T-cell lymphoma in Hashimoto's thyroiditis

An elderly Caucasian woman with a 2-year-history of hypothyroidism, treated with thyroxine, presented with a rapidly growing mass in the thyroid. The morphological and immunological features of this thyroid tumour were those of a peripheral T-cell lymphoma with an immunophenotype commonly associated with HTLV-1 positive-adult T-cell leukaemia/lymphoma, although serology for HTLV1 antibody was negative. Monoclonal gene rearrangements were demonstrated with T-cell receptor beta- and gamma-specific primers. There are several interesting features in this case (i): although primary B-cell lymphomas (MALT-associated lymphomas) of thyroid are a well-recognized sequel to thyroiditis, primary T-cell lymphomas are rare, even in areas of the world where adult T-cell lymphomas predominate; (ii) the tumour showed the typical immunophenotype of an HTLV-1 positive T-cell lymphoma but the patient is English, has not visited endemic areas, and is serologically negative for HTLV–1; (iii) the residual thyroid gland showed a florid lymphocytic thyroiditis with Hu¨rthle cell change, typical of Hashimoto's thyroiditis; (iv) unlike other reports of thyroid T-cell lymphoma, which have presented with stage III-IV disease, this tumour presented in the favourable clinical stage of IE.     

Primary non-Hodgkin's lymphoma of the thyroid gland: a population based study

During a 9-year-period, 50 cases of primary non-Hodgkin's lymphoma (NHL) of the thyroid gland were reported to a population-based lymphoma registry covering western Denmark giving an incidence of 2.06×10⁻⁶ cases per year. The male:female ratio was 1:4, and the mean age was 72.8 years for women and 62.8 years for men. On histomorphological reclassification 83% of the cases showed a high grade and 17% a low grade morphology. 98% had a B-phenotype and 2% a T-phenotype. In at least 33 of the cases, primary NHL of the thyroid gland was preceded by Hashimoto's thyroiditis and at least 25 of the patients had a high grade NHL which was transformed from Hashimoto's thyroiditis through a low grade B-cell lymphoma of MALT type. The most frequent presenting symptoms were goitre (100%), hoarseness (57%), stridor/dyspnoea (55%) and dysphagia (45%); thirty-six percent of the patients were hypothyroid at the time of diagnosis. Seventy-six percent of the patients had localized disease (stages 1–2) and 24% had disseminated lymphoma (stages 3–4). Five year survival was 34.5% and 5 year cause-specific survival 46.2%. The following factors were associated with a poor prognosis: stage 3–4 disease, elevated S-urate, presence of hoarseness and age >66 years. Morphological subtype did not correlate significantly with survival.     

Mutations of the BRAF gene in papillary thyroid carcinoma and in Hashimoto's thyroiditis

The purpose of the present study was to investigate the frequency of BRAF mutations in human papillary thyroid carcinoma (PTC) and Hashimoto's thyroiditis (HT) and to evaluate the association of the BRAF mutation with the clinicopathological features of both of these thyroid disorders. A total of 51 PTC with no HT, 28 PTC with HT and 27 HT with no PTC were evaluated using DNA extracted from paraffin-embedded specimens. BRAF mutations were analyzed by direct DNA sequencing of the polymerase chain reaction (PCR)-amplified exon 15. The BRAF missense mutation at codon 599 (T1796A) was present in 46 of 51 PTC (90%) with no HT, 18 of 28 PTC (64%) with HT, four of 28 HT (14%) with PTC, and zero of 27 HT with no PTC. The BRAF mutation at codon 600 (A1798G) was not detected in any case. Clinicopathological examination of 106 patients with either PTC or HT showed that the BRAF mutation was significantly correlated with patient age. These data indicate that the BRAF mutation is associated with a valuable biological property of PTC and may participate in the pathogenesis of PTC arising in HT. These results indicate that the detection of the BRAF mutation in HT can be helpful for prediction of progress to PTC.     

