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.     

Regenerative hyperplasia of follicular epithelium in chronic lymphocytic thyroiditis.

The thyroid gland is an endocrine organ composed of stable cells. It is well known that regenerative capacity of the thyroid tissue is minimal. Various degrees of morphologic alterations do occur in chronic lymphocytic thyroiditis (CLT), including Hashimoto's thyroiditis. Eighty-five CLT cases were analyzed for these morphologic alterations. Small, irregular, atrophic or hyperplastic thyroid follicles were seen adjacent to the lymphocytic infiltration. There was nuclear enlargement, loss of nuclear polarity in thyrocytes and intrafollicular thyrocyte proliferation in these follicles. We thought that the morphologic alterations in involved follicles could be due to regenerative hyperplasia with increased proliferative activity and basement membrane abnormalities. To examine this hypothesis we investigated Ki-67 and laminin immunoreactivity in the involved follicles adjacent to lymphocytic infiltration areas. The uninvolved follicles were used as controls. Immunopositivity of Ki-67 in involved follicles was significantly higher than that in uninvolved follicles (2.97% +/- 2.16 versus 0.83% +/- 1.63, P < 0.001). Laminin immunostaining indicated the destruction or irregular distribution of basement membrane in involved follicles. We conclude that the increased cell proliferation activity and basement membrane abnormalities in the follicles with morphologic changes adjacent to CLT occur in conjunction with regenerative hyperplasia.     

The association between chronic lymphocytic thyroiditis and thyroid tumors

An association between lymphocytic thyroiditis and thyroid papillary carcinoma is still controversial. To assess the relationship, a histopathologic analysis of surgically resected thyroid tumors together with the frequency and severity of chronic lymphocytic infiltration of the thyroid among patients with follicular adenoma, follicular carcinoma, and papillary carcinoma was performed. The prevalence of lymphocytic infiltrate, which is indicative of autoimmune thyroiditis, was significantly higher in patients with papillary carcinoma (58%) than in patients with follicular carcinoma (20%) or follicular adenoma (14%). The lymphocytic infiltration within the tumor compared with the severity of thyroiditis in the nontumorous tissue. Therefore, the association between chronic lymphocytic thyroiditis and papillary carcinoma was confirmed. The possibility that an immunologic mechanism involved in the pathogenesis of papillary carcinoma stimulates lymphocytic infiltration in the thyroid tissue through an autoimmune mechanism is suggested.     

Focal lymphocytic thyroiditis in Southampton

The presence of focal collections of lymphocytes within the thyroid gland has been associated with autoimmune thyroiditis. In a prospective study 197 thyroid glands were examined from post mortems performed in two Southampton hospitals over a 12 month period. The mean thyroid mass was 19.5 g in women and 22.2 g in men. Varying degrees of focal lymphocytic thyroiditis were present in 54 per cent of women and 24 per cent of men. Morphometry showed that on average less than 4 per cent of the gland was infiltrated by lymphocytes. There was no significant relationship with age. A possible association between focal lymphocytic thyroiditis and circulating thyroid autoantibodies has been shown.     

慢性淋巴细胞性甲状腺炎患者外周血Th17的检测及意义

目的:探讨慢性淋巴细胞性甲状腺炎(CLT)患者外周血辅助性T细胞17(Th17)的水平及意义.方法:收集甲状腺功能正常组CLT患者15例,甲状腺功能减退组CLT患者30例及20例健康对照组研究者的外周血样.采用胞内细胞因子染色流式细胞术(FCM)分析法,检测各组外周血Th17细胞占CD4+T细胞比值.应用电化学发光法检测CLT患者及健康对照组血清中抗甲状腺过氧化物酶抗体(TPO-Ab)和抗甲状球蛋白抗体(TG-Ab)水平.结果:与健康对照组比较:甲状腺功能正常组及甲状腺功能减退组的CLT患者外周血Th17/CD4+T细胞比值分别为(3.64±1.96)%、(3.13±1.56)%,均高于健康对照组(0.50±0.32%,P<0.01);两组CLT患者血清TPO-Ab和TG-Ab水平分别为(398.99±222.88;1456.02±1054.97)IU/L和(423.26±167.21;1587.94±1210.36)IU/L,均明显高于健康对照组(15.23±10.36;36.32±26.99)IU/L;差异有统计学意义(P<0.01).CLT患者外周血Th17/CD4+T细胞比值改变与血清TPO-Ab及TG-Ab阳性表达呈显著正相关(分别为r=0.50,r=0.43;P<0.01).结论:两组CLT患者外周血Th17细胞比率增加,且与甲状腺自身抗体水平存在显著正相关,Th17细胞可能参与CLT的发生发展.     

