Thyroid Follicular Epithelium Research Articles

Sex Differences in the Production of SLC5A5, Thyroid Peroxidase, and Thyroid Hormones in Pubertal Rats Exposed to Endocrine Disruptor Dichlorodiphenyltrichloroethane (DDT) during Postnatal Ontogeny.

Sex differences in the expression of iodide transporter SLC5A5 and thyroid peroxidase in thyroid follicular epithelium and thyroid serum profile were assessed in pubertal rats exposed to endocrine disruptor DDT starting from the first postnatal day. It was found that exposure to DDT reduced expression of SLC5A5 in peripheral regions of thyroid lobes in males and in central regions in females. The most pronounced sex differences were observed in thyroid peroxidase expression that remained sensitive to thyroid stimulating hormone regulation in males and lost sensitivity to pituitary stimulation in females after exposure to disruptor, which determines more pronounced hypothyroidism in females.

Growth performance, morphometric analysis of the intestinal mucosa and thyroid of broiler fed canola meal

ABSTRACT The aim of this study was to evaluate the effect of replacing soybean meal with canola meal in broiler diets on performance, liver histopathology, morphometry of the intestinal mucosa and thyroid. One-day-old Cobb chicks (n=300) were distributed in a completely randomized design, with increasing levels of replacement of soybean meal with canola meal (0, 25, 50, 75 and 100%) and 6 repetitions of 10 birds each. Weight gain decreased linearly (P< 0.05) with increasing levels of inclusion of canola meal, in all stages. Villus height in the duodenum and jejunum linearly decreased (P< 0.05). Follicle diameter and thyroid follicular epithelium height increased linearly with increasing levels of canola meal (P< 0.05). Similarly, there was an increase in relative weight of liver and heart, and liver steatosis in the highest levels of replacement. In conclusion, the replacement of soybean meal with canola meal can reduce performance, adversely affecting the thyroid, liver and the morphometric characteristics in the duodenum and jejunum.

Isolation and Culture of Juvenile Pig Thyroid Follicular Epithelia.

Epithelial tissues are defined by their polarity and their ability to transport directionally. Thyroid is a tissue comprising functional epithelial units organized as enclosed follicles, with their luminal spaces defined by thyrocyte apices. Thus, the native arrangement of thyroid epithelia limits accessibility to the follicular space, presenting a challenge in studying transepithelial movements. This limitation can be overcome by studying thyrocytes grown as two-dimensional cultures. Herein we present methods for isolation of thyroid follicles from juvenile pigs and preparation of high-resistance, polarized cultures.

Stereoselective degradation and thyroid endocrine disruption of lambda-cyhalothrin in lizards (Eremias argus) following oral exposure

The disturbance of the thyroid system and elimination of chiral pyrethroid pesticides with respect to enantioselectivity in reptiles have so far received limited attention by research. In this study, bioaccumulation, thyroid gland lesions, thyroid hormone levels, and hypothalamus-pituitary-thyroid axis-related gene expression in male Eremias argus were investigated after three weeks oral administration of lambda-cyhalothrin (LCT) enantiomers. In the lizard liver, the concentration of LCT was negatively correlated with the metabolite-3-phenoxybenzoic acid (PBA) level during 21 days of exposure. (+)-LCT exposure induced a higher thyroid follicular epithelium height than (−)-LCT exposure. The thyroxine levels were increased in both treated groups while only (+)-LCT exposure induced a significant change in the triiodothyronine (T3) level. In addition, the expressions of hypothalamus-pituitary-thyroid axis-related genes including thyroid hormone receptors (trs), deiodinases (dios), uridinediphosphate glucuronosyltransferase (udp), and sulfotransferase (sult) were up-regulated after exposure to the two enantiomers. (+)-LCT treatment resulted in higher expression of trs and (−)-LCT exposure led to greater stimulation of dios in the liver, which indicated PBA-induced antagonism on thyroid hormone receptors and LCT-induced disruption of thyroxine (T4) deiodination. The results suggest the (−)-LCT exposure causes higher residual level in lizard liver while induces less disruption on lizard thyroid activity than (+)-LCT.

Genetically engineered suicide gene in mesenchymal stem cells using a Tet-On system for anaplastic thyroid cancer.

