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Background: In risk assessment of recurrence, papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) are often grouped together as differentiated thyroid cancer (DTC). However, while risk factors affecting recurrence of PTC are well established, risk factors for recurrence of FTC are not. This systematic review examines risk factors for recurrence of FTC and evaluates their significance. Methods: A systematic search on PubMed and Embase was performed in September 2020, including studies evaluating risk factors for recurrence of FTC. A quality assessment of the enrolled studies was performed. Results: Nine studies ( n  = 1544 patients) from eight countries were included. The average recurrence rate was 13.6%, and distant metastasis (DM) constituted 64.8% of the recurrent cases. The risk factors examined were sex, age at diagnosis, primary tumor size, degree of invasiveness, focality, positive resection margin, lymph node (LN) metastasis, and DM at diagnosis. Risk factors correlated with recurrence of FTC were age older than 45 years, primary tumor size above 40 mm, widespread invasion, multifocality, positive resection margin, LN metastasis, and DM at diagnosis. Sex was not a statistically significant risk factor. Conclusions: We identified seven risk factors associated with recurrence of FTC. Age and multifocality were found to be of greater impact regarding recurrence risk of FTC compared with PTC. Future research needs to address the impact of different risk factors for recurrence of FTC particularly including age, primary tumor size, angioinvasion, and mutational status.

An increasing number of children are diagnosed with differentiated thyroid cancer. With an excellent prognosis for the majority of pediatric patients, the goal of therapy is to optimize outcome while reducing complications. Increased knowledge of the somatic, oncogenic driver mutations provides opportunities to improve the accuracy of diagnosis, to stratify surgery, and to treat patients with morbidly invasive or refractory disease. Treatment complications can be reduced by referral to regional, high-volume pediatric thyroid centers., (Copyright © 2020. Published by Elsevier Inc.)

Objective: The CADIT-CAM study was designed to retrospectively analyze the clinical characteristics, treatments, and outcomes of patients with differentiated thyroid carcinoma (DTC) in Castilla La Mancha., Patients and Methods: A total of 1434 patients from 7 hospitals in Castilla La Mancha were enrolled into the study from 2001 to 2015., Results: Seventy-seven percent of patients were female, with a mean age at diagnosis of 48 years. Papillary thyroid carcinoma accounted for 93% of cases. Mean tumor size was significantly smaller at final follow-up (P<.05). Radioiodine ablation (RA) was performed in 84% of patients, and its use decreased during the study, especially in tumors with low recurrence risk. Recurrence occurred in 22% of patients and was associated to male gender, greater tumor size, multifocality, lymph node metastases, extrathyroid involvement, distant metastases and increasing thyroglobulin antibody titers. At the end of follow-up 76.2% of patients were alive and free of disease, 2.4% had died from DTC. Overall survival of the cohort was 95.1% at 15 years of follow-up., Conclusions: Characteristics of DTC in this Spanish cohort are similar to those reported in other studies in our country. Final results were excellent and use of treatment (RA) was consistent with risk-stratified recommendations., (Copyright © 2018 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.)

Although childhood exposure to ionizing radiation is a well-established risk factor for thyroid cancer, the risk associated with adulthood exposure remains unclear. We prospectively examined the association between cumulative, low-to-moderate dose occupational radiation exposure to the thyroid and thyroid cancer incidence in the U.S. Radiologic Technologists cohort. The study included 89,897 members who completed at least two of four mailed questionnaires and were cancer-free at the time of the first questionnaire. Cumulative occupational thyroid radiation dose (mean = 57 mGy, range = 0-1,600 mGy) was estimated based on self-reported work histories, historical data and, during the years 1960-1997, 783,000 individual film badge measurements. During follow-up, we identified 476 thyroid cancer cases. We used Poisson regression to estimate excess relative risk of thyroid cancer per 100 milliGray (ERR/100 mGy) absorbed dose to the thyroid gland. After adjusting for attained age, sex, birth year, body mass index and pack-years smoked, we found no association between thyroid dose and thyroid cancer risk (ERR/100 mGy = -0.05, 95% CI <-0.10, 0.34). In this large cohort study of radiologic technologists, protracted, low-to-moderate dose ionizing radiation exposure to the thyroid gland in adulthood was not associated with an increased risk of thyroid cancer., (© 2018 UICC.)

The aim of this study was to evaluate the associations between menstrual and reproductive factors and thyroid cancer risk among Japanese women. A total 54 776 women aged 40-69 years completed a self-administered questionnaire, which included menstrual and reproductive history. During 1990-2012, 187 newly diagnosed cases of thyroid cancer were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) for menstrual and reproductive factors and incidence of thyroid cancer were estimated using Cox proportional hazards regression. Postmenopausal women who had natural menopause were at reduced risk of thyroid cancer than premenopausal women in the age-area-adjusted model (HR: 0.62 per 1 year increase, 95% CI: 0.39-0.99), but this association was slightly attenuated and no longer statistically significant in the multivariable-adjusted model. On analysis by menopausal status, an inverse association between age at menarche and risk of thyroid cancer was observed for premenopausal women (HR: 0.83 per 1 year increase, 95% CI: 0.70-0.98, P trend=0.03), but not for postmenopausal women. The risk of thyroid cancer increased with surgical menopause compared with natural menopause (HR: 2.34, 95% CI: 1.43-3.84). Although increasing age at menopause and duration of fertility were associated with an increased risk of thyroid cancer, this association was not observed among postmenopausal women. This study confirmed that early age at menarche for premenopausal women and surgical menopause and late age at natural menopause for postmenopausal women were associated with the development of thyroid cancer. Our results support the hypothesis that exposure to estrogens increases the risk of thyroid cancer.

Aim: To determine biological and clinical features of papillary and follicular thyroid carcinomas associated or not associated with chronic thyroiditis., Materials and Methods: The study was conducted by retrospective analysis of medical histories of 2,459 patients with thyroid cancer. Tumor size, its category according to the TNM system, multi-focal properties of tumor growth, carcinoma invasiveness, as well as disease stage, rates of relapses and metastasis, and also cumulative survival rates were analyzed., Results: The tumor size in patients with papillary or follicular carcinoma associated with thyroiditis was smaller compared to the patients without thyroiditis. In the first case, the invasion frequency into extrathyroid structure and into the capsule was also lower. Multi-focal growth of both carcinoma types was registered more frequently in the presence of thyroiditis. The frequency of papillary carcinoma metastasis to lateral cervical lymph nodes was lower in the presence of thyroiditis, the frequency being equal for metastasis into lymph nodes of the VI lymph outflow zone in both groups of patients (with and without thyroiditis). In the presence of thyroiditis, the frequency of distant papillary carcinoma metastasis was decreased, no metastases were detected in patients with follicular carcinoma. In the group of patients with papillary carcinoma there was found no relation between the presence of thyroiditis and disease stage, relapse rates, and mortality levels; however, the risk of follicular carcinoma relapse was significantly lower in patients with thyroiditis., Conclusions: The presence of chronic thyroiditis in papillary carcinoma patients showed a certain positive impact on the course of the disease, in particular, primary tumor growth, invasion, and metastasis. Such effect is even more expressed in the patients with follicular thyroid carcinoma.

