Hashimoto's thyroiditis lacks detectable clonal immunoglobulin and T cell receptor gene rearrangements

The development of B cell lymphoma, predominantly of the large-cell type, in patients with autoimmune diseases such as Hashimoto's thyroiditis or Sjogren's syndrome is well known. In Sjogren's syndrome, it has been recently shown that the benign-appearing lymphocytic infiltrates of the lymphoepithelial lesions in the salivary glands have clonal rearrangements of immunoglobulin genes in their DNA, even in the absence of malignant lymphoma. To investigate whether a similar situation occurs in Hashimoto's thyroiditis, we studied the thyroid glands from four patients with this disease. In all four cases, there was a benign-appearing lymphocytic infiltrate in the thyroid, with eosinophilic changes in the Hurthle cells. In immunologic studies, we determined that the lymphocytes were polyclonal in each case. We extracted DNA from the frozen tissue blocks of these four patients and analyzed it by molecular hybridization for the presence of clonal immunoglobulin (IgH, kappa, and lambda) and T cell receptor beta chain gene rearrangements, and detected none in any case. Therefore, we conclude that the lymphocytes in Hashimoto's thyroiditis are immunologically and immunogenetically polyclonal proliferations of cells, and that the initial lesion of Hashimoto's thyroiditis does not contain a detectable clone of cells that may eventually develop into malignant lymphoma.     

Expression of intercellular adhesion molecule-1 (ICAM-1) on thyroid epithelial cells in Hashimoto's thyroiditis but not in Graves' disease or papillary thyroid cancer.

In order to study the possible role of antigen-independent adhesion systems in thyroid autoimmunity, we evaluated by indirect immunofluorescence the expression of lymphocyte functional antigen-1 (LFA-1) and its ligand ICAM-1 on mononuclear cell infiltrates (when present) and thyroid follicular cells of four patients with Hashimoto's thyroiditis, 30 with Graves' disease, five with papillary cancer, two with follicular adenoma, and two normal thyroid specimens. The expression of MHC class I and class II antigens was also evaluated. Most mononuclear infiltrates were LFA-1 positive, as expected. A positivity for ICAM-1 on follicular cells was observed in three out of four Hashimoto's thyroiditis specimens; such a phenomenon was totally absent in Graves' disease or any other pathological condition, or in normal tissue. MHC class II expression on thyrocytes was observed in all the patients with Hashimoto's thyroiditis, in 27 out of 30 with Graves' disease and in three out of five papillary cancer specimens.     

Hashimoto's thyroiditis as a risk factor of thyroid lymphoma

Hashimoto's thyroiditis (struma lymphomatosa), first described by Hashimoto in 1912, is an autoimmune inflammation of the thyroid commonly affecting middle-aged women. Histologic features of Hashimoto's thyroiditis (HT) include diffuse infiltration of lymphoid cells usually with formation of lymphoid follicles, varying degrees of fibrosis, oxyphilic change or squamous metaplasia in the epithelial cells. When the presence of focal lymphocytic infiltration is assumed to be an adequate criterion for diagnosis of autoimmune thyroiditis, the incidence appears to be as high as 16-23% in elderly females. An etiologically important role of HT in the development of thyroid lymphoma had been postulated, and recently, this was confirmed by epidemiological studies. In this article, a brief review of HT is given, together with results of our studies on thyroid lymphoma, and a discussion in the light of the pertinent literature. Immunologic and immunohistologic studies revealed that all of the thyroid lymphomas were of the B-cell type. Malignant lymphomas developing in patients with other autoimmune diseases such as Sj?gren syndrome and rheumatoid arthritis have also been reported to be B-cell derived. Therefore it is suggested that immune deficiency is a causal factor for B-cell lymphoma.     

Primary B cell lymphoma of the thyroid and its relationship to Hashimoto's thyroiditis

Twenty-one cases were selected from 236 thyroidectomies with a diagnosis of Hashimoto's disease for detailed clinicopathologic study on the basis of "early" changes in three cases and an unusually heavy lymphoplasmacytic infiltrate in 18 cases. These cases were studied in conjunction with ten cases of high-grade non-Hodgkin's lymphoma of the thyroid. Immunoglobulin light chain restriction was demonstrated in five cases of Hashimoto's thyroiditis and the diagnosis was accordingly changed to low-grade lymphoma. All ten high-grade lymphoma cases were of B phenotype and light chain restriction could be demonstrated in eight of them. The study revealed close homology between the lymphoplasmacytic infiltrate in Hashimoto's thyroiditis and normal mucosa-associated lymphoid tissue (MALT). Like lymphomas of mucosal sites, thyroid lymphoma appears to be derived from the parafollicular ("centrocyte-like") B cells. The high-grade thyroid lymphomas appear to be derived from low-grade tumors. There were close histologic, immunohistologic, and clinical similarities between low- and high-grade non-Hodgkin's lymphomas of the thyroid and those appearing in mucosal sites. This study confirms the close association between Hashimoto's thyroiditis and B cell lymphoma of the thyroid gland and suggests that this tumor belongs to the group of non-Hodgkin's lymphomas derived from MALT.     

