Background/Objectives:Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, with a lifetime risk of 14–20% that is rising every year. Although prognosis for cSCC is generally good, certain high-risk features of cSCC portend increased rates of nodal and distant metastasis, recurrence, and disease-specific mortality. One such high-risk factor is perineural invasion (PNI), which is broadly defined as the invasion of cancer into and around nerves. Compared to other high-risk factors, PNI presence is associated with the highest risk for locoregional and distant metastasis. Still, the mechanisms underlying the pathogenesis of PNI remain poorly understood. Recent studies suggest the migration and invasion of tumors into nerves is a result of complex molecular crosstalk within the tumor-nerve microenvironment, wherein the milieu of signaling molecules simultaneously promote neuronal growth and tumor cell invasion.Methods:Understanding the molecular and cellular mechanisms that promote PNI will lead to future developments of targeted therapies that may improve locoregional control and survival.Results/Conclusions:In our article, we aim to provide a comprehensive review of recent findings about the pathogenesis of PNI, clinical implications of PNI-positive disease in cSCC, available treatment modalities, and potential future therapeutic targets.
背景/目的：皮肤鳞状细胞癌（cSCC）是第二常见的皮肤癌，终生患病风险达14-20%，且呈逐年上升趋势。尽管cSCC的预后通常良好，但其某些高风险特征预示着淋巴结转移、远处转移、复发及疾病特异性死亡率的增加。神经周围侵犯（PNI）即属此类高风险因素，其广义定义为癌细胞侵入神经及其周围组织。相较于其他高风险因素，PNI的存在与最高的局部区域转移和远处转移风险相关。然而，PNI发病机制的内在机理仍不甚明确。近期研究表明，肿瘤向神经组织的迁移和侵袭是肿瘤-神经微环境中复杂分子相互作用的结果，其中信号分子环境同时促进神经元生长和肿瘤细胞侵袭。 方法：阐明促进PNI的分子与细胞机制，将推动靶向治疗的发展，从而可能改善局部区域控制并提高生存率。 结果/结论：本文旨在全面综述PNI发病机制的最新发现、PNI阳性cSCC的临床意义、现有治疗模式以及未来潜在的治疗靶点。
Perineural Invasion in Head and Neck Cutaneous Squamous Cell Carcinoma
肿瘤(癌症)患者之家