骨内原发Rosai-Dorfman病14例临床病理学分析

Primary intraosseous Rosai-Dorfman disease:a clinicopathological analysis of fourteen cases

目的:探讨骨内原发Rosai-Dorfman病(Rosai-Dorfman disease,RDD)的临床病理学特征、免疫表型、分子表型特征及鉴别诊断思路。方法:回顾性分析2009年1月至2019年1月就诊于北京积水潭医院的14例骨内原发RDD确诊病例,采用免疫组织化学EnVision法检测S-100蛋白、cyclin D1、CD1a、CD207等蛋白表达情况;采用蝎形探针扩增突变系统(ARMS)荧光定量PCR检测BRAF V600E和KRAS基因突变情况。结果:14例RDD中女性6例,男性8例,年龄2~64岁,平均年龄31.4岁。14例均为不伴淋巴结病变的骨内原发病灶,1例为伴椎体和鼻腔累及的多发病变。骨内RDD影像学全部为溶骨性,常伴有硬化缘。光镜下病变破坏骨小梁,可见明暗相间结构,组织细胞增生伴伸入现象,部分病例背景纤维化显著,淋巴细胞或浆细胞弥漫浸润,多发病变的病灶中浆细胞显著增多,并可见血管炎。其中罕见1例为RDD和Langerhans组织细胞增生症(Langerhans cell histiocytosis,LCH)同时存在,可见Langerhans细胞增生。免疫表型:组织细胞S-100蛋白、cyclin D1、CD68、CD163阳性,其中cyclin D1呈核阳性,阳性比例为13/14,伴LCH的病例可见CD1a、CD207阳性的细胞。分子检测:伴LCH的病例ARMS-PCR结果显示BRAF V600E基因突变,所有病例KRAS基因无突变(7/7)。12例随访9~49个月,3例复发。结论:骨内原发RDD罕见,偶可和LCH伴发,临床、影像及组织形态表现需与其他骨内病变鉴别。BRAF V600E基因检测及cyclin D1可为鉴别诊断提供帮助。

Objective To investigate the clinicopathological characteristics,histogenesis,immunophenotypes and molecular genetic features of primary intraosseous Rosai-Dorfman disease(RDD)for improving diagnostic accuracy and differential diagnosis.Methods This retrospective study included 14 RDD cases diagnosed from January 2009 to January 2019 at Beijing Jishuitan Hospital,China.The immunohistochemical staining for S-100,cyclin D1,CD1a and CD207 expression was analyzed.The BRAF V600E and KRAS mutation analyses were performed using the Scorpions amplification refractory mutation system(ARMS)fluorescence quantitative PCR.Results There were 6 female and 8 male patients,aged from 2 to 64 years(mean 31.4 years).All of the 14 cases occurred in the bone without lymph node disease,while one patient developed additional lesions within vertebra and nasal cavity.Radiographically,the lesions were lytic with sclerotic margins.Histologically,the lesions percolated through the medullary cavity in an infiltrative fashion and alternating hyper-and hypo-cellular regions of histiocytic clusters(seen as alternating dark and light zones at low magnification).Large histiocytes also showed emperipolesis.Some cases had areas of fibrosis and dense lymphoplasmacytic infiltrates.There were vasculitis and an increased number of plasma cells in the cases involving multiple sites.One case showed concurrence of RDD and Langerhans cell histiocytosis(LCH)with inconspicuous increase of Langerhans histiocytes.Immunohistochemical staining showed that the large histiocytes were positive for S-100,CD68 and CD163 in all cases.The nuclear immunoreactivity for cyclin D1 was observed in 13 of the 14 cases.S-100,CD1a and CD207 were positive in the case with concurrence of RDD and LCH.ARMS-PCR results showed that BRAF V600E mutation was observed in the cases with concurrence of RDD and LCH,while there were no KRAS mutations(7/7).Follow-up information was available for 12 patients and ranged from 9 to 49 months.Three of the 12 patients experienced recurrences after the first surgery.Conclusions Primary intraosseous RDD is rare,and its concurrence with LCH is a very rare phenomenon.Its clinical symptoms,imaging,and pathological manifestations need to be distinguished from other bone lesions.The molecular detection of BRAF V600E and the nuclear expression of cyclin D1 mutations can be used for the diagnosis and differential diagnosis of RDD.