Background: The Chernobyl nuclear power plant accident occurred in Ukraine on April 26th 1986. In France, the radioactive fallout and thyroid radiation doses were much lower than in highly contaminated areas. However, a number of risk projections have suggested that a small excess in differentiated thyroid cancer (DTC) might occur in eastern France due to this low-level fallout. In order to investigate this potential impact, a case-control study on DTC risk factors was started in 2005, focusing on cases who were less than 15 years old at the time of the Chernobyl accident. Here, we aim to evaluate the relationship between some specific reports of potentially contaminated food between April and June 1986 - in particular fresh dairy products and leafy vegetables - and DTC risk., Methods: After excluding subjects who were not born before the Chernobyl accident, the study included 747 cases of DTC matched with 815 controls. Odds ratios were calculated using conditional logistic regression models and were reported for all participants, for women only, for papillary cancer only, and excluding microcarcinomas., Results: The DTC risk was slightly higher for participants who had consumed locally produced leafy vegetables. However, this association was not stronger in the more contaminated areas than in the others. Conversely, the reported consumption of fresh dairy products was not statistically associated with DTC risk., Conclusion: Because the increase in DTC risk associated with a higher consumption of locally produced vegetables was not more important in the most contaminated areas, our study lacked power to provide evidence for a strong association between consumption of potentially contaminated food and DTC risk., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The aim of the present study was to assess the clinical applicability of the TIR3A category in managing thyroid nodules, to examine the malignancy rates of TIR 3A and TIR 3B nodules, and to suggest management guidelines for these nodules., Materials and Methods: Thyroid cytologies performed in patients referred to our Department between January 2014 and August 2016 were classified according to the guidelines published by the SIAPEC. 102 cases were included in this retrospective study and were divided into two groups: 19 TIR3A were included in group A and 83 TIR3B in group B., Results: In group A, malignancy was diagnosed in 4 (21.1%) cases, papillary thyroid cancer was found in 3 patients and follicular thyroid cancer in 1; one case was classified as microcarcinoma, in two cancer was multicentric and bilateral and in one central node metastases were observed. In Group B malignancy was diagnosed in 48 (57.8%) patients, papillary thyroid cancer was found in 36 patients and follicular cancer in 12; microcarcinoma was observed in 25 cases, 12 were unilateral multicentric and 7 bilateral multicentric; in 3 cases central node metastases were present., Conclusion: Thyroid nodules with TIR3A cytology have a lower risk of malignancy than TIR3B cases, for which the new SIAPEC classification has proved accurate and effective. Malignancy rates in nodules with TIR3A cytology are higher than expected, although the real and accurate definition of the risk is extremely difficult. The recommendation to perform an accurate follow-up and repeat the fine-needle aspiration still appears the best option. For better management of patients with TIR3A cytology a careful assessment of risk factors and ultrasound characteristics is always needed. Further multicenter studies with longer follow-up are needed to better define the efficacy of this classification, the actual cancer risk, and the best management of these lesions., (Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: The most appropriate surgical procedure for multinodular goiter (MNG) remains under debate. Incidental thyroid carcinoma (ITC) is often identified on histopathological examination after thyroidectomy performed for presumed benign MNG., Aim of the Study: The aim of the study was to determine the value of radical surgery for MNG patients considering the prevalence of ITC diagnosed postoperatively., Materials and Methods: We conducted retrospective analysis of the medical records of 2,306 patients surgically treated for MNG between 2008 and 2013 at one center. None of the patients presented with any suspicion of malignancy, history of familial thyroid cancer, multiple endocrine neoplasia syndrome or previous head or neck radiation exposure., Results: Among the 2,306 MNG patients, ITC was detected in 49 (2.12%) (44 women and 5 men, with average ages of 52.2 (21-79) and 55.6 (52-62), respectively). Papillary thyroid carcinoma was significantly more frequently observed than other types of ITC (p<0.00001). Among the MNG patients, 866 (37.5%) underwent total/near total surgery, 464 (20.1%) received subtotal thyroidectomy, and 701 (30.3%) received the Dunhill operation. The remaining 275 (11.9%) patients underwent a less radical procedure and were classified as "others." Among the 49 (100%) patients with ITC, 28 (57.1%) underwent radical surgery. Another 21 (42.9%) patients required completion surgery due to an insufficient primary surgical procedure. A total of 21 (2.42%) patients in the total/near total surgery group were diagnosed with ITC, as well as 16 (2.48%) in the subtotal thyroidectomy group and 12 (1.71%) in the Dunhill operation group; 21 (100%), 4 (25%) and 3 (25%) of these patients, respectively, underwent radical surgery; thus, 0 (0%), 12 (75%) and 9 (75%) required completion surgery. The prevalence rates of ITC were comparable between the radical and subtotal surgery groups (2.42% and 3.44%, respectively, p = 0.4046), and the prevalence was higher in the radical surgery group than in the Dunhill operation group (2.42% and 1.71%, respectively, p = 0.0873). A significant difference was observed between the group of patients who underwent total/near total surgery, among whom all of the patients with ITC (100%) received primary radical surgery, and the groups of patients who received the subtotal and Dunhill operations, among whom only 25% of the patients with ITC in each group received primary radical surgery (p<0.0001)., Conclusions: More radical procedures for MNG result in a lower risk of reoperation for ITC. The prevalence of ITC on postoperative histopathological examination should determine the extent of surgery in MNG patients. In the future, total/near total thyroidectomy should be considered for MNG patients due to the increased prevalence of ITC to avoid the necessity for reoperation., Competing Interests: The authors have declared that no competing interests exist.

The increased thyroid cancer incidence in volcanic areas suggests an environmental effect of volcanic-originated carcinogens. To address this problem, we evaluated environmental pollution and biocontamination in a volcanic area of Sicily with increased thyroid cancer incidence. Thyroid cancer epidemiology was obtained from the Sicilian Regional Registry for Thyroid Cancer. Twenty-seven trace elements were measured by quadrupole mass spectrometry in the drinking water and lichens (to characterize environmental pollution) and in the urine of residents (to identify biocontamination) in the Mt. Etna volcanic area and in adjacent control areas. Thyroid cancer incidence was 18.5 and 9.6/10(5) inhabitants in the volcanic and the control areas, respectively. The increase was exclusively due to the papillary histotype. Compared with control areas, in the volcanic area many trace elements were increased in both drinking water and lichens, indicating both water and atmospheric pollution. Differences were greater for water. Additionally, in the urine of the residents of the volcanic area, the average levels of many trace elements were significantly increased, with values higher two-fold or more than in residents of the control area: cadmium (×2.1), mercury (×2.6), manganese (×3.0), palladium (×9.0), thallium (×2.0), uranium (×2.0), vanadium (×8.0), and tungsten (×2.4). Urine concentrations were significantly correlated with values in water but not in lichens. Our findings reveal a complex non-anthropogenic biocontamination with many trace elements in residents of an active volcanic area where thyroid cancer incidence is increased. The possible carcinogenic effect of these chemicals on the thyroid and other tissues cannot be excluded and should be investigated.

