The thyroid tissue of juvenile Oncorhynchus mykiss is tubular, not follicular

The three dimensional morphology of the thyroid tissue in juvenile rainbow trout Oncorhynchus mykiss was determined using serial transverse and longitudinal sections of lower jaws stained with haematoxylin and eosin. The thyroid tissue comprised interconnecting tubular units not the follicles that are widely described in the literature. Some of these tubules were subdivided by branching, giving the appearance of follicles in the sections. The thyroid tissue was aggregated into two major concentrations of tissue, associated with the first and second branchial arteries, with the majority of the tissue located dorsal and lateral to the aorta. These observations in juvenile rainbow trout suggest that thyroid tissue of some species of fishes may not be follicular, as previously assumed. The physiological and evolutionary implications have yet to be determined.     

Update on: proteome analysis in thyroid pathology – part II: overview of technical and clinical enhancement of proteomic investigation of the thyroid lesions

ABSTRACT

Introduction: An accurate diagnostic classification of thyroid lesions remains an important clinical aspect that needs to be addressed in order to avoid ‘diagnostic’ thyroidectomies. Among the several ‘omics’ techniques, proteomics is playing a pivotal role in the search for diagnostic markers. In recent years, different approaches have been used, taking advantage of the technical improvements related to mass spectrometry that have occurred.

Areas covered: The review provides an update of the recent findings in diagnostic classification, in genetic definition and in the investigation of thyroid lesions based on different proteomics approaches and on different type of specimens: cytological, surgical and biofluid samples. A brief section will discuss how these findings can be integrated with those obtained by metabolomics investigations.

Expert commentary: Among the several proteomics approaches able to deepen our knowledge of the molecular alterations of the different thyroid lesions, MALDI-MSI is strongly emerging above all. In fact, MS-imaging has also been demonstrated to be capable of distinguishing thyroid lesions, based on their different molecular signatures, using cytological specimens. The possibility to use the material obtained by the fine needle aspiration makes MALDI-MSI a highly promising technology that could be implemented into the clinical and pathological units.     

The number of nucleoli in benign and malignant thyroid lesions: a useful diagnostic sign in cytological preparations

The slides of fine needle aspiration cytology specimens from 99 cases of cold thyroid nodules with known histology were reviewed and the number of nucleoli per nucleus counted and correlated with the different histopathological groups. Significant differences were observed between benign and malignant thyroid lesions in the number of nucleoli in the cytological material. Lower values were present in nodular goitres and follicular adenomas compared to carcinomas. In benign lesions the majority of nuclei contained one nucleolus and nuclei with two, three or more nucleoli were less frequent than in follicular, papillary, medullary and anaplastic carcinomas. Only one case of follicular adenoma had cells containing three or more nucleoli compared to more than half the cases of follicular carcinoma.     

Selenium and rubidium changes in subjects with pathologically altered thyroid

Concentrations of selenium and rubidium in groups of subjects with hyperthyroidism, carcinomas, or adenomas and in controls were determined by neutron activation analysis with coirradiated inorganic standards and IAEA reference material. Se was decreased in all pathological groups with the greatest modification in thyroids with carcinomas. Rb was elevated in all pathological groups with the greatest increase in carcinomas as well. According to the literature, Se has a protective effect on carcinogenity as well as on biochemical pathways in thyroid cells. There are no data in the literature on the effects of Rb in those cells. On the grounds of the present results, it seems possible to use the trapping of Rb for diagnostic purposes in cases of pathologically altered thyroids.     

Cytopathology of Follicular Tumours of the Thyroid With Clear Cell Change

A retrospective cytological study of nine follicular tumours of the thyroid with clear cell change was undertaken. In five clear cell adenomas and one moderately differentiated clear cell follicular carcinoma the epithelial cells occurred singly or in sheets and clusters; they sometimes assumed a trabecular or follicular pattern. The cells usually had pale diffusely vacuolated cytoplasm with ill-defined boundaries, a variable degree of anisonucleosis, nucleolar enlargement, and nuclear overlapping. Smears from a signet-ring cell adenoma contained in addition a few cells with large cytoplasmic vacuoles and compressed eccentric nuclei. In these cases a cytological diagnosis of 'follicular lesion' (or follicular neoplasia), clear cell type or signet-ring cell type, was given. A cytodiagnosis of 'carcinoma' was made only in the poorly differentiated follicular carcinoma-clear cell variant studied which showed unequivocal features of malignancy. Features suggestive of thyroid cyst, nodular goitre, Hashimoto's thyroiditis, and cell hyperactivity (marginal vacuoles, 'fire flare') were also found in the aspirated specimens of these cases of clear cell tumour of the thyroid.     