Anaplastic thyroid cancer (ATC) is the most aggressive malignancy of the thyroid, during which undifferentiated tumors arise from the thyroid follicular epithelium. ATC has a very poor prognosis due to its aggressive behavior and poor response to conventional therapies. Gene-directed enzyme/prodrug therapy using genetically engineered mesenchymal stromal cells (MSC) is a promising therapeutic strategy. The doxycycline (DOX)-controlled Tet inducible system is the most widely utilized regulatory system and could be a useful tool for therapeutic gene-based therapies. For example, use a synthetic “tetracycline-on” switch system to control the expression of the therapeutic gene thymidine kinase, which converts prodrugs to active drugs. The aim of this study was to develop therapeutic MSCs, harboring an inducible suicide gene, and to validate therapeutic gene expression using optical molecular imaging of ATC. We designed the Tet-On system using a retroviral vector expressing herpes simplex virus thymidine kinase (HSV1-sr39TK) with dual reporters (eGFP-Fluc2). Mouse bone marrow-derived mesenchymal stromal cells (BM-MSC) were transduced using this system with (MSC-Tet-TK/Fluc2) or without (MSC-TK/Fluc) the Tet-On system. Transduced cells were screened and characterized. Engineered MSCs were co-cultured with ATC (CAL62/Rluc) cells in the presence of the prodrug ganciclovir (GCV) and stimulated with DOX. The efficiency of cell killing monitored by assessing Rluc (CAL62/Rluc) and Fluc (MSC-Tet-TK/Fluc and MSC-TK/Fluc) activities using IVIS imaging. Fluc activity increased in MSC-Tet-TK/Fluc cells in a dose dependent manner following DOX treatment (R2 = 0.95), whereas no signal was observed in untreated cells. eGFP could also be visualized after induction with DOX, and the HSV1-TK protein could be detected by western blotting. In MSC-TK/Fluc cells, the Fluc activity increased with increasing cell number (R2 = 0.98), and eGFP could be visualized by fluorescence microscopy. The Fluc activity and cell viability of MSC-Tet-TK/Fluc and MSC-TK/Fluc cells decreased significantly following GCV treatment. A bystander effect of the therapeutic cells confirmed in co-cultures of CAL62 cells, an anaplastic thyroid cancer cell line, with either MSC-Tet-TK/Fluc cells or MSC-TK/Fluc cells. The Rluc activity in MSC-Tet-TK/Fluc co-cultures, derived from the CAL62/Rluc cells, decreased significantly with GCV treatment of DOX treated cultures, whereas no significant changes were observed in untreated cultures. In addition, the Fluc activity of MSC-Tet-TK/Fluc cells also decreased significantly with DOX treatment whereas no signal was present in untreated cultures. A bystander effect also be demonstrated in co-cultures with MSC-TK/Fluc cells and CAL62/Rluc; both the Rluc activity and the Fluc activity were significantly decreased following GCV treatment. We have successfully developed a Tet-On system of gene-directed enzyme/prodrug delivery using MSCs. We confirmed the therapeutic bystander effect in CAL62/Rluc cells with respect to MSC-Tet-TK/Fluc and MSC-TK/Fluc cells after GCV treatment with and without DOX. Our results confirm the therapeutic efficiency of a suicide gene, with or without the Tet-On system, for ATC therapy. In addition, our findings provide an innovative therapeutic approach for using the Tet-On system to eradicate tumors by simple, repeated administration of MSC-Tet-TK/Fluc cells with DOX and GCV.

Cytophysiological Changes in the Follicular Epithelium of the Thyroid Gland after Long-Term Exposure to Low Doses of Dichlorodiphenyltrichloroethane (DDT).

Exposure to endocrine disruptors is considered as a risk factor thyroid gland diseases. We analyzed cytophysiological changes in rat thyroid follicular epithelium after long-term exposure to low doses of the most widespread disruptor DDT. Analysis of thyroid hormone production and light and electron microscopy of thyroid gland samples revealed cytophysiological changes in thyroid epithelium related to impaired transport through the apical membrane, suppressed Golgi complex activity, and impaired thyrotrophic hormone regulation of the secretory functions of thyroid cells, which led to compensatory transition from merocrine to microapocrine secret release.

