Localized cutaneous squamous cell carcinoma (cSCC) has a favorable prognosis, unlike advanced disease, especially with clinical perineural invasion (PNI), which poses substantial management challenges due to aggressivity and higher recurrence, metastasis, and mortality risks. PNI, a high-risk staging feature, has worse outcomes, particularly when clinically evident rather than incidental. Clinical PNI (cPNI) is evident by clinical symptoms (such as pain, paresthesia, or motor deficits) or radiologic findings, whereas incidental PNI (iPNI) is identified only histologically without associated symptoms or radiologic evidence. PNI remains a novel area with varying practice patterns across institutions. Improving risk stratification and tailoring multidisciplinary approaches are critical for optimizing outcomes. Our review outlines clinical practice patterns at our institution, providing insights into managing cSCC with PNI, focusing on diagnosis, imaging, staging, and emerging immunotherapies. A structured search was conducted using the terms “perineural invasion,” “cutaneous squamous cell carcinoma,” and “immunotherapy.” cPNI has a poor prognosis and requires nuanced clinical decision-making. Surgery and radiation remain central to management. Adjuvant therapy offers substantial survival benefit in cSCC with PNI, with improved disease-free and overall survival compared with surgery alone, supporting its use in appropriately selected high-risk patients. Traditional systemic therapies, including cisplatin and cetuximab, remain foundational but have shown only moderate response rates and limited durability in advanced or neurotropic cSCC. In contrast, immunotherapy—now preferred for advanced or unresectable cases—has transformed management, with programmed cell death protein-1 (PD-1) inhibitors showing promising results (up to 69% response rate) and disease stabilization. Neoadjuvant immunotherapy may enable tumor downstaging, improve radiation planning, and reduce surgical morbidity. Imaging for squamous cell carcinoma (SCC) with PNI aids staging and surveillance, but symptoms remain key for detecting recurrence. Our multidisciplinary approach emphasizes personalized care. Larger trials are needed to define the optimal role and sequencing of immunotherapy in this high-risk patient population.
局限性皮肤鳞状细胞癌（cSCC）预后良好，而进展期疾病则不然，尤其是伴有临床神经周围侵犯（PNI）时，因其侵袭性强、复发、转移及死亡风险更高，给临床管理带来巨大挑战。PNI作为高风险分期特征，其预后更差，在临床显性表现时尤为明显，而非偶然发现。临床PNI（cPNI）通过临床症状（如疼痛、感觉异常或运动功能障碍）或影像学表现得以明确，而偶然性PNI（iPNI）则仅在组织学检查中发现，无相关症状或影像学证据。PNI仍是一个新兴领域，各机构的诊疗模式存在差异。完善风险分层并制定个体化多学科综合治疗方案对优化预后至关重要。本文综述了我院的临床实践模式，重点围绕PNI相关cSCC的诊断、影像学检查、分期及新兴免疫疗法，为临床管理提供见解。我们使用“神经周围侵犯”“皮肤鳞状细胞癌”及“免疫疗法”等关键词进行了系统性文献检索。cPNI预后较差，需进行精细的临床决策。手术与放疗仍是治疗的核心手段。辅助治疗可为PNI阳性cSCC患者带来显著的生存获益，与单纯手术相比，其无病生存期和总生存期均有所改善，支持在经恰当筛选的高危患者中应用该疗法。传统全身治疗（包括顺铂和西妥昔单抗）仍是基础方案，但在晚期或嗜神经性cSCC中仅显示中等缓解率且疗效持续时间有限。相比之下，免疫疗法——现已成为晚期或不可切除病例的首选方案——已彻底改变了治疗格局，程序性细胞死亡蛋白-1（PD-1）抑制剂显示出令人鼓舞的疗效（缓解率高达69%）和疾病稳定作用。新辅助免疫治疗可能实现肿瘤降期、优化放疗计划并降低手术并发症风险。PNI相关鳞状细胞癌（SCC）的影像学检查有助于分期和监测，但症状仍是检测复发的关键。我们的多学科诊疗模式强调个体化治疗。未来需要更大规模的临床试验来确定免疫疗法在这一高危人群中的最佳应用时机和序贯策略。
Immunotherapy and Radiation for Clinical Perineural Invasion in Cutaneous Squamous Cell Carcinoma
肿瘤(癌症)患者之家