An alternate model of thyroid cytology: practical not perfect

A sample of 384 thyroid cytology specimens prepared by cytospin over a 2.5-year period was classified by original report into inadequate, non-neoplastic and suspicious of neoplasia or worse. This was then compared with subsequent histology. The resulting data showed an inadequacy rate of 33%, a sensitivity of 55%, a specificity of 59%, a positive predictive value of 64% and a negative predictive value of 93%. On review of the cytology, in knowledge of the subsequent histology, the maximum achievable results were determined to have a positive predictive value of 79% and a negative predictive value of 97%. No clinically significant adverse event was detected.     

Role of Dicer1 in thyroid cell proliferation and differentiation

DICER1 plays a central role in the biogenesis of microRNAs and it is important for normal development. Altered microRNA expression and DICER1 dysregulation have been described in several types of tumors, including thyroid carcinomas. Recently, our group identified a new somatic mutation (c.5438A>G; E1813G) within DICER1 gene of an unknown function. Herein, we show that DICER1 is overexpressed, at mRNA level, in a significant-relative number of papillary (70%) and anaplastic (42%) thyroid carcinoma samples, whereas is drastically downregulated in all the analyzed human thyroid carcinoma cell lines (TPC-1, BCPAP, FRO and 8505c) in comparison with normal thyroid tissue samples. Conversely, DICER1 is downregulated, at protein level, in PTC in comparison with normal thyroid tissues. Our data also reveals that DICER1 overexpression positively regulates thyroid cell proliferation, whereas its silencing impairs thyroid cell differentiation. The expression of DICER1 gene mutation (c.5438A>G; E1813G) negatively affects the microRNA machinery and cell proliferation as well as upregulates DICER1 protein levels of thyroid cells but has no impact on thyroid differentiation. In conclusion, DICER1 protein is downregulated in papillary thyroid carcinomas and affects thyroid proliferation and differentiation, while DICER1 gene mutation (c.5438A>G; E1813G) compromises the DICER1 wild-type-mediated microRNA processing and cell proliferation.     

碘与甲状腺疾病

碘是人体必需的微量元素,是合成甲状腺激素（thyroid hormone,TH）的主要原料。人体内的碘主要从饮水及食物中获取。碘的摄入缺乏或过量,不仅对TH的合成及分泌有至关重要的影响,而且与甲状腺形态及多种甲状腺疾病的发生、发展及转归密切相关。加碘盐的推广有效预防了碘缺乏可能引起的相关疾病;而碘过量导致的甲状腺疾病谱和发病率的急剧变化,也引起各界高度重视。流行病学调查表明,碘的摄入量与甲状腺功能亢进、自身免疫性甲状腺炎、甲状腺功能减退、甲状腺肿大和甲状腺癌等疾病的发病率密切相关。针对碘的相关生物学问题,对近年来的基础研究和人群研究进行综述,希望借此抛砖引玉,引起相关部门的重视,提高人民群众对碘营养的科学认识水平。     

The impact of the non‐invasive follicular thyroid neoplasm with papillary‐like nuclear feature terminology in the routine diagnosis of thyroid tumours

Background

Due to the recent proposal of the non‐invasive follicular thyroid neoplasm with papillary‐like nuclear feature (NIFTP) category, the authors analyse the state of the art in the challenging diagnosis of follicular thyroid neoplasms in routine practice.

Methods and results

A consecutive series of 200 histological diagnoses, with complete cytological correlation, was analysed following the introduction of the NIFTP definition. The study was conducted in a general hospital with a high prevalence of thyroid benign nodules that accounted for approximately 60% of surgically‐treated nodules. The significant incidence of the new NIFTP category was 7%. Concurrently, a gradual decrease of the follicular variant of papillary thyroid carcinoma (fvPTC) was observed (3.5%). When evaluating the FNA biopsies within the NIFTP group, despite the systematic evaluation of nuclear crowding, enlargement, irregularities and clearing, the final cytological class was often indeterminate for malignancy (Thy3/III‐IV, 71%). At histology, the application of the semiquantitative NIFTP score for the evaluation of the PTC‐like nuclear features was able to discriminate benign lesions (score 0/1) from fvPTC (score 2/3). A certain degree of overlapping still persisted between NIFTP and fvPTC (score 2) or between NIFTP and benign lesions (score 1).

