背景

IgG4相关疾病（Immunoglobulin G4 related disease ，IgG4-RD）是新近认识的一种免疫介导性疾病，可累及全身多个器官、部位。相对于其它器官而言，甲状腺IgG4相关性疾病研究较少，认识不足。桥本甲状腺炎（Hashimoto Thyroidities，HT）和木样甲状腺炎（Riedle Thyroidities，RT）与IgG4-RD病理组织学形态相似，二者与IgG4-RD的关系以及二者是否属于IgG4-RD的范畴有待进一步澄清。本研究回顾性研究HT与RT，对比其与IgG4-RD的差异，初步探讨三者之间的相互关系。

材料与方法

课题研究分两部分：

第一部分对我院2012年4月--2015年8月期间确诊的5例Riedle甲状腺炎病例进行病例资料搜集，并对送检活体组织蜡块进行HE染色，CD38、CD138、IgG、IgG4免疫组织化学染色，Masson三色染色(Masson Trichrome,MT)染色，弹力纤维染色(Elastic-Van Gieson,EvG)。计算IgG4阳性浆细胞数值，对比组织病理学特点以及临床特征，探讨其与IgG4-RD之间的关系。

第二部分是对我院2014年—2016年期间病理科工作站上诊断为桥本甲状腺炎的57例病例进行病例资料收集，并对送检活体组织蜡块进行HE染色，CD38、CD138、IgG、IgG4免疫组织化学染色，MT染色，EvG染色。根据IgG4阳性浆细胞数值，分为分为IgG4亚型组与非IgG4亚型组，对比两组组织病理学特征及临床学特征。

结果

第一部分：5例患者，男性1例，女性4例，年龄52～78岁，平均59岁。5例患者都是出现甲状腺双叶多发结节，结节逐年增大，并且在出现周围组织压迫症状及体征时就诊。2例女性患者出现甲状腺功能减低。术前血清IgG水平升高2例，其余3例未测。B超显示结节多表现低回声或中低回声，偶有病例是低回声结节内部出现散在强回声。光镜下显示大量纤维组织增生伴不等量淋巴细胞及浆细胞浸润，4例可见闭塞静脉炎，3例出现嗜酸性粒细胞。5例患者的免疫组织化学IgG4计数与IgG4/IgG比值分别为：20个/HPF，16%；60个/HPF，82%；22个/HPF，28%；400个/HPF，266%；33个/HPF，71%。3例符合IgG4-RD的诊断。

第二部分：57例患者，男2例，女55例，年龄14～73岁，平均43岁。18例IgG4亚型和39例非lgG4亚型。显微镜下纤维化程度、淋巴滤泡形成程度、血清A-Tg水平在两组之间的差异有统计学意义。其余包括年龄、性别、甲减或亚甲减出现程度、纤维化类型等指标在两组之间的差异并无统计学。

结论

(1) RT与IgG4-RD光镜下具有相似的病理组织学表现，部分符合IgG4-RD的诊断标准，推测部分RT属于IgG4-RD。

(2) 57例桥本氏甲状腺炎均无合并其他器官的IgG4相关性疾病。

(3)桥本氏甲状腺炎IgG4亚型具有IgG4相关性疾病的典型特征，主要包括：弥漫性淋巴浆细脆浸润，间质不同类型的纤维化，以及大量IgG4阳性浆细胞浸润。

(4)在组织病理学特征上，HT的IgG4亚型在纤维化程度、淋巴滤泡形成程度较非IgG4亚型程度更高，两组之间具有统计学差异。

(5)与IgG4亚型比较，桥本甲状腺炎非IgG4亚型的血清A-Tg水平较低，两组之间有统计学差异。

(6)桥本氏甲状腺炎IgG4亚型并非完全等同于桥本氏甲状腺炎纤维化亚型，二者只是部分重合。

(7)在纤维化类型方面（小叶间纤维化与滤泡间纤维化），桥本甲状腺炎两组之间无统计学差异。

[关键词] 免疫球蛋白G4 免疫组织化学 桥本 木样甲状腺炎

Background  

IgG4 related diseases (IgG4-RD) is a recently recognized syndrome which is also an immune-mediated disease.it can involve with multiple organs or tissues. In comparation with the orther organs, there are fewer studies about IgG4 related disease of the thyroid. On the other hand, we still don’t know too much about that. The pathological histology of Hashimoto thyroiditis (HT) and Riedle thyroidities ( RT) are similar to IgG4-RD. So the relationships between IgG4 - RD and those two kinds of disease and whether both HT and RT belong to the category of IgG4-RD need to further clarification. This study retrospectively observed the clinical and pathological datas of HT and RT, by comparing and discussing the differences and relationships between them and IgG4-RD respectively and preliminarily.