Response of trabecular bone, thyroid C and follicular cells to synthetic salmon calcitonin in middle-aged orchidectomized male rats.

In contrast to studies in women, male osteoporosis is poorly understood and strictly related to advancing age. Among the first antiresorptive substances used in the prevention and treatment of osteoporosis is calcitonin (CT), a hypocalcemic hormone that potently inhibits osteoclastic bone resorption. Natural CT is produced and secreted by thyroid C-cells. The other endocrine population of thyroid cells produces thyroid hormones (TH), which also affect bone turnover. The aim of this study was to evaluate the influence of salmon CT on trabecular bone microarchitecture with special reference to effects on the structure and function of both CT- and TH-producing thyroid cells in orchidectomized (Orx) middle-aged rats. Twenty-four male Wistar rats aged 15months were randomly divided into Orx and sham-operated (SO) groups. One group of Orx animals received (s.c.) synthetic salmon CT (Orx+CT; 100IUkg-1 b.w.) subcutaneously every second day for 6 weeks. The second Orx group and SO rats were given the same volume of vehicle alone by the same schedule. Trabecular bone histomorphometrical parameters were: cancellous bone area (B.Ar), trabecular thickness (Tb.Th), trabecular number (Tb.N) and trabecular separation (Tb.Sp) were obtained with an ImageJ public-domain image-processing program. The peroxidase-antiperoxidase method was applied for localization of CT in C-cells. Anti-human CT antisera served as the primary antibodies. For immunohistochemical characterization of vascular endothelial growth factor (VEGF) in thyroid tissue, rabbit antisera against human VEGF, served as primary antibodies. CT-immunopositive thyroid C-cells, thyroid follicular epithelium, interstitium and colloid were evaluated morphometrically. Blood serum samples were analyzed for CT, osteocalcin (OC), and thyroxine (T4 ), and calcium (Ca2+ ) concentration was determined in urine samples. Salmon CT application significantly increased B.Ar, TbTh and TbN, but markedly decreased Tb.Sp. Administration of exogenous CT significantly decreased mean volume (Vc) and relative volume density (Vv) of thyroid C-cells in relation to both SO and Orx groups. The Vv of the colloid was higher, whereas the VV of the follicular epithelium was lower after CT treatment compared with Orx alone. CT treatment markedly elevated serum CT, whereas serum OC, T4 and urinary Ca2+ concentrations were lower than in the Orx group. These results indicate that salmon CT stimulates trabecular bone microarchitecture, strongly inhibits thyroid C-cells and changes the structure of the thyroid gland, indicating hypoactivity.

APLP2, RRM2, and PRC1: New Putative Markers for the Differential Diagnosis of Thyroid Follicular Lesions.

Current methods based on fine-needle aspiration biopsy (FNAB) are not sufficient to distinguish among follicular thyroid lesions, follicular adenoma (FA), follicular thyroid carcinoma (FTC), and the follicular variant of papillary thyroid cancer (FVPTC). Furthermore, none of the immunohistochemical markers currently available are sensitive or specific enough to be used in the clinical setting, necessitating a diagnostic hemithyroidectomy. The aim of this study was to identify proteins of value for differential diagnosis between benign and malignant thyroid follicular lesions. This retrospective analysis is based on an assessment of the immunoexpression of 19 proteins on 81 benign thyroid lesions (FA) and 50 malignant tumors (FTC/FVPTC). The resulting expression profile allowed the design of a scoring system model to improve the differential diagnosis of benign and malignant thyroid lesions. The model was validated using an independent series of 69 FA and 40 FTC and an external series of 40 nodular hyperplasias, and was further tested in a series of 38 FNAB cell blocks. A model based on the nuclear and cytoplasmic expression of APLP2, RRM2, and PRC1 discriminated between benign and malignant lesions with 100% sensitivity in both main and validation groups, with specificities of 71.3% and 50.7%, respectively. For the nodular hyperplasia series, specificity reached 94.8%. Finally, in FNAB samples, the sensitivity was 100% and the specificity was 45% for discrimination between benign and malignant lesions. These findings suggest that the identified APLP2, RRM2, and PRC1 signature could be useful for distinguishing between benign (FA) and malignant (FTC and FVPTC) tumors of the thyroid follicular epithelium.

Effects of dietary exposure of polycyclic musk HHCB on the metamorphosis of Xenopus laevis.