Loss of heterozygosity mutations of tumor suppressor genes in cytologically atypical areas in chronic lymphocytic thyroiditis

The relationship between chronic lymphocytic thyroiditis (CLT) and papillary thyroid carcinoma (PTC) is a subject of controversy. Some investigators suggest a causal relationship, whereas others regard the two as only a coincidental occurrence. An additional complicating factor is the presence of atypical nuclei frequently found within lymphoid infiltrates in CLT, which resemble those in PTC. The finding of the RET-PTC translocations in CLT has been reported by two independent groups of investigators, suggesting that the areas of nuclear atypia in CLT are neoplastic rather than reactive. In the present study, we report additional molecular findings that support the hypothesis that the atypical nuclear changes in CLT may be preneoplastic or neoplastic. We microdissected small areas with atypical nuclei in glands with CLT and observed loss-of-heterozygosity mutations of tumor suppressor genes. These genetic mutations are evidence of clonal preneoplastic or neoplastic changes in the follicular cells of CLT. The clinical malignant potential of these minute foci is likely to be very small but remains to be determined.     

Expression of tenascin in lymphocytic autoimmune thyroiditis.

AIMS: To study the distribution of tenascin by immunocytochemistry in autoimmune diseases of the thyroid. METHODS: Thyroids from patients with inflammatory lesions of the thyroid (lymphocytic thyroiditis Hashimoto, Grave's disease, thyroiditis DeQuervain) were studied by immunocytochemistry using antibodies against tenascin, collagen III, and collagen IV. RESULTS: In autoimmune lymphocytic thyroiditis Hashimoto there was a characteristic corona-like staining pattern of tenascin around all activated lymph follicles with germinal centres. This staining pattern contrasted with the immunoreactions for collagen III and IV, which were not enhanced in the perilymphofollicular interstitium. In cases of thyroiditis DeQuervain the areas of early and ongoing fibrosis showed some diffuse staining for tenascin and for collagen III. Enhanced diffuse immunostaining for collagen IV in the perivascular and interfollicular interstitium was present in cases of Grave's disease. In Grave's disease no characteristic immunoreaction was detectable for tenascin. CONCLUSIONS: The corona-like expression of tenascin around lymphofollicular infiltrates is distinctive of cases of lymphocytic thyroiditis. A similar staining pattern for tenascin has been reported in lymphoid hyperplasia of the thymus associated with myasthenia gravis, another autoimmunological disorder. There are good arguments that the activation and infiltration of lymph follicles in the thyroid during the course of autoimmune diseases lead to stimulation and activation of the surrounding mesenchyme producing tenascin as part of the extracellular matrix.     

NO介导细胞因子失衡致儿童慢性淋巴细胞性甲状腺炎发病的作用

目的探讨一氧化氮(nitricoxide,NO)介导的细胞因子失衡 ,在儿童慢性淋巴细胞性甲状腺炎(CLT)发病中的作用。方法对初诊(CLT)患儿13例外周血单个核细胞(PBMC)产生的NO水平及其与IFN γ和IL 4水平失衡和甲状腺功能受损的关系进行了研究。结果与正常组相比 ,患儿NO和IFN γ水平明显升高(P<0.001) ,IL 4的水平明显降低(P<0.002) ;NO水平与IFN γ和血清TSH水平呈显著的正相关(P<0.05) ,而与IL 4及血清T3 ,T4的水平呈显著的负相关(P<0.05)。结论NO作为细胞因子水平失衡的介质 ,参与了CLT的发病。     

Loss of heterozygosity mutations to tumor suppressor genes in cytologically atypical areas in chronic lymphocytic thyroiditis

The relationship between chronic lymphocytic thyroiditis (CLT) and papillary thyroid carcinoma (PTC) is a subject of controversy. Some investigators suggest a causal relationship, whereas others regard the two as only a coincidental occurrence. An additional complicating factor is the presence of atypical nuclei frequently found within lymphoid infiltrates in CLT, which resemble those in PTC. The finding of the RET-PTC translocations in CLT has been reported by two independent groups of investigators, suggesting that the areas of nuclear atypia in CLT are neoplastic rather than reactive. In the present study, we report additional molecular findings that support the hypothesis that the atypical nuclear changes in CLT may be preneoplastic or neoplastic. We microdissected small areas with atypical nuclei in glands with CLT and observed loss-of-heterozygosity mutations of tumor suppressor genes. These genetic mutations are evidence of clonal preneoplastic or neoplastic changes in the follicular cells of CLT. The clinical malignant potential of these minute foci is likely to be very small but remains to be determined.     

