Chronic myelomonocytic leukemia beyond the marrow: biology, patterns, and management of extramedullary disease.

Extramedullary disease (EMD) refers to clonal myelomonocytic infiltration outside the bone marrow and is an underrecognized, consequential manifestation that can dominate presentation, drive morbidity, and identify adverse disease biology.

髓外疾病（EMD）指的是骨髓外的克隆性粒单核细胞浸润，这是一种未被充分认识但后果严重的表征，可以主导临床表现，驱动疾病相关发病率，并标识出不良的疾病生物学特性。

While hepatosplenic involvement, often reflecting extramedullary hematopoiesis, is common, biopsy proven non-hepatosplenic EMD occurs in a subset of patients, 10-15 percent, and most frequently involves skin, lymph nodes, serosal fluids, and soft tissue, with visceral sites including lung, kidney, and central nervous system.

尽管肝脾受累常见，通常反映了髓外造血，但在10-15%的患者中，活组织检查证实了非肝脾EMD（髓外髓系病变）的发生，这些病变最常累及皮肤、淋巴结、浆膜液和软组织，以及包括肺、肾和中枢神经系统在内的内脏器官。

Importantly, EMD is enriched in proliferative and higher grade CMML and is associated with inferior outcomes, including shorter overall survivaland increased AML transformation, with poor prognosis after EMD onset.

重要的是，EMD在增殖性和高分级的CMML中更为常见，并且与较差的临床结果相关，包括较短的总生存期和增加的AML转化风险，以及EMD发生后的不良预后。

Biologically, EMD appears linked to mutation-driven proliferative signaling, enrichment of RAS MAPK pathway alterations, co-occurring with adverse epigenetic lesions such as ASXL1, together with cytokine-mediated inflammation and dysregulated trafficking and retention programs that facilitate tissue homing and persistence.

从生物学角度来看，EMD似乎与突变驱动的增殖信号、RAS MAPK通路改变的富集有关，这些改变与ASXL1等不良表观遗传损伤共存，同时伴有细胞因子介导的炎症以及促进组织归巢和持续性的失调的运输和保留程序。

Because EMD frequently mimics infection, autoimmune and inflammatory syndromes common in CMML, or second malignancy, diagnosis requires an integrated strategy incorporating cross sectional imaging, PET-CT to localize and prioritize biopsy targets, and tissue confirmation with immunophenotyping including CD68, CD163, and lysozyme and selective molecular profiling to establish clonality.

由于EMD常常模仿感染、自身免疫和炎症综合征，这些在CMML中很常见，或者模仿第二恶性肿瘤，因此诊断需要采取综合策略，包括横断面成像、PET-CT以定位和优先考虑活检目标，以及通过包括CD68、CD163和溶菌酶在内的免疫表型确认和选择性分子谱分析来确定克隆性。

Management is primarily systemic, with hypomethylating agents as the backbone, cytoreduction for proliferative disease, local radiotherapy for symptomatic lesions, and early consideration of allogeneic transplantation in eligible high risk or refractory cases.

治疗主要采用系统性方法，以低甲基化药物为基础，对于增殖性疾病进行细胞减少治疗，对有症状的病变进行局部放疗，并在符合条件的高风险或难治性病例中早期考虑异基因移植。

This review synthesizes current evidence on the epidemiology, biology, diagnostic approach, prognostic implications, and treatment of EMD in CMML and highlights the need for standardized definitions and prospective, genomics-informed studies to improve detection and outcomes.

本综述综合了当前关于CMML中EMD的流行病学、生物学、诊断方法、预后意义和治疗的证据，并强调了需要标准化定义和前瞻性、基因组学指导的研究，以改善检测和结果。