The compound 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-[γ]-2-benzopyrane (HHCB; galaxolide, Chemical Abstracts Service number 1222-05-5) is a synthetic musk used extensively as a fragrance in many consumer products and classified as an emerging pollutant. The ecotoxicological information available for HHCB addresses exposure via water, but this compound is frequently adsorbed into particulate matter. The goal of the present study was to assess the effects of dietary exposure to several environmentally relevant HHCB concentrations adsorbed in food during Xenopus laevis metamorphosis. The authors sought to determine if such exposure to this synthetic musk resulted in histological changes in the thyroid gland in conjunction with changes in development (staging, timing to metamorphosis), body weight, and length. Developmental acceleration on day 14, together with hypertrophy of the thyroid follicular epithelium in tadpoles, suggested a possible agonistic effect of HHCB, which would have been compensated after metamorphosis by regulatory mechanisms to maintain homeostasis. Further research into the potential thyroid-related mechanisms of action of HHCB should be conducted. Environ Toxicol Chem 2016;35:1428-1435. © 2015 SETAC.

Thyroid Swelling and Thyroiditis in the Setting of Recent hCG Injections and Fine Needle Aspiration

A 60-year-old woman presented with a neck mass and underwent fine needle aspiration of a left thyroid nodule. During this time, she had been injected with hCG for weight loss. Soon after, she developed rapid diffuse thyroid growth with pain. She was ultimately diagnosed with thyrotoxicosis due to postaspiration subacute thyroiditis and subsequently became hypothyroid. This condition is rare in the nonpregnant state in noncystic nodules with a smaller needle gauge approach. The incidence of thyroid nodule discovery and evaluation is increasing. As more procedures are undertaken, understanding of potential complications is important. This case highlights potential complications of thyroid fine needle aspiration including diffuse thyroid swelling and thyroiditis. The role of hCG injections is speculated to have potentially stimulated thyroid follicular epithelium via cross-reactivity with the TSH receptor and contributed to the acute inflammatory response after fine needle aspiration.

CD56, HBME-1 and cytokeratin 19 expressions in papillary thyroid carcinoma and nodular thyroid lesions.

Background:Carcinomas of the thyroid follicular epithelium are the most common cancers of the endocrine system. In the diagnosis of thyroid nodules and tumors, the gold standard is histological evaluation. In cases which have morphological overlap, immunohistochemistry is needed for differential diagnosis. The purpose of this study is to investigate the expressions of CD56, HBME-1, cytokeratin 19 (CK19) antibodies in papillary thyroid carcinoma (PTC) and thyroid nodular lesions and their contributions to differential diagnosis.Materials and Methods:In this study, 47 PTCs (26 follicular variant, 21 classic type) and 26 benign thyroid lesions (15 nodular hyperplasia, 10 follicular adenomas, 1 Hurtle cell adenoma) were analyzed retrospectively. HBME-1, CK19, and CD56 antibodies were performed with immunohistochemical methods. The results were evaluated statistically.Results:+3 staining with HBME-1 and CK19 was observed in 72.3% and 83% of patients with PTC. In 95.7% of PTC cases, loss of CD56 expressions in various degrees was identified. A statistically significant difference was detected in HBME-1, CK19, and CD56 expressions between PTCs and benign lesions (P < 0.001).Conclusion:In our study, positive staining of HBME-1, CK19, and loosing expression of CD56 that supports malignancy was found and concluded that CD56 is a helpful antibody for the differential diagnosis of benign and malignant lesions and may increase the diagnostic accuracy when used with HBME-1 and CK19.

γ-Aminobutyric acid ameliorates fluoride-induced hypothyroidism in male Kunming mice