Background: Epidemiological data on thyroid cancer and associated risk factors are scarce in our setting. The present study was therefore designed to gather data which could be helpful in providing insights to thyroid physicians and surgeons for better management of affected patients., Purpose: To determine the frequency of carcinoma thyroid among patients presenting with goiter and its association with TSH, Tg/ATg and other demographic factors., Materials and Methods: A total of 73 adult patients of either gender with solitary solid cold nodules and/or multi-ndoular goiter (MNG) with predominant solid cold nodules were enrolled. All surgically resected samples were sent for histopathology. The frequency of thyroid cancer and its subtypes was noted and tested for association with gender, age (< or ≥40 years), recent increase in swelling size, TSH, Tg and ATg., Results: Thyroid cancer was diagnosed in 26% (n=19) of the patients, 14 (73.7%) being diagnosed with papillary thyroid cancer and 5 (26.3%) with follicular thyroid cancer. No other subtypes were noted. Presence of thyroid cancer was significantly associated with recent increase in swelling size and higher TSH Values mean TSH values (P<0.05). No significant association was found with gender, age, Tg and ATg values (P>0.05)., Conclusions: Overall percentage of thyroid cancer in our study sample was found to be 26%, with a predominance of papillary over follicular lesions. Rates were significantly higher in patients who had history of recent increase in swelling size and higher and higher pre-surgery TSH values.

Data from the National Cancer Institute and from the literature have disclosed an increasing incidence of thyroid cancer in children, adolescents and adults. Although children and adolescents with thyroid cancer tend to present with more advanced disease than adults, their overall survival rate is excellent; however, there is no clear explanation for the differences observed in the clinicopathological outcomes in these age groups. There has been an ongoing debate regarding whether the clinicopathological differences may be due to the existence of distinct genetic alterations. Efforts have been made to identify these acquired genetic abnormalities that will determine the tumor's biological behavior and ultimately allow molecular prognostication. However, most of the studies have been performed in radiation-exposed pediatric thyroid carcinoma. Therefore, our understanding of the role of these driver mutations in sporadic pediatric differentiated thyroid cancer development is far from complete, and additionally, there is a strong need for studies in both children and adolescents. The aim of this review is to present an extensive literature review with emphasis on the molecular differences between pediatric sporadic and radiation-exposed differentiated thyroid carcinomas and adult population., (© 2015 Society for Endocrinology.)

Alström syndrome (AS) is an autosomal recessive disorder, characterized by cone-rod dystrophy, sensorineural hearing loss, obesity, hyperinsulinemia with insulin resistance, type 2 diabetes mellitus and progressive pulmonary, hepatic and renal dysfunction. AS is caused by mutations in the ALMS1 gene, located on the short arm of chromosome 2. We report a 35-year-old woman with known history of AS, who developed a follicular variant of papillary thyroid carcinoma. To our knowledge this is the first association of AS with thyroid malignancy, among the approximately 450 cases reported since the first description of the syndrome. We conclude that papillary thyroid carcinoma should be considered in the differential diagnosis of thyroid nodules in patients with AS.

Thyroid cancer incidence and diagnostic radiography exposures, particularly computed tomography (CT) scanning and nuclear medicine examinations, have increased substantially in the USA. However, very few epidemiologic studies have directly investigated their associations. A population-based case-control study was conducted in Connecticut in 2010-2011, including 462 histologically confirmed incident thyroid cancer cases and 498 population-based controls. Multivariate unconditional logistic regression models were used to estimate the associations between diagnostic radiography and the risk of thyroid cancer, controlling for potential confounding factors. Exposure to any form of diagnostic radiography was associated with an increased risk of well-differentiated thyroid microcarcinoma [tumor size≤10 mm, odds ratio (OR)=2.76, 95% confidence interval (CI): 1.31-5.81]. The highest risk increase occurred with nuclear medicine examinations (excluding cardiology tests and thyroid uptake studies; OR=5.47, 95% CI: 2.10-14.23), followed by chest CT scanning (OR=4.30, 95% CI: 1.66-11.14), head and neck CT scanning (OR=3.88, 95% CI: 1.75-8.63), upper gastrointestinal series (OR=3.56, 95% CI: 1.54-8.21), lower gastrointestinal series (OR=3.29, 95% CI: 1.41-7.66), kidney radiography involving dye injection into a vein or artery (OR=3.21, 95% CI: 1.20-8.54), mammography (OR=2.95, 95% CI: 1.14-7.61), chest radiography (OR=2.93, 95% CI: 1.37-6.29), and abdomen CT scanning (OR=2.54, 95% CI: 1.02-6.30). No significant associations were found between these imaging modalities and thyroid tumors larger than 10 mm. This study provides the first direct evidence that CT scanning and nuclear medicine examinations are associated with an increased risk of thyroid cancer. The novel finding that an array of diagnostic radiography procedures are associated with thyroid microcarcinomas warrants further investigation.

Background: Graves' disease is a common cause of thyrotoxicosis. Treatment options include anti-thyroid medications or definitive therapy: thyroidectomy or radioactive iodine (I(131) ). Traditionally, I(131) has been the preferred definitive treatment for Graves' disease in New Zealand. Reports of concomitant thyroid cancer occurring in up to 17% of Graves' patients suggest surgery, if performed with low morbidity, may be the preferred option. The aim of this study was to determine the rate of thyroid cancer and surgical outcomes in a New Zealand cohort of patients undergoing thyroidectomy for Graves' disease., Method: This study is a retrospective review of Waikato region patients undergoing thyroid surgery for Graves' disease during the 10-year period prior to 1 December 2011., Results: A total of 833 patients underwent thyroid surgery. Of these, 117 were for Graves' disease. Total thyroidectomy was performed in 82, near-total in 33 and subtotal in 2 patients. Recurrent thyrotoxicosis developed in one subtotal patient requiring I(131) therapy. There were two cases of permanent hypoparathyroidism and one of permanent recurrent laryngeal nerve palsy. Eight patients (6.8%) had thyroid cancer detected, none of whom had overt nodal disease. Five were papillary microcarcinomas (one of which was multifocal), two were papillary carcinomas (11 mm and 15 mm) and one was a minimally invasive follicular carcinoma., Conclusion: Thyroid cancer was identified in approximately 7% of patients undergoing surgery for Graves' disease. A low complication rate (<2%) of permanent hypoparathyroidism and nerve injury (<1%) supports surgery being a safe alternative to I(131) especially for patients with young children, ophthalmopathy or compressive symptoms., (© 2012 The Authors. ANZ Journal of Surgery © 2012 Royal Australasian College of Surgeons.)

