IgG4相关眼病泪腺病变的临床及病理学研究

Clinical and pathological study on IgG4-related ophthalmic disease involving the lacrimal gland

目的总结IgG4相关眼病(IgG4-ROD)泪腺病变的临床及病理学特征。方法回顾性系列病例研究。选取2003年1月至2018年1月于天津市眼科医院经泪腺肿物切除术且组织病理学检查证实以泪腺淋巴细胞和浆细胞浸润伴纤维化为主并排除淋巴瘤、上皮性肿瘤、间叶性肿瘤及转移性肿瘤的泪腺病变患者40例(56只眼)的临床资料及组织病理学检查标本。分析患者临床表现、血清学检查及影像学检查结果,同时对组织蜡块标本切片行HE染色及IgG、IgG4免疫组织化学染色。根据相关IgG4-ROD诊断标准将患者分为IgG4-ROD组和非IgG4-ROD组。采用χ^2检验及Wilcoxon秩和检验对两组患者的临床及组织病理学指标进行比较。结果40例(56只眼)患者中有15例(25只眼)纳入IgG4-ROD组,25例(31只眼)纳入非IgG4-ROD组。IgG4-ROD组与非IgG4-ROD组双眼发病分别有10、6例(χ^2=7.111),上睑下垂分别有21、5只眼(χ^2=25.631),突眼分别有4、21只眼(χ^2=14.992),肿物边界清晰分别有23、15只眼(χ^2=12.069),病变累及眶内组织分别有4、18只眼(χ^2=10.266),伴随其他系统疾病分别有7、3例(χ^2=6.009),两组间差异均有统计学意义(均P<0.05)。组织病理学表现,淋巴细胞和浆细胞浸润程度为+++、++、+在IgG4-ROD组分别有10、4、1只眼,非IgG4-ROD组中分别有6、5、12只眼(Z=-3.153);淋巴滤泡数量为+++、++、+在IgG4-ROD组分别有3、6、4只眼,非IgG4-ROD组中分别有1、2、7只眼(Z=-3.339);席纹状纤维化IgG4-ROD组10只眼,非IgG4-ROD组5只眼(χ^2=8.711);IgG4^+浆细胞数IgG4-ROD组为[96(67,135)个/高倍视野],非IgG4-ROD组为[4(0,12)个/高倍视野](Z=-5.271),IgG4^+浆细胞数/IgG^+浆细胞数比值IgG4-ROD组为0.570(0.500,0.754),非IgG4-ROD组为0.046(0.000,0.143)(Z=-5.268),两组患者间差异均有统计学意义(均P<0.05)。具有血清学检查结果的10例IgG4-ROD患者中,9例表现为血清IgG、IgG4值均升高;IgG4-ROD组彩色超声及CT表现泪腺病变多为梭形或肾形,边界清晰,非IgG4-ROD组多为类圆形或不规则形,边界不清。结论IgG4-ROD泪腺病变最常表现为双眼泪腺呈边界清晰的梭形或肾形肿大,多伴其他系统疾病;组织病理学特征为泪腺组织间大量IgG4^+浆细胞浸润、间质呈席纹状纤维化以及大量淋巴滤泡形成。

Objective To summarize the clinical and pathological characteristics of IgG4-related ophthalmic disease(IgG4-ROD)involving the lacrimal gland.Methods A retrospective case series study.Forty cases(56 eyes)of lacrimal gland lesions were collected in Tianjin Eye Hospital from January 2003 to January 2018 and confirmed by histopathology as lymphocyte and plasma cell infiltration with fibrosis of lacrimal gland tissue,excluding lymphoma,epithelial tumor,mesenchymal tumor and metastasis tumor.The clinical manifestations,serological and imaging examination of the patients were analyzed.Meanwhile,HE staining and immunohistochemical staining of IgG and IgG4 were performed on the pathological specimens.According to the diagnostic criteria,the cases were divided into the IgG4-ROD group and the non-IgG4-ROD group.The clinical and pathological characteristics of the two groups were statistically analyzed by Pearson chi-square and signed-rank test.Results In the 40 cases(56 eyes),there were 15 cases(25 eyes)of IgG4-ROD and 25 cases(31 eyes)of non-IgG4-ROD.Statistically significant differences were observed between the two groups in the clinical and pathological characteristics(all P<0.05).About the distribution of eyes position,there were 10 binocular cases and 5 monocular cases in the IgG4-ROD group,and 6 binocular cases and 19 monocular cases in non-IgG4-ROD group(χ^2=7.111).There were 21 eyes in the IgG4-ROD group and 5 eyes in the non-IgG4-ROD group about ptosis(χ^2=25.631),4 eyes in the IgG4-ROD group and 21 eyes in the non-IgG4-ROD group about ocular protrusion(χ^2=14.992),23 eyes in the IgG4-ROD group and 15 eyes in the non-IgG4-ROD group about the clear boundary of the tumor(χ^2=12.069),4 eyes in the IgG4-ROD group and 18 eyes in the non-IgG4-ROD group about the involvement of other orbital tissues(χ^2=10.266)and 7 cases in the IgG4-ROD group and 3 cases in the non-IgG4-ROD group about the association with other systemic diseases(χ^2=6.009).Compared with the non-IgG4-ROD group,the IgG4-ROD group had a heavier lymphocyte and plasma cell infiltration(+++,++,+;10,4,1 vs.6,5,12 eyes,Z=-3.153),and more lymphoid follicles(+++,++,+;3,6,4 vs.1,2,7 eyes,Z=-3.339),interstitial fibrosis was mostly striate(10 vs.5 eyes,χ^2=8.711),and there were a large number of IgG4^+ plasma cells[96(67,135)vs.4(0,12)cells per high power field,Z=-5.271]and ratio of IgG4^+ plasma cells/IgG^+ plasma cells[0.570(0.500,0.754)vs.0.046(0.000,0.143),Z=-5.268,all P<0.05).Among the 10 cases of IgG4-ROD with serological examination,9 cases showed elevated serum in IgG and IgG4.The ultrasonography and CT findings showed the lacrimal gland lesions in the IgG4-ROD group were mostly spindle or kidney shaped with clear boundaries,while the lesions in non-IgG4-ROD were mostly round or irregular with unclear boundaries.Conclusions The lacrimal gland lesions of IgG4-ROD are characterized by bilaterally spindle or kidney shaped enlargement with clear boundaries.They are more associates with other systemic diseases.The pathological characteristics are a large number of IgG4^+ plasma cells infiltration among the lacrimal gland tissue,interstitial striate fibrosis and a large number of lymphoid follicles.