AimThis study evaluated the protective effects of γ-aminobutyric acid (GABA), a non-protein amino acid and anti-oxidant, against fluoride-induced hypothyroidism in mice. Main methodsLight microscope sample preparation technique and TEM sample preparation technique were used to assay thyroid microstructure and ultrastructure; enzyme immunoassay method was used to assay hormone and protein levels; immunohistochemical staining method was used to assay apoptosis of thyroid follicular epithelium cells. Key findingsSubacute injection of sodium fluoride (NaF) decreased blood T4, T3 and thyroid hormone-binding globulin (TBG) levels to 33.98μg/l, 3 2.8ng/ml and 11.67ng/ml, respectively. In addition, fluoride intoxication induced structural abnormalities in thyroid follicles. Our results showed that treatment of fluoride-exposed mice with GABA appreciably decreased metabolic toxicity induced by fluoride and restored the microstructural and ultrastructural organisation of the thyroid gland towards normalcy. Compared with the negative control group, GABA treatment groups showed significantly upregulated T4, T3 and TBG levels (42.34μg/l, 6.54ng/ml and 18.78ng/ml, respectively; P<0.05), properly increased TSH level and apoptosis inhibition in thyroid follicular epithelial cells. SignificanceTo the best of our knowledge, this is the first study to establish the therapeutic efficacy of GABA as a natural antioxidant in inducing thyroprotection against fluoride-induced toxicity.

Trace Amine-Associated Receptor 1 Localization at the Apical Plasma Membrane Domain of Fisher Rat Thyroid Epithelial Cells Is Confined to Cilia

Background: The trace amine-associated receptor 1 (Taar1) is one member of the Taar family of G-protein-coupled receptors (GPCR) accepting various biogenic amines as ligands. It has been proposed that Taar1 mediates rapid, membrane-initiated effects of thyronamines, the endogenous decarboxylated and deiodinated relatives of the classical thyroid hormones T₄ and T₃. Objectives: Although the physiological actions of thyronamines in general and 3-iodothyronamine (T₁AM) in particular are incompletely understood, studies published to date suggest that synthetic T₁AM-activated Taar1 signaling antagonizes thyromimetic effects exerted by T₃. However, the location of Taar1 is currently unknown. Methods: To fill this gap in our knowledge we employed immunofluorescence microscopy and a polyclonal antibody to detect Taar1 protein expression in thyroid tissue from Fisher rats, wild-type and taar1-deficient mice, and in the polarized FRT cells. Results: With this approach we found that Taar1 is expressed in the membranes of subcellular compartments of the secretory pathway and on the apical plasma membrane of FRT cells. Three-dimensional analyses further revealed Taar1 immunoreactivity in cilial extensions of postconfluent FRT cell cultures that had formed follicle-like structures. Conclusions: The results suggest Taar1 transport along the secretory pathway and its accumulation in the primary cilium of thyrocytes. These findings are of significance considering the increasing interest in the role of cilia in harboring functional GPCR. We hypothesize that thyronamines can reach and activate Taar1 in thyroid follicular epithelia by acting from within the thyroid follicle lumen, their potential site of synthesis, as part of a nonclassical mechanism of thyroid autoregulation.

Research Progress on IgG4-Related Hashimoto’s Thyroiditis

AbstractIgG4-related disease is a systemic autoimmune disease with unknown cause and involves multiple organs and tissues. This disease became one of research hotspots in the last ten years. IgG4-related Hashimoto’s thyroiditis (HT) exhibits unique clinical pathological characteristics: serum-free thyroxine reduction and increases in thyroid peroxidase antibody and IgG4; massive IgG4-positive plasmocyte infiltration in tissues; significant matrix fibrosis; and severe degeneration of thyroid follicular epithelium. IgG4-related HT is a subtype of HT; it presents relatively good therapeutic effect after thyroxine treatment. Cortical hormones can be used for IgG4 HT patients who may suffer from hypothyroidism with significant thyroid injury during early stage to constrain immune injury. This thesis summarizes clinical and pathological histology of IgG4-related HT based on its characteristics.

Chronic autoimmune thyroiditis and thyroid cancer

d a t t O b b u c r The relationship between chronic autoimmune thyroiditis and mucosa-associated lymphoid tissue (MALT) thyroid lymphoma is well known.1 By contrast, its relationship to thyroid follicular epithelium cancer, such as papillary carcinoma, has been for a long time and continues to be controversial, because the concept of chronic inflammation leading to neoplasm is also well established in other tissues. Coexistence of chronic thyroiditis and differentiated thyroid carcinoma is a real clinical situation whose significance is still unknown2; in addition, thyroiditis itself may sometimes be associated to both papillary thyroid carcinoma and MALT lymphoma.3 The first difficulty lies is that the criteria for defining autoimmune thyroiditis are quite heterogeneous, as are the patient groups studied, which may be surgical series or cytological studies with no subsequent surgery. Differentiation between chronic thyroiditis as a nosological entity and lymphocyte infiltration may be another confounding factor. In this regard, such infiltration represents that the immune system, through lymphocytes, could locate the tumor, and thus prevent recurrence. This potential mechanism has led to consider immunotherapy in advanced thyroid cancer, as there would be a generalized immune defect, and a response to cancer could be triggered by tumor cells or specific tumor antigens. An alternative explanation to lymphocyte infiltration is that the tumor itself acts locally, triggering a

