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PubMed2003

14-3-3 sigma possibly plays a constitutive role in papillary carcinoma, but not in follicular tumor of the thyroid.

14-3-3 sigma is a negative regulator of the cell cycle and contributes to G2 arrest. Thus far, the lack of its expression due to hypermethylation of the CpG islands has been reported in some carcinomas. In this study, we investigated the expression of 14-3-3 sigma in thyroid neoplasms by means of immunohistochemistry as well as Western blot analysis. Normal follicules did not express 14-3-3 sigma. In 82 papillary carcinomas, all the cases expressed 14-3-3 sigma and its expression was not reduced but even enhanced in the advanced stage and in poorly differentiated types. Furthermore, 21 of the 23 anaplastic carcinomas expressed 14-3-3 sigma and its expression level tended to be higher than in papillary carcinoma. On the other hand, none of the 34 follicular carcinomas or 29 follicular adenomas expressed 14-3-3 sigma. These results suggest that 14-3-3 sigma plays a constitutive role in papillary carcinoma rather than acting as a cell cycle regulator, whereas it is not required for the occurrence and development of follicular tumor.

14-3-3 Proteins↗
PubMed2001

[Laryngeal-tracheal resection in the treatment of thyroid malignancies: description of a case and review of literature].

Well-differentiated thyroid carcinomas infiltrate into the respiratory tract in between 0.9 and 7% of the cases. Laryngeal-tracheal involvement--most often discovered intra-operatively--can substantially modify the surgical approach. It should be evaluated pre-operatively through laryngo-tracheoscopy with a flexible fibroscope and, in some selected cases, using CT or NMR. Thyroidectomy, associated with laryngeal-tracheal resection and termino-terminal anastomosis, ensures good oncological results without any negative effect on the incidence of post-operative complications. The present work reports the case of a 64-year-old patient who, for 5 months, had presented a swelling of increasing consistency in the left hemithyroid, fixed on the deep planes. Echography showed a 5 cm mass in the left lobe and thyroid isthmus, without suspected lymphadenopathy for metastasis. Fine needle cytology was compatible with papillary carcinoma. CT using a contrast medium revealed an infiltration into the left antero-lateral wall of the I and II tracheal ring, with submucosal extension with no significant signs of stenosis of the airway. Esophagogastroscopy was normal while tracheobroncoscopy confirmed the radiological picture and made it possible to perform a tracheal biopsy which proved positive for papillary carcinoma. The patient underwent total thyroidectomy associated with anterior compartment lymphadenectomy and crico-tracheal resection of the cricoid arch and the first 5 tracheal rings. When surgery was completed, the patient was extubated without complications. Post-operative recovery was uneventful and the patient was discharged on the 9th day after surgery. Histopathological examination confirmed the pre-operative diagnosis and made it possible to stage the lesion as pT4N1bM0 because of the presence of one prelaryngeal lymph node metastasis and another one at the right paratracheal space. Complementary I131 therapy was scheduled along with periodic laryngo-tracheoscopic controls. 16 months after surgery the anastomotic line is perfectly healed and the patient is clinically disease free. A review of the literature on the surgical treatment of well-differentiated malignant thyroid neoplasms with respiratory tract involvement through resection and laryngo-tracheal anastomosis has made it possible to trace the indications, limits and results of this type of therapeutic approach.

Anastomosis, Surgical↗
PubMed2003

High prevalence of BRAF gene mutation in papillary thyroid carcinomas and thyroid tumor cell lines.

The RAS-RAF-MEK-ERK-MAP kinase pathway mediates the cellular response to extracellular signals that regulate cell proliferation, differentiation, and apoptosis. Mutation of the RAS proto-oncogene occurs in various thyroid neoplasms such as papillary thyroid carcinomas (PTCs), follicular thyroid adenomas and carcinomas. A second genetic alteration frequently involved in PTC is RET/PTC rearrangements. Recent studies have shown that BRAF, which is a downstream signaling molecule of RET and RAS, is frequently mutated in melanomas. This study tests whether BRAF is also mutated in thyroid tumors and cell lines. We analyzed BRAF gene mutation at codon 599 in thyroid tumors using mutant-allele-specific PCR and in 10 thyroid tumor cell lines by DNA sequencing of the PCR-amplified exon 15. We found that BRAF was mutated in 8 of 10 thyroid tumor cell lines, including 2 of 2 papillary carcinoma cell lines, 4 of 5 anaplastic carcinoma cell lines, 1 of 2 follicular carcinoma cell lines, and 1 follicular adenoma cell line. BRAF mutation at codon 599 was detected in 21 of 56 PTC (38%) but not in 18 follicular adenomas and 6 goiters. BRAF mutation occurred in PTC at a significantly higher frequency in male patients than in female patients. To test whether BRAF mutation may cooperate with RET/PTC rearrangements in the oncogenesis of PTC, we tested whether BRAF-mutated PTCs were also positive for RET/PTC rearrangements. Immunohistochemical staining was conducted to evaluate RET/PTC rearrangements by using two different anti-RET antibodies. Surprisingly, we found that a large number of BRAF-mutated PTCs (8 of 21) also expressed RET, indicating that the RET proto-oncogene is rearranged in these BRAF-mutated PTCs. These observations suggest that mutated BRAF gene may cooperate with RET/PTC to induce the oncogenesis of PTC.