Hashimoto's Thyroiditis as a Risk Factor of Thyroid Lymphoma

Hashimoto's thyroiditis (struma lymphomatosa), first described by Hashimoto in 1912, is an autoimmune inflammation of the thyroid commonly affecting middle aged women. Histologic features of Hashimoto's Thyroiditis (HT) include diffuse infiltration of lymphoid cells usually with formation of lymphoid follicles, varying degrees of fibrosis, oxyphilic change or squamous metaplasia in the epithelial cells. When the presence of focal lymphocytic infiltration is assumed to be an adequate criterion for diagnosis of autoimmune thyroiditis, the incidence appears to be as high as 16–23% in elderly females. An etiologically important role of HT in the development of thyroid lymphoma had been postulated, and recently, this was confirmed by epidemiological studies. In this article, a brief review of HT is given, together with results of our studies on thyroid lymphoma, and a discussion in the light of the pertinent literature. Immunologic and immunohis-tologic studies revealed that all of the thyroid lymphomas were of the B cell type. Malignant lymphomas developing in patients with other autoimmune diseases such as Sj-gren syndrome and rheumatoid arthritis have also been reported to be B cell derived. Therefore it is suggested that immune deficiency is a causal factor for B cell lymphoma.     

Immunohistochemical detection of p53 and Bcl-2 proteins in Hashimoto's thyroiditis and primary thyroid lymphomas.

AIMS--To investigate whether immunohistochemical staining using p53 and/or bcl-2 distinguishes between florid Hashimoto's thyroiditis and low grade mucosa associated lymphoid tissue (MALT) lymphoma of the thyroid. METHODS--Ten cases of Hashimoto's thyroiditis and eight of primary thyroid lymphoma were stained with monoclonal antibodies directed against p53 and bcl-2. RESULTS--In Hashimoto's thyroiditis most small lymphoid cells in mantle zones, within the thyroid parenchyma and in lymphoepithelial lesions expressed bcl-2 protein. Very occasional centroblasts in reactive germinal centres were positive for p53, but all other lymphoid cells from cases of Hashimoto's disease were negative for p53. In diffuse, low grade lymphomas bcl-2 protein was uniformly expressed by most tumour cells. However, low grade lymphomas with a follicular pattern did not express bcl-2. The diffuse, low grade lymphomas were negative for p53, while occasional larger cells in the follicular subtype were positive. Both high grade lymphomas were bcl-2 negative but strongly p53 positive. CONCLUSIONS--This study indicates that there is an inverse correlation between p53 and bcl-2 immunostaining in thyroid lymphomas (low grade lymphomas: bcl-2 positive, p53 negative; high grade lymphomas: bcl-2 negative, p53 positive). Furthermore, immunohistochemical staining for bcl-2 and p53 proteins does not distinguish florid Hashimoto's thyroiditis from diffuse, low grade thyroid lymphoma.     

Intrathyroidal HLA-DR expression and T lymphocyte phenotypes in Graves'' thyrotoxicosis, Hashimoto''s thyroiditis and nodular colloid goitre.

Thyroid surgical biopsies from 21 individuals were examined by a double immunoenzymatic technique with respect to HLA-DR expression and lymphocytic infiltration. HLA-DR positive thyrocytes were observed in two examined Hashimoto goitres and in nine of 11 specimens from patients with Graves' disease. HLA-DR positive thyrocytes were localized to areas harbouring infiltrating lymphocytes, whereas regions with no lymphocytes only rarely expressed HLA-DR antigens. In two specimens of nodular goitre HLA-DR positive thyrocytes were observed in the vicinity of lymphocytic infiltration. Tissues from another three nodular goitres, from one follicular adenoma and from two normal individuals contained no HLA-DR positive thyrocytes and no or only a few lymphocytes. The lymphocytic infiltrates were dominated by cells with the Leu 3a helper/inducer phenotype irrespective of underlying disease, although most pronounced in Hashimoto's thyroiditis. The results indicate that HLA-DR antigens is expressed on thyrocytes in thyroid disorder. The extent of expression correlated with lymphocytic infiltration, which suggests that the two findings are related and of importance for the development of thyroid autoimmunity.     

