类固醇激素反应性慢性淋巴细胞性炎症伴脑桥血管周围强化症演变为淋巴瘤样肉芽肿1例临床病理观察

Lymphomatoid granulomatosis following chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids(CLIPPERS):report of one case and review of literature

目的探讨类固醇激素治疗后反应性慢性淋巴细胞性炎伴脑桥血管周围强化症(CLIPPERS)发展为淋巴瘤样肉芽肿的发病机制、临床表现及病理学特征。方法结合临床、影像、组织学特点及预后对解放军总医院第一医学中心病理科1例患者资料进行回顾性分析。结果本文1例患者,女性、52岁,主因出现头晕、行走不稳,口角左歪10天入院;随后临床症状加重,并出现右侧肢体活动笨拙,行走困难,右侧口角歪斜,饮水呛咳,言语不清,视物模糊,右侧听力下降。影像学起病时可见双侧枕叶、脑桥及小脑半球多灶点、斑片状信号,随后临床给予激素治疗,症状减轻且原有病灶减弱或消失;6个月后再次发病可见右侧侧脑室旁、右侧桥臂出现新的异常信号。病理学改变:(第一次)送检少许破碎小脑皮层组织,小脑颗粒细胞层、白质区见多发小灶肉芽肿样炎,病变有组织细胞及淋巴细胞构成,不伴有坏死及多核巨细胞反应,并血管周围淋巴组织套袖形成,未见血管壁坏死及中性粒细胞浸润,分子检测EBER阴性,考虑为CLIPPERS综合征;(第二次)镜下见富于淋巴、组织细胞增生性病变伴大片坏死,其间偶见核大异型单核及多核细胞,部分呈围血管性排列及血管破坏性改变,分子检测EBER阳性细胞5~10个/HPF,结合组织形态、免疫组化及分子病理结果,符合淋巴瘤样肉芽肿(II级)。结论CLIPPERS是新近提出的具有独特放射学和临床特征的中枢神经系统病变的综合征,该综合征确切的病因不详,在病理上缺乏特异性的生物标志物及组织学改变,可能是一种具有异质性病因的综合征,部分病例存在向中枢神经系统淋巴瘤转化的风险(即淋巴瘤的前哨病变)。增加EBV原位杂交分子检测有助于诊断及鉴别诊断,对治疗及预后具有重要意义。

Objective To investigate the pathogenesis,clinical manifestations and pathological characteristics of lymphomatoid granulomatosis following chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids(CLIPPERS).Methods One case was diagnosed by the clinical,imaging,histological characteristics and prognosis from the Department of Pathology of the First Medical Center of PLA General Hospital with review of the relevant literature.Results A 52-year-old female was admitted to the hospital because of dizziness,walking instability,and deflection of angle of mouth for 10 days.Later,the clinical symptoms worsened,and he had awkward limb movements,difficulty walking,choking as drinking water,barylalia,blurred vision,and right hearing loss.Imaging findings showed multiple punctuate hyperintense lesion involving the bilateral occipital lobe,pons and cerebellum.The symptom and radiology were improved quickly with treatment.Six months later,the new abnormal signals appeared,involving the right lateral ventricle and right pontibrachium.Brain biopsy firstly showed that multiple granulomatous inflammation was found in the cerebellar granular cell layer and white matter area.The lesions were composed of histiocytic cells and lymphocytes,without necrosis,multinucleated giant cell reactions and perivascular lymphatic cuff,vascular wall necrosis and neutrophilic infiltration.Epstein-Barr virus(EBV)analysis was negative.The patient was diagnosed with CLIPPERS.Brain biopsy second showed histiocytic proliferative lesion with extensive necrosis rich in lymphocytes.The lymphoid component did not show evident atypia,with few large transformed B cells.EBV analysis showed EBV-infected cells(5-10/High power field).The lesion was diagnosed as LYG grade II.Conclusion CLIPPERS is a newly proposed syndrome of central nervous system disease with unique radiological and clinical features.The pathogenesis of CLIPPERS is still unclear and lack of specific biomarkers and histological changes in pathology.It is considered a syndrome with heterogeneous aetiologies.Some cases have a risk of transformation to central nervous system lymphoma(sentinel lesions of the lymphoma).Increasing the detection of EBV in situ hybridization molecules is helpful for diagnosis and differential diagnosis,and is of great significance for treatment and prognosis.