Adenocarcinoma, Follicular↗
PubMed1990

Uncommon types of thyroid cancer.

Anaplastic carcinoma of the thyroid is rare, making up 5% to 14% of primary malignant thyroid neoplasms. Lymphoma of the thyroid is even rarer, accounting for only 1% to 2% of thyroid malignancies. Other even rarer tumors of the thyroid, such as liposarcoma and angiosarcoma, have also been described. Although these thyroid tumors are rare, it is very important to recognize them because they may present as medical emergencies and constitute a challenge for endocrinologists, surgeons, radiotherapists, and oncologists. Anaplastic carcinoma grows rapidly and has a dismal prognosis. A significant number of patients with anaplastic carcinoma have areas of well differentiated thyroid carcinoma, which supports the hypothesis that anaplastic thyroid carcinoma arises from a pre-existing well differentiated thyroid carcinoma. Younger patients do better than older patients, and those diagnosed at an earlier stage do better than those with metastases at presentation. Multimodality therapy with surgery, radiotherapy, and chemotherapy appears to be of value. Lymphoma of the thyroid may be a primary disease or may involve the gland as part of a systemic disease. It is not usually suspected before surgery or fine-needle aspiration biopsy. Radiotherapy alone, if the disease is limited to the neck, produces good results; however, in patients with mediastinal extension, chemotherapy is indicated.

Carcinoma↗
PubMed1984

Expression of intermediate filament proteins in thyroid gland and thyroid tumors.

The presence of intermediate filament proteins of cytokeratin/prekeratin type and vimentin type was evaluated in non-neoplastic thyroid glands and in different types of thyroid neoplasms. Follicular epithelium of both normal and goitrous thyroids showed a strong reaction with anticytokeratin antibodies that widely cross-react with various simple epithelia. On the other hand, in normal thyroid, there were only occasionally (in one of 12 cases) solitary cells reacting with antibodies to epidermal prekeratin. In nodular goiters, such cells were often seen (eight of 18), especially among the lining cells of cysts, and in chronic thyroiditis in all (12 of 12) cases. Only the stromal cells and intraluminal macrophages reacted with antibodies to vimentin. Neoplastic cells of papillary carcinomas showed a positive staining reaction both with antibodies to cytokeratins and to epidermal prekeratin. Follicular carcinoma cells, although positive for cytokeratins, could generally not be stained with antibodies to epidermal prekeratin. Medullary carcinoma cells also showed cytokeratin positivity and, only occasionally, positivity for epidermal prekeratin. Anaplastic carcinomas were also reactive with antibodies to cytokeratin but, for the most part, were negative for epidermal prekeratin. Interestingly, some neoplastic cells of all types of thyroid carcinomas also appeared to contain vimentin, as shown with both polyclonal and monoclonal antivimentin antibodies. In contrast to carcinomas, the intermediate filaments of thyroid sarcomas and lymphomas were only of vimentin type. Furthermore, it was found that the papillary structures in benign goiters were only reactive with cytokeratin antibodies and lacked, in contrast to papillary carcinomas, epidermal prekeratin-like immunoreactivity. Hence, the analysis of intermediate filament proteins of thyroid tumors can be utilized to differentiate between papillary and follicular carcinomas and between benign and malignant papillary lesions as well as between anaplastic thyroid carcinomas and sarcomas or lymphomas.

Adenocarcinoma↗
PubMedDate not supplied

Incidence of thyroid carcinoma in a common surgical practice: the problems.

Over a two-year period, seven hundred twenty-three operations for thyroid disease were performed in the department of endocrine surgery on 717 patients; 7.1% of these patients had neoplastic lesions. If we consider only the solitary nodules, the incidence is 8.8%; while it is only 5.0% in patients with diffuse goiter. In 27.5% of the cases of thyroid neoplasm, peroperative analysis on thyroid tissue is falsely encouraging; yet, on the whole, such analysis reassures 98% patients. Preoperative fine needle aspiration and cytology--of little impact in that series--can bring interesting informations in particular circumstances, while keeping in mind that microscopic diagnosis of follicular carcinoma of the thyroid is histological and not cytological.