Hashimoto's thyroiditis shares features with early papillary thyroid carcinoma

Neoplastic transformation is a multistep process that results in a continuous spectrum from the normal (physiological) state to a fully established neoplasm. The gold standard for diagnosis of papillary thyroid carcinoma is conventional histology, the essential element being the characteristic nuclear features, regardless of whether papillary structures are present or not. However, other criteria are being used increasingly in the diagnosis of neoplasms, including immunohistochemical staining and molecular profile. The RET/PTC gene rearrangement is highly specific for papillary thyroid carcinoma and is associated with the characteristic nuclear features seen in papillary thyroid carcinoma. There is an overlap in the morphological features, immunohistochemical staining pattern, and most importantly, molecular profile between papillary thyroid carcinoma and Hashimoto's thyroiditis. Although considered a 'benign' condition, Hashimoto's thyroiditis almost always harbours a genetic rearrangement that is strongly associated with and is highly specific for papillary thyroid carcinoma. Submicroscopic foci of papillary thyroid carcinoma must be present in Hashimoto's thyroiditis, although the clinical behaviour is still benign. Further studies are required to predict which foci will progress to papillary thyroid carcinoma.     

Plasmacytoma and follicular lymphoma in a case of Hashimoto''s thyroiditis

Monoclonal gammopathy (IgG, lambda) in a 37-year-old man with Hashimoto's thyroiditis, was markedly decreased after thyroidectomy. Histological examination of the thyroid showed large lymphoid follicles surrounded by a massive proliferation of plasma cells. Immunological studies revealed that interfollicular plasma cells stained monotypically for lambda chain, findings in keeping with a diagnosis of plasmacytoma of the thyroid. In addition, there was kappa monotypic staining of the lymphoid follicles and absence of tangible body macrophages, indicating the presence of a follicular lymphoma derived from a separate cell line from the plasmacytoma.     

桥本甲状腺炎伴甲状腺癌临床病理分析

目的　探讨桥本甲状腺炎 (Hashimoto’sthyroiditis,HT)与甲状腺癌的关系。 方法　对 80例HT和其中 14例并发甲状腺癌的HE片进行形态学观察 ,部分病例进行PCNA、p5 3免疫组化标记。结果　HT及甲状腺癌旁组织有滤泡上皮细胞增生、乳头状增生、不典型增生至癌变移行 (过渡 )的形态 ,其PCNA表达逐渐增强 (P <0 0 1) ,p5 3在少数不典型增生及癌变区呈低度阳性表达 (P <0 0 5 )。结论　HT与甲状腺癌发生关系密切 ,HT中甲状腺滤泡上皮增殖活跃 ,易于癌变。HT是一种具有恶变潜能的病变 ,应引起高度重视。     

Postpartum silent thyroiditis simulating a malignant lymphoma of the thyroid

A case of postpartum silent thyroiditis simulating a malignant lymphoma of the thyroid is reported. The patient was a 30-yr-old female who had received irradiation thearapy to the neck for malignant lymphoma of the thyroid 9 yr previously. She was referred to our department because of a struma associated with acute aggravation of chronic thyroiditis after parturition. In this case, the mechanism of the disease was explained by the “immune rebound hypothesis”. It was difficult to differentiate postpartum silent thyroiditis from malignant lymphoma of the thyroid, either clinically or cytologically, when the immune-rebound phenomenon with lymphocytic infiltration and the appearance of lymphoid follicles were prominent. The immunological status of patients with chronic thyroiditis accompanied by morphological changes should be taken into consideration before establishing the diagnosis of malignant lymphoma of the thyroid.     

