A case of Langerhans cell sarcoma on the scalp: Whole-exome sequencing reveals a role of ultraviolet in the pathogenesis
A case of Langerhans cell sarcoma on the scalp: Whole-exome sequencing reveals a role of ultraviolet in the pathogenesis
复制标题
头皮朗格汉斯细胞肉瘤一例：全外显子组测序揭示紫外线在发病机制中的作用
作者：
Katsuragawa H;Yamada Y;Ishida Y;Kaku Y;Fujimoto M;Kataoka TR;Haga H.
朗格汉斯细胞肉瘤（LCS）是一种具有明显恶性细胞学特征和朗格汉斯细胞表型的高级肿瘤。人们对潜在的遗传特征知之甚少，仅报道了一些改变，例如 MARK 通路相关基因、CDKN2A 和 TP53 的改变。在此，我们介绍了一名 70 岁男性，患有头皮 LCS 和肺部转移。多结节性肿瘤直径 3.0 厘米，由弥漫增殖的多形性细胞组成，具有大量有丝分裂 (53/10 HPF)。免疫组化结果显示，肿瘤细胞CD1a、Langerin和PD-L1呈阳性，Ki-67标记指数为50%。这些病理特征与LCS一致，并且在转移性肿瘤中也观察到。全外显子组测序显示，原发性和转移性肿瘤均含有大量突变（>20 个突变/兆碱基），其中 CDKN2A 和 TP53 突变缺失，并强调突变特征主要是紫外线 (UV) 暴露的特征 (W = 0.828)。我们的结果首次表明，紫外线造成的 DNA 损伤可能在朗格汉斯细胞中积累，并在 LCS 的发病机制中发挥作用。肿瘤中的高突变负荷和 PD-L1 表达将为使用免疫检查点抑制剂治疗不可切除的 LCS 提供依据。
Langerhans cell sarcoma (LCS) is a high‐grade neoplasm with overtly malignant cytological features and a Langerhans cell phenotype. The underlying genetic features are poorly understood, and only a few alterations, such as those of the MARK pathway‐related genes,CDKN2AandTP53have been reported. Here we present a 70‐year‐old male with LCS on the scalp and pulmonary metastasis. The multinodular tumor, 3.0 cm in diameter, consisted of diffusely proliferated pleomorphic cells with numerous mitoses (53/10 HPFs). Immunohistochemically, the tumor cells were positive for CD1a, Langerin and PD‐L1, and the Ki‐67 labeling index was 50%. These pathological features were consistent with LCS, and were also observed in the metastatic tumor. Whole‐exome sequencing revealed that both the primary and metastatic tumors harbored a large number of mutations (>20 mutations/megabase), with deletion ofCDKN2AandTP53mutation, and highlighted that the mutational signature was predominantly characteristic of ultraviolet (UV) exposure (W = 0.828). Our results suggest, for the first time, that DNA damage by UV could accumulate in Langerhans cells and play a role in the pathogenesis of LCS. The high mutational burden and PD‐L1 expression in the tumor would provide a rationale for the use of immune checkpoint inhibitors for treatment of unresectable LCS.