Humans↗
PubMed1981

[Cold thyroid nodules: study of 163 cases (author's transl)].

A group of 163 patients with cold thyroid nodules was studied. Of these, 131 underwent surgery with thyroid neoplasms being found in 33 cases (22.13%). No statistically significant differences were seen in frequency of neoplastic cold thyroid nodules between males and females; in time of evolution between neoplastic and non-neoplastic cold thyroid nodules; or in mean age of the groups with neoplastic and non-neoplastic cold nodules. On the other hand, there were significant differences between the mean age of patients with different types of thyroid neoplasms. In conclusion, as at present no diagnostic technique allowing a clear differentiation between neoplastic and non-neoplastic cold thyroid nodules is available for preoperative use, surgical intervention is desirable in cases of this type.

Adult↗
PubMed2005

Stromal elastosis in papillary thyroid carcinomas.

Stromal elastosis, defined as dense aggregations of elastic fibers, is found in some neoplastic tissues especially in malignant tumors of the breast and lung. Although also found in thyroid tissue, stromal elastosis in thyroid neoplasms have received little attention. To clarify the histopathological significance of stromal elastosis in the thyroid, we examined neoplastic (n = 223) and hyperplastic (n = 82) thyroid tissues in conjunction with cancer tissues (n = 193) of various other organs. Stromal elastosis was observed as deposits of pale homogeneous material in hematoxylin and eosin stain, and distinctively highlighted by elastic-van Gieson's stain. On immunohistochemical examination, elastin and tropoelastin were confirmed in these deposits. Stromal elastosis was found in 66% of papillary thyroid carcinomas (PTCs), although it was not identified in other histological types of thyroid neoplasms. In PTCs, deposits of elastic fibers varied in size and shape, and were more frequently distributed in the periphery of the tumor tissue. The histological subtypes of PTC varied in prevalence of elastosis with the follicular variant's (9%) prevalence being significantly lower than that of the classical type (72%). The frequency of stromal elastosis in PTCs was very similar to the frequencies in breast and lung adenocarcinomas, and higher than the frequencies in carcinomas of other organs. In conclusion, our results suggest that stromal elastosis is a characteristic histological finding of PTCs, presumably associated with their growth pattern and/or histological architecture. It is, therefore, reasonable to propose that stromal elastosis is an ancillary feature in the histopathological diagnosis of PTCs.

Carcinoma, Papillary↗
PubMed1982

Thyrotropin binding and adenylate cyclase activation in normal and neoplastic human thyroid tissue: lack of effect of thyroglobulin.

The effects of bovine TSH (bTSH) and bovine (bTg) and human thyroglobulin (hTg) on the binding of [125I] bTSH and the activation of adenylate cyclase (AC) were studied in both normal and neoplastic human thyroid homogenates in vitro using adenylate cyclase conditions. [125I]bTSH bound specifically and with high affinity to a particulate fraction from normal thyroid and from benign and malignant thyroid neoplasms; this binding was inhibited by unlabeled bTSH (approximate Kd = 10.0 mU/ml for normal tissue; Kd = 2.5 mU/ml for thyroid neoplasms). Half-maximal activation of AC was obtained at a TSH concentration of approximately 2.5 mU/ml for both normal and neoplastic thyroid tissue, indicating that the high affinity TSH receptors are coupled to AC, at least in the neoplastic thyroid tissue. bTg and hTg did not inhibit [125I]bTSH binding to high affinity TSH receptors in either normal or neoplastic thyroid tissue. bTSH increased AC activity up to 25-fold in neoplastic thyroid tissue and up to 4-fold in normal thyroid tissue, whereas at concentrations up to 1 mg/ml, bTg had no effect. The current study demonstrates that bTSH binds to specific, high affinity receptors and stimulates AC activity in both normal and neoplastic thyroid tissue. bTg and hTg, under the conditions used in this experiment, do not influence TSH binding to its high affinity receptor in these tissues. Since Tg does not influence high affinity TSH binding or AC activity in a particulate fraction rich in plasma membranes from normal or neoplastic thyroid tissue, it is unlikely to have a modulating role on TSH action at the thyroid plasma membrane.

Adenoma↗
PubMed1998

Measurement of serum TSH in the investigation of patients presenting with thyroid enlargement.