Hashimoto's thyroiditis with papillary thyroid carcinoma (PTC)-like nuclear alterations express molecular markers of PTC

AIMS: Focal papillary thyroid carcinoma (PTC)-like nuclear alterations have been documented in Hashimoto's thyroiditis; however, the molecular association between PTC and Hashimoto's thyroiditis is poorly understood. The aim of this study was to determine whether molecular expression patterns of PTC are present in association with PTC-like nuclear alterations in Hashimoto's thyroiditis. METHODS AND RESULTS: The expression of four genes known to be up-regulated in PTC [LGALS3 (galectin3), CITED1, KRT19 (cytokeratin 19) and FN1 (fibronectin-1)] and the human mesothelial cell protein identified by monoclonal antibody HBME1 was evaluated. Immunohistochemistry was performed on 23 cases of Hashimoto's thyroiditis with focal or diffuse Hürthle cell change and PTC-like nuclear alterations, 37 PTC and 18 normal thyroids. Focal expression of galectin3 (GAL3), CITED1, cytokeratin 19 (CK19), HBME1 and fibronectin-1 (FN1) was seen in 87%, 65%, 43%, 26% and 17% of Hashimoto's thyroiditis, respectively, only in thyrocytes showing PTC-like nuclear alterations. In contrast, diffuse expression of GAL3, CITED1, CK19, HBME1 and FN1 was seen in 100%, 95%, 70%, 87% and 89% of PTC, respectively. Normal thyroid tissues did not express any of these proteins. Following immunohistochemistry, four Hashimoto's thyroiditis cases were found to contain foci of PTC. These foci were highlighted by the diffuse and strong expression of PTC-associated proteins, which prompted additional retrospective scrutiny of the haematoxylin and eosin-stained sections leading to appreciation of complete PTC-type nuclear atypia. CONCLUSIONS: Focal PTC-like immunophenotypic changes in Hashimoto's thyroiditis suggest the possibility of early, focal premalignant transformation in some cases of Hashimoto's thyroiditis.     

Immunohistological findings in Hashimoto's thyroiditis,focal lymphocytic thyroiditis and Thyroiditis de Quervain

Summary 65 cases of focal lymphocytic thyroiditis and Hashimoto's disease and five cases of thyroiditis de Quervain were studied with immunohistological methods. In both focal lymphocytic thyroiditis and Hashimoto's disease, lymph follicles with active germinal centers were found which contained germinal center cells that stained positively for intracytoplasmic immunoglobulins (heavy and/or light chains). Positively staining germinal center cells made up only a minor portion of overall immunoglobulin-positive cells; most of the positive infiltrating cells were plasmacytes arranged in small groups or clusters among thyroid follicles. Thus the number of immunoglobulin-containing cells differed greatly between focal lymphocytic thyroiditis, where sites of infiltration were represented by lymph follicles, and Hashimoto's disease. In the former, only a few cells outside lymph follicles stained positively for intracytoplasmic immunoglobulins, whereas in the latter numerous cells within areas of coherent infiltration did. Furthermore, in most cases of Hashimoto's disease macrophages and giant cells with positive staining for lysozyme were present in variable numbers, while in focal thyroiditis they were less frequent or absent. Between these two immunohistologically separable groups, i.e. focal lymphocytic thyroiditis and Hashimoto's disease, there were many cases with features of both. Considering the occurrence of such intermediate forms and some immunohistological similarities between Hashimoto's disease and focal lymphocytic thyroiditis (nearly identical ratio of the different immunoglobulin classes and similar distribution of immunoglobulin-positive germinal center cells), it is likely that these lesions represent different activities of a same immunological process.Thyroiditis de Quervain was characterized immunologically by numerous macrophage clusters and giant cells that both stained positively for lysozyme. Compared with the giant cells seen in Hashimoto's disease (mainly of Langhans type), those of de Quervain's thyroiditis (mainly of foreign body type) were larger and more numerous. Lymph follicles (with or without active germinal centers) were not observed. Among infiltrating cells, numerous plasmacytes that stained positively for intracytoplasmic immunoglobulins were identified. Their number and the distribution pattern of the different classes of immunoglobulins contained within them was similar to those seen in Hashimoto's disease.     

