IgG4 Thyroiditis Research Articles

FRI531 IgG4 Related Mass -forming Thyroid Disease: Two Case Reports

Abstract Disclosure: R.S. Braham: None. C. Droumaguet: None. M. Vitellius: None. J. Tran-van-nhieu: None. E. Béquignon: None. P. Desgranges: None. N. Limal: None. M. Mahevas: None. B. Godeau: None. IgG4 thyroiditis is an invasive fibrotic process involving the thyroid in a systemic disease. It is a rare inflammatory autoimmune disease with insidious presentation and nonspecific symptoms.We describe two unusual cases of mass forming IgG4 thyroiditis that were diagnosed recently in our department. The first case is about a 42-year-old woman who has a history of Hashimoto thyroiditis with hypothyroidism presenting with a rapid goiter growth, neck pain, dysphagia and hoarseness. A lymphoma was suspected. Ultrasonography shows heterogeneous hypoechoic lesions that may infiltrate the perithyroid muscles. Fine-needle aspiration (FNA) was suspicious of IgG4 infiltrative disease which was confirmed by microbiopsy. Only the thyroid was hypermetabolic on fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) Scan. No improvement under corticosteroid treatment and Rituximab. Surgery was planified to relieve pressure symptoms. The thyroid surgery was very difficult because of the extensive fibrosis and only a biopsy was performed, confirming the diagnosis and excluding malignancy. The second case is about a 68-year-old woman with a history of hypertension and Graves disease presented with a neck right mass that was suspected to be a paraganglioma, hypermetabolic on FDG PET scan with no other localisation. This mass was surrounding the right primitive carotid artery, associated with thrombi of the internal jugular vein. FNA and microbiopsy found a fibrotic non specific tissue. Thyroidectomy and surgical biopsy of the neck mass were performed with histopathology confirming IgG4 disease on the thyroid gland with fibrosis. There were no hypocalcemia in the two cases and no other localisation. IgG4 related mass-forming thyroiditis is an extremely rare disease. It is now a recognizable pattern of IgG4 thyroiditis, and has as differential diagnosis Hashimoto’s thyroiditis, Graves disease and thyroidal carcinoma.We will discuss through these cases the different clinical presentation of this rare disease, the diagnostic tools, the treatment and the long term follow up. Presentation: Friday, June 16, 2023

Isolated IgG4 thyroiditis: Two case reports and review of the literature

Isolated IgG4 thyroiditis: Two case reports and review of the literature

IgG4 thyroiditis in the Asian population.

Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated fibro-inflammatory condition that often causes the formation of tumefactive lesions. The discovery of IgG4-RD linked many well-known isolated conditions as a distinct multi-organ disease, and started an era of promoting investigation and treatment in relevant fields. In the thyroid gland, a subcategory of Hashimoto thyroiditis (HT) with IgG4-rich inflammation was first discovered and named IgG4 thyroiditis by our group. This subtype of HT presents with rapidly progressive clinical manifestations and destructive histopathological features underlying thyroid dysfunction, which are significantly different from the common type of HT. Moreover, other IgG4-rich thyroid conditions in patients with Graves' disease and systemic IgG4-RD have been described. These observations are most frequently reported in the Asian population for unknown reasons. Although recent studies demonstrated that IgG4 thyroiditis is a specific entity independent from IgG4-RD, recognition of this unique subset of thyroid disease has yielded important insights into understanding its pathogenesis and the development of novel therapeutic approaches.

Identification of Thyroglobulin and its Isoforms as Target Antigens for IgG4 Thyroiditis

Identification of Thyroglobulin and its Isoforms as Target Antigens for IgG4 Thyroiditis

IgG4‐positive extranodal marginal zone lymphoma arising in Hashimoto's thyroiditis: clinicopathological and cytogenetic features of a hitherto undescribed condition