In otherwise euthyroid patients presenting with thyroid enlargement, reduction in serum thyrotrophin (TSH) concentrations measured in a sensitive assay may be a marker of thyroid autonomy and may therefore indicate a benign underlying pathology. We investigated prospectively a cohort of 467 subjects presenting consecutively to our thyroid clinic with nodular or diffuse enlargement of the thyroid. Subjects were divided into those with normal (0.4-5.5 mU/l), low but detectable (0.1-0.39 mU/l) or undetectable (< 0.1 mU/l) serum TSH concentrations. The final pathological diagnosis was defined by fine-needle aspiration cytology and clinical follow-up of at least 2 years or by fine-needle aspiration cytology and histology following surgical treatment. Serum TSH concentrations below normal were found in 75 patients (16.1%), those with low serum TSH results having higher mean free T4 concentrations, were older and were more likely to be female. In those with undetectable serum TSH, no patient had a diagnosis of thyroid neoplasia and in those with low but detectable TSH, thyroid neoplasms were diagnosed in two patients (3.4%). In those with normal serum TSH, 12.0% had a final diagnosis of thyroid neoplasm (p = 0.013). Overall, thyroid malignancy was found in one patient (1.3%) of those with a serum TSH measurement below the normal range and 6.9% of those with normal serum TSH (p < 0.06). Reduction in serum TSH at presentation may identify a group which requires less intensive investigation and follow-up than those without biochemical evidence of thyroid autonomy.

Biomarkers↗
PubMed2006

Simultaneous immunohistochemical expression of HBME-1 and galectin-3 differentiates papillary carcinomas from hyperfunctioning lesions of the thyroid.

AIMS: The histological diagnosis is critical for the postsurgical management and follow-up of thyroid malignancies. The differential diagnosis between papillary carcinoma and hyperfunctioning lesions, either with papillary hyperplasia or with a follicular architecture, can create real diagnostic difficulty. The aim of this study was to evaluate the expression of several antibodies considered to be markers of malignancy in malignant and hyperfunctioning thyroid neoplasms and to include the most effective of them in a diagnostic panel. METHODS AND RESULTS: One hundred resected thyroid nodules--58 hyperfunctioning benign lesions and 42 papillary carcinomas (14 follicular variant, 14 macrofollicular variant and 14 classic type)--were immunohistochemically studied for HBME-1, galectin-3, cytokeratin (CK) 19 and RET-proto-oncogene. HBME-1 and galectin-3 showed 92.8% and 89% sensitivity, respectively, and their coexpression was present in 36 out of 42 papillary carcinomas (85.7%) and absent in non-malignant lesions. Their association increased sensitivity to 94.7% and the diagnostic accuracy to 97.9% and involved the highest number of cases (95%) in comparison with two other panels including, respectively, three (HBME-1, galectin-3, CK19) and all four antibodies. CONCLUSION: An immunohistochemical panel consisting of HBME-1 and galectin-3 can make a correct distinction between malignant and hyperfunctioning thyroid neoplasms with high diagnostic accuracy.

Biomarkers, Tumor↗
PubMed1992

NTP Toxicology and Carcinogenesis Studies of Ethylene Thiourea (CAS: 96-45-7) in F344 Rats and B6C3F1 Mice (Feed Studies).

