Background: Langerhans cell histiocytosis (LCH) is a rare and highly heterogeneous histiocytosis. There are currently few studies examining the correlation between molecular profiling and clinical phenotype or outcome in adult patients with LCH. The objective of this study was to characterize the genomic landscape of adult LCH and correlate molecular findings with clinical features and patient outcomes. Methods: This study included 254 patients aged ≥18 years with biopsy-proven LCH from January 2000 to December 2023. All patients underwent next-generation sequencing (NGS) or fluorescence quantitative PCR (qPCR) for the BRAFV600E mutation. Patient demographics, disease characteristics and treatments were collected through electronic medical records. Patient outcomes were collected through clinical and telephone follow-up. Results: Overall, 254 patients were enrolled. MAPK/PI3K pathway alterations were observed in 77.6%（n=197）of the patients. BRAFV600E mutation was the most common (30.7%, n=78), followed by BRAFindel (18.1%, n=46) andMAP2K1 mutations (12.6%, n=32). The proportion of BRAFindel was much higher in patients with MS involvement than single system disease (24.5% vs 6.6%, p＜0.001). In overall patients, BRAFindel was associated with inferior overall survival (3-year OS 89.6% vs 99.0%, p=0.014) and progression-free survival (3-year PFS 50.0% vs 78.6%, p＜0.001). In MS LCH patients, BRAFindel was associated to worse PFS (3-year PFS 47.8% vs 76.0%, p=0.001). Conclusions: This large study provides molecular and clinical pathologic characterization of adult LCH. BRAFindel was highly correlated with MS LCH, and was associated to worse outcome.

中文翻译：

---

朗格汉斯细胞组织细胞增生症成年患者的 BRAF 缺失与多系统疾病和不良结局相关


背景：朗格汉斯细胞组织细胞增生症 （LCH） 是一种罕见且高度异质性的组织细胞增生症。目前很少有研究检查成年 LCH 患者的分子分析与临床表型或结果之间的相关性。本研究的目的是表征成人 LCH 的基因组景观，并将分子发现与临床特征和患者预后相关联。方法： 本研究包括 2000 年 1 月至 2023 年 12 月的 254 例年龄在 ≥18 岁、经活检证实为 LCH 的患者。所有患者均接受了 BRAFV600E 突变的下一代测序 （NGS） 或荧光定量 PCR （qPCR）。通过电子病历收集患者人口统计学、疾病特征和治疗。通过临床和电话随访收集患者结局。结果： 共纳入 254 例患者。在 77.6%（n=197） 的患者中观察到 MAPK/PI3K 通路改变。BRAFV600E突变最常见 （30.7%，n=78），其次是 BRAFindel （18.1%，n=46） 和 MAP2K1 突变 （12.6%，n=32）。MS 受累患者中 BRAFindel 的比例远高于单一系统疾病 （24.5% vs 6.6%，p<0.001）。在总体患者中，BRAFindel 与较差的总生存期 （3 年 OS 89.6% vs 99.0%，p=0.014） 和无进展生存期 （3 年 PFS 50.0% vs 78.6%，p<0.001） 相关。在 MS LCH 患者中，BRAFindel 与较差的 PFS 相关 （3 年 PFS 47.8% vs 76.0%，p=0.001）。结论： 这项大型研究提供了成人 LCH 的分子和临床病理特征。BRAFindel 与 MS LCH 高度相关，并且与较差的结局相关。