Background: During the past 25 years, the incidence of thyroid papillary carcinoma (TPC), especially the micropapillary subtype, has been increasing in different countries worldwide. The rise in the rate of thyroid malignancies were also determined in Turkey in the last two decades. This fact was attributed to the Chernobyl accident because Turkey is one of the affected countries by the radioactive fallout. The aim of this study was to assess the changes in the parameters of the thyroid and put forth the reasons in a 14-year period., Methods: The patient records, demographic and malignancy characteristics, and operations of 1,585 patients who had a thyroidectomy from 1996 to 2009 were reviewed retrospectively. The study was divided in two equal time periods for comparison of data., Results: A total of 216 thyroid carcinomas (13.6%) were diagnosed in the study period. There was a significant increase in the frequency of papillary (P <0.023) and micropapillary (P <0.001) carcinomas when the two different time periods were compared. The rate of follicular, medullary and other types of malignancies did not change. In the second period (2003 to 2009) of analysis, the rate of micropapillary carcinoma (P = 0.001) and within male (P = 0.031) and female (P <0.001) genders, application of total thyroidectomy (p = 0.029), and multicentric disease (P = 0.015) increased significantly. A slight decrease in the mean age of the whole number of patients and patients with papillary and micropapillary carcinomas (P >0.05) was observed. The increased number of TPC >10 mm was insignificant. Geographic region and age specific malignancy increase was not determined., Conclusions: Micropapillary carcinoma has become a dominant type of thyroid malignancy in Turkey. The main reasons of this transition were mandatory iodization and much higher application of total thyroidectomy in surgery. Improvement in healthcare and diagnostic techniques are the complementary factors. Due to its lack of molecular and genetic basis from the perspective of thyroid cancer, the Chernobyl disaster has lost its importance in Turkey.

Background: To investigate differentiated thyroid cancer risk factors in natives of French Polynesia is of interest because of the very high incidence of this cancer in the archipelago., Materials and Methods: To assess the role of various potential risk factors of thyroid cancer in the natives of French Polynesia we performed a case-control study. The study included almost all the French Polynesians diagnosed with differentiated thyroid carcinoma between 1981 and 2003 (n=229) and 373 French Polynesian control individuals from the general population without cancer., Results: Thyroid radiation dose received from nuclear fallout before the age of 15, a personal history of neck or/and head medical irradiation, obesity, tallness, large number of children, an artificial menopause, a familial history of thyroid cancer, a low dietary iodine intake, and having a spring as the main source of drinking water were found to be significant risk factors. No roles of smoking habits, alcohol consumption, iodine containing drugs, and exposure to pesticides were evidenced., Conclusions: Except for smoking, differentiated thyroid carcinoma risk factors in natives of French Polynesia are similar to those in other populations. Our finding on the role of having a spring as a drinking water origin is coherent with some other studies and could be due to geological factors.

Aims and Background: Thyroid cancers are relatively rare tumors that appear more frequently in women than in men. Accordingly, most studies focus on studying risk factors for thyroid cancer in women and consequently on various hormonal or reproductive factors that are specific for women. The aim of our study was to examine risk factors for developing well-differentiated thyroid cancer in men. Heretofore, we did not encounter in the literature a study that was solely focused on studying risk factors for well-differentiated thyroid cancer in men., Methods: A case-control study was performed from 2005 to 2010. The case group included 204 consecutive well-differentiated thyroid cancers in male patients (180 papillary and 24 follicular including Hürthle cell). The control group comprised the same number of cases. Patients were individually matched by gender, age and place of residence. Statistical analysis included conditional univariate and multivariate logistic regression methods., Results: According to univariate logistic regression, well-differentiated thyroid cancer in men was significantly related to smoking status, duration of smoking, number of cigarettes smoked per day, history of goiter or thyroid nodules, history of non-thyroid cancer, diabetes mellitus, radiotherapy of the head and neck, and history of malignant tumors. According to multivariate logistic regression, it was independently related to smoking status (OR = 0.36; 95% CI, 0.19-0.69), history of goiter or thyroid nodules (OR = 9.19; 95% CI, 1.25-64.58), and a history of malignant tumors (OR = 2.11; 95% CI, 1.19-7.33)., Conclusions: Risk factors for well-differentiated thyroid cancer in men were goiter or thyroid nodules and family history of malignant tumors. Cigarette smoking was negatively associated with the disease.

Background: Thyroid cancer incidence has risen steadily over the last few decades in most of the developed world, but information on incidence trends in developing countries is limited. Sao Paulo, Brazil, has one of the highest rates of thyroid cancer worldwide, higher than in the United States. We examined thyroid cancer incidence patterns using data from the Sao Paulo Cancer Registry (SPCR) in Brazil and the National Cancer Institute's Surveillance Epidemiology End Results (SEER) program in the United States., Methods: Data on thyroid cancer cases diagnosed during 1997-2008 were obtained from SPCR (n=15,892) and SEER (n=42,717). Age-adjusted and age-specific rates were calculated by sex and histology and temporal patterns were compared between the two populations., Results: Overall incidence rates increased over time in both populations and were higher in Sao Paulo than in the United States among females (SPCR/SEER incidence rate ratio [IRR]=1.65) and males (IRR=1.23). Papillary was the most common histology in both populations, followed by follicular and medullary carcinomas. Incidence rates by histology were consistently higher in Sao Paulo than in the United States, with the greatest differences for follicular (IRR=2.44) and medullary (IRR=3.29) carcinomas among females. The overall female/male IRR was higher in Sao Paulo (IRR=4.17) than in SEER (IRR=3.10) and did not change over time. Papillary rates rose over time more rapidly in Sao Paulo (annual percentage change=10.3% among females and 9.6% among males) than in the United States (6.9% and 5.7%, respectively). Regardless of sex, rates rose faster among younger people (<50 years) in Sao Paulo, but among older people (≥50 years) in the United States. The papillary to follicular carcinoma ratio rose from <3 to >8 among both Sao Paulo males and females, in contrast to increases from 9 to 12 and from 6 to 7 among U.S.males and females, respectively., Conclusions: Increased diagnostic activity may be contributing to the notable rise in incidence, mainly for papillary type, in both populations, but it is not likely to be the only reason. Differences in iodine nutrition status between Sao Paulo and the U.S. SEER population might have affected the observed incidence patterns.

Thyroid cancer has an increasing incidence in the US population and worldwide, with 95% of the cancers being of follicular cell origin-papillary, follicular, or anaplastic thyroid carcinomas. Both follicular and papillary thyroid cancers portend good survival rates, with estimated 5-year survival amongst differentiated thyroid cancer approaching 97%. On the other hand, the median survival for a patient with anaplastic thyroid carcinoma is measured in months. Despite the optimistic survival rates for papillary and follicular thyroid carcinoma, a subset of this population demonstrates resistance to radioactive iodine, and a proclivity for more aggressive tumors with higher rates of recurrence and metastasis.As there is an increased understanding of the molecular etiology of thyroid cancer, there is also a new interest in alternative treatment methods for those nonresponsive to typical treatment. Multiple signaling pathways have been identified, including the mitogen activated protein kinase pathway, as crucial to thyroid tumor formation and progression. Additionally, particular oncogenes have been identified as prevalent in anaplastic thyroid carcinoma and thought to be involved in the transformation from differentiated to anaplastic histology.We review the current literature and evidence describing the molecular and genetic etiology of non-medullary (follicular cell derived) thyroid carcinomas including papillary, follicular, and anaplastic thyroid carcinoma. Additionally, we evaluate the current literature on emerging and established therapies of molecular and genetic targets in these cancers.