Hashimoto's thyroiditis was recently divided into IgG4-plasma cell-rich and IgG4-plasma cell-poor subtypes. The former, also known as IgG4 thyroiditis, is associated with clinical, serological, sonographic and morphological features that are distinctive from those of the non-IgG4 subgroup. We describe an interesting case of IgG4-positive mucosa-associated lymphoid tissue (MALT) lymphoma arising in a background of IgG4 thyroiditis. The thyroid gland showed typical features of IgG4 thyroiditis, including characteristic patterns of fibrosis. A dense lymphoplasmacytic infiltrate diffusely involved the entire gland without formation of a destructive tumour mass. Lymphoepithelial lesions were prominent. There were abundant IgG4-positive plasma cells, with the IgG4/IgG ratio exceeding 40%. The IgG4-positive plasma cells were monotypic for kappa light chain, and there was monoclonal IGH rearrangement. Fluorescence in-situ hybridization revealed IGH translocation without translocation of MALT1, bcl-10, or FOXP1. This represents the first case of IgG4-producing MALT lymphoma associated with IgG4 thyroiditis. IGH translocation with an unknown partner gene was identified. We suggest the performance of serum and immunohistochemical investigations for IgG and IgG4 in all cases of Hashimoto's thyroiditis to diagnose IgG4 thyroiditis. In addition, clonality assays and light chain studies are useful to exclude a low-grade lymphoma arising in this context.

The importance of IgG4 in the predictive model of thyroiditis.

SummaryImmunoglobulin (Ig)G4-related sclerosing disease (IgG4-RSD) is a new disease entity first proposed with regard to autoimmune pancreatitis. A 67-year-old male patient was examined because of weight loss and an abdominal pain. Based on the clinical characteristics, laboratory parameters and ultrasound features, we identified the diagnosis of the IgG4-related systemic disease (IgG4-RSD), that was confirmed by the histopathological analysis after the biopsy of the head of pancreas. After confirmation, we started with the corticosteroid therapy with a good clinical, biochemical and morphological response. During the previous therapy, the disturbance of glucoregulation appeared, so we had to change the modality of treatment. We decided to add Azathioprine to the therapy in a dose of 150 mg/day. We achieved a stable phase of the disease with IgG 4.37 g/l and IgG4 0.179 g/l, and with no side effects from the therapy.Learning points There are potential clinical applications of identifying subsets of patients with IgG4 thyroiditis (FVHT and Riedel thyroiditis).A trial of immunosuppressive therapy should be included if a resection is deemed inadvisable.In particular, cases of FVHT that mimic malignancy, tissue and serum IgG4 may provide supportive diagnostic information.

Distribution of serum immunoglobulin G4 levels in Hashimoto's thyroiditis and clinical features of Hashimoto's thyroiditis with elevated serum immunoglobulin G4 levels.

Immunoglobulin G4-related disease (IgG4-RD) is characterized by elevated serum IgG4 levels, IgG4-positive plasmacytes, and lymphocyte infiltration into multiple organs. IgG4 thyroiditis is a subset of patients with Hashimoto's thyroiditis (HT) who exhibited histopathological features of IgG4-RD; its source of serum IgG4 is suggested to be the thyroid gland. Although a relationship between IgG4-RD and IgG4 thyroiditis has been reported, the meaning of serum IgG4 in HT is uncertain. In this report, we prospectively evaluated serum IgG4 levels and clinical features of patients with HT. A total of 149 patients with HT were prospectively recruited into this study. According to the comprehensive diagnostic criteria of IgG4-RD, patients were divided into two groups: elevated IgG4 (>135 mg/dL) and non-elevated IgG4 (≤135 mg/dL). Median serum IgG4 levels of HT patients were 32.0 mg/dL (interquartile range, 20.0-65.0), with a unimodal non-normal distribution. Six patients (4.0%) had elevated serum IgG4 levels above 135 mg/dL. The elevated IgG4 group was older and exhibited enlarged hypoechoic areas in the thyroid gland, as revealed by ultrasonography, relative to the non-elevated IgG4 group. Levothyroxine (L-T4) replacement doses and titers of anti-thyroid antibodies did not differ significantly between the two groups. Two out of six HT patients with elevated serum IgG4 levels had extra-thyroid organ involvement as seen in IgG4-RD. In conclusion, HT patients with elevated serum IgG4 levels shared clinical features with both IgG4-RD and IgG4 thyroiditis. Longer follow-up periods and histopathological assessments are needed to further understand the meaning of elevated serum IgG4 levels in HT.