Conclusions

In the routine evaluation of FNA biopsies, the presence of subtle and questionable PTC‐like nuclear features still remains a controversial aspect of the diagnostic workflow. Given that the NIFTP category was introduced to stratify the low‐risk group of thyroid tumours more precisely, pathologists should force themselves to apply the nuclear score rigorously and to classify cases assigned a score of 1 as benign proliferations.

     

有机磷阻燃剂TDCIPP对雌性大鼠甲状腺的潜在毒性作用

目的: 研究磷酸三(1, 3-二氯-2-丙基)酯(TDCIPP)对雌性大鼠甲状腺系统的潜在毒性作用及机制。方法: 将32只离乳3周的雌性SD大鼠随机分为对照组(玉米油灌胃)及TDCIPP低、中、高剂量组(50、100、250 mg/kg·d,溶于玉米油)(n=8),灌胃给药21 d,每天1次。于末次给药后处死动物,取血和甲状腺、肝脏,检测血清中促甲状腺激素(TSH)、三碘甲腺原氨酸(T3), 甲状腺素(T4)和游离甲状腺素(FT4)水平变化;组织切片(HE染色)用于检测甲状腺形态学病变;RT-PCR技术与Western blot技术检测与甲状腺功能相关的基因和蛋白表达的变化。结果: 与对照组比较,TDCIPP染毒后大鼠甲状腺出现滤泡排列不规则、胶质变少、滤泡增生、肥大等现象,TDCIPP低剂量组的血清TSH水平和高剂量组的T3水平均显著升高(P＜0.05),低剂量组促甲状腺激素受体(TSHR)mRNA表达和中、高剂量组甲状腺激素受体β(TRβ)蛋白表达均显著降低(P＜0.05,P＜0.01),中、高剂量组甲状腺过氧化物酶(TPO)mRNA表达显著增高(P＜0.05,P＜0.01),三个剂量组尿苷二磷酸葡萄糖醛酸转移酶(UGTs)、细胞色素氧化酶-3A1(CYP3A1)蛋白表达水平显著上调(P＜0.05)。结论: 大鼠暴露在50 mg/(kg·d)以上剂量的TDCIPP,即可以刺激甲状腺组织的增生,改变血清中甲状腺素的水平,干扰甲状腺的功能,表现出对甲状腺的毒性作用。     

Propranolol has direct antithyroid activity: Inhibition of iodide transport in cultured thyroid follicles

The effect of propranolol on the process of thyroid hormone formation was studied in a physiological culture system. Porcine thyroid follicles were preincubated with propranolol for 24 h. Iodide transport, iodine organification, and de novo thyroid hormone formation were measured by incubating these follicles with the mixture of carrier-free 0·1 μCi Na ¹²⁵I and 50 nM NaI for 2 to 6 h at 37°C. A concentration of propranolol greater than 100 μM inhibited iodide transport in a dose-dependent manner; this inhibition was non-competitive with iodide and independent of thyrotropin (TSH). Reduced iodine organification and thyroid hormone formation was seen with 150 μM propranolol or greater. The inhibitory action of propranolol was not caused by beta-blocking activity, since D -propranolol (devoid of beta-blocking activity) inhibited iodide transport, and other beta-blockers (metoprolol, atenolol, and labetalol) did not inhibit iodide transport. The inhibition of iodide transport was most likely caused by membrane stabilizing activity since quinidine, which possess the same membrane stabilizing activity as propranolol, also inhibited iodide transport. TSH-mediated cAMP generation and Na ⁺K⁺ ATPase activity, membrane functions for iodide transport, were unaffected by propranolol. Our study has shown, for the first time, that propranolol has a direct antithyroid action, namely inhibition of iodide transport in the intact thyroid follicle.     