Genetic factors can modify susceptibility to the carcinogenic effect of ionising radiation. To establish if radioiodine-induced thyroid cancer is similarly genetically influenced, we studied F1 hybrid crosses between inbred mouse strains. Mice were perinatally exposed to iodine-131 and thyroid tissues examined after 18 months. Differences in the incidence and distribution of histological subtypes were quantified in relation to genetic background. As expected, the occurrence of thyroid lesions was significantly higher in irradiated mouse hybrids than in unirradiated controls. The most frequent alterations were the simple and the complex hyperplasias, followed by follicular adenoma and, less frequently, follicular carcinoma. Both the incidence and distribution of the histiotype were different between the hybrid mouse crosses. Crosses using JF1 mice (M. m. molossinus) produced F1 offspring that were more resistant to radiation-induced thyroid lesions. Sequence analysis of Braf, Ret, Hras, Kras, Kit and Trp53, all genes that are commonly mutated in human thyroid cancers, did not show any evidence of mutation in the tumours. However, microsatellite analysis of genomic DNA revealed frequent allelic imbalances in complex hyperplasia and follicular adenoma. We conclude that genetic background, in particular the JF1 genotype, confer differences in susceptibility to the carcinogenic effects of radioiodine on the thyroid.

Introduction: Radioiodine treatment (RT) of benign thyroid diseases is a well-known, safe, and effective treatment. In a group of patients after RT, who remained in long-term follow-up, sporadic cases of malignant thyroid lesions occurred. The aim of the study was to estimate how often it happened despite the exclusion of malignancy before RT., Material and Method: A group of 4314 patients (7438 person-years) underwent RT and subsequently were followed-up for 1-8 years (mean 20.69 months). Apart from thyroid function estimation, if needed, fine needle aspiration biopsy (FNAB) of the thyroid or neck focal lesions was performed based on ultrasonographic or clinical examination. Patients with pathological FNAB were analyzed and histopathologically verified., Results: In 12 out of 4314 cases (0.27%) suspicious FNAB results were found. Suspicious thyroid lesion results were found in 9 patients (8 F, 1 M), aged 46-73 (average 56 years) followed up for 3-57 months after RT: papillary cancer in two patients, Hürthle cell tumour in one patient, and suspicious cells in two patients (with benign lesions on postoperative histopathology). Two patients refused surgery (a suspicion of papillary cancer in one case and suspicious cells in FNAB in the second case). A follicular tumour in FNAB was suspected in two cases (no data about the first, and the second with lung cancer was not operable). In the remaining 3 cases FNAB revealed lymph node metastases due to other cancers., Conclusions: Malignant thyroid lesions in patients after RT due to benign thyroid diseases are seldom detected. However, periodical clinical and ultrasonographic evaluation is recommended.

Epidemiological, clinical, and molecular studies suggest a role for oestrogen in thyroid cancer. How oestrogen mediates its effects and the consequence of it on clinical outcome has not been fully elucidated. The participation of coregulatory proteins in modulating oestrogen receptor (ER) function and input of crosstalk with the tyrosine kinase receptor HER2 was investigated. Oestrogen induced cell proliferation in the follicular thyroid cancer (FTC)-133 cells, but not in the anaplastic 8305C cell line. Knockdown of the coactivator steroid receptor coactivator (SRC)-1 inhibited FTC-133 basal, but not oestrogen induced, cell proliferation. Oestrogen also increased protein expression of SRC-1 and the ER target gene cyclin D1 in the FTC-133 cell line. ERalpha, ERbeta, the coregulatory proteins SRC-1 and nuclear corepressor (NCoR), and the tyrosine kinase receptor HER2 were localised by immunohistochemistry and immnofluorescence in paraffin-embedded tissue from thyroid tumour patients (n=111). ERalpha was colocalised with both SRC-1 and NCoR to the nuclei of the tumour epithelial cells. Expression of ERalpha and NCoR was found predominantly in non-anaplastic tumours and was significantly associated with well-differentiated tumours and reduced incidence of disease recurrence. In non-anaplastic tumours, HER2 was significantly associated with SRC-1, and these proteins were associated with poorly differentiated tumours, capsular invasion and disease recurrence. Totally, 87% of anaplastic tumours were positive for SRC-1. Kaplan-Meier estimates of disease-free survival indicated that in thyroid cancer, SRC-1 strongly correlates with reduced disease-free survival (P<0.001), whereas NCoR predicted increased survival (P<0.001). These data suggest opposing roles for the coregulators SRC-1 and NCoR in thyroid tumour progression.

Background: The steadily increasing incidence of thyroid cancer has been attributed mostly to more sensitive thyroid nodule screening. However, various environmental factors, such as those associated with volcanic areas, cannot be excluded as risk factors. We evaluated thyroid cancer incidence in Sicily, which has a homogenous population and a province (Catania) that includes the Mt Etna volcanic area., Methods: In a register-based epidemiological survey, we collected all incident thyroid cancers in Sicily from January 1, 2002, through December 31, 2004. The age-standardized incidence rate for the world population (ASR(w)) was calculated and expressed as the number of thyroid cancer diagnoses per 100 000 residents per year. The association of thyroid cancer incidence rate with sex, age, tumor histotype, and various environmental factors was evaluated by modeling the variation of the ASR(w). All statistical tests were two-sided., Results: In 2002-2004, 1950 incident thyroid cancers were identified in Sicily (among women, ASR(w) = 17.8, 95% confidence interval [CI] = 16.9 to 18.7; and among men, ASR(w) = 3.7, 95% CI = 3.3 to 4.1). Although the percentage of thyroid cancers that were microcarcinomas (ie, < or = 10 mm) and ratio of men to women with thyroid cancer were similar in all nine Sicilian provinces, thyroid cancer incidence was statistically significantly higher in the province of Catania (among women, ASR(w) = 31.7, 95% CI = 29.1 to 34.3; and among men, ASR(w) = 6.4, 95% CI = 5.2 to 7.5) than in the rest of Sicily (among women, ASR(w) = 14.1, 95% CI = 13.2 to 15.0; and among men, ASR(w) = 3.0, 95% CI = 2.6 to 3.4) (all P values < .001). Incidence of papillary, but not follicular or medullary, cancers was statistically significantly increased in Catania province, and papillary tumors from patients in Catania more frequently carried the BRAF V600E gene mutation (55 [52%] of 106 tumors) than tumors from patients elsewhere in Sicily (68 [33%] of 205 tumors) (relative risk = 1.7, 95% CI = 1.0 to 2.8, P = .02). Cancer incidence was statistically significantly lower in rural areas than in urban areas of Sicily (P = .003). No association with mild iodine deficiency or industrial installations was found. Levels of many elements (including boron, iron, manganese, and vanadium) in the drinking water of Catania province often exceeded maximum admissible concentrations, in contrast to water in the rest of Sicily., Conclusion: Residents of Catania province with its volcanic region appear to have a higher incidence of papillary thyroid cancer than elsewhere in Sicily.

