Cases Of Differentiated Thyroid Carcinoma Research Articles

Clinicopathological Characteristic of Radioactive Iodine-Refractory Differentiated Thyroid Carcinoma at Dr. Hasan Sadikin Hospital 2016-2021

Background Initial therapy for differentiated thyroid carcinoma (DTC) is thyroidectomy with or without cervical lymph node dissection. Furthermore, radioactive iodine (RAI) is given to patients by considering risk stratification and other patient factors. Although most cases of DTC have a good prognosis after standard therapeutic approaches, the risks of local recurrence and distant metastases can be as high as 20% and 10%. Among these patients, two-thirds showed RAI-refractory. This is concerning because 10-year survival rate is less than 10%. This study aimed to analyze the clinicopathological characteristics of RAI-refractory DTC. Methods This is a case-control study. Data was collected from the Department of Nuclear Medicine and Molecular Theranostics and Department of Anatomical Pathology, Faculty of Medicine, Universitas Padjadjaran/Dr. Hasan Sadikin Hospital, Bandung period 1 January 2016 - 31 December 2021. Results Clinicopathological factors associated with RAI-refractory DTC are age, sex, aggressive histologic subtype, LVI (lymphovascular invasion), m-ETE (microscopic extrathyroid extension), TNM (tumor, nodal, metastasis) stage, and ENE (extranodal extension), with p-value <0.05. Meanwhile, there was no significant difference in the histologic type between RAI-refractory and non-RAI-refractory groups. Conclusion In the pathology report, it is necessary to include prognostically relevant tumor histopathological characteristics. In addition to histologic type, histologic subtype, and tumor size, other features such as presence and extent of capsular invasion, LVI, microscopic and macroscopic ETE, ENE, and number and size of metastatic lymph nodes, have been shown to provide additional prognostic information and are required in standard pathology reports for DTC.

Wide Composite Resection of Sternal Metastasis & Reconstruction Using Titanium Mesh Implant and Myocutaneous Flap in Differentiated Thyroid Carcinoma: Case Report of Two Cases.

Differentiated Thyroid carcinoma (DTC) with distant skeletal metastases is associated with a very poor prognosis and are unfortunately resistant to radioiodine therapy (RIT). Surgical removal of the metastases in such selected cases is a beneficial adjunct to RIT. We report two cases of DTC with sternal metastases whom we successfully managed with surgical resection of the sternal lesion with reconstruction of the chest wall defect using titanium mesh implant and myocutaneous flap.

Assessment of Differentiated Thyroid Carcinomas in French Polynesia After Atmospheric Nuclear Tests Performed by France

Due to the amount of iodine 131 released in nuclear tests and its active uptake by the thyroid, differentiated thyroid carcinoma (DTC) is the most serious health risk for the population living near sites of nuclear tests. Whether low doses to the thyroid from nuclear fallout are associated with increased risk of thyroid cancer remains a controversial issue in medicine and public health, and a misunderstanding of this issue may be associated with overdiagnosis of DTCs. This case-control study was conducted by extending a case-control study published in 2010 that included DTCs diagnosed between 1984 and 2003 by adding DTCs diagnosed between 2004 and 2016 and improving the dose assessment methodology. Data on 41 atmospheric nuclear tests conducted by France between 1966 and 1974 in French Polynesia (FP) were assessed from original internal radiation-protection reports, which the French military declassified in 2013 and which included measurements in soil, air, water, milk, and food in all FP archipelagos. These original reports led to an upward reassessment of the nuclear fallout from the tests and a doubling of estimates of the mean thyroid radiation dose received by inhabitants from 2 mGy to nearly 5 mGy. Included patients were diagnosed from 1984 to 2016 with DTC at age 55 years or younger and were born in and resided in FP at diagnosis; 395 of 457 eligible cases were included, and up to 2 controls per case nearest by birthdate and matched on sex were identified from the FP birth registry. Data were analyzed from March 2019 through October 2021. The radiation dose to the thyroid gland was estimated using recently declassified original radiation-protection service reports, meteorological reports, self-reported lifestyle information, and group interviews of key informants and female individuals who had children at the time of these tests. The lifetime risk of DTC based on Biological Effects of Ionizing Radiation (BEIR) VII models was estimated. A total of 395 DTC cases (336 females [85.1%]; mean [SD] age at end of follow-up, 43.6 [12.9] years) and 555 controls (473 females [85.2%]; mean [SD] age at end of follow-up, 42.3 [12.5] years) were included. No association was found between thyroid radiation dose received before age 15 years and risk of DTC (excess relative risk [ERR] per milligray, 0.04; 95% CI, -0.09 to 0.17; P = .27). When excluding unifocal noninvasive microcarcinomas, the dose response was significant (ERR per milligray, 0.09; 95% CI, -0.03 to 0.02; P = .02), but several incoherencies with the results of the initial study reduce the credibility of this result. The lifetime risk for the entire FP population was 29 cases of DTC (95% CI, 8-97 cases), or 2.3% (95% CI, 0.6%-7.7%) of 1524 sporadic DTC cases in this population. This case-control study found that French nuclear tests were associated with an increase in lifetime risk of PTC in FP residents of 29 cases of PTC. This finding suggests that the number of thyroid cancer cases and the true order of magnitude of health outcomes associated with these nuclear tests were small, which may reassure populations of this Pacific territory.