Ethylene thiourea is a white crystalline solid used extensively in the rubber industry as an accelerator in the vulcanization of elastomers. It is also a trace contaminant and metabolic degradation product of a widely used class of ethylene bisdithiocarbamate fungicides. Ethylene thiourea is known to produce thyroid neoplasms in rats and liver neoplasms in mice following long-term administration; thus, it was chosen by the National Toxicology Program in an investigation of the potential value of perinatal exposures in assessing chemical carcinogenicity. Chronic toxicity and carcinogenicity studies of ethylene thiourea, 99% pure, were conducted in F344/N rats and B6C3F1 mice of each sex. The studies were designed to determine 1) the effects of ethylene thiourea in rats and mice receiving adult exposure only (a typical carcinogenicity study), 2) the toxic and carcinogenic effects of ethylene thiourea on rats and mice receiving perinatal exposure only (dietary exposure of dams prior to breeding and throughout gestation and lactation), and 3) the effects of combined perinatal and adult exposure to ethylene thiourea. STUDIES IN F344/N RATS: In a preliminary study to determine the perinatal dietary concentrations for the 2-year studies, female F344/N rats were fed 0, 8, 25, 83, or 250 ppm ethylene thiourea in the feed beginning 2 weeks prior to breeding and continuing throughout gestation and lactation, and the pups were fed at these same concentrations up to 9 weeks postweaning. Based on decreased survival of rat pups between postnatal days 0 to 4 and reduction in body weight gains in male weanling rats receiving 250 ppm, dietary concentrations of 0, 9, 30, and 90 ppm were selected for the perinatal (F0) exposure levels in the 2-year studies. Groups of 10 male and 10 female rats, 8 to 9 weeks of age, were fed diets containing 0, 60, 125, 250, 500, or 750 ppm ethylene thiourea for 13 weeks to determine the adult dietary concentrations. Because of reduced weight gains and decreased feed consumption in rats receiving 500 or 750 ppm ethylene thiourea, dietary concentrations of 0, 25, 83, and 250 ppm were selected for the adult (F1) exposure during the 2-year studies. In the 2-year studies, perinatal and adult exposures to ethylene thiourea were applied separately and together to groups of male or female rats as shown in the following table. The principal toxic effects of ethylene thiourea involved the thyroid gland. Serum levels of thyroxine (T4) and/or triiodothyronine (T3) were significantly decreased in rats receiving adult concentrations of 83 or 250 ppm, and thyrotropin (thyroid-stimulating hormone, TSH) was significantly increased at these concentrations. In male and female rats receiving adult-only exposure of 83 or 250 ppm, the incidences of follicular cell hyperplasia or follicular cell adenoma of the thyroid gland were significantly increased relative to the controls. The incidences of follicular cell carcinoma were significantly increased in the 250 ppm groups, and carcinomas occurred more frequently in males than in females. Exposure Groups of Rats in the 2-Year Feed Studies of Ethylene Thiourea a F1 Concentration (ppm)b F0(ppm)c 0 25 83 250 0 60 -- 60 60 9 -- 60 -- -- 30 -- -- 60 -- 90 60 -- 60 60 a Ten rats from each group were sacrificed and evaluated at 9 months b Concentration of ethylene thiourea in feed given to rats beginning at 8 weeks of age for 24 months c Concentration of ethylene thiourea in feed through breeding, gestation, and lactation until pups were 8 weeks of age Perinatal-only exposure to 90 ppm had no effect on the incidence of thyroid neoplasms in these studies, although there was a marginal increase in follicular cell hyperplasia relative to the controls. However, for groups of rats receiving combined perinatal and adult exposure (F0:F1), males and females receiving concentrations of 90:250 ppm ethylene thiourea had significantly increased incidences of thyroid follicular cell neoplasms relative to those receiving adult-only exposure to 250 ppm. Further, groups of male rats receiving 90:83 ppm 83 ppm showed a significantly increased incidence of follicular cell hyperplasia. Final mean body weights of males and survival of males and females receiving combined perinatal (90 ppm) and adult (250 ppm) exposure were lower than those receiving adult-only exposure of 250 ppm. Thus, in rats, combined perinatal and adult exposure slightly enhanced the toxicity and proliferative effects on the thyroid gland observed with adult-only exposure to ethylene thiourea. Neoplasms of the Zymbal's gland were marginally increased in rats receiving 90:250 ppm (males - 0:0, 1/50; 90:250, 5/50; females - 0:0, 1/50; 90:250, 4/50). Mononuclear cell leukemia occurred with a significant trend in groups of male and female rats receiving perinatal exposure of 90 ppm and increasing adult concentrations (90:0, 90:83, and 90:250 ppm), and for female rats without perinatal exposure (0:0, 0:83, and 0:250 ppm). The incidences of mononuclear cell leukemia in males receiving 90:83 ppm and males and females receiving 90:250 ppm were statistically significant relative to the respective 0:0 ppm groups. Low incidences of renal tubule cell adenomas occurred in most dose groups of male rats, but not in the highest dose group or the controls. STUDIES IN B6C3F1 MICE: In a preliminary study to determine the perinatal dietary concentrations for the 2-year studies, adult female C57BL/6N mice were fed 0, 33, 100, 330, or 1,000 ppm ethylene thiourea in the feed beginning 2 weeks prior to breeding and continuing throughout gestation and lactation and up to 9 weeks postweaning. Because of reduced survival of mouse pups at postnatal day 28 and lower final mean body weights in weanlings receiving perinatal exposure of 1,000 