Second primary neoplasms (SPNs) are a recognised late effect of treatment for childhood cancer. Thyroid SPNs can develop after exposure to low-dose radiation, due to the radio-sensitivity of the thyroid gland. The British Childhood Cancer Survivor Study (BCCSS) was set up to directly monitor the late effects of treatment, including risk of SPNs, in childhood cancer survivors and includes 17,980 5-year survivors. We carried out a cohort analysis to determine the risk of thyroid SPNs in the BCCSS, and estimated risk using standardised incidence ratios (SIRs), relative risk (RR) using multivariate Poisson regression and cumulative incidence curves. There were 340,202 person years at risk subsequent to a 5-year survival, median follow-up 17.4 years per survivor. We identified 50 thyroid SPNs including 31 (62%) papillary carcinomas, 15 (30%) follicular carcinomas and 4 (8%) other types. 88% of thyroid SPNs developed after exposure to radiotherapy in or around the thyroid gland. SIR overall was 18.0 (95% confidence interval 13.4-23.8). Risk of thyroid cancer was highest after Hodgkin's disease: RR 3.3 (1.1-10.1) and Non Hodgkin's Lymphoma: RR 3.4 (1.1-10.7) relative to leukaemia (RR 1.0) (p < 0.001). Survivors treated with radiotherapy in childhood had a RR of 4.6 (1.4-15.1) relative to survivors not treated with radiotherapy (RR 1.0), p = 0003. In conclusion, the risk of thyroid cancer in childhood cancer survivors is relatively high in this cohort of childhood cancer survivors. These results will be of use in counselling survivors of childhood cancer exposed to radiation in or around the thyroid area.

Background: New cases of well-differentiated thyroid cancer (DTC) are diagnosed more frequently worldwide. We investigated trends and differences in clinical and histological characteristics of new DTC cases presenting in one large center., Methods: During the last 34 years 852 follicular cell-derived DTC cases (83% papillary [PTC], 17% follicular [FTC] carcinoma) presented in the Endocrine Unit of the Department of Clinical Therapeutics in Alexandra Hospital (18.8% men, mean age 42.4 +/- 14.5 years). Patients were classified in three period groups according to year of diagnosis: period 1, 1963-1982; period 2, 1983-1992; and period 3, 1993-2007. We recorded the histological type, age at diagnosis, and, in period 3, the type of pre-existing thyroid disease, the stage, and tumor size., Results: During periods 1, 2, and 3, the mean age at diagnosis was 37.7 +/- 12.3, 42.4 +/- 14.53, and 44.1 +/- 14.9 years (p = 0.001), respectively, and the male to female ratio was similar. The prevalence of FTC was 22.7%, 28.1%, and 6.5%, respectively. In period 3, 51.6% of the PTCs were microcarcinomas (microPTC)

Background: Risk of thyroid cancer has already been related to refined cereals and starch food, but the association has not been studied in terms of glycemic index (GI) and glycemic load (GL)., Patients and Methods: We analyzed data from a case-control study conducted in Italy from 1986 to 1992 and including 399 histologically confirmed and incident cases of thyroid cancer and 616 control subjects. Information on dietary habits was derived through a food-frequency questionnaire and multivariate odds ratios (ORs) for GI and GL levels were estimated with adjustment for age, education, sex, area of residence, history of diabetes, body mass index, smoking, alcohol consumption, intake of fruit and vegetables, and noncarbohydrate energy intake., Results: Compared with the lowest tertile, the ORs in subsequent tertiles were 1.68 and 1.73 for GI, and 1.76 and 2.17 for GL. The OR for highest tertile of GI compared with lowest one was 1.70 for papillary and 1.57 for follicular thyroid cancer. The ORs for GL were 2.17 for papillary and 3.33 for follicular thyroid cancer., Conclusion: Our study shows that high dietary levels of GI and GL are associated with thyroid cancer risk.

Exceptionally high incidence rates of thyroid cancer are observed in New Caledonia, particularly in Melanesian women. To investigate further the etiology of thyroid cancer and to clarify the reasons of this elevated incidence, the authors conducted a countrywide population-based case-control study in this multiethnic population. The study included 332 cases with histologically verified papillary or follicular carcinoma (293 women and 39 men) diagnosed in 1993-1999 and 412 population controls (354 women and 58 men) frequency matched by gender and 5-year age group. Thyroid cancer was negatively associated with tobacco smoking and alcohol drinking, but no inverse dose-response relation was observed. Height was positively associated with thyroid cancer, particularly in men. Strong positive associations with weight and body mass index were observed in Melanesian women aged 50 years or more, with an odds ratio of 5.5 (95% confidence interval: 1.5, 20.3) for a body mass index of 35 kg/m2 or greater compared with normal-weight women, and there was a clear dose-response trend. This study clarifies the role of overweight for thyroid cancer in postmenopausal women. Because of the high prevalence of obesity among Melanesian women of New Caledonia, this finding may explain in part the exceptionally elevated incidence of thyroid cancer in this group.

The incidence of thyroid cancer has been reported to be 0.5-1.3%, when assessed by sonographic examination and 3.7-28.4% by histologic examination at autopsies. These incidences are much higher than those of clinically evident thyroid cancer, which are 2.0/100,000 for males and 7.2/100,000 for females, reported in Japan. In iodine deficient areas, chronic stimulation by TSH causes multinodular autonomous growth and function, leading to hyperthyroidism in middle-aged and elderly subjects. Incidence of Plummer's disease among Japanese with sufficient iodine intake is very low, accounting for 0.5-0.8% of all thyroid nodules and 0.3% of all thyrotoxic patients. The Plummer/Graves ratio was higher than 1 in endemic goiter area before iodine supplementation. Iodine intake affects the type of thyroid carcinoma. Decreased intake of iodine is associated with higher frequency of follicular and anaplastic cancers and lower frequency of papillary cancer. The high prevalence of papillary cancer(>85%) with good prognosis may explain the preferred selection of partial rather than total thyroidectomy in Japan.

Unlabelled: Iodine is a trace element that is essential for the synthesis of thyroid hormone. Both chronic iodine deficiency and iodine excess have been associated with hypertrophy and hyperplasia of follicular cells, attributed to excessive secretion of TSH. This may be associated to thyroid cancer risk, particularly in women. Experimental studies have documented thyroid cancer induction by elevation of endogenous TSH, although in a small number of animals. Iodine deficiency associated with carcinogenic agents and chemical mutagens will result in a higher incidence of thyroid malignancy. Inadequate low iodine intake will result in increased TSH stimulation, increased thyroid cell responsiveness to TSH, increased thyroid cell EGF-induced proliferation, decreased TGFbeta 1 production and increased angiogenesis, all phenomena related to promotion of tumor growth. Epidemiological studies associating iodine intake and thyroid cancer led to controversial and conflicting results. There is no doubt that introduction of universal iodine prophylaxis in population previously in chronic iodine-deficiency leads to a changing pattern of more prevalent papillary thyroid cancer and declining of follicular thyroid cancer. Also anaplastic thyroid cancer is practically not seen after years of iodine supplementation. Iodine excess has also been indicated as a possible nutritional factor in the prevalence of differentiated thyroid cancer in Iceland, Hawaii and, more recently, in China., In Conclusion: available evidence from animal experiments, epidemiological studies and iodine prophylaxis has demonstrated a shift towards a rise in papillary carcinoma, but no clear relationship between overall thyroid cancer incidence and iodine intake.

