Risk Factors for Recurrence of Follicular Thyroid Cancer: A Systematic Review.

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.

Papillary and Follicular Thyroid Cancer in children and adolescents: Current approach and future directions.

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.

Follow-up and results in patients with differentiated thyroid carcinoma in Castilla-La Mancha (2001-2015). The CADIT-CAM study. / Resultados del seguimiento de pacientes con carcinoma diferenciado de tiroides en Castilla-La Mancha (2001-2015). Estudio CADIT-CAM.

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.

Differentiated thyroid carcinomas associated with chronic thyroiditis: biological and clinical properties.

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.

Occupational radiation exposure and thyroid cancer incidence in a cohort of U.S. radiologic technologists, 1983-2013.

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.

Dietary habits during the 2 months following the Chernobyl accident and differentiated thyroid cancer risk in a population-based case-control study.

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.

Menstrual and reproductive factors in the risk of thyroid cancer in Japanese women: the Japan Public Health Center-Based Prospective Study.

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.

Risk of malignancy in thyroid nodules classified as TIR-3A: What therapy?

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.

Should the Prevalence of Incidental Thyroid Cancer Determine the Extent of Surgery in Multinodular Goiter?

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.

Risk Factors Associated with Thyroid Carcinoma in North Pakistan.

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.

Increased thyroid cancer incidence in a basaltic volcanic area is associated with non-anthropogenic pollution and biocontamination.

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.

Are we really at the dawn of understanding sporadic pediatric thyroid carcinoma?

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.

Follicular variant of papillary thyroid cancer in Alström syndrome.

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.

Diagnostic radiography exposure increases the risk for thyroid microcarcinoma: a population-based case-control study.

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.

Differentiated thyroid carcinoma risk factors in French Polynesia.

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.