Abstract：
Histiocytic neoplasms are diverse clonal haematopoietic disorders, and clinical disease is mediated by tumorous infiltration as well as uncontrolled systemic inflammation. Individual subtypes include Langerhans cell histiocytosis (LCH), Rosai-Dorfman-Destombes disease (RDD) and Erdheim-Chester disease (ECD), and these have been characterized with respect to clinical phenotypes, driver mutations and treatment paradigms. Less is known about patients with mixed histiocytic neoplasms (MXH), that is two or more coexisting disorders. This international collaboration examined patients with biopsy-proven MXH with respect to component disease subtypes, oncogenic driver mutations and responses to conventional (chemotherapeutic or immunosuppressive) versus targeted (BRAF or MEK inhibitor) therapies. Twenty-seven patients were studied with ECD/LCH (19/27), ECD/RDD (6/27), RDD/LCH (1/27) and ECD/RDD/LCH (1/27). Mutations previously undescribed in MXH were identified, including KRAS, MAP2K2, MAPK3, non-V600-BRAF, RAF1 and a BICD2-BRAF fusion. A repeated-measure generalized estimating equation demonstrated that targeted treatment was statistically significantly (1) more likely to result in a complete response (CR), partial response (PR) or stable disease (SD) (odds ratio [OR]: 17.34, 95% CI: 2.19-137.00, p = 0.007), and (2) less likely to result in progression (OR: 0.08, 95% CI: 0.03-0.23, p < 0.0001). Histiocytic neoplasms represent an entity with underappreciated clinical and molecular diversity, poor responsiveness to conventional therapy and exquisite sensitivity to targeted therapy.
摘要：
组织细胞肿瘤是多种克隆性造血疾病，和临床疾病是由肿瘤浸润以及不受控制的全身性炎症介导的。个体亚型包括朗格汉斯细胞组织细胞增生症（LCH），Rosai-Dorfman-Destombes病（RDD）和Erdheim-Chester病（ECD），这些已经根据临床表型进行了表征，驱动突变和治疗范例。对混合性组织细胞肿瘤（MXH）患者的了解较少，即两种或两种以上并存的疾病。这项国际合作检查了活检证实的MXH患者的成分疾病亚型，致癌驱动突变和对常规（化疗或免疫抑制）与靶向（BRAF或MEK抑制剂）治疗的反应。27例患者接受了ECD/LCH（19/27），ECD/RDD（6/27），RDD/LCH(1/27)和ECD/RDD/LCH(1/27)。先前未在MXH中描述的突变被鉴定,包括KRAS,MAP2K2,MAPK3,非V600-BRAF,RAF1和BICD2-BRAF融合。重复测量的广义估计方程表明，靶向治疗具有统计学意义（1）更可能导致完全反应（CR），部分反应（PR）或疾病稳定（SD）（比值比[OR]：17.34，95％CI：2.19-137.00，p=0.007），和（2）不太可能导致进展（OR：0.08，95％CI：0.03-0.23，p<0.0001）。组织细胞肿瘤代表了一个被低估的临床和分子多样性的实体，对常规治疗的反应性差，对靶向治疗的敏感性高。