Immunohistological phenotyping of thyroid infiltrating lymphocytes in Graves'' disease and Hashimoto''s thyroiditis.

Subsets of lymphocytes in the thyroid were immunophenotyped by their surface antigens in frozen tissues of Hashimoto's thyroiditis and Graves' disease. Using triple layer immunoperoxidase staining (IP), monoclonal antibodies (T3, Leu 3, T8, anti-Tac and Leu 7) were employed to detect markers of T cell subsets, activated T cells, and a natural killer associated antigen. B cells were identified by 2 step IP with anti-IgD antisera. Excluding those cells forming lymphoid follicles, the density of lymphocytes infiltrating between thyroid epithelial cells was much higher in Hashimoto's thyroiditis than in Graves' disease. However, relative proportions of subsets were similar in both diseases. Most of the infiltrating cells were T3 positive T cells (T3+), with more T8+ (suppressor/cytotoxic T) than Leu 3+ (inducer/helper T). Some Leu 7+ were occasionally seen, but surface IgD positive mature B cells (IgD+) were almost absent. In contrast, IgD+ cells were densely aggregated in primary lymphoid follicles and mantle zones of secondary follicles. In these regions, Leu 3+ cells were about twice as frequent as T8+ cells. Some Leu 7+ and scarce Tac+ cells were also found. The present study indicates a major involvement of immunoregulatory T cells in autoimmune thyroid disease, and also suggested intrathyroidal maturation of B cells.     

Nodal and extranodal lymphoproliferative disorders in Sjogren's syndrome: a clinical and immunopathologic study

Sjogren's syndrome (SS) is frequently associated with both reactive and neoplastic lymphoproliferative disease. Over a 12-year period beginning in 1970, 21 of 138 patients with SS followed at two tertiary university medical centers had biopsies taken of enlarged lymph nodes (18) or extranodal lymphoid infiltrates (8). Many had immunologic studies performed on fresh tissue and all had paraffin-embedded tissue available for histochemical and immunoperoxidase studies. Eight of our patients had malignant lymphomas which were chiefly B cell neoplasms including two lymphoplasmacytic lymphomas and two follicular center cell lymphomas. The remaining 13 patients had either reactive adenitis (usually with follicular hyperplasia) or atypical lymphoid hyperplasia which failed to meet both histopathologic and immunopathologic criteria for malignancy. None of the nine patients with reactive hyperplasia has yet progressed to lymphoma, while one of four patients with atypical lymphoid hyperplasia progressed to overt lymphoma. Clinical features such as age, duration of disease, extent of lymphadenopathy, splenomegaly, or parotid swelling failed to identify those subsets of patients with lymphadenopathy at increased risk for lymphoma. Recognition of lymphoma in two patients was greatly facilitated by tissue immunologic studies demonstrating focal areas of monotypic B cell proliferation. In one patient in whom the histopathologic diagnosis was immunoblastic sarcoma of B cells, tumor cells were L26-negative and strongly UCHL1-positive suggesting T cell differentiation. In three patients with relatively homogeneous extranodal lymphoid infiltrates, B cell polyclonality on tissue immunoperoxidase studies, and the absence of cytologic atypia, precluded a diagnosis of malignant lymphoma; none of these three patients has progressed to overt lymphoma. Our results indicate that (1) patients with SS develop a variety of B cell lymphomas and other lymphoproliferative disorders, and (2) the nature of the lymphoproliferative disorder is best determined by multiparameter analysis including immunologic phenotyping.     