Hemangioma of the thyroid gland in an adolescent with chronic lymphocytic thyroiditis and adenomatous hyperplasia

We report a case of benign hemangioma of the thyroid gland which involved one lobe of the thyroid gland in an adolescent female with classic chronic lymphocytic thyroiditis and adenomatous hyperplasia. The lesion produced a clinical picture suspicious for malignancy owing to the presence of a very large cold nodule on scan, lack of response to TSH suppression, and the subsequent development of an enlarged cervical lymph node. The histologic and immunohistologic findings, including positive staining for factor VIII-related antigen,Ulex europaeous lectin, CD31, CD34, and the presence of linear staining for type IV collagen and laminin are consistent with a hemangioma. In our review of the literature, only one other report of a hemangioma of the thyroid gland was found.     

Concurrent T-cell lymphocytic lymphoma and malignant histiocytosis

A case in which both malignant histiocytosis and T-cell lymphocytic lymphoma occurred together is presented. Examples of malignant histiocytosis-like syndromes associated with lymphoreticular malignancies have been previously reported. Many of these represent reactive haemophagocytic syndromes, probably virally induced. The considerable degree of cytological atypia and frequent mitotic figures seen in the histiocytes in this case were indicative of a true malignant histiocytosis.     

Medullary thyroid carcinoma co‐existent with Hashimoto's thyroiditis diagnosed by a comprehensive cytological approach

Fine‐needle aspiration cytology (FNAC) is a preliminary test for the diagnosis of thyroid lesions. We hereby report a rare case of medullary thyroid carcinoma (MTC) co‐existing with Hashimoto's thyroiditis (HT). This case was substantiated with ancillary tests on cytology material to give a novel insight. A 60‐year‐old female presented clinically with diffuse enlargement of the thyroid, and right‐side nodule on ultrasonography. FNAC of the isthmic area showed features of HT, while cytology of right‐side nodule displayed sheets of plasmacytoid cells and frequent scattered large bizarre and pleomorphic cells, lymphoglandular bodies and pale eosinophilic material. The differential diagnosis of MTC with co‐existent HT or high‐grade lymphoma was considered. To establish the diagnosis, serum calcitonin and ancillary studies on aspirated material were carried out. High serum calcitonin (7251 pg/mL), Congophilia on smears, and CD 45?ve; CD56+ve expression of tumor cells on flowcytometric analysis established the diagnosis of MTC over lymphoma. This diagnosis was further confirmed upon histopathology. Ancillary studies on aspirated material established the diagnosis of MTC and excluded the diagnosis of lymphoma. Establishing the correct diagnosis was cardinal in such a scenario as these diseases have extremely diverse management.     

Evidence of HTLV-I in thyroid tissue in an HTLV-I carrier with Hashimoto's thyroiditis

Human T-lymphotropic virus type I (HTLV-I) protein and messenger RNA (mRNA) for HTLV-I were examined in thyroid tissues from two patients with Hashimoto's thyroiditis and serum anti-thyroid antibody. The virus envelope protein and signals for the mRNA were detected in many of the follicular epithelial cells of the thyroid tissue from one of the patients, respectively, by immunohistochemistry and in situ hybridization. PCR-Southern blotting revealed the presence of HTLV-I DNA in the thyroid tissue, in which the viral protein and mRNA were detected, although no virus particles were found in the epithelial cells by electron microscopy. HTLV-I virus was not present in the thyroid tissue from the second patient. The present findings suggest that infection of thyroid tissue with HTLV-I is associated with the pathogenesis of Hashimoto's thyroiditis in some patients.Abbreviations HTLV-I Human T-lymphotropic virus type 1     

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.     