Materials and methods

The study was divided into two parts:

In the first part, five cases of Riedle thyroiditis confirmed in our hospital during April 2012 to August 2015 were collected. HE staining, CD38,CD138, IgG, IgG4 immunohistochemistry staining , Masson and Elastic fiber staining were carried out on these tissue paraffin blocks. Observe the histopathological features and clinical features of these five cases according to the numbers of IgG4 positive plasma cells.

In the second part, collect data of 57 cases diagnosed as Hashimoto thyroiditis in our hospital from 2014 to 2016.HE staining, CD38, CD138, IgG, IgG4 immunohistochemistry staining , Masson and Elastic fiber staining were carried out on these tissue paraffin blocks. The 57 cases were divided into IgG4 subtype group and non-IgG4 subtype group. In terms of histopathological features and clinical features, to see wether the differences between these two groups were statistically significant by comparing these two groups.

Results

In the first part: There were one male and four female patients, aged 52 to 78 years (median 59 years).5 cases were characterized by multiple nodules of thyroid, which increased year by year. All patients were found to have surrounding tissue compression symptoms and signs. 2 female patients were found to have hypothyroidism. The serum concentration of IgG was elevated in 2 cases, and the serum concentration of IgG was not tested before operation in the remaining patients. By ultrasound, all presented as Low echo or medium low echo. Strong echo occasionally appeared in hypoechoic nodules. Microscopically, fibrous tissue hyperplasia were infiltrated with varying amounts of lymphocytes and plasma cells. The occlusion of phlebitis were found in 4 cases and eosinophils were found in 3 cases. IgG4 counts and IgG4/IgG ratios in 5 cases respectively were: 20/HPF,16%;60/HPF,82%; 22/HPF,28%;400/HPF, 266%; 33/HPF,71%. There were 3 cases were diagnosed with IgG4-RD finally.

The second part: There were 57 patients, 2 males and 55 females, aged 14 to 73 years, with an average age of 43. And there were 18 IgG4 subtypes and 39 non-IgG4 subtypes. The differences of the degree of fibrosis and the formation of lymph follicles under the microscope between these two groups were statistically significant as well as the level of serum A-Tg between the two groups. There were  no statistically significant differences between the two groups in the other medical indexes which included age, gender, hypothyroidism,fibrosis and so on.

Conclusions

(1) With the similar pathological manifestation results betwwen RT and IgG4-RD, immunohistochemical staining showed that the number of IgG4 positive plasma cells and IgG4/IgG ratio of RT were Increased in varying degrees. Some cases meet with the diagnostic criteria of IgG4-RD，and speculate that some cases of RT belong to IgG4-RD.

(2) None of the 57 cases of hashimoto's thyroiditis were associated with IgG4 related disease in the other organs.

(3)The IgG4 subtype of HT showed the typical features of the IgG4 related disease which mainly including: the diffuse infiltration of lymphoplasmatic cells, different types of interstitial fibrosis, and as well as a large number of IgG4 positive plasma cells infiltrated.

(4)Histopathologically, IgG4 subtype of HT showed higher grade of stromal fibrosis,lymphoplasmacytic infiltration, and lymphoid follicles formation.There were statistical differences between these two groups.

(5) Compared with IgG4 subtype, the non-IgG4 subtype of hashimoto's thyroiditis came up with a lower level of blood A-Tg .And there was a statistical difference between the two groups.

(6) Hashimoto's thyroiditis IgG4 subtype is not completely equal to hashimoto's thyroiditis fibrosis subtypes. They were only partially overlapped.

(7) There was no statistical difference between the two groups of hashimoto thyroiditis in the type of fibrosis (interlobular fibrosis and follicular fibrosis). 

key words：immunoglobulin G4  Immunohistochemistry  Hashimoto  Riedle