Exposure to monocrotophos pesticide causes disruption of the hypothalamic–pituitary–thyroid axis in adult male goldfish (Carassius auratus)

The thyroid hormones (THs) 3,3′,5-triiodo-l-thyronine (T3) and l-thyroxine (T4) exert a wide range of biological effects on physiological processes of fish. To elucidate the thyroid disruption effects of monocrotophos (MCP), an organophosphate pesticide, on male goldfish (Carassius auratus), thyroid follicle histology, plasma total T3 (TT3), total T4 (TT4), free T3 (FT3) and free T4 levels, and the mRNA expression of indices involved in the hypothalamic–pituitary–thyroid axis (HPT axis) were examined following 21-day exposure to 0.01, 0.10 and 1.00mg/L of a 40% MCP-based pesticide. The results showed that MCP exposure induced the hyperplasia and hypertrophy of thyroid follicular epithelium and led to decreased plasma TT3 levels and TT3-to-TT4 ratios, without effect on plasma TT4 levels. Profiles of the changes in the relative abundance of deiodinase (D1, D2 and D3) transcripts were observed in the liver, brain and kidneys, during MCP exposure. An increase in the metabolism of T3, expressed as highly elevated hepatic d1 and d3 mRNA levels, might be associated with the reduction in plasma TT3 levels in both the 0.01 and 0.10mg/L groups, while in the 1.00mg/L MCP group, inhibited hepatic d2 transcripts might have also resulted in decreased TT3 levels by preventing the activation of T4 to T3. As a compensatory response to decreased T3 levels, pituitary thyroid-stimulating hormone β subunit mRNA transcription was up-regulated by the MCP pesticide. Decreases in plasma FT3 levels were also correlated with the modulation of hepatic transthyretin mRNA expression. Overall, the MCP pesticide exhibited thyroid-disrupting effects via interference with the HPT axis at multiple potential sites, resulting in disturbance of TH homeostasis.

Neural lineage-specific homeoprotein BRN2 is directly involved in TTF1 expression in small-cell lung cancer

Thyroid transcription factor 1 (TTF1) plays crucial roles in thyroid, lung, and developing brain morphogenesis. Because TTF1-expressing neoplasms are generated from organs and tissues that normally express TTF1, such as the thyroid follicular epithelium and peripheral lung airway epithelium, TTF1 is widely used as a cell lineage-specific and diagnostic marker for thyroid carcinomas and for lung adenocarcinomas with terminal respiratory unit (TRU) differentiation. However, among lung neuroendocrine tumors, small-cell carcinomas (small-cell lung cancers (SCLCs)), most of which are generated from the central airway, also frequently express TTF1 at high levels. To clarify how SCLCs express TTF1, we investigated the molecular mechanisms of its expression using cultivated lung cancer cells and focusing upon neural cell-specific transcription factors. Both SCLC cells and lung adenocarcinoma cells predominantly expressed isoform 2 of TTF1, and TTF1 promoter assays in SCLC cells revealed that the crucial region for activation of the promoter, which is adjacent to the transcription start site of TTF1 isoform 2, has potent FOX-, LHX-, and BRN2-binding sites. Transfection experiments using expression vectors for FOXA1, FOXA2, LHX2, LHX6, and BRN2 showed that BRN2 substantially upregulated TTF1 expression, whereas FOXA1/2 weakly upregulated TTF1 expression. BRN2 and FOXA1/2 binding to the TTF1 promoter was confirmed through chromatin immunoprecipitation experiments, and TTF1 expression in SCLC cells was considerably downregulated after BRN2 knockdown. Furthermore, the TTF1 promoter in SCLC cells was scarcely methylated, and immunohistochemical examinations using a series of primary lung tumors indicated that TTF1 and BRN2 were coexpressed only in SCLC cells. These findings suggest that TTF1 expression in SCLC is a cell lineage-specific phenomenon that involves the developing neural cell-specific homeoprotein BRN2.