Diagnostic value of qualitative and quantitative variables in thyroid lesions

Two hundred and thirty-three thyroid lesions were studied by fine needle aspiration (FNA) cytology using standard cytologic criteria available in the literature. These included 114 cases of nodular colloid goitre (NCG), 47 cases of Hashimoto's thyroiditis (HT), 12 follicular adenomas (FAd), five cases of subacute thyroiditis and three cases of thyrotoxicosis among the benign lesions. The malignant lesions seen were 30 cases of papillary carcinoma (PCa), 16 follicular carcinomas (FCa), three cases with double lesions, e.g. papillary carcinoma with coexisting NCG, and three of papillary carcinoma with HT. Emphasis was given to eight qualitative and quantitative (morphometric) variables in these various thyroid lesions. Cell measurements were done using a Visopan Lux projection microscope. The three qualitative variables included type of nuclear membrane (regular/irregular), type of nuclear chromatin and the presence or absence of conspicuous nucleoli. The quantitative variables studied were nuclear diameter, nuclear area, cytoplasmic diameter, cytoplasmic area & N/C ratio. Statistical analysis was performed in order to know whether the standard cytologic criteria used at FNA cytology in the literature (increased cellularity, microfollicles, increased N/C ratio, absence of significant haemosiderin-laden macrophages and scanty colloid) could differentiate a follicular adenoma from a follicular carcinoma. A statistical analysis was also performed to establish the utility of the qualitative and quantitative variables. The results showed that none of the standard cytologic criteria applied could differentiate follicular adenoma from a follicular carcinoma. With regard to qualitative variables, irregularity of nuclear membrane and presence of conspicuous nucleoli were most significant in papillary carcinoma, followed by follicular carcinoma, then by follicular adenoma; these features being hardly evident in nodular colloid goitre and Hashimoto's thyroiditis. A coarse nuclear chromatin was most significant in follicular carcinomas followed by follicular adenomas. It was less obvious in the benign conditions, but more prominent in Hashimoto's thyroiditis compared with a goitre. It was also not obvious in a papillary carcinoma. Of the quantitative variables, all measurements were greatest in PCa > FCa > FAd > NCG = HT. When differentiating follicular adenoma from follicular carcinoma the qualitative variables of significance were the presence or absence of nucleoli, the chromatin pattern and regularity/irregularity of nuclear membrane; the nuclear area was the most important feature among quantitative variables.     

The role of FNA in the initial management of thyroid lesions: 7-year experience in a district general hospital

Fine needle aspiration (FNA) cytology plays a major role in the diagnosis of the thyroid lesions in university hospitals and tertiary referral institutions. Our aim was to find out if this was possible in small district hospitals with limited resources. Over a 7-year period, from October 1994 to April 2002, 303 patients with thyroid swellings underwent FNA with an overall adequacy rate of 97.7%. FNAs were performed specifically by the pathologists, so that our inadequacy rate, 2.3% was far lower than 11-29% reported elsewhere. The FNA findings were compared with subsequent histology results in 67 cases. The diagnosis of benign and neoplastic lesions was predicted accurately by FNA in 93% and 94.7% of cases, respectively. The latter reached 100% if results of FNA in follicular neoplasms were excluded. Sensitivity and specificity were 85.6% and 97.6%, respectively, which is comparable with results from tertiary institutions. The commonest thyroid lesions in our hospital were nodular goitre (52.4%), followed by thyroiditis (17.6%) and neoplasia (13.9%). We conclude that, with the availability of appropriate personnel, FNA is feasible as the major modality in district general hospitals. FNA in follicular lesions remains challenging but could be overcome in part by recognizing the criteria to differentiate follicular variant of papillary carcinoma and other follicular proliferations. Aspiration, smearing, staining and interpretation should be left to pathologists or other well-trained personnel to ensure good quality and consistency.     

Necrotic Debris In Thyroid Aspirates: A Feature of Follicular Carcinoma of the Thyroid

Fine needle aspirates from 44 follicular thyroid tumours (30 adenomas, 14 carcinomas) have been studied. All aspirates contained neoplastic cells in follicular and trabecular arrangements. The individual tumour cells showed varying degrees of anisonucleosis and nuclear pleomorphism. Colloid was scanty or absent from all smears. Granular or filamentous necrotic material was observed in both biopsies and smears from one moderately and two poorly differentiated follicular carcinomas, but in none of the adenomas. This suggests that necrotic debris may be a feature of follicular carcinoma of the thyroid.