Background: The Ukrainian American Cohort Study evaluated the risk of thyroid disorders in a group of individuals who were younger than age 18 years at the time of the Chornobyl (Chernobyl) accident. In this article, the authors describe the pathology of thyroid carcinomas detected in the first screening., Methods: From 1998 to 2000, 13,243 individuals completed the first cycle of screening examinations. Eighty patients underwent surgery between 1998 and 2004. Intraoperative and postoperative pathologic studies were performed at the Institute of Endocrinology and Metabolism, Kyiv., Results: Pathologic analysis revealed 45 thyroid carcinomas, including 43 papillary thyroid carcinomas (PTCs) (95.6%) and 2 follicular thyroid carcinomas (FTCs) (4.4%). TNM classification (5th edition) of the PTCs included 8 T1 tumors (18.6%), 16 T2 tumors (37.2%), and 19 T4 tumors (44.2%). Fifteen PTCs (34.9%) were N1a,N1b, and 3 PTCs (7.0%) were M1. Among the PTCs, 8 exhibited the classical papillary histologic pattern (18.6%), 14 exhibited a follicular histologic pattern (32.6%), 5 exhibited a solid histologic pattern (11.6%), and 16 exhibited a mixed histologic pattern (37.2%). Both FTCs had a microfollicular-solid structure. Eleven of 20 cohort members who underwent surgery before the first screening had PTCs. Regional metastases (63.6%) and distant metastases (18.2%) were more common in this group., Conclusions: Multifocal growth, lymphatic and blood vessel invasion, extrathyroid spread, and regional and distant metastases were more frequent in less differentiated PTCs (>30% solid structure). Small carcinomas (

Context: Defects in thyroglobulin (Tg) synthesis are one of the causes of thyroid dyshormonogenesis. Only a few mutations in the Tg gene have been described., Objectives: We describe a novel Tg gene mutation and discuss the mechanisms by which it causes dyshormonogenesis with subsequent malignant transformation., Cases: Two siblings aged 21 and 19 yr presented with recurrent goiters for which they had undergone multiple thyroid surgeries since early childhood. The older sibling was diagnosed with metastatic follicular thyroid carcinoma at age 15 yr., Methods: The entire coding region and intron-exon boundaries of the Tg gene were amplified and sequenced from the patients. We also sequenced the boundaries of exon 5 and intron 5 from both parents. RT-PCR amplification of a cDNA fragment encompassing exons 4-6 was also performed., Results: A homozygous G to A point mutation at position +1 of the splice donor site of intron 5 (g.IVS5+1G-->A) was detected in both patients, whereas a monoallelic mutation was found in their parents. RT-PCR amplification of a cDNA fragment covering exons 4-6 revealed a 191-bp fragment in the patients and 351- and 191-bp fragments in the parents. Sequence analysis of these two fragments confirmed deletion of exon 5 in the 191-bp fragment., Conclusions: Aberrant splicing occurred as a result of the g.IVS5+1G-->A mutation, which caused fusion of exons 4 and 6, resulting in the frame shift at codon position 141 and a premature stop codon at position 147 (FS141-->147X). The malignant transformation is likely a result of prolonged TSH stimulation.

Molecular targeting of protein kinases is a new paradigm in the treatment of cancer. The clinical efficacy of low-molecular weight inhibitors of ABL, stem-cell growth-factor receptor, and the epidermal growth factor receptor in different tumor types is witness to the power of this approach. The presence of activating mutations of a kinase, or an increased gene copy number, might anticipate tumor responsiveness to its targeting. Thyroid cancer is the most prevalent endocrine malignancy and is frequently associated with the oncogenic conversion of two specific protein kinases, RET and BRAF. Small-molecule inhibitors of both kinases have already reached the clinical testing stage. Protein kinases other than RET and BRAF are also being evaluated for their potential in thyroid-cancer treatment.

Papillary carcinoma and follicular carcinoma are types of differentiated thyroid carcinomas, develop from the same thyroid follicular epithelial cells and show distinct biological behavior. Although several studies have demonstrated differences in the biological characteristics of these carcinomas, little is known about the genetic backgrounds that underlie these differences. The clarification of the genetic background can lead to the understanding of thyroid carcinogenesis, proper therapeutic strategies, and development of the molecular targeting drugs. Recently, aberrant activation of RAS-RAF-MEK-MAP kinase signaling pathway is frequently found in thyroid carcinoma. The pathway transmits a mitogenic signal to the nucleus, and constitutive activation of the pathway is thought to promote uncontrolled cell division. In our series, BRAF mutation was detected exclusively in papillary carcinoma (54%), and was exclusively V599E (a single nucleotide change of A-T at nucleotide 1796). NRAS mutation was observed in follicular carcinoma (50%) and in anaplastic carcinoma (28%), and was exclusively Q61R (a single nucleotide change of A-G at nucleotide 182). No mutations were found in KRAS or HRAS. In this chapter, we explain the role of RAS-RAF-MEK-MAP kinase pathway in carcinogenesis of the thyroid and its clinical implication based on our study. In addition, we review the current knowledge in this field.

The authors have analyzed the results of treatment of 147 patients with diffuse toxic goiter (DTG) operated upon in the St. Petersburg Center of the surgery of the endocrine system organs. Questions of surgical strategy are considered when DTG is combined with nodular forms. The diagnostic potentialities of the methods used are assessed. The incidence of carcinomas in patients with nodular formations and DTG was determined. It was shown that the presence of nodules in the thyroid gland did not influence the nearest and distant results when using the corresponding surgical strategy.

Thyroid carcinoma is a rare disease in childhood. The only known causative factor is radiation exposure during childhood. Most cases can be cured by surgery and eventually radioiodine. The aim of initial treatment should be the total removal of neoplastic foci with a minimal morbidity. Some cancer-related deaths have been reported decades after initial treatment., (Copyright 2005 S. Karger AG, Basel.)

Thyroid carcinoma is a rare disease in children, and is mostly of the papillary histological type. It is often extended at presentation with frequent lymph node metastases. Treatment includes surgery (total thyroidectomy and lymph node dissection) and radioiodine therapy in case of extensive disease. Life long thyroxine treatment is given to all patients and when carefully controlled is devoided of adverse effects. Long term prognosis is favorable, but a few deaths have been reported some decades after initial treatment. Adverse prognostic indicators are younger age at discovery and presence of distant metastases.

Background and Aims: Although exposure to ionizing radiation is a well-known risk factor for well-differentiated thyroid cancer, its effects on tumor behavior remain unclear. This study was undertaken to address this question., Materials and Methods: We randomly selected 426 patients who underwent thyroidectomy for cancer between 1964 and 2000 and divided them into two groups: previously exposed (ExR); not exposed to radiation (nExR). Data were retrospectively collected., Results: There were 340 female patients and 86 male, age 9-89 years with mean follow-up of 56 months. The ExR group (n=68) was smaller than the nExR group (n=358). Most patients in the ExR group (64.5%) had previously received therapeutic radiation, whereas 25% were occupationally exposed and 10.5% were at risk from environmental radiation. Both groups were similar with regard to extent of thyroidectomy and adjuvant treatment, but neck dissections were more frequent in the nExR group. There were no significant differences between both groups for age, gender, tumor multicentricity, frequency of microcarcinoma, histology, lymph node disease, distant metastasis, and local recurrence. Incidental microcarcinomas were more frequent in the ExR (35.3%) group than in the nExR group (22.1%). Mean tumor size in the ExR group (18.7 mm) was smaller than in the nExR group (22.3 mm)., Conclusion: Ionizing radiation increases risk for well-differentiated thyroid cancer (WDTC) but not adverse cancer behavior. Surgeons should be aware of the high incidence of microcancer among patients with previous exposure to radiation.

