influence patient's overall condition. In our cases, PNS resolved after tumor-directed treatment.

FGD1 is an X-linked gene and acts as a guanine nucleotide exchange factor that activates guanosine triphosphatase Cdc42 and influences cell cycle progression, cell morphology, motility, and extracellular matrix degradation. In this study, we aim to understand FGD1 function in melanoma to better understand the correlation between poor survival and high FGD1 expression identified in The Cancer Genome Atlas messenger RNA data, especially in patients with BRAF mutations. FGD1 knockdown in BRAF V600E-mutated melanoma cell lines reduces cell proliferation and induces secondary resistance to BRAF inhibition, while increasing sensitivity to p21-activated kinase inhibition. Markedly, when FGD1 knockdown becomes ineffective, resistant cells not only restore endogenous FGD1 expression but also exhibit upregulation of epidermal growth factor receptor and phospho-p21-activated kinase, both known markers of BRAF inhibition resistance, highlighting a shift toward an adaptive resistance phenotype. Furthermore, we show that secondary resistance induced by prolonged exposure of melanoma cells to BRAF inhibitor is associated with reduced FGD1 levels. These findings highlight the importance of FGD1 in melanoma progression and the acquisition of secondary resistance, positioning the FGD1-mediated signaling pathway as a putative therapeutic target.

To compare ultrasonographic and histopathological measurements of tumor size in enucleated eyes with choroidal melanoma and to evaluate the prognostic significance of tumor dimensions and morphological characteristics in a Serbian cohort. This retrospective study included 59 consecutive patients with histopathologically confirmed choroidal melanoma who underwent enucleation at the University Eye Hospital, Clinical Centre of Serbia. All ultrasonographic examinations, surgical procedures, and histopathological assessments were performed by single dedicated subspecialists. Preoperative B-scan ultrasonography was used to measure tumor base diameter and thickness, which were compared with postoperative macroscopic histopathological dimensions using paired statistical tests, Bland-Altman analysis, and intraclass correlation coefficients (ICC). Survival outcomes were assessed using Pearson and Spearman correlations and Kaplan-Meier analysis. Patients were followed for a minimum of 1 year, with some monitored for up to 5 years. Data are presented as mean ± SD. The mean ultrasonographic base diameter and thickness were 14.63 ± 3.98 and 10.34 ± 3.54 mm, respectively, compared with 18.04 ± 6.54 and 10.55 ± 3.72 mm on pathology. Bland-Altman analysis demonstrated good agreement for tumor thickness (mean difference 0.2 mm; limits of agreement -5.5 to +5.5 mm) and acceptable agreement for base diameter (mean difference 3.4 mm; limits -8.2 to +15.1 mm). ICC indicated moderate agreement for base diameter (0.501) and excellent agreement for thickness (0.843). Pathological thickness correlated significantly with shorter metastasis-free survival (r = -0.293, P = 0.024). Kaplan-Meier analysis showed significantly poorer survival for patients with T3-T4 tumors. Ultrasonography provides a reliable preoperative estimation of choroidal melanoma size, particularly for tumor thickness, although histopathology remains essential for prognostication. Survival patterns in this cohort align with international data, highlighting the relevance of tumor thickness and morphology and emphasizing the value of data from an underrepresented region.

Given the therapeutic challenges posed by the unique molecular genetic mechanisms and immune-privileged microenvironment of uveal melanoma, this review aims to systematically evaluate the latest research on the molecular genetics and immune microenvironment of uveal melanoma, providing insights for translational research and the development of clinical treatment strategies. In gene therapy, a recombinant adeno-associated viral vector engineered to target the oncogenic GNAQ Q209L mutation achieved single-base-pair precision knockdown, offering a novel approach to overcoming the complex therapeutic challenges posed by downstream signaling in this pathway. Regarding tumor metastasis, BAP1 inactivation induces a low-metabolic state by inhibiting the mTORC1/p70S6K1 pathway, enabling tumor cells to adapt to nutritional stress during metastasis. Concurrently, BAP1 mutations regulate cell adhesion molecules and suppress the nuclear factor-κB pathway, collectively establishing an immunosuppressive microenvironment that drives the highly metastatic nature of uveal melanoma. The predictive value of chromosome 8q amplification was shown to be context-dependent, with high-risk subgroups exhibiting extremely poor prognosis, particularly in BAP1-mutant cases. At the epigenetic level, miR-181a-5p demonstrates therapeutic potential by inducing uveal melanoma apoptosis through targeting GNAQ and AKT3. Clinically, the bispecific T-cell redirection drug Tebentafusp has achieved a major breakthrough in metastatic uveal melanoma immunotherapy. This review systematically elucidates key driver gene mutations, chromosomal abnormalities, epigenetic alterations, and the unique immunosuppressive microenvironment of uveal melanoma, providing new insights into mechanisms of treatment resistance and guiding the development of innovative therapeutic strategies.

Longitudinal melanonychia is a pigmented band on the nail plate that may be caused by both benign or malignant changes. There is often concern that the pigment may indicate subungual melanoma or melanoma in-situ and the diagnosis can be challenging. Consequently, a scoring system that aids clinicians in identifying high-risk lesions will be beneficial. This was a retrospective, cohort analysis of patients undergoing nail unit biopsies, with clinical images available, at a tertiary skin cancer unit. Patient images were reviewed by skin cancer specialists, and a new scoring system was applied. Scoring characteristics were: nail dystrophy, more than 40% nail involvement, Hutchinson's sign, and asymmetry. The number of nails involved (i.e. single or multiple) and the change over time were also obtained from the clinical notes. Median scores for each patient were then calculated, and a receiver operating characteristic curve was utilized to identify the score with the highest sensitivity and specificity. Seven malignant and 33 benign lesions were included. Utilizing a score of greater than or equal to 4, the London Melanonychia Assessment Tool (LMAT) had a sensitivity of 86% and a specificity of 73%. There is increasing pressure on skin cancer units, with greater numbers of urgent referrals. Although other tools for the assessment of melanonychia have been published, the LMAT includes a wide variety of lesions, making it transferable to clinical practice. The LMAT may help clinicians in identifying lesions that are higher risk and therefore should undergo biopsy or closer monitoring.