Discrepancies of RET gene and risk of differentiated thyroid carcinoma.

Somatic variations in rearranged during transfection (RET) proto-oncogene acts to influence Thyroid cancer (TC) in a low penetrance manner, but their effects tend to vary between different populations. This case-control study was aimed to evaluate effect of RET G691S, S904S and L769L single nucleotide polymorphisms (SNPs) on the risk for differentiated thyroid carcinoma (DTC). A total of 180 patients and 220 controls were genotyped by Polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP). Di-Deoxy Sanger sequencing was performed on 100 samples with variations and 20 wild samples for each amplified exon. In addition, In Silico tools were used to evaluate structural and functional impact of individual SNPs in disease progression. In RET G691S/L769L/S904S SNPs, frequency of variant genotypes in DTC cases was 61.1%, 54.4% and 76.6% as compared to 45.9%, 43.6% and 89.09% in controls respectively (P⩽ 0.05). In Silico analysis revealed that different protein formed due to G691S substitution decreases the stability of 3D structure of protein. The RET G691S and L769L SNP followed "Dominant" but RET S904S SNP confirmed an "Additive" mode of inheritance. RET G691S/L769L/S904S SNPs are significantly associated with DTC with G691S SNP declining the stability of final protein product.

Variations in MAP kinase gladiators and risk of differentiated thyroid carcinoma

Thyroid carcinoma (TC) accounts for ~2.1% of newly diagnosed cancer cases. Mutations in KRAS, HRAS, NRAS and BRAF are primary participants in the development and progression of various types of malignancy, including differentiated TC (DTC). Therefore, the present prospective cohort study aimed to screen patients with DTC for variations in RAS gene family and BRAF gene. Exon 1 and 2 of KRAS, HRAS, NRAS and exon 15 of BRAF gene were screened for hotspot mutations in 72 thyroid tumor and adjacent normal tissue samples using di-deoxy Sanger sequencing. HRAS T81C mutation was found in 21% (15 of 72) of DTC tissue samples, therefore this mutation was investigated in blood samples from patients with DTC and controls as a genetic polymorphism. In addition, HRAS T81C genotypes were determined in 180 patients with DTC and 220 healthy controls by performing restriction fragment length polymorphism. BRAFV600E mutation was confined to classical variant of papillary thyoid cancer (CPTC; 44.4%) and was significantly associated with multifocality and lymph node (LN) metastasis. No mutation was found in exons 1 and 2 of KRAS and NRAS and exon 2 of HRAS genes, however, mutation was detected in exon 1 of HRAS gene (codon 27) at nucleotide position 81 in 21% (15 of 72) of DTC tumor tissue samples. Furthermore, HRAS T81C single nucleotide polymorphism was significantly associated with the risk of DTC with variant genotypes more frequently detected in cases compared with controls (P≤0.05). Moreover, frequency of variant genotypes (TC+CC) was significantly higher among DTC cases with no history of smoking, males, greater age, multifocality and LN metatasis compared with healthy controls (P<0.05). BRAFV600E mutation was primarily present in CPTC and associated with an aggressive tumor phenotype but mutations in RAS gene family were not present in patients with DTC. HRAS T81C polymorphism may be involved in the etiopathogenesis of DTC in a Pakistani cohort. Furthermore, testing for the BRAFV600E mutation may be useful for selecting initial therapy and follow-up monitoring.

