Fusco Nicola, Bonometti Arturo, Augello Claudia, Fabris Sonia, Boiocchi Leonardo, Fiori Stefano, Morotti Denise, Fracchiolla Nicola, Berti Emilio, Gianelli Umberto
Division of Pathology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
Department of Biomedical, Surgical and Dental Sciences, Milan, Italy.
Histopathology. 2017 May;70(6):1000-1008. doi: 10.1111/his.13166. Epub 2017 Feb 28.
The aims of this study were to define whether diffuse cutaneous reticulohistiocytosis could be underpinned by somatic genetic alterations and represent a precursor of more aggressive forms of disease.
A 59-year-old man with diffuse cutaneous reticulohistiocytosis experienced bone marrow localization of the disease, with associated systemic mastocytosis and acute myeloid leukaemia. Cytogenetic analyses of the bone marrow aspirate revealed the presence of a derivative chromosome giving rise to a partial trisomy of chromosome 1q and a partial monosomy of chromosome 9q. Therefore, we characterized the cutaneous lesions before and after chemotherapy by using an integrative approach combining histopathology, electron microscopy, and fluorescence in-situ hybridization. Histologically, the skin lesions belonged to the spectrum of diffuse cutaneous reticulohistiocytoses, as confirmed by immunohistochemistry and ultrastructural analyses. Fluorescence in-situ hybridization in the skin nodules confirmed the presence of the genetic alterations previously detected in the bone marrow.
Here, we provide circumstantial evidence to suggest that at least a subset of cutaneous reticulohistiocytoses harbour clonal molecular alterations. Furthermore, we confirm that these lesions have the potential to arise in the setting of concurrent haematological disorders. In this hypothesis-generating study, two possible tumorigenesis models are proposed.
本研究旨在确定弥漫性皮肤网状组织细胞增生症是否由体细胞基因改变引起，并是否代表更具侵袭性疾病形式的前驱病变。
一名患有弥漫性皮肤网状组织细胞增生症的59岁男性出现了疾病的骨髓定位，伴有系统性肥大细胞增多症和急性髓系白血病。对骨髓穿刺液进行的细胞遗传学分析显示存在一条衍生染色体，导致1号染色体部分三体和9号染色体部分单体。因此，我们采用组织病理学、电子显微镜和荧光原位杂交相结合的综合方法，对化疗前后的皮肤病变进行了特征描述。组织学上，皮肤病变属于弥漫性皮肤网状组织细胞增生症范畴，免疫组织化学和超微结构分析证实了这一点。皮肤结节中的荧光原位杂交证实了先前在骨髓中检测到的基因改变的存在。
在此，我们提供间接证据表明，至少一部分皮肤网状组织细胞增生症存在克隆性分子改变。此外，我们证实这些病变有可能在并发血液系统疾病的情况下出现。在这项提出假设的研究中，提出了两种可能的肿瘤发生模型。