ppm, dietary concentrations of 0, 33, 110, and 330 ppm were selected for the perinatal exposure levels in the 2-year studies. Groups of 10 male and 10 female mice, 8 to 9 weeks of age, were fed diets containing 0, 125, 250, 500, 1,000, or 2,000 ppm ethylene thiourea for 13 weeks to determine the adult dietary concentrations. Moderately severe diffuse follicular cell hyperplasia in the thyroid gland and centrilobular cytomegaly of the liver occurred in mice receiving 2,000 ppm. Because the severity of the thyroid lesion (and degree of hypothyroidism) at this concentration was considered potentially life threatening in 2-year studies, dietary concentrations of 0, 100, 330, and 1,000 ppm ethylene thiourea were selected for adult exposure during the 2-year studies. In the 2-year studies, perinatal and adult exposures to ethylene thiourea were applied separately and together to groups of male or female mice as shown in the following table. Exposure Groups of Mice in the 2-Year Feed Studies of Ethylene Thiourea a F1 Concentration (ppm)b F0(ppm)c 0 100 330 1,000 0 69 -- 60 60 33 -- 34/29d -- -- 110 -- -- 60 -- 330 60 -- 60 60 a Ten mice from each group except the 33:100 ppm group were sacrificed and evaluated at 9 months b Concentration of ethylene thiourea in feed given to mice beginning at 8 weeks of age for 24 months c Concentration of ethylene thiourea in feed through breeding, gestation, and lactation until pups were 8 weeks of age d 34 males and 29 females assigned to group The principal toxic effects of ethylene thiourea in mice occurred in the thyroid gland, liver, and pituitary gland. Serum levels of T3 were significantly decreased in groups of mice receiving adult concentrations of 1,000 ppm; TSH was significantly increased in mice receiving 330 and 1,000 ppm. The incidences of follicular cell hyperplasia and neoplasia increased principally in males receiving 1,000 ppm and in females receiving 330 or 1,000 ppm. Follicular cell carcinomas were significantly increased in mice receiving 1,000 ppm. Incidences of centrilobular hepatocellular cytomegaly (males and females), hepatocellular adenoma (females), hepatocellular carcinoma (males and females), and adenoma or carcinoma combined (males and females) also were significantly increased in mice receiving F1 concentrations of 330 or 1,000 ppm. In the pituitary gland, incidences of focal hyperplasia (males) or adenoma (males and females) of the pars distalis were significantly increased in groups of mice receiving 1,000 ppm ethylene thiourea. Perinatal exposure to concentrations of 330 ppm had no effect on the incidences of nonneoplastic lesions or neoplasms in mice. For groups of mice receiving combined perinatal and adult exposure, females receiving F0:F1 concentrations of 330:330 ppm had significantly increased incidences of follicular cell adenoma relative to those receiving adult-only exposure to 330 ppm. Similarly, male mice receiving F0:F1 concentrations of 330:330 ppm had significantly increased incidences of follicular cell hyperplasia. Thus, in mice, perinatal exposure slightly enhanced the proliferative effects on the thyroid gland of adult exposure. There were no effects of perinatal exposure in mice at sites other than in the thyroid gland. CONCLUSIONS: 2-Year Adult-Only Exposure:Under the conditions of these 2-year adult-only dietary exposures, there was clear evidence of carcinogenic activity of ethylene thiourea in male and female F344/N rats, as shown by increased incidences of thyroid follicular cell neoplasms. There was clear evidence of carcinogenic activity of ethylene thiourea in male and female B6C3F1 mice as shown by increased incidences of thyroid follicular cell neoplasms, hepatocellular neoplasms, and adenomas of the pars distalis of the pituitary gland. Nonneoplastic lesions associated with the administration of ethylene thiourea included follicular cell hyperplasia in rats and mice and follicular cell cytoplasmic vacuolation, centrilobular hepatocellular cytomegaly, and focal hyperplasia of the pars distalis of the pituitary gland in mice. Other effects associated with the administration of ethylene thiourea included decreased serum levels of T4 and/or T3 in rats and increased serum levels of TSH in rats and mice. Perinatal-Only Exposure:Perinatal exposure alone had no effect on the incidences of neoplasms in rats or mice after 2 years. Animals may have been able to tolerate higher perinatal exposure concentrations. Combined Perinatal and 2-Year Adult Exposures:Combined perinatal and 2-year adult dietary exposure to ethylene thiourea confirmed the findings of the 2-year adult-only exposures for the incidences of neoplasms in the thyroid gland of rats and mice and the liver and pituitary gland of mice. In male and female rats, combined perinatal and adult exposure to 90:250 ppm was associated with marginal increases, relative to the untreated (0:0 ppm) controls, in Zymbal's gland neoplasms and mononuclear cell leukemia, which may have been related to chemical administration. In rats receiving adult exposure to 250 ppm ethylene thiourea, perinatal exposure to 90 ppm was associated with a slightly enhanced incidence of thyroid neoplasms compared to adult-only exposure. However, increasing perinatal exposure from 0 to 90 ppm had no effect on incidences of thyroid neoplasms in rats receiving adult exposure to 83 ppm. Increasing perinatal exposure from 0 to 330 ppm was associated with a marginally increased incidence of thyroid neoplasms in female mice receiving adult exposure to 330 ppm, but there were no enhancing effects of perinatal exposure in mice receiving adult exposure to 1,000 ppm. Synonyms: 2-Imidazolidinethione; Imidazoline-2-thiol; 2-mercaptoimidazoline; N,N'-ethylenethiourea; 1,3-ethylenethiourea; 2-imadazoline-2-thiol