The role of IgG4 (+) plasma cells in the association of Hashimoto's thyroiditis with papillary carcinoma.

Hashimoto's thyroiditis (HT) is considered to be a risk factor for the formation of papillary carcinoma. The association of IgG4-related sclerosing disease with tumor is reported to be as sporadic cases in many organs. In this study, it was intended to re-classify the HT diagnosed cases on the basis of the existence of IgG4 (+) plasma cells; to investigate the clinicopathologic and histopathologic features of the both groups; and in addition, to evaluate the papillary carcinoma prevalence in IgG4 (+) and IgG4 (-) HT cases as well as the prognostic parameters between these groups. Totally 59 cases between the years 2008-2013, 29 of which contain Hashimoto thyroiditis diagnosis in total thyroidectomy materials, and 30 of which contain the diagnosis of HT+papillary carcinoma, were included in the study. The materials were immunohistochemically applied IgG and IgG4; and the cases were classified in two groups as IgG4-positive HT and IgG4-negative HT containing cases, on the basis of IgG4/IgG rate. All histopathologic and clinicopathologic parameters between these two groups, as well as their association with papillary carcinoma were investigated. Thirty eight (64.4%) of total 59 cases were NonIgG4 thyroiditis, and 21 (35.5%) were IgG4 thyroiditis. Tumors were detected in 14 (36.8%) of the NonIgG4 thyroiditis cases, and in 16 (76.1%) of the IgG4 thyroiditis cases. The association of IgG4 thyroiditis with tumor is statistically significant (p < 0.004). Multifocality was found to be at a higher rate in IgG4 thyroiditis cases. Perithyroidal extension was detected in six of the cases with tumor, and five of the six cases were IgG4 thyroiditis cases. The association of IgG4 (+) HT cases with increased papillary carcinoma prevalence is suggestive of that IgG4 (+) plasma cells can play a role in carcinogenesis in papillary carcinomas developed in HTs, without a chronic sclerosing ground. In addition, although the number of cases is limited, the high-association of IgG4 (+) plasma cells with adverse prognostic parameters such as multifocality and extrathyroidal extension is attention-grabbing. To render these possibilities evaluable, studies to be carried out with larger case series are needed.

A new type of natural bispecific antibody with potential protective effect in Hashimoto thyroiditis.

As a new antibody concept, natural bispecific antibodies (nBsAbs) have been detected in long-term passive immunization and some diseases, but their potential immunomodulatory role remains unclear. Hashimoto thyroiditis (HT) appears to fulfill the condition for nBsAb production but has not yet been characterized. The objective of the study was to identify a new nBsAb against thyroid peroxidase (TPO) and thyroglobulin (Tg) in HT patients and to preliminarily explore its immunomodulatory role. Serum samples were obtained from 136 HT patients, 92 diseased controls, and 99 healthy controls for anti-TPO/Tg nBsAb detection. The relationship between anti-TPO/Tg nBsAb and other clinical parameters was also analyzed. The anti-TPO/Tg nBsAb was detected using a double-antigen sandwich ELISA. Higher nBsAb levels were found to be associated with decreased inflammation in HT patients. The prevalence of anti-TPO/Tg nBsAb in HT was 44.9% (61 of 136), significantly higher than that of diseased controls (2.2%, 2 of 92) (P < .0001) and healthy controls (0%, 0 of 99) (P < .0001). HT patients who were nBsAb positive were prone to have significantly lower levels of serum C-reactive protein and TNF-α compared with the nBsAb-negative individuals (P < .05). The serum amyloid A and interferon-γ levels also showed a similar trend in the two groups. The IgG subclass of anti-TPO/Tg nBsAb was IgG4. Further analysis showed a negative correlation between anti-TPO/Tg nBsAb and serum total IgG4 (r = -0.697, P = .025) in IgG4 thyroiditis patients. A new type of nBsAb against TPO and Tg in HT patients is identified. Our data also indicate a protective effect of anti-TPO/Tg nBsAb in the pathogenesis of HT and extend prior knowledge about nBsAb in diseases.

