Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, United States; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Semin Cell Dev Biol. 2019 Feb;86:62-76. doi: 10.1016/j.semcdb.2018.03.002. Epub 2018 Mar 16.
The systemic histiocytoses encompass a clinically heterogeneous group of disorders leading to tissue damage secondary to the accumulation and infiltration of pathological cells thought to be derived from the dendritic or monocytic lineages with accompanying inflammation. For decades, whether or not the histiocytoses were inflammatory or neoplastic disorders was unclear, and their cellular origins have long been obscure and heavily debated. However, the rise of the molecular era led to the discovery of recurrent BRAF mutations in approximately 50% of patients with Langerhans cell and non-Langerhans cell histiocytoses, which provided the first convincing evidence that these are indeed histiocytic neoplasms. This also supplied a molecular biomarker for potentially mapping the cell(s)-of-origin of these neoplasms. The purpose of this review will be to highlight the barrage of recent molecular advancements in the histiocytic neoplasms and discuss the impact these insights have had on our understanding of the molecular pathophysiology and cellular origins of these rare, enigmatic diseases.
系统性组织细胞增多症包括一组临床表现异质性的疾病，这些疾病导致组织损伤，继发于病理性细胞的积累和浸润，这些细胞被认为来源于树突状细胞或单核细胞谱系，并伴有炎症。几十年来，组织细胞增多症是炎症性还是肿瘤性疾病一直不清楚，其细胞起源长期以来一直不明确，且存在激烈争论。然而，分子时代的兴起导致约 50%的朗格汉斯细胞和非朗格汉斯细胞组织细胞增多症患者中发现了反复出现的 BRAF 突变，这为这些疾病确实是组织细胞肿瘤提供了第一个令人信服的证据。这也为这些肿瘤的起源细胞提供了分子生物标志物。本综述的目的将重点介绍组织细胞肿瘤中最近涌现的大量分子进展，并讨论这些见解对我们理解这些罕见的、神秘疾病的分子病理生理学和细胞起源的影响。