TERT Promoter Mutations and the 8th Edition TNM Classification in Predicting the Survival of Thyroid Cancer Patients.

Our research group has previously shown that the presence of TERT promoter mutations is an independent prognostic factor, by applying the TERT mutation status to the variables of the AJCC 7th edition. This study aimed to determine if TERT mutations could be independent predictors of thyroid cancer-specific mortality based on the AJCC TNM 8th edition, with long-term follow-up. This was a retrospective study of 393 patients with pathologically confirmed differentiated thyroid carcinoma (DTC) after thyroidectomy at a tertiary Korean hospital from 1994 to 2004. The thyroid cancer-specific mortality rate was 6.9% (5.2% for papillary and 15.2% for follicular cancers). TERT promoter mutations were identified in 10.9% (43/393) of DTC cases (9.8% of papillary and 16.7% of follicular cancer) and were associated with older age (p < 0.001), the presence of extrathyroidal invasion (p < 0.001), distant metastasis (p = 0.001), and advanced stage at diagnosis (p < 0.001). The 10-year survival rate in mutant TERT was 67.4% for DTC patients (vs. 98% for wild-type; adjusted hazard ratio (HR) of 9.93, (95% CI: 3.67-26.90)) and 75% for patients with papillary cancer (vs. 99%; 18.55 (4.83-71.18)). In addition, TERT promoter mutations were related to poor prognosis regardless of histologic type (p < 0.001 for both papillary and follicular cancer) or initial stage (p < 0.001, p = 0.004, and p = 0.086 for stages I, II, and III and IV, respectively). TERT promoter mutations comprise an independent poor prognostic factor after adjusting for the clinicopathological risk factors of the AJCC TNM 8th edition, histologic type, and each stage at diagnosis, which could increase prognostic predictability for patients with DTC.

Pituitary neuroendocrine tumors and differentiated thyroid cancer: do metabolic and inflammatory risk factors play roles?

It is postulated that patients with different types of pituitary neuroendocrine tumors (PitNETs) may present a higher incidence of cancer. Factors underlying individuals becoming overweight, such as insulin resistance, hyperleptinemia, and low-grade inflammation, may play a role in the risk of differentiated thyroid carcinoma (DTC) in such patients. This study aimed to investigate the frequency of and obesity-related risk factors associated with DTC in patients with PitNETs. This cross-sectional study involved 149 patients with nonacromegalic PitNETs (AG group), 71 patients with acromegaly (ACRO group), and 156 controls (CG group). All participants underwent insulin and blood glucose measurements with the determination of the homeostatic model assessment-insulin resistance (HOMA-IR) index, leptin, and high-sensitivity C-reactive protein (hsCRP), and they also underwent thyroid ultrasound. Clinically significant nodules were biopsied for subsequent cytopathological evaluation, and participants were operated on when indicated. Patients in the AG group had high levels of insulin resistance and significantly higher levels of leptin and hsCRP compared with those of patients in the ACRO group. There were no cases of DTC in the AG group; two findings, one incidental, of DTC occurred in the CG group, and three cases of DTC were present in the ACRO group. Acromegaly was associated with DTC after adjusted analysis. Our findings in patients with nonacromegalic PitNETs do not indicate a high risk for DTC despite the presence of metabolic and inflammatory risk factors for neoplastic events. In contrast, acromegaly promotes a greater risk of DTC.

Pulmonary and overall healthcare utilization after childhood and young adult thyroid cancer.