Graves' disease: phenotypic and functional analysis at the clonal level of the T-cell repertoire in peripheral blood and in thyroid

We have investigated at the clonal level the repertoire of intrathyroid and peripheral T lymphocytes in three patients with Graves' disease using a high efficiency cloning technique. Clonal efficiencies ranged from 10 to 31% for intrathyroid, and from 19 to 100% for peripheral T cells. In Graves' disease the phenotypic analysis showed similar percentages of CD3+ CD4+ CD8- and CD3+ CD4- CD8+ clones in thyroid infiltrates and peripheral blood. The functional evaluation showed similar or lower proportions of cytolytic clones in thyroid infiltrates with respect to peripheral blood. Furthermore, the proportions of intrathyroid and peripheral T-cell clones capable of releasing interleukin-2 and/or gamma-interferon in response to mitogen stimulation were similar. Finally, 44% of intrathyroid clones were neither cytolytic nor able to release IL-2 and gamma-interferon. These results are strikingly different from those obtained in Hashimoto's thyroiditis, where the large majority of intrathyroid T-cell clones are cytolytic and the proportions of clones able to release gamma-IFN are remarkably increased in thyroid infiltrates when compared to those obtained from peripheral blood. Taken together, these data suggest a different role for T lymphocytes in the pathogenesis of the two major human autoimmune thyroid diseases.     

Malignant T-cell lymphoma of the thyroid gland associated with Hashimoto's thyroiditis

Reported herein is a rare case of malignant T-cell lymphoma of the thyroid gland that developed in a 71-year-old woman with a past history of chronic thyroiditis. The chief complaints were rapidly growing neck mass, weight loss and hoarseness. Presence of abnormal lymphoid cells in the peripheral blood, and an increase in anti-microsome antibodies and anti-thyroglobulin antibodies were found on preoperative laboratory tests. A diagnosis of suspicious malignant lymphoma of the thyroid gland accompanied by Hashimoto's thyroiditis was made, and a total thyroidectomy was performed. Histological examination revealed diffuse small lymphocytic infiltration in the thyroid gland associated with Hashimoto's thyroiditis. Immunohistochemical examination showed that the small lymphocytes were positive for T-cell markers with CD4 predominance. Southern blot analysis of tumor specimens revealed a monoclonal T-cell receptor gene rearrangement. Peripheral T-cell lymphoma was diagnosed. No adjuvant therapy was performed because of the tumor stage and its subtype. The patient is well with no recurrence or metastasis 25 months after the surgical removal of the thyroid. The present case suggests that Hashimoto's thyroiditis might play an important role in the carcinogenesis of thyroid lymphoma not only of B-cell lineage but also of T-cell lineage.     

肺黏膜相关淋巴组织边缘区B细胞淋巴瘤及良性淋巴组织增生性疾病的临床病理分析

目的 研究肺原发性黏膜相关淋巴组织边缘区B细胞(MALT)淋巴瘤及良性淋巴组织增生性疾病的临床病理形态、免疫组织化学表型和B细胞重链基因重排,比较肺MALT淋巴瘤和良性淋巴组织增生性疾病的差异.方法 回顾性的分析原发性肺MALT淋巴瘤13例,7例肺良性淋巴组织增生性疾病资料.对标本行常规HE染色,EnVision免疫组织化学染色(抗体包括AE1/AE3、CD20、CD79α、CD3、CD5、CD10、CD21、bel-2、bcl-6、cyclinD-1)及免疫球蛋白重链IgH基因重排检测.结果 13例肺MALT淋巴瘤,细胞成分多样,分别由不同比例的小淋巴细胞样细胞、中心细胞样细胞、单核样B细胞组成,常伴有浆细胞分化.肿瘤细胞以弥漫性和滤泡边缘区排列为主,常见反应性淋巴滤泡和滤泡中心的植入.肿瘤细胞呈串珠状直接侵犯肺泡间隔和沿支气管血管束向周边及肺膜扩散.MALT淋巴瘤中,均未见坏死.9例可见肿瘤细胞侵犯血管壁,6例可见胸膜累及,2例肺门淋巴结侵犯.9例肺MALT淋巴瘤可见淋巴上皮样病变,免疫组织化学显示上皮细胞内的淋巴细胞CD20阳性,CD3阴性.7例肺良性淋巴组织增生性疾病,2例可见淋巴上皮样病变,免疫组织化学显示,其淋巴上皮样病变内的淋巴细胞,部分CD20阳性,部分CD3阳性.9例肺MALT淋巴瘤进行了免疫球蛋白重链IgH基因重排,8例阳性;7例良性淋巴组织增生性疾病均为阴性.结论 肺MALT淋巴瘤在细胞组成和排列上与其他部位结外MALT淋巴瘤相同,肿瘤细胞呈串珠状直接侵犯肺泡间隔和沿支气管血管束向周边及肺膜扩散.在肺内淋巴上皮样病变常见于MALT淋巴瘤,并有助于诊断,但并非其特异性病变,一些肺的反应性淋巴组织增生也可出现,用免疫组织化学有助于区别两种病变.免疫球蛋白重链IgH基因重排可以帮助鉴别肺MALT淋巴瘤和良性淋巴组织增生性疾病.     

