眶周黄色斑块和腹膜后纤维化1例

2019-04-23 不详 CSDCMA资讯平台

患者女性,50余岁,右下眼睑黄色斑块,伴腹部和背部持续疼痛。胸部、腹部和骨盆CT扫描示胸腔经腹膜后间隙广泛浸润。可见多个骨结构硬化改变。活检后诊断为特发性腹膜后纤维化。患者开始使用泼尼松和硫唑嘌呤治疗。下眼睑黄色斑块活检显示为黄色瘤复发(图A)。输尿管梗阻、慢性肾病和淋巴水肿使患者病程复杂化。1年后患者停用硫唑嘌呤,并逐渐较少泼尼松用量,但3年后患者复发。第二次腹膜后活检示纤维脂肪组织、泡沫状巨噬

患者女性,50余岁,右下眼睑黄色斑块,伴腹部和背部持续疼痛。胸部、腹部和骨盆CT扫描示胸腔经腹膜后间隙广泛浸润。可见多个骨结构硬化改变。活检后诊断为特发性腹膜后纤维化。患者开始使用泼尼松和硫唑嘌呤治疗。下眼睑黄色斑块活检显示为黄色瘤复发(图A)。输尿管梗阻、慢性肾病和淋巴水肿使患者病程复杂化。1年后患者停用硫唑嘌呤,并逐渐较少泼尼松用量,但3年后患者复发。第二次腹膜后活检示纤维脂肪组织、泡沫状巨噬细胞和慢性炎症伴纤维化。患者重新使用硫唑嘌呤和泼尼松,且需多次手术治疗椎管狭窄和输尿管梗阻。患者肾功能持续下降。随后,因膝关节疼痛,平片检查示股骨远端骨硬化。因此,对先前眼睑和腹膜后活检进行了审查。临床病理表现经分子检测证实。


Erdheim-Chester(脂质肉芽肿病)病

组织病理学检查和临床病程

眼睑活检示淋巴细胞浸润和Touton巨细胞散在分布部位乳头状和网状真皮扩张,且满布泡沫组织细胞(图B)。组织细胞检查示CD68(图C)和因子XIIIa阳性, S100、CD1a结果呈阴性。CT检查示广泛腹膜后纤维化和毛状肾脏外观(图D)。采用等位基因特异性PCR技术,从福尔马林固定、石蜡包埋皮肤和腹膜后活检组织中提取DNA。通过毛细管电泳法检测到BRAF V600E突变。腹膜后活检结果与眼睑活检结果类似,可见泡沫组织细胞片、散在淋巴细胞浸润和纤维化。

患者被确诊为Erdheim-Chester 病后,采用威罗菲尼,480 mg,每日两次治疗。BRAF抑制剂(BRAFi)治疗前几个月患者耐受,尽管间接性采用泼尼松治疗,但疲劳和炎症性关节炎最终促使停药。患者共减药2次,第一次减至240mg,每天2次,随后每天240 mg,但关节炎未缓解。患者停用威罗菲尼并开始使用甲氨蝶呤。反复CT检查示患者病情稳定,皮损消退。



讨论

1930年奥地利病理学家Jakob Erdheim 及其学生William Chester 首次描述了Erdheim-Chester 病。数以百计的病例突出了L组疾病显著临床变异性,即非朗格汉斯细胞组织细胞增生症,从骨限制性疾病到多系统受累,预后较差。

Erdheim-Chester病好发于男性,多见于60岁左右患者。组织病理学特征为组织细胞克隆瘤形成,其产生强大Th1细胞因子谱。组织学上,皮肤活检结果示泡沫状组织细胞和散在分布Touton巨细胞真皮浸润。相比之下,朗格汉斯细胞组织细胞增生症显示嗜酸性组织细胞阳性,且嗜酸性细胞浸润部位呈肾形豆样核。 ECD组织细胞对CD68、CD163和XIIIa因子具有免疫反应,而S100、CD1a和Langerin呈阴性。BRAF V600E驱动突变为肿瘤理论提供了证据。

诊断为坏死性黄色肉芽肿(NXG)的患者最常见的是一种潜在的单克隆性肉芽肿,组织学表现为层状坏死和周围多核巨细胞,细胞核排列不均匀。临床上,两种疾病组织病理学表现均可表现为眶周受累。

32%的ECD患者皮肤受累。皮肤受累患者中,30%患者该病的第一症状为皮肤受累。如该患者所见,黄斑样皮损(XLL)具有特异性,可见于25%的患者,最常见于内眼角。XLL可能难以与睑黄瘤区分,特别是这种差别极小的病例中。两者均可见CD68,CD163和Cd1a组织细胞。ECD浸润累及网状真皮,多核细胞和Touton巨细胞密度较高,真皮纤维化较少,与血脂异常的关系不大。其他皮肤表现包括红褐色局部或播散性斑块、丘疹样结节和罕见红皮病。描述了一些儿童病例,其中一些患者皮肤受累。许多报告显示LCH和ECD共存,LCH典型皮损可能存在,并且任何有皮肤受累的ECD患者都应进行活检。

54%~60%的ECD患者表现为BRAF V600E突变,且XLL 患者BRAF V600E突变比例更高。该突变在其他皮肤病变中并不常见。与骨活检、腹膜后活检或其他内部表现相比,XLL活检更容易进行。

自21世纪初以来,干扰素-α(IFN-α)是一线疗法,是第一种使存活率增加的药物。其他治疗方法包括高剂量类固醇、克拉屈滨、imatanib、阿那白滞素、托法替尼、cobimetinib、甲氨蝶呤和环磷酰胺。鉴于所研究的药物数量相对较少,疗效很难确定。然而,自2012年发现大多数ECD患者存在BRAF突变以来,BRAF抑制剂已成为一种有前景的一线疗法。在迄今规模最大的LOVE研究中,BRAF突变患者vemurafanib和dabrafenib治疗反应率高达91%(包括76%的部分反应和15%的完全反应患者)。此外,cobimetinib(一种MEK抑制剂)对野生型突变患者、联合BRAF抑制剂治疗的BRAF突变患者以及BRAF抑制剂治疗未改善的患者有益。中断BRAF抑制剂治疗后复发是标准反应;然而,在LOVE研究中,所有的患者在再次接受治疗后都再次出现了反应。BRAF抑制的不良事件与之前对黑色素瘤的研究相似。

皮肤科医生可识别ECD皮肤表现,通过皮肤活检确认BRAF突变,并帮助诊断和治疗与BRAF抑制相关的皮肤不良反应。

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    2019-04-25 laoli

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    2019-04-25 xuyong530