Hashimoto’s thyroiditis manifesting as IGG4 related disease in a thyroid remnant following total thyroidectomy for grave’s disease

IgG4 related disease (IgG4-RD) is now a widely recognised multi-organ system disease and is an emerging entity characterised by a diffuse or mass forming inflammatory reaction. Recent reports show that it can involve various organs including thyroid and that there is a unique subtype of Hashimoto’s thyroiditis, termed IgG4 thyroiditis, which is histopathologically characterised by lympho-plasmacytic infiltration, fibrosis, increased numbers of IgG4-positive plasma cells, and may have high serum IgG4 levels. Furthermore, IgG4 thyroiditis and non-IgG4 thyroiditis present different clinical features, with IgG4 thyroiditis being more prevalent in males, closely associated with rapid progress, subclinical hypothyroidism, higher levels of circulating antibodies, and more diffuse low echogenicity. We report a case of a 46-year-old woman with Hashimoto’s thyroiditis with histopathological features of fibrosing variant of Hashimoto’s thyroiditis and IgG4 related disease in a remnant thyroidectomy, 6 years after total thyroidectomy for Grave’s disease. It is not unusual for Grave’s disease and Hashimoto’s thyroiditis to coexist or follow one another. Awareness of clinico-pathological and possible radiological features of IgG4 related subset of Hashimoto’s thyroiditis would help better diagose this entity, rationalise treatment and avoid surgical options to diagnose and treat this variant.

Autoimmune thyroiditis in children and adolescents with type 1 diabetes mellitus is associated with elevated IgG4 but not with low vitamin D.

To assess levels of vitamin D and of immunoglobulin G subclasses in children and adolescents with type 1 Diabetes Mellitus with or without autoimmune thyroiditis. Among 213 patients with type 1 diabetes, the cases with thyroid-specific autoantibodies formed Group 1 [n=19, M/F: 7/12, median age 13 years (10.1-14.7)]. Nineteen age-, gender-, and diabetes duration-matched cases with type 1 diabetes without any other systemic disease were designated as controls [Group 2, M/F: 7/12, median age 12.9 years (10.5-14.9)]. Levels of thyroid hormones, vitamin D, total IgG and IgG subclasses, as well as IgG subclasses/total IgG ratios were similar between the groups. Five cases (26%) in Group 1 had IgG4 levels > + 2 SDS, whereas there were no such cases in Group 2 (p=0.046). These five patients had similar clinical features but higher median IgG4 levels and IgG4/Total IgG ratios compared to the subjects with IgG4 levels < + 2 SDS in Group 1 and Group 2. There was no difference of vitamin D levels between the groups. Only a small percentage of patients with type 1 diabetes also having autoimmune thyroiditis had elevated serum IgG4 levels, revealing the heterogeneity of autoimmune thyroiditis and existence of IgG4 thyroiditis in the pediatric age group. Total IgG, the other IgG subclasses, and vitamin D levels did not differ in patients with autoimmune thyroiditis and type 1 diabetes compared to those suffering only from type 1 diabetes.

A Classification of Hashimoto's Thyroiditis Based on Immunohistochemistry for IgG4 and IgG

Hashimoto's thyroiditis (HT) is a common organ-specific autoimmune disease. Antithyroglobulin antibodies (TgAb) and antithyroperoxidase antibodies (TPOAb), predominantly of the immunoglobulin (Ig) G class, are hallmarks of HT. It has been reported that HT can be divided into IgG4 and non-IgG4 thyroiditis. The aim of our study was to investigate the meaning of this classification. Thyroid sections from 53 Hashimoto's patients with stored serum samples were collected to detect IgG4, IgG, α-smooth muscle actin, and transforming growth factor-β1 expression by immunohistochemical staining. The degree of fibrosis of thyroid parenchyma was qualitatively evaluated by Masson's trichrome. Serum total IgG, IgG4, TPOAb IgG, TgAb IgG, TPOAb IgG4, and TgAb IgG4 were detected by enzyme-linked immunosorbent assays (ELISAs). Based on immunohistochemistry for IgG4 and IgG, 12 cases of IgG4-positive HT and 41 cases of IgG4-negative HT were identified in our study. The patients in the IgG4-positive HT group were significantly younger than those in the IgG4-negative HT group (p=0.023), and no significant differences were found in sex distribution, disease duration, and distribution of thyroid functional status between these two groups. The degree of fibrosis evaluated by Masson's trichrome and the immunohistochemical expression score of TGF-β1 in the IgG4-positive HT were significantly higher than those in the IgG4-negative HT (p<0.05). No significant differences were found in the levels of serum IgG4, total IgG, or IgG4/IgG ratio. However, TPOAb IgG4 and TgAb IgG4 levels and the ratios of TPOAb IgG4/TPOAb IgG, TgAb IgG4/TgAb IgG, TPOAb IgG4/IgG4, and TgAb IgG4/IgG4 were significantly higher in the IgG4-positive HT group than those in the IgG4-negative HT group respectively (p<0.05). Our study indicates that HT can be divided into IgG4-positive and IgG4-negative HT, and this classification might have important clinical implications. The levels of IgG4 binding to specific thyroid antigens might be noninvasive markers to differentiate these two different immunophenotypes.