Differentiated thyroid carcinoma (DTC) in children, adolescents, and young adults is associated with excellent prognosis. However, little is known about the long-term utilization of healthcare resources among survivors. The objective of this study was to compare the utilization of healthcare resources among DTC survivors to the general population, with a focus on pulmonary-related resource utilization. Population-based linked data were used to retrospectively ascertain DTC patients from the Ontario Cancer Registry, age <30 years at diagnosis between 1992 and 2011. DTC cases were individually matched 1:10 to the general population on age, sex, diagnosis year, and rural status. Billing records for all-cause hospitalizations, emergency department visits, pulmonary subspecialist visits, and chest imaging were compared using incidence rate ratios (IRR). A total of 2456 individuals with DTC were identified, with women representing the majority (82.8%) of cases. Compared to controls, hospitalization and emergency department visit IRRs were 2.56 (95% CI, 2.49-2.63) and 2.22 (95% CI, 2.18-2.26), respectively. An excess of pulmonary diagnostic imaging was observed for chest radiography (IRR, 2.7; 95% CI, 2.6-2.8) and pulmonary CT's (IRR, 17.5; 95% CI, 15.8-19.3). Patients who underwent radioactive iodine therapy had a higher incidence of pulmonary-related healthcare utilization than those who did not. The highest healthcare utilization for all modalities was observed in the 30 to 90 days after DTC diagnosis with a steady decline further from diagnosis; however, elevated utilization was observed throughout the observation period. Health services utilization is high for primary DTC survivors, irrespective of the time since diagnosis. Radioactive iodine therapy is associated with higher rates of utilization. These findings have ramifications for treatment, surveillance and for policy formulation.

Prognostic values of m6A RNA methylation regulators in differentiated Thyroid Carcinoma.

N6-methyladenosine (m6A) is the most prevalent modification of RNA in mammals. m6A RNA methylation levels are dynamically regulated by m6A RNA methylation regulators. While increasing evidence has suggested that m6A RNA methylation is vital in the initiation and progression of human carcinoma, little is known about the expression and effect of m6A RNA methylation regulators in differentiated thyroid carcinoma (DTC). Herein, we demonstrate that most of the thirteen main m6A RNA methylation regulators are differentially expressed in DTC tissues and normal thyroid tissues. Based on consensus clustering of m6A RNA methylation regulators, DTC cases were divided into two subgroups (TC1 and TC2). Compared with the TC1 subgroup, the TC2 subgroup was associated with a poorer prognosis, older age, higher T grade, higher N grade and higher TNM stage. The results indicated that alteration of m6A RNA methylation regulators was closely related to DTC. We further established a risk signature of four m6A RNA methylation regulators that could evaluate prognosis and clinicopathological features in DTC. Finally, the results of the TCGA analysis were verified by other cohorts from Gene Expression Omnibus (GEO) database. In conclusion, m6A RNA methylation regulators play a crucial part in the progression of DTC and are potentially useful for evaluating the prognosis and providing potential novel insights into treatment strategies.

Correlation studies of ultrasonic morphological types and the biological variation in calcification of the differentiated thyroid cancer