Follicular thyroid lesions coexisting with Hashimoto's thyroiditis: incidence and possible sources of diagnostic errors

Our objectives were to study the types and incidence of thyroid follicular lesions coexisting with Hashimoto's thyroiditis (HT), the pitfalls in their cytodiagnosis, and the effect on management. All cases of HT diagnosed by fine-needle aspiration (FNA) and/or histology over a 7-yr period were retrospectively studied. HT coexisted with follicular adenoma (FA) in 6 cases, follicular variant of papillary carcinoma (FVPC) in 1 case, and goitrous nodule (GN) in 2 cases. The overall incidence rates of thyroid neoplasm and goitrous nodules coexistent with HT were 15% and 3.5%, respectively. A preoperative FNA diagnosis was available in 10 histologically proven cases of HT. A false-positive diagnosis of follicular neoplasm (FN) that led to unnecessary thyroidectomies was given in 3 cases. In 2 of these, the cytological diagnosis was HT with the possibility of coexisting FN, and in the third case, the cytological finding of HT was misinterpreted as FN. The main causes of these diagnostic pitfalls were the presence of hyperplastic follicular cells with nuclear pleomorphism, a paucity of lymphoid cells in burned-out HT, and lack of ones exposure. Nuclear pleomorphism was observed in none of the follicular adenomas. FNA diagnosed accurately the coexisting lesions in 6 cases; 3 FA, 1 FVPC, and 2 GN, but it did not sample HT. In one case, FNA diagnosed correctly both HT and the coexisting FA. Therefore, the presence of a coexistent neoplasm or goitrous nodule reduced the chances of sampling HT by 85.7%, with no false-negative results. Indeed, aspiration on and around the thyroid nodule helps in sampling HT. However, HT may dominate the smear and obscure neoplasia. This can be avoided if the procedure is performed by the pathologist and the aspiration is done on the nodule only. The overlapping cytological features of FN and HT were the main causes of false-positive results. This can be reduced by avoiding the diagnosis of FN in the presence of follicular-cell pleomorphism and/or moderate to excessive numbers of lymphoid cells, provided proper aspiration technique is maintained.     

甲状腺粘膜相关淋巴瘤与淋巴细胞性甲状腺炎的临床病理及免疫组化研究

报道甲状腺粘膜相关淋巴瘤１２例，淋巴性甲状腺炎６例。淋巴性甲状腺炎分为轻、中、重三级。研究上述１８例有免疫组化结果的资料，发现粘膜相关淋巴瘤多见于老年女性，并从淋巴细胞性甲状腺炎发展演变而来，以中心细胞样细胞为多见，免疫组化示Ｂ－细胞性单克隆性。组织病理学上常形成淋巴上皮病变，瘤栓样或戒指样结构。本文探讨了淋巴性甲状腺炎与甲状腺粘膜相关淋巴瘤的发病机理、鉴别诊断及治疗方法的选择等。     

CTLA-4 promoter variants in patients with Graves' disease and Hashimoto's thyroiditis

Abstract: Graves' disease (GD) and Hashimoto's thyroiditis (HT) are T-cell mediated organ-specific autoimmune disorders with a genetic predisposition. The cytotoxic T-lymphocyte antigen 4 (CTLA-4) molecule is the predominant receptor for B7 on activated T cells and represents a negative regulator for T-cell function. Since the CTLA-4-guanine at position 49 of exon 1 is associated with susceptibility to GD as well as to HT and IDDM, we investigated a recently detected cytosine/thymine substitution at position -318 within the CTLA-4 promoter region in patients with GD and HT. 125 patients with GD were significantly more often homozygous for cytosine (86% vs. 73% in controls, P=0.006) and less frequently heterozygous for cytosine and thymine (14% vs. 27%, P=0.008). In 64 patients with HT, the distribution was similar but not significant (81% homozygous for cytosine and 16% heterozygous). When correlating the promoter and the exon 1 polymorphism we found the strongest linkage between thymine (promoter) and adenine (exon 1). In conclusion, a promoter variant of the CTLA-4 gene represents an additional risk marker for GD and HT, but their predisposition is linked to the exon 1 alleles.