Distinct histopathological features of Hashimoto's thyroiditis with respect to IgG4-related disease

AbstractA form of Hashimoto's thyroiditis with lymphoplasmacytic sclerosing changes and increased numbers of IgG4-positive plasma cells has recently been reported in the literature. These histopathological features suggest that this subtype of Hashimoto's thyroiditis may be closely related to IgG4-related disease. Therefore, this unique form of IgG4-related Hashimoto's thyroiditis, which is referred to as IgG4 thyroiditis, has its own clinical, serological, and sonographic features that are distinct from those associated with non-IgG4 thyroiditis. IgG4 thyroiditis shares similarities with the well-known fibrous variant of Hashimoto's thyroiditis; however, the detailed histopathological features of IgG4 thyroiditis have not been well established. Based on immunostaining results, 105 patients with Hashimoto's thyroiditis were divided into an IgG4 thyroiditis group (n=28) and a non-IgG4 thyroiditis group (n=77). As in our previous reports, IgG4 thyroiditis was associated with a patient population of a younger age, a lower female-to-male ratio, rapid progression, higher levels of thyroid autoantibodies, subclinical hypothyroidism, and diffuse sonographic echogenicity. Histopathologically, this group revealed severe lymphoplasmacytic infiltration, dense stromal fibrosis, marked follicular cell degeneration, numerous micro-follicles, and notable giant cell/histiocyte infiltration. Importantly, the IgG4-related group did not completely overlap with fibrous variant of Hashimoto's thyroiditis. Four cases (14%) in the IgG4 thyroiditis group presented only mild fibrosis in the stroma, whereas 29 cases (38%) in the non-IgG4 thyroiditis group met the diagnostic criteria for fibrous variant of Hashimoto's thyroiditis. Furthermore, we observed three patterns of stromal fibrosis in Hashimoto's thyroiditis: interfollicular fibrosis, interlobular fibrosis, and scar fibrosis. The IgG4 thyroiditis group was significantly associated with the presence of predominant interfollicular fibrosis. In conclusion, IgG4 Hashimoto's thyroiditis presents histopathological features quite distinct from its non-IgG4 counterpart.

IgG4-related disease of the thyroid glands [Review

Recent reports on Hashimoto's thyroiditis (HT) with increased numbers of IgG4-positive plasma cells suggest that this type of HT may have a close relationship to IgG4-related disease (IgG4-RD). This unique subgroup of HT is termed as IgG4 thyroiditis and reveals distinct clinical, serological, and sonographic features from the non-IgG4 thyroiditis group. On the basis of immunostaining for IgG4, HT was divided into an IgG4 thyroiditis group and a non-IgG4 thyroiditis group. Clinically, IgG4 thyroiditis was associated with younger age group, lower female-male ratio, higher levels of thyroid autoantibodies, diffuse low echogenicity, more rapid progress requiring surgical treatment and more subclinical hypothyroidism. Serum IgG4 concentrations elevated in IgG4 thyroiditis and decreased significantly after a thyroidectomy. Histopathologically, IgG4 thyroiditis showed a higher grade of stromal fibrosis, lymphoplasmacytic infiltration, and follicular cell degeneration than non-IgG4 thyroiditis. IgG4 thyroiditis may represent IgG4-RD of thyroid gland, because it shares common histopathological characteristics with IgG4-RD in other organs. The identification of IgG4-RD of the thyroid gland opens new insights not only for patient's treatment with HT but also for the development of new therapeutic approaches for this rapidly progressive destructive subtype of HT. This article mainly focuses on reviewing the unique histopathological, clinical, and serological features of IgG4 thyroiditis group of HT. The etiology and genetic changes of HT are also discussed.

