Non-melanomatous cutaneous spindle cell neoplasms are a rare group of malignancies that present a diagnostic challenge, and for which there is a lack of consensus on how to best manage patients with advanced disease and only limited reports of immune-checkpoint inhibitor (ICI) responses. In this study, we performed a single-center retrospective review of treatment outcomes for all advanced non-melanomatous cutaneous spindle cell neoplasms treated with ICIs. Blinded histopathology reviews occurred to confirm each diagnosis. Comprehensive tumour profiling included whole exome sequencing for tumour mutational burden (TMB) and ultraviolet(UV) signatures, and immunohistochemistry for immune-cell infiltration (CD4/CD3/CD8/CD103/CD20) and immune-checkpoint expression (PD-L1/LAG3/TIGIT). Seven patients were identified. The objective response rate was 86% (6/7) with five complete responses (CR). Responses were durable with two patients in CR > 30 months after ICI commencement. All patients had high TMB and UV signatures. One patient had PD-L1 100% (combined positive score) with abundant immune-cell infiltration and LAG3 expression. In advanced non-melanomatous cutaneous spindle cell neoplasms, excellent responses to ICIs with durable disease control were observed. ICIs are worthy of further exploration in these patients. UV signatures and high TMB could be used to help select patients for treatment.
非黑色素瘤皮肤梭形细胞肿瘤是一组罕见的恶性肿瘤，其诊断具有挑战性，且对于晚期患者的最佳治疗方案缺乏共识，关于免疫检查点抑制剂（ICI）治疗反应的报道也十分有限。本研究对单中心所有接受ICI治疗的晚期非黑色素瘤皮肤梭形细胞肿瘤患者的治疗结果进行了回顾性分析。通过盲法组织病理学复核以确认诊断。全面的肿瘤分析包括全外显子测序以评估肿瘤突变负荷（TMB）和紫外线（UV）特征，以及免疫组化检测免疫细胞浸润（CD4/CD3/CD8/CD103/CD20）和免疫检查点表达（PD-L1/LAG3/TIGIT）。共纳入7例患者。客观缓解率为86%（6/7），其中5例达到完全缓解（CR）。缓解持久，2例患者在开始ICI治疗后超过30个月仍保持CR。所有患者均具有高TMB和UV特征。1例患者PD-L1表达为100%（联合阳性评分），并伴有丰富的免疫细胞浸润和LAG3表达。在晚期非黑色素瘤皮肤梭形细胞肿瘤中，观察到ICI治疗可带来优异的缓解和持久的疾病控制。ICI值得在此类患者中进一步探索。UV特征和高TMB可用于帮助筛选适合治疗的患者。
肿瘤(癌症)患者之家