Poly(I∶C)加重碘过量诱发的NOD鼠慢性淋巴细胞性甲状腺炎

目的:探讨poly(I∶C)作为病毒类似物对碘过量所致NOD鼠慢性淋巴细胞性甲状腺炎的影响。方法:将32只雌性NOD鼠,随机分为4组,每组8只,分别为:(1)对照组;(2)碘过量组;(3)poly(I∶C)组;(4)碘过量联合poly(I∶C)组。作用9周后处死动物:观测体重、甲状腺重量及其解剖形态;采用放射免疫分析法检测血清中甲状腺激素(T4)水平;HE染色观察甲状腺组织形态变化,TUNEL技术检测甲状腺组织细胞凋亡情况,定量PCR法检测凋亡相关基因(TRAIL、TRAIL-sR1)和炎症相关基因(ICAM-1、CXCL10)mRNA表达。结果:碘过量组较对照组、Poly(I∶C)组甲状腺绝对重量及相对重量均明显增加(P0.01);血清总T4水平下降(P0.05);炎症破坏和细胞凋亡明显加强;上调TRAIL、TRAIL-sR1、ICAM-1、CXCL10mRNA表达(P0.05)。碘过量联合poly(I∶C)组较单纯碘过量组甲状腺绝对重量及相对重量均进一步增加;血清总T4水平显著下降(P0.05);炎症进一步加重,破坏程度IV级所占比例升至50.0%;凋亡细胞数量明显增加,进一步上调TRAIL、TRAIL-sR1、ICAM-1、CXCL10mRNA表达(P0.05)。Poly(I∶C)组各值与对照组趋势一致(P0.05)。结论:Poly(I∶C)加重碘过量所致慢性淋巴细胞性甲状腺炎发病程度,其作用途径与增加淋巴细胞浸润和甲状腺细胞凋亡有关。     

Neuropsychological functioning in depressed adolescent girls

BACKGROUND: Neuropsychological impairment has been demonstrated in adults with depression. Whether depression arising during adolescence is associated with similar changes is unknown. We describe the neuropsychological functioning of a referred sample of medication-na?ve adolescent girls meeting criteria for a diagnosis of Depressive Episode (ICD-10). METHODS: A cross-sectional study of 28 girls (ages 12-16); 14 with depression, 14 healthy controls matched for age, IQ and socio-economic status. Neuropsychological testing was conducted using the CANTAB automated test battery. RESULTS: Depressed adolescent girls showed performance deficits on visual memory tasks (Pattern Recognition, Delayed Matching to Sample and Paired Associates Learning), one measure of motor speed and on a test of Spatial Working Memory. LIMITATIONS: A restricted range of neuropsychological testing was performed on a female-only sample of modest size. CONCLUSIONS: Depressive episodes in adolescent girls are associated with neurocognitive deficits similar to those previously defined in adult populations and these impairments can be detected prior to exposure to psychotropic drugs. Neuropsychological impairment may be an important, neglected clinical feature in adolescent depression.     

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.     

Coexistence of chronic lymphocytic thyroiditis with papillary thyroid carcinoma: clinical manifestation and prognostic outcome

The study aimed to identify the clinical characteristics of coexisting chronic lymphocytic thyroiditis (CLT) in papillary thyroid carcinoma (PTC) and to evaluate the influence on prognosis. A total of 1,357 patients who underwent thyroid surgery for PTC were included. The clinicopathological characteristics were identified. Patients who underwent total thyroidectomy (n = 597) were studied to evaluate the influence of coexistent CLT on prognosis. Among the total 1,357 patients, 359 (26.5%) had coexistent CLT. In the CLT group, the prevalence of females was higher than in the control group without CLT (P < 0.001). Mean tumor size and mean age in the patients with CLT were smaller than without CLT (P = 0.040, P = 0.047, respectively). Extrathyroidal extension in the patients with CLT was significantly lower than without CLT (P = 0.016). Among the subset of 597 patients, disease-free survival rate in the patients with CLT was significantly higher than without CLT (P = 0.042). However, the multivariate analysis did not reveal a negative association between CLT coexistence and recurrence. Patients with CLT display a greater female preponderance, smaller size, younger and lower extrathyroidal extension. CLT is not a significant independent negative predictive factor for recurrence, although presence of CLT indicates a reduced risk of recurrence.     