Journal Article↗
PubMed2005

Hodgkin's lymphoma of the thyroid: a clinicopathologic study of five cases and review of the literature.

Hodgkin's lymphoma rarely involves the thyroid gland. We report the clinical and pathologic features of five cases of Hodgkin's lymphoma that presented as thyroid lesions. All five patients were females, aged 29-59 years. Three patients had a history of chronic thyroiditis and hypothyroidism and two were euthyroid. One patient had a remote history of Hodgkin's lymphoma. Imaging studies showed a 'cold' nodule (three cases) or a diffusely enlarged thyroid gland, resembling goiter or fibrosclerosing thyroiditis (two cases). Thyroid fine-needle aspiration was performed before thyroidectomy in all cases; three of these cases contained some atypical cells, raising the possibility of Hodgkin's lymphoma. Histologically, all cases were classical Hodgkin's lymphoma, nodular sclerosis subtype. The four patients with primary thyroid lymphoma had Stage IIE disease. All patients were treated with surgical excision and chemotherapy, with or without radiation therapy, and were alive after 2 months to 7 years of follow-up. A review of the English literature between 1962 and 2005 revealed 16 cases of thyroid Hodgkin's lymphoma, with a female preponderance and generally favorable outcome similar to the cases in our series. Hodgkin's lymphoma of the thyroid is rare and can mimic a primary thyroid epithelial tumor or thyroiditis clinically. Histologic diagnosis may be difficult due to marked fibrosis. Hodgkin's lymphoma should be considered in the differential diagnosis of thyroid neoplasms.

Adult↗
PubMed1994

Polysialic acid of the neural cell adhesion molecule in the human thyroid: a marker for medullary thyroid carcinoma and primary C-cell hyperplasia. An immunohistochemical study on 79 thyroid lesions.

We recently reported that the gold-labeled monoclonal antibody MAb 735, reactive with a long-chain form of alpha-2,8-linked polysialic acid (polySia) found on the neural cell adhesion molecule (NCAM), is useful to immunohistochemically distinguish small-cell lung carcinomas from neuroendocrine carcinomas with higher grade of differentiation (carcinoids) and other types of lung carcinomas (Am J Pathol 1991;139:297). In this study, we tested the occurrence of polySia in various types of malignant thyroid tumors and C-cell hyperplasia to determine whether polySia is a useful adjunct for the differential diagnosis of medullary thyroid carcinoma (MTC) and other thyroid neoplasms and to distinguish primary from secondary (reactive) C-cell hyperplasia (CCH). We examined formaldehyde-fixed and paraffin-embedded sections of 79 thyroid lesions, consisting of 33 MTC (14 familial and 19 sporadic tumors), 13 follicular, 11 papillary, 16 anaplastic carcinomas, and four glands with primary and two with secondary CCH. We applied a direct and an indirect immunogold-silver technique for polySia, CT, and CEA detection, respectively. All 33 MTC showed a strong cell-surface-associated immunoreactivity for polySia, which was sensitive to endoneuraminidase digestion. The polySia immunoreactivity of nerves served as an internal control in all specimens. Immunoreactivity for CT and CEA was present in all MTC with the exception of one recurrent tumor with features of an anaplastic MTC type. All other thyroid neoplasms were nonreactive for polySia, CT, and CEA. Primary CCH associated with MTC showed a strong polySia immunostaining, which was less intense in primary CCH not combined with MTC. In normal-appearing C cells and in secondary CCH, staining for polySia was absent in the majority of cases. We conclude that polySia of NCAM is a valuable marker to distinguish medullary carcinomas from other types of thyroid carcinomas. Furthermore, it allows for the discrimination of primary from secondary C-cell hyperplasia and may be helpful to better define the normal range of C cells in unaffected members of a family with a history of multiple endocrine neoplasia (MEN)-II.

Adolescent↗
PubMedDate not supplied

[Malignant lymphoma of the thyroid gland].