Ultrastructural localization of thyroid peroxidase, hydrogen peroxide-generating sites, and monoamine oxidase in benign and malignant thyroid diseases

Despite thyroid tissue heterogeneity, biochemical and morphological features have been associated with certain thyroid diseases. We analyzed the ultracytochemical localization of thyroperoxidase (TPO), TPO-associated hydrogen peroxide-generating sites (H(2)O(2) sites), and monoamine oxidase (MAO) in terms of morphology and biochemical TPO activity in abnormal thyroids. We examined 11 cases of nontoxic multinodular goiter, 5 cases of Hashimoto's thyroiditis, 1 case of oncocytic (Hürthle or oxyphilic cell) adenoma, 5 cases of Graves' disease, 4 cases of papillary carcinoma, and 4 cases of perinodular normal tissue. In the perinodular tissue, TPO was detected mainly in the nuclear envelope, rough endoplasmic reticulum (RER), and subapical vesicles, but not in the apical surface. In multinodular goiter, heterogeneous TPO reactivity ranging from almost null to strongly positive was detected in similar locations as in the perinodular tissue, and was absent in the microvilli. Follicular cells from Hashimoto's thyroiditis displayed TPO in the nuclear envelope and the scarce RER. Remarkably, oncocytic cells from both Hashimoto's thyroiditis and oncocytic adenoma, typically packed with mitochondria, displayed evident TPO reaction exclusively in mitochondrial cristae. In Graves' disease, the nuclear envelope, enlarged RER, and apical vesicles were strongly TPO positive, and microvilli also exhibited TPO activity. Papillary carcinoma cells were negative for TPO. The localization and characteristics of TPO activity in the H(2)O(2) sites were similar to that of TPO in all tissues. MAO was positive in mitochondria of perinodular tissues, multinodular goiter, and oncocytes and negative in Hashimoto's thyroiditis and Graves' disease. Interestingly, MAO was intensely positive in the nuclear envelope of papillary carcinoma but unreactive in mitochondria. Biochemical TPO activity was increased in multinodular goiter and Graves' disease. In conclusion, several changes in ultracytochemical characteristics of TPO, H(2)O(2) sites, and MAO were associated with thyroid disease. Nonmalignant oncocytic cells exhibited an unusual mitochondrial location of TPO and H(2)O(2) sites. The distribution of MAO in nuclear envelope of papillary carcinoma cells could be a further feature of malignancy.     

Thyroid low-grade B-cell lymphoma (MALT type) with extreme plasmacytic differentiation: report of a case diagnosed by fine-needle aspiration and flow cytometric study

We describe a case of thyroid marginal-zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) with extreme plasmacytic differentiation in an 80-year-old woman who had presented with a rapidly growing thyroid swelling. The diagnosis was initially suspected on fine-needle aspiration (FNA) and subsequently confirmed by flow cytometric analysis of the aspirated material. The smears revealed features of Hashimoto's thyroiditis admixed with large numbers of atypical large plasmacytoid lymphoid cells accompanied by variable numbers of small lymphocytes and mature plasma cells. The differential diagnosis of a predominantly plasmacytic smears on FNA of the thyroid is discussed herein, with emphasis on the role of immunophenotypic studies to exclude or confirm the diagnosis of lymphoma.     

Intrathyroidal lymphocyte subsets, including unusual CD4+ CD8+ cells and CD3loTCR alpha beta lo/-CD4-CD8- cells, in autoimmune thyroid disease.

Intrathyroidal lymphocyte subsets were analysed in 13 euthyroid patients with autoimmune thyroid disease by two-colour flow cytometry and compared with subsets in peripheral blood. In both Graves' and Hashimoto's diseases, proportions of intrathyroidal CD5- B cells were higher than in peripheral blood. The numbers of such cells were correlated with serum levels of anti-thyroid microsomal antibodies. Proportions of T cells bearing alpha beta chains of T cell receptors (TCR alpha beta+ T; T alpha beta) and CD16+CD57+ natural killer (NK) cells were lower in the thyroid, but proportions of CD3hiTCR alpha beta-TCR gamma delta+ (T gamma delta) cells were not different. Proportions of CD4+Leu-8- helper T cells and CD4+CD57+ germinal centre T cells were higher and proportions of CD4+Leu-8+ suppressor-inducer T cells and CD8+CD57+ or CD8+CD11b+ suppressor T cells were lower than in the blood in both diseases. Proportions of CD5+ B cells were high in Graves' disease, and proportions of CD8+CD11b- cytotoxic T cells were high in Hashimoto's disease. Unexpectedly, CD4+CD8+ cells and CD3loTCR alpha beta lo/-CD4-CD8- cells were present in thyroid tissues of both diseases. These findings suggest that: (i) an imbalance in the numbers of regulatory T cells and of NK cells that had appeared in the thyroid resulted in the proliferation of CD5- B cells, which were related to thyroid autoantibody production; (ii) CD5+ B cells and cytotoxic T cells are important for the different pathological features in Graves' and Hashimoto's diseases, respectively; and (iii) intrathyroidal CD4+CD8+ cells and CD3loTCR alpha beta lo/-CD4-CD8- cells may be related to the pathogenesis of autoimmune thyroid disease.     