The familial occurrence of lymphocytic thyroiditis in borzoi dogs

A group of related borzoi dogs were studied over a 6-year period to ascertain the cause of primary hypothyroidism. Four generations of dogs were analyzed. Two littermates with lymphocytic thyroiditis were mated and the 10 offspring were all diagnosed, on the basis of thyroid biopsy evaluation, as having lymphocytic thyroiditis by age 2.5 years. A wide range of thyroid gland lesions was demonstrated in this litter of dogs. This report documents the occurrence of lymphocytic thyroiditis in three successive generations of an inbred group of borzoi dogs. An autosomal recessive mode of inheritance for the trait in this group of dogs is proposed.     

Hashimoto''s thyroiditis manifesting monoclonal lymphocytic infiltration.

Hashimoto's thyroiditis (HT) and lymphoma are sometimes difficult to distinguish between. Moreover, lymphoma sometimes develops in a thyroid gland from pre-existing HT. Open- or large-needle biopsy usually distinguishes between them; the specimen may be examined histologically and subjected to immunohistochemistry. Another possible method of examination is fine-needle aspiration biopsy (FNAB). The cells obtained may be evaluated cytologically, and subjected to flow cytometry, using various antibodies. In this study, anti-kappa and anti-lambda antibodies are especially important, as a gross predominance of kappa or lambda B lymphocytes infiltrating the thyroid is evidence for a B cell monoclone. In this study, 15 patients were selected because of their rapidly growing goitres. They all underwent FNAB. Five had cytology typical of HT, and no evidence of monoclonality on flow cytometry. They were diagnosed as HT without further histopathology. The remaining 10 patients had cytology suspected of lymphoma, or evidence of monoclonality on flow cytometry, or both. These patients underwent open- or large-needle biopsy. Only three of them were diagnosed histopathologically as lymphoma; the other seven were diagnosed histopathologically as HT, making 12 cases of HT in all. Five of these 12 cases, and one of the three cases of lymphoma showed flow cytometrical evidence of monoclonality; thus evidence of monoclonality from FNAB, while interesting, does not necessarily serve to differentiate between HT and lymphoma. Furthermore, the immunohistochemical assessment of monoclonality did not correlate with the flow cytometrical assessment. Follow-up evidence will be required to discover whether those patients with a B cell monoclone in their HT are the ones who develop a lymphoma.     

Relational spirituality and depression in adolescent girls

This study examines the possibility that relational spirituality may be inversely associated with the relatively higher rates of adolescent depression found in girls as compared with boys. Subjects were 615 adolescents, representing a diverse range of religious, ethnic, and socioeconomic backgrounds. Overall spirituality and depression were measured using The Brief-Multidimensional Measure of Religiosity/Spirituality and the Beck Depression Inventory, respectively. Overall, both level of depression and level of relational spirituality were higher in girls as compared with boys. Regression analyses conducted independently for boys and girls revealed that daily spiritual experiences, forgiveness, and religious coping were associated with less-depressive symptomatology exclusively in girls. This pattern in the findings suggests that uniquely in girls, depression may be associated with disruptions in a relational form of spirituality.     

Ultrastructural findings in Hashimoto's thyroiditis and focal lymphocytic thyroiditis with reference to giant cell formation

Ultrastructural findings in two cases of Hashimoto's disease and two cases of focal lymphocytic thyroiditis are reported. Stimulated thyrocytes, oncocytes and degenerating thyrocytes were observed in all cases. Multinucleated thyrocytes and epithelial pseudogiant cells were identified in Hashimoto's disease only. Infiltrating lymphocytes, plasma cells, monocytes and macrophages were present in all cases. The ultrastructure of germinal centres was similar to that seen in lymphatic organs. Giant cells of both intra- and extrafollicular localization were seen in Hashimoto's disease. Most of the giant cells were macrophage-derived. Two different ways of giant cell formation were identified: besides the familiar dissolution of plasma membranes of adjacent macrophages, another mechanism of fusion was observed. At sites of contact, peculiar membrane structures were developed and disintegration of plasma membranes occurred in parts adjacent to these structures. These are not identical to desmosomes and are different from Langerhans' granules. They probably represent special organelles for the initiation of cellular fusion.