INTRODUCTION: Malignant lymphoma of the thyroid gland can be defined as a lymphoma arising from the thyroid gland. Lymphomas of the thyroid gland represent less than 5% of primary thyroid neoplasms and are two to three times more common in women than in men, whereas the median age is usually close to 60 years. Majority of thyroid lymphomas are diffuse, large-cell lymphomas. The incidence of thyroid lymphomas in patients with Hashimoto thyroiditis has markedly increased and this phenomenon is probably related to their pathogenesis. CLINICAL PRESENTATION: Unlike most other thyroid neoplasms, lymphomas are usually rapidly enlarging masses and local symptoms are common: pain, hoarseness, dysphagia, and dyspnea or stridor. DIAGNOSIS: To evaluate the extent of disease, a chest x-ray and CT scans of the head and neck, chest, abdomen, and pelvis are necessary. An excisional or large-needle biopsy may also be necessary to make the correct diagnosis. Occasionally, these tumors can be confused with anaplastic thyroid carcinomas, which can lead to serious mistakes in management. A gallium scan or a positron emission tomography (PET) scan can help later to establish whether any residual abnormality, observed on x-ray studies after treatment, contains active lymphoma or scar tissue. After diagnosis, patients are clinically staged (without surgery) using appropriate computed tomography scans or magnetic resonance imaging. THERAPY: Assessment of the extent of thyroid lymphomas is crucial for prognosis and treatment. Total thyroidectomy may improve the prognosis in patients with intrathyroidal disease only. It is very important to identify patients with favorable prognostic factors and to treat them with standard chemotherapy (CHOP) and radiotherapy protocols. Patients with diffuse large-cell primary thyroid lymphomas should not be treated with radiation therapy alone. CONCLUSION: The best treatment results for malignant lymphomas of the thyroid gland are achieved using a combined-modality therapy.

Aged↗
PubMed1988

Immunohistochemical studies on the localization of fibronectin in human thyroid neoplastic tissues.

Fibronectin (FN) has been considered to be involved in the malignant transformation of cells. It was thus of interest to morphologically study the cell surface distribution of FN in various types of thyroid neoplasms employing immunohistochemical techniques. Immunohistochemical staining using the specific anti-human FN antibody was performed by the avidin-biotin-peroxidase complex procedure. Compared to the staining pattern of normal thyroid tissues (control), differences in staining in malignant thyroid lesions and even in fetal and embryonal adenomas were evident, often on the lateral and basal aspects of the cell membrane. Colloid adenomas, however, showed FN staining on the basement membrane, basically similar to the controls. Moreover, in thyroid carcinoma, different staining patterns relating to each of the histological types were observed. The present investigation demonstrates the heterogeneity of the thyroid neoplasms in terms of FN binding.

Adenocarcinoma↗
PubMedDate not supplied

Decreased expression of p107 is correlated with anaplastic transformation in papillary carcinoma of the thyroid.

BACKGROUND: Previous studies have demonstrated that two members of the Rb family, pRb and p130, are expressed in thyroid neoplasms. However, our knowledge about the expression and physiological role of the third member of this family, p107, remains poor. We therefore investigated p107 expression in various thyroid neoplasms. MATERIALS AND METHODS: We immunohistochemically investigated p107 expression in 16 anaplastic carcinomas, 50 papillary carcinomas, 15 follicular carcinomas and 17 follicular adenomas using a rabbit polyclonal antibody against p107. RESULTS: Normal follicular cells only occasionally expressed p107. In papillary carcinoma, p107 was positive in 84.0% of the cases, regardless of various biological characteristics. Follicular carcinoma less frequently expressed p107 than follicular adenoma (p = 0.0278). Furthermore, only 12.5% of anaplastic carcinomas were p107-positive and the incidence was significantly less than that in papillary carcinoma (p < 0.0001). CONCLUSION: Our findings suggest that p107 plays a constitutive role in the progression of papillary carcinoma and that decreased p107 expression may contribute to the transformation from follicular adenoma to follicular carcinoma and anaplastic transformation.

Carcinoma↗
PubMedDate not supplied

Problems in the cytologic diagnosis of the "cold' thyroid nodule in patients with lymphocytic thyroiditis.

The cytologic diagnosis of the coexistence of lymphocytic thyroiditis (LT) and thyroid neoplasms presented certain problems. Fine needle aspirations of 117 "cold' nodules were reviewed because they were or should have been diagnosed as LT. Of five cases of LT plus lymphoma, two were correctly diagnosed and three were diagnosed as LT only. All seven cases of LT plus papillary carcinoma were correctly identified, as were four of those in patients operated upon for LT plus a cellular neoplasm. From a total of 1,600 biopsies, 7 "probable' and 5 "possible' cancers were LT at operation. The causes of diagnostic error were identified as: (1) similarity of epithelial cell nuclear atypia in LT and cellular neoplasm, (2) inexperience and (3) inadequate sampling. The presence of diffuse thyroid abnormality, of significant titers of antithyroglobulin and antimicrosomal antibodies and of chemical evidence of thyroid insufficiency should alert the examiner to the possibility of LT. Large needle biopsy may clarify difficult cases.

Adenoma↗