Diagnosis of Hashimoto's thyroiditis and IgG4‐related sclerosing disease

It is about 100 years since the publication of the original description of the disorder now termed as Hashimoto's thyroiditis (HT) or Hashimoto's disease. Hashimoto's thyroiditis has been commonly considered as a well-defined clinicopathological entity, characterized by the presence of goiter and serum thyroid autoantibodies. Very recently, new studies have reported that there is a unique subtype of HT, termed as immunoglobulin (Ig)G4 thyroiditis, which is characterized by lymphoplasmacytic infiltration, fibrosis, increased IgG4-positive plasma cell in the thyroid and high IgG4 level in the serum. Furthermore, from a clinical aspect, IgG4 thyroiditis presents significantly different characteristics from non-IgG4 thyroiditis, with IgG4 thyroiditis being more closely associated with rapid progress, subclinical hypothyroidism, higher levels of circulating antibodies and more diffuse low echogenicity. This review will introduce the most recent concepts about etiologic mechanisms, clinical, imaging and laboratory features of HT and its histological characteristics. Especially, recent advances in recognizing HT with special reference of IgG4-related sclerosing disease (IgG4-RSD) will be summarized. Furthermore, the differences and close relationship between HT and Riedel's thyroiditis (RT), which was also demonstrated to be involved in IgG4-RSD spectrum, will be reviewed.

Hashimoto's thyroiditis: old concepts and new insights

Hashimoto's thyroiditis is commonly considered as a well defined clinicopathological entity. Its diagnosis and treatment have changed little over the last few decades. This review examines the recent progress in understanding Hashimoto's thyroiditis, particularly with regard to its close relationship to IgG4-related systemic disease (IgG4-RSD). During the 1-year review period, new studies have reported that there is a unique subtype of Hashimoto's thyroiditis, termed IgG4 thyroiditis, which is histopathologically characterized by lymphoplasmacytic infiltration, fibrosis, increased numbers of IgG4-positive plasma cells, and high serum IgG4 levels, which indicate that this group of Hashimoto's thyroiditis is closely related to IgG4-RSD. Furthermore, IgG4 thyroiditis and non-IgG4 thyroiditis present different clinical features, with IgG4 thyroiditis being more closely associated with rapid progress, subclinical hypothyroidism, higher levels of circulating antibodies, and more diffuse low echogenicity. In addition, Riedel's thyroiditis was recently demonstrated to be a thyroid manifestation in patients with systemic IgG4-RSD, which calls for the definition of IgG4 thyroiditis to be expanded. New insights into Hashimoto's thyroiditis with special reference to IgG4-positive plasma cells offer a novel way of viewing this well defined disease. IgG4-RSD occurring in the thyroid gland may involve two different manifestations: the organ-specific Hashimoto's thyroiditis type and the systemic Riedel's thyroiditis type, which share similar IgG4-related sclerosing features.

Distribution of IgG4- and/or IgG-Positive Plasma Cells in Hashimoto’s Thyroiditis: An Immunohistochemical Study

Background and Study Aim: Recently, immunohistochemistry has shown numerous IgG4-positive plasma cells in a subset of Hashimoto’s thyroiditis (HT), and this type of HT (IgG4 HT) appears to be a subtype of IgG4-related sclerosing disease. However, little is known about the distribution pattern of plasma cells in IgG4 thyroiditis. To clarify the distribution pattern of IgG4-positive plasma cells, 33 cases of HT demonstrating abundant lymphoplasmacytic infiltrate were studied. Methods: Using formalin-fixed paraffin-embedded sections, histological, immunohistochemistry and polymerase chain reaction were performed. Results: Fourteen cases were classified as IgG4 HT and 19 cases were non-IgG4 HT. Histologically, there was no significant difference between the 2 groups with regard to the degree of stromal fibrosis, lymphoid follicle formation, or the presence of phlebitis or fibrous thyroiditis. The present study demonstrated 2 distribution patterns of IgG4- and/or IgG-positive plasma cells, namely the interfollicular (n = 31) and intrafollicular + interfollicular patterns (n = 2). Interfollicular plasma cells were always polytypic intracytoplasmic immunoglobulin in all 33 cases. However, intrafollicular plasma cells in 2 lesions had monotypic kappa light chain by immunohistochemistry. Conclusion: The present study demonstrated that the majority of IgG4 HT and non-IgG HT cases showed an interfollicular distribution pattern of IgG4- and/or IgG-positive plasma cells.