Aims and Background: Thyroid cancer, whose etiology is largely uncertain, has been negatively associated with cigarette smoking in a several studies. We examined the association between cigarette smoking and risk for female thyroid cancer., Methods: A case-control study including 204 histologically verified female thyroid cancer patients and an equal number of hospital controls individually matched with cases by sex, age (+/- 2 years), place of residence and time of hospitalization was carried out during the period 1996-2000. In the analysis of data, univariate and multivariate conditional logistic regression methods were applied., Results: According to univariate analysis, female thyroid cancer was negatively associated with the initiation of smoking at a younger age, before the age of 20 (OR = 0.66, 95% CI = 0.50-0.90). None of the smoking habits remained independently related to female thyroid cancer after adjustment for other factors which were significantly associated with thyroid cancer in the present study., Conclusions: The results of the study do not suggest a role of cigarette smoking in the development of thyroid cancer in women.

Background: In Poland, where soil is deficient in iodine, supplementation of iodine was introduced in 1935, discontinued in 1980, and then re-introduced in 1997. One of the effects of inadequate iodine intake, prior to 1997, was an increase in the prevalence of thyroid nodular disease (TND) in children. Chernobyl, located in the neighbouring country of Ukraine, suffered a catastrophic nuclear explosion in April 1986., Procedure: A total of 411 children with TND (an incidence of 7.53/100,000) were diagnosed and registered in western Poland between 1996 and 2000 and further evaluated as a population-based study., Results: Based on the patient's clinical status, ultrasound examination, scintiscan, laboratory tests, cytology and the family history, many of the patients qualified for surgery and, as a result, histopathologic data were obtained from 155 of the 411 patients operated on to date (37.7% of all TND). Thyroid carcinoma was detected in 37 of the operated children, i.e. 23.9% or 9.0% of all children with TND with a median incidence of 0.68/100,000. Papillary carcinoma was the predominant histologic type (26-70.3%) compared to follicular carcinoma (10-27.0%) and medullary carcinoma (1-2.7%). Retrospective analysis of the figures for the 23 years (1972-1995) showed that in that period a total of 23 thyroid carcinomas were registered. However, only 12 of these were detected in the 20-year period between 1972 and 1991, none in the years 1992-1993 and, significantly, 11 from 1994 to 1995., Conclusions: Thyroid carcinoma appears to be an ongoing and increasing problem in the children and adolescents of our region, and it is developing more intensively when compared, both to other parts of Poland and to previous statistics (2000 vs. 1985; P<0.002). Iodine deficiency and radiation resulting from the Chernobyl disaster might be important risk factors in the development of thyroid carcinoma in the young population analysed in our region in the period since 1994. The high percentage of follicular carcinoma and follicular adenoma with an undetermined prognosis (19 out of 46) indicates that the long-term iodine deficiency in our region may be more significant in the pathogenesis of malignant transformation than has previously been postulated., (Copyright 2003 Wiley-Liss, Inc.)

Although an uncommon clinical entity, a pediatric patient with a solitary thyroid nodule requires a thorough assessment because of the increased incidence of thyroid carcinoma in this population. In the future, one may expect the widespread clinical use of genetic markers in identifying children, who are at risk for, or who have developed, thyroid carcinomas, with the hopes that these molecular markers will lead to the prevention, or earlier detection and cure, of these malignancies.

In this study some of the clinical and pathological aspects of thyroid carcinomas in Iran are defined. Until fairly recently, Iran was an area of endemic iodine deficiency. The medical records of 1177 confirmed cases of thyroid cancer treated over a 15-year period at 5 tertiary referral centers were reviewed. The female/male ratio was 1.8/1. Mean age was 42.8 +/- 0.9 years, male patients being significantly older. The most common clinical presentation (initial manifestation) was a central neck mass; 28.6% of the tumors had metastasized, usually to the cervical lymph nodes, by the time the patient presented with disease. The mean size of non-metastatic tumors was 5.0 cm at their longest diameter. The distribution of tumors in our study did not reflect the expectations for an iodine-deficient area, where follicular thyroid carcinoma is common, but rather what is seen in iodine-rich areas. Papillary and follicular types accounted for79.7% and 8.8% of cases, respectively.

A correlation between iodine excess and deficiency, on the one hand, and excessive relative risk (ERR) of thyroid cancer in children and adolescents following Chernobyl disaster, on the other, was investigated in a cohort of 119,785 patients born in 1968-1986. Thirty-four cases of thyroid cancer were registered within 12 years after the accident. Tumor-promoting effect of iodine deficiency was established. The ERR of thyroid cancer in the young patients suffering from severe iodine deficiency was almost twice as high as in healthy subjects.

Follicle-derived thyroid cancer is rare in the young. The authors examined a population with a low rate of radiation exposure and who were treated at a single institution. The records of 56 patients diagnosed before the age of 25 years were analyzed. The majority of patients presented with an asymptomatic thyroid mass. All patients were treated surgically and half received postoperative ablation with 131I. Recurrent disease was detected in 29%. The presence of local metastases at initial surgery was a predictor of recurrence. No patient presented with distant metastases and no patient died of thyroid cancer. Although radiation exposure remains a risk factor for thyroid cancer in the young, only a minority of patients with thyroid cancer have a known history of exposure. Patients who are diagnosed at a young age have a high rate of long-term recurrence, and should be followed closely throughout their lives.

Four types of thyroid cancer comprise more than 98% of all thyroid malignancies. Papillary thyroid carcinoma (PTC) may have a very benign course while undifferentiated thyroid carcinoma (UTC) belongs to the most aggressive human malignancies. A variety of genes have been identified to be involved in the pathogenesis of thyroid carcinoma. Somatic Ras mutations seem to be an early event and are frequently found in follicular thyroid carcinomas. Somatic rearrangements of RET and TRK are almost exclusively found in PTC and may be found in early stages. Germline RET missense mutations lead to hereditary medullary thyroid carcinoma (MTC). In contrast, the significance of somatic RET mutations in sporadic MTC is unknown. p53 seems to play a crucial role in the dedifferentiation process of thyroid carcinoma. The precise role of PTEN remains to be elucidated. The only clearly identified exogenous factor that may lead to thyroid carcinoma (mainly PTC) is radiation. Of interest, radiation is capable to induce RET rearrangements. In general, early diagnosis is mandatory to enable the chance of cure. Surgery is the treatment of choice. Depending on the tumour type, surgery in combination with either radioiodine, external radiation or chemotherapy often enables the control of local tumour burden. In MTC and UTC, once thyroid cancer is spread to distant organs, efficacious therapeutic agents are almost non-existing. However, our growing knowledge of genes involved in thyroidal oncogenesis may contribute to the development of more effective treatment modalities. Some preliminary data on gene therapy are quite promising.