Evidence of integrity of the follicular basement membrane in Hashimoto's thyroiditis

The basement membrane as an antigenic structure in autoimmune diseases has been a matter of controversy. The purpose of our study was to determine possible structural changes in the follicular basement membrane (FBM) in thyroid autoimmune and non-autoimmune diseases. Immunohistochemical staining for collagen IV and laminin showed that the continuity of the FBM was preserved in toxic adenoma (three cases), atoxic multinodular goiter (nine cases) as well as in autoimmune disease. Integrity of the FBM was observed in all 11 cases of Graves' disease and Hashimoto's thyroiditis (seven cases) studied. In some instances, the FBM was thinned in areas of contact with inflammatory infiltrate. We conclude that the auto-antibodies, and possibly other factors present in autoimmune thyroid diseases, do not significantly alter the integrity of the FBM.     

Increase of peripheral B lymphocytes in Graves' disease.

Peripheral T and B lymphocytes were examined in autoimmune thyroid diseases. The percentages of T and B lymphocytes were calculated from the proportions of E and EAC rosette-forming cells and peroxidase-positive cells determined by micromethods. In thyrotoxic Graves' disease, the percentage of T cells was significantly lower, and the percentage of B cells was higher than in normal controls. The absolute count of B lymphocytes was also markedly increased. The serum levels of thyroid hormones showed a significant correlation with the percentage of B cells and an inverse correlation with that of T cells in untreated cases of Graves' disease. Similar abnormalities of lymphocyte subpopulations were observed in patients with thyrotoxic Graves' disease under drug therapy, but the proportions and absolute counts of T and B lymphocytes were normal in euthyroid patients with Graves' disease, either under drug therapy or in remission. No abnormalities in T and B cells were found in Hashimoto's disease. The data indicate that the main feature of the abnormality of the lymphocyte subpopulations in thyrotoxic Graves' disease is an increase of B lymphocytes. The reasons for the discrepancy between our results and those of earlier reports and for the B cell abnormality in Graves' disease are discussed.     

Ultrastructure of plasma cells containing Russell bodies in human stomach and thyroid

The fine structure is illustrated of plasma cells containing Russell bodies. The material is from chronic inflammatory cell infiltrates in human gastric mucosa and thyroid glands in Graves' disease and Hashimoto's thyroiditis. It is noted that the Russell bodies lie in distended cisternae of rough endoplasmic reticulum and are easily distinguished from less electron-dense ;secretory granules' covered by a smooth membrane that are situated in the Golgi complex.     

Spatial correlation between thyroid epithelial cells expressing class II MHC molecules and interferon-gamma-containing lymphocytes in human thyroid autoimmune disease

In this immunohistochemical study we addressed the question whether aberrant class II MHC expression by thyroid epithelial cells (thyrocytes) in established thyroid autoimmune disease is the result of release of interferon-gamma (IFN-gamma) by adjacent lymphocytes. Thyroids from eight cases of Hashimoto's thyroiditis, 13 cases of Graves' disease and 10 cases of focal thyroiditis were studied. Both thyrocytes expressing class II MHC and lymphocytes containing immunoreactive IFN-gamma were found in all 31 autoimmune thyroids. In a serial section study of these thyroids, IFN-gamma-expressing lymphocytes were found within 50 microns of class II MHC-positive thyrocytes in 89% of 282 randomly selected fields. Conversely, class II MHC-positive thyrocytes were found within 50 micron of aggregates of IFN-gamma-positive lymphocytes in 82% of 272 randomly selected fields. These findings support the view that in established thyroid autoimmune disease expression of class II MHC by thyrocytes is the result of local release of IFN-gamma.