隐性营养不良性大疱性表皮松解症（RDEB）是一种罕见的严重遗传性皮肤病，其特征是皮肤和粘膜脆弱，导致水疱形成。 RDEB 患者最严重的并发症是皮肤鳞状细胞癌 (SCC)，导致过早死亡。大量证据表明，宽松的肿瘤微环境 (TME) 是 RDEB 患者鳞状细胞癌发展的驱动因素。在一组 RDEB 患者中，我们描述了 RDEB-SCC 的免疫特征，并将其与临床、组织病理学和预后特征进行比较。根据 RDEB-SCC 的发生情况（首次发病或复发）以及根据侵袭性的临床、组织病理学参数进行分级，将 RDEB-SCC 细分为四组。对来自 20 名 RDEB 患者的 38 个 SCC 进行了分析。 5 名 RDEB 患者在诊断出第一个 SCC 后经历了不利的病程，早期复发或转移，而 15 名患者出现多个 SCC 而没有转移。高危原发性 RDEB-SCC 在肿瘤微环境中表现出较高的中性粒细胞与淋巴细胞比率，并且中性粒细胞胞外陷阱 (NET) 的比例增加。此外，瓜氨酸组蛋白 H3（NET 的标志物）在患有高危原发性 SCC 的 RDEB 患者血清中增加，表明组蛋白 H3 的这种修饰形式可能作为 RDEB-SCC 不良预后的潜在血液标志物。

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare severe hereditary skin disease characterized by skin and mucosa fragility, resulting in blister formation. The most severe complication in RDEB patients is the development of cutaneous squamous cell carcinoma (SCC), leading to premature death. There is a great deal of evidence suggesting a permissive tumor microenvironment (TME) as a driver of SCC development in RDEB patients. In a cohort of RDEB patients, we characterized the immune profiles of RDEB-SCCs and compared them with clinical, histopathological, and prognostic features. RDEB-SCCs were subdivided into four groups based on their occurrence (first onset or recurrences) and grading according to clinical, histopathological parameters of aggressiveness. Thirty-eight SCCs from 20 RDEB patients were analyzed. Five RDEB patients experienced an unfavorable course after the diagnosis of the first SCC, with early recurrence or metastasis, whereas 15 patients developed multiple SCCs without metastasis. High-risk primary RDEB-SCCs showed a higher neutrophil-to-lymphocyte ratio in the tumor microenvironment and an increased proportion of neutrophil extracellular traps (NETs). Additionally, citrullinated histone H3, a marker of NETs, was increased in the serum of RDEB patients with high-risk primary SCC, suggesting that this modified form of histone H3 may serve as a potential blood marker of unfavorable prognosis in RDEB-SCCs.