Primary Thyroid Lymphoma

Eight cases of primary thyroid lymphoma were reported in a tertiary government hospital from January 2005 to August 2011. All patients presented with a diffuse enlargement of both thyroid lobes with associated obstructive symptoms. Five of these cases were extranodal marginal zone lymphoma and three were diffuse large B-cell lymphoma. Clinical features that would favor a thyroid lymphoma include tumor size of greater that 7cm, obstructive symptoms, clinical hypothyroidism or history of Hashimoto thyroiditis. Thus, these features must be considered in evaluating thyroid nodules during fine-needle aspiration biopsy. Histologically, extranodal marginal zone B-cell lymphoma shows vaguely nodular to diffuse infiltrates of small to intermediate size atypical lymphoid cells infiltrating the thyroid follicles, while diffuse large B-cell lymphoma shows sheets of large atypical lymphoid cells infiltrating the thyroid follicular epithelium.&#x0D; Keywords: Primary Thyroid Lymphoma, Extranodal Marginal Zone B-cell Lymphoma, Diffuse Large B-cell Lymphoma.

Sorting nexin 5 of a new diagnostic marker of papillary thyroid carcinoma regulates Caspase‐2

Papillary thyroid carcinoma (PTC) is a well-differentiated endocrine malignant tumor that develops from thyroid follicular epithelium. The tumor represents the most common type of endocrine malignancy; however, its tumorigenesis is not fully elucidated. The aim of this study was to address the functional role of the sorting nexin (SNX) family in PTC because of recent experimental evidence suggesting that the SNX family members actively control endocytotic transportation as well as cell fate. Expression profiles of SNX family members of PTC showed a significant quantity of transcripts of SNX5. Further immunohistochemical analysis with an SNX5-specific monoclonal antibody established in this study consistently demonstrated the preferential expression of SNX5 in PTC (94.2%, 113/120 cases) as indicated by studies on 440 cases of various tumors. In contrast, other major carcinomas originating from the lung (2.6%, 1/38 cases), breast (5.1%, 2/39 cases), and intestine (4.2%, 1/24 cases) scarcely expressed SNX5. When we investigated models of murine thyroid tumors induced by the administration of carcinogens, high expression of Snx5 was also observed in well-differentiated thyroid tumors, further implying that the tumorigenesis of the thyroid gland was tightly associated with the abundance of SNX5/Snx5. Moreover epithelial cells expressing excess SNX5 showed high levels of Caspase-2 of an initiator caspase. Collectively these findings suggest that the evaluation of SNX5 expression would support pathological diagnosis of primary and secondary PTC.

Mucoepidermoid Carcinoma of the Thyroid: A Report of Three Cases and Postulated Histogenesis

Primary mucoepidermoid carcinoma (MEC) of the thyroid is a rare clinical and pathological entity that accounts for <0.5% of all thyroid malignancies. Although the histogenesis has been controversial, most investigators now favor it as arising from either metaplasia of thyroid follicular epithelium or heterologous de-differentiation from papillary thyroid carcinoma (PTC). We report three cases of thyroid MEC found in continuity with, and clearly arising from de-differentiation of, well-differentiated thyroid carcinomas (WDTCs). The cases presented here included two women (aged 22 and 52) and one man (aged 58). One of these cases arose in conjunction with PTC, one with follicular thyroid carcinoma (FTC), and one with Hurthle cell carcinoma (HCC). In all three cases, there was a gradual transition in morphology between the areas of typical WDTC and the areas showing MEC differentiation. In addition, immunohistochemistry demonstrated a gradual loss of thyroid specific markers (thyroid transcription factor-1, thyroglobulin) mirroring the change in morphology. We conclude that thyroid MEC can arise from metaplastic de-differentiation of WDTC, including FTC or HCC in addition to PTC. Currently, we recommend that after excision, each of the WDTC and MEC components of these tumors be treated with targeted adjuvant therapies, which may involve radioactive-iodine ablation, thyrotropin suppression, and external beam radiotherapy.