Distinct Clinical, Serological, and Sonographic Characteristics of Hashimoto’s Thyroiditis Based with and without IgG4-Positive Plasma Cells

IgG4-related sclerosing disease is a new syndrome characterized by high serum IgG4 levels and increased IgG4-positive plasma cells in the involved organs. Recently the first description was made by our group of a subsection of Hashimoto's autoimmune thyroiditis (HT) patients showing indistinguishable histopathological features with IgG4-related sclerosing disease, which was termed as IgG4 thyroiditis. The objective of the study was analysis of the immunophenotypic features of IgG4 in 70 cases of HT patients and to clarify the histopathological and clinical characteristics of the patients with IgG4 thyroiditis. Thyroid tissue samples were obtained from 70 patients with HT who were treated surgically. Quantitative analyses of the expression of IgG4 and IgG were performed. Statistical analyses of clinical and histopathological parameters were also conducted. On the basis of immunohistochemistry of IgG4 and IgG4/IgG ratio, the 70 patients with HT were divided into two groups: IgG4 thyroiditis (19 cases) and non-IgG4 thyroiditis (51 cases). Histopathologically, IgG4 thyroiditis showed higher grade of stromal fibrosis, lymphoplasmacytic infiltration, and follicular cell degeneration than non-IgG4 thyroiditis. Moreover, these two groups were also demonstrated to be related with different clinical features, with IgG4 thyroiditis associated more with male gender, rapid progress, subclinical hypothyroidism, more diffuse low echogenicity, and higher level of circulating antibodies. From both clinical and histopathological aspects, IgG4 thyroiditis and non-IgG4 thyroiditis were demonstrated to be distinct entities. Measuring serum IgG4 concentration provides a useful method of distinguishing IgG4 thyroiditis from non-IgG4 thyroiditis.

Immunohistochemistry of IgG4 can help subclassify Hashimoto's autoimmune thyroiditis

IgG4-related sclerosing disease has been recently recognized as a systemic disease entity characterized by an elevated serum IgG4 level, sclerosing fibrosis and diffuse lymphoplasmacytic infiltration by many IgG4-positive plasma cells. Similar histopathological features have often been noted in the fibrous variant of Hashimoto's autoimmune thyroiditis, but thyroid gland involvement has been only briefly mentioned with regard to IgG4, and no immunohistochemistry for IgG4 has been reported in Hashimoto's autoimmune thyroiditis. Herein, the purpose of the present study was to investigate the infiltration of IgG- and IgG4-positive plasma cells on immunohistochemistry for a panel of thyroiditis samples (Hashimoto's autoimmune thyroiditis, n= 13; subacute thyroiditis, n= 2; lymphocytic thyroiditis, n= 2). Cases of Hashimoto's thyroiditis could be classified into two groups based on immunostaining of IgG4: IgG4 thyroiditis (IgG4-related, IgG4-positive plasma cell-rich thyroiditis) and non-IgG4 thyroiditis (non-IgG4-related, IgG4-positive plasma cell-poor thyroiditis). IgG4 thyroiditis presents with severe lymphoplasmacytic infiltration, dense fibrosis, marked follicular cell degeneration, oxyphilic change and lymphoid follicle formation, while non-IgG4 thyroiditis presents with relatively mild or absent histopathological characteristics. In conclusion, immunostaining of IgG4 can help subclassify Hashimoto's thyroiditis; and IgG4 thyroiditis may have a close relationship with IgG4-related sclerosing disease.