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结膜黑色素瘤:对临床特征、基因改变及现代治疗方法的全面见解

Conjunctival melanoma: comprehensive insights into clinical features, genetic alterations, and modern treatment approaches.

作者信息

Kaštelan Snježana, Mrazovac Zimak Danijela, Ivić Luka, Gverović Antunica Antonela, Nikuševa-Martić Tamara

机构信息

Department of Ophthalmology, School of Medicine University of Zagreb, University Hospital Dubrava, Zagreb, Croatia.

Department of Ophthalmology, University Hospital Centre Zagreb, Zagreb, Croatia.

出版信息

Pathol Oncol Res. 2025 Aug 4;31:1612085. doi: 10.3389/pore.2025.1612085. eCollection 2025.

Abstract

Conjunctival melanoma (CoM) is a rare and aggressive ocular surface malignancy, characterised by increasing incidence, clinical complexity, and substantial challenges in diagnosis and treatment. This review consolidates current knowledge on epidemiology, clinical presentation, genetic and epigenetic foundations, molecular mechanisms, emerging therapeutic strategies, and prognostic factors for localised and metastatic CoM. CoM exhibits distinct biological behaviours, sharing molecular traits with cutaneous and mucosal melanomas, while significantly diverging from uveal melanoma. Key genetic alterations include mutations in BRAF, NF1, and PTEN, elevated mTOR expression, and specific miRNA profiles, which influence tumour progression and response to therapy. Recent advances in treatment, especially immune checkpoint inhibitors such as CTLA-4 and PD-1 receptor inhibitors, along with targeted therapies like BRAF and MEK inhibitors, have led to marked improvements in outcomes for advanced cases. Emerging strategies, including dendritic cell vaccines and epigenetic therapies, hold considerable promise in addressing ongoing clinical challenges. This review integrates case studies and clinical research to demonstrate the practical application of these therapies, highlighting their efficacy and limitations. Combining clinical expertise, genetic insights, and the latest therapeutic developments, offers a comprehensive overview of CoM, underscoring the critical role of a multidisciplinary approach in optimising diagnosis, management, and prognosis to improve patient outcomes.

摘要

结膜黑色素瘤(CoM)是一种罕见且侵袭性强的眼表恶性肿瘤,其特点是发病率不断上升、临床情况复杂,以及在诊断和治疗方面存在重大挑战。本综述整合了关于局限性和转移性CoM的流行病学、临床表现、遗传和表观遗传基础、分子机制、新兴治疗策略以及预后因素的现有知识。CoM表现出独特的生物学行为,与皮肤和黏膜黑色素瘤具有共同的分子特征,同时与葡萄膜黑色素瘤有显著差异。关键的基因改变包括BRAF、NF1和PTEN的突变、mTOR表达升高以及特定的miRNA谱,这些都会影响肿瘤进展和对治疗的反应。治疗方面的最新进展,特别是免疫检查点抑制剂如CTLA-4和PD-1受体抑制剂,以及BRAF和MEK抑制剂等靶向疗法,已使晚期病例的治疗效果有了显著改善。包括树突状细胞疫苗和表观遗传疗法在内的新兴策略,在应对当前临床挑战方面具有很大潜力。本综述结合病例研究和临床研究,展示了这些疗法的实际应用,突出了它们的疗效和局限性。综合临床专业知识、遗传学见解和最新治疗进展,全面概述了CoM,强调了多学科方法在优化诊断、管理和预后以改善患者结局方面的关键作用。

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