Department of Medical Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.
Annu Rev Pathol. 2013 Jan 24;8:1-20. doi: 10.1146/annurev-pathol-020712-163959. Epub 2012 Aug 6.
Langerhans cell histiocytosis (LCH) combines in one nosological category a group of diseases that have widely disparate clinical manifestations but are all characterized by accumulation of proliferating cells with surface markers and ultrastructural features similar to cutaneous Langerhans cells (LCs). Despite this unified nosology, important questions about LCH remain unanswered. First, despite having phenotypic features of LCs, LCH cell gene-expression patterns differ from those in LCs. Although this observation suggests that LCH may arise from an earlier precursor, it is not necessarily inconsistent with the hypothesis that LCs are the cell of origin for LCH. Second, LCH's prominent inflammatory component and occasional benign clinical course suggest that LCH may not be a neoplasm. However, the demonstration that LCH cells are clonal, along with the recent discovery of activating BRAF mutations in LCH cells, strongly suggests that LCH is a neoplastic disease. These new observations point the way to rationally targeted therapies.
朗格汉斯细胞组织细胞增生症（LCH）将一组临床表现差异很大的疾病归为一类，但这些疾病均以增殖细胞的积聚为特征，这些细胞具有与皮肤朗格汉斯细胞（LC）相似的表面标志物和超微结构特征。尽管有这种统一的分类法，但关于 LCH 的一些重要问题仍未得到解答。首先，尽管 LCH 细胞具有 LC 的表型特征，但它们的基因表达模式与 LC 不同。尽管这一观察结果表明 LCH 可能来自更早的前体，但这并不一定与 LC 是 LCH 起源细胞的假说相矛盾。其次，LCH 明显的炎症成分和偶尔良性的临床过程表明 LCH 可能不是一种肿瘤。然而，LCH 细胞具有克隆性的证明，以及最近在 LCH 细胞中发现激活的 BRAF 突变，强烈提示 LCH 是一种肿瘤性疾病。这些新的观察结果为合理的靶向治疗指明了方向。