Objective To explore the correlation between ultrasound features and tumor biological variation with calcification morphological types in differentiated thyroid carcinoma (DTC). Methods The clinical data of 598 patients with DTC calcification diagnosed by ultrasound, surgery and clinicopathology were retrospectively analyzed. According to the 2017 edition of the American College of Radiology (ACR) Thyroid Imaging Report and Data System (TI-RADS) classification system standard, DTC ultrasonic calcification morphological characteristics were divided into 5 types, and the correlation between DTC ultrasonic calcification morphological types and tumor biological characteristics and their variations were analyzed by Spearman correlation analysis. Results Of the 598 patients, 527 cases (88.13%) were typical papillary thyroid cancer(PTC), 27 cases (4.52%) were typical follicular thyroid cancer(FTC), and 44 cases (7.36%) were variant subtype (including 25 cases of follicular type, 9 cases of high cell type, 6 cases of clear cell type and 4 cases of eosinophilic type). TI-RADS diagnosis: 44 cases (7.36%) were Ⅰ~Ⅲ class, 179 cases (29.93%) were Ⅳ class performing fine needle aspiration cytology(FNAC), 375 cases (62.71%) were Ⅴ class. The coincidence rate between ultrasound and clinicopathological diagnosis was 92.64% (554/598). Morphological types of ultrasonic calcification in 554 cases of DTC: type Ⅰ microcalcification in 416 cases (75.09%); type Ⅱ calcification in 71 cases (12.82%); type Ⅲ calcification in 41 cases (7.40%); type Ⅳ calcification in 20 cases (3.61%); type Ⅴ calcification in 6 cases (1.08%). There were correlations between type Ⅰ, Ⅱ, Ⅲ ultrasonic calcification morphological types and the tumor biological characteristics and its variant subtypes of DTC(r=0.634, 0.592, 0.479; all P=0.01). Conclusions TI-RADS Ⅳ-Ⅴ class level+ Adler Ⅱ-Ⅲ blood flow has a high practical value for the ultrasonic diagnosis of DTC, and FNAC can be performed in suspicious type Ⅳ DTC. Type Ⅰ-Ⅲ ultrasonic calcification morphological types and the main types of tumor biological characteristics and its variant of DTC, and has an important clinical value for the diagnosis of DTC by ultrasound, which provides an important reference basis for guiding FNAC, selecting surgical procedure, postoperative follow-up and prognosis judgment. Key words: Ultrasonography; Thyroid cancer, differentiated; Calcification type; Tumor biology

Scabrous patrinia root inhibits circulating tumor cells in differentiated thyroid carcinoma - a clinical observation ⁎

Abstract Objective To observe the clinical inhibition of circulating tumor cells (CTCs) in differentiated thyroid carcinoma (DTC) by the extract of scabrous patrinia root (Huikangling). Methods Eighty-seven DTC patients tested positive for CTCs were randomly divided into two groups; all patients were treated with oral levothyroxine sodium in accordance with the DTC endocrine inhibition treatment criteria. Patients (n = 45) in the treatment group were provided the standard endocrine therapy along with oral Huikangling (0.4 g/tablet, 0.4 g × 3 / time, 3 times / day, 12 weeks). Patients (n = 42) in the control group were only provided the standard therapy. After 4 and 12 weeks, CTCs in the blood were detected by flow cytometry. Results After 4 weeks of oral Huikangling treatment, CTCs were detected in 18 (40%) and 29 (69%) patients in the treatment and control groups, respectively; the difference was statistically significant (χ2 = 8.49, P &lt; 0.05). After 12 weeks, CTCs were detected in 7 (15.6%) and 17 (44.7%) patients in the treatment and control groups, respectively; the difference was statistically significant (χ2 = 5.68, P &lt; 0.05). Follow-up evaluation revealed two patients with lung metastasis and one patient with bone metastasis in the control group; one patient showed lateral neck lymph node metastasis without local recurrence in the treatment group. Conclusion Huikangling treatment reduces the number of CTC-positive DTC cases; however, further studies are needed to elucidate the underlying mechanisms.

BRAF V600E/TERT promoter mutations and NIS/TSHR expression in differentiated thyroid carcinoma and their clinical significance ⁎

Abstract Objective Telomerase reverse transcriptase (TERT) promoter mutations have recently been described in thyroid carcinoma. The purpose of this study was to investigate the clinical significance of (v-raf murine sarcoma viral oncogene homolog B1) BRAF V600E and TERT promoter mutations in differentiated thyroid carcinoma (DTC). The relationship between the two mutations and NIS/TSHR expression was also analyzed. Methods We have detected BRAF V600E and TERT promoter mutations by direct sequencing and NIS/TSHR expression by immunohistochemistry in 229 cases of DTC, 52 cases of benign nodular goiter, and 31 cases of normal thyroid tissue. Results The BRAF V600E mutation was detected in 142 (62.0%) of 229 cases of DTC [141 cases of papillary thyroid carcinoma (PTC) and 1 case of follicular thyroid carcinoma (FTC)]. TERT promoter mutations were detected in 18 (7.9%) of 229 cases of DTC (14 cases of PTC and 4 cases of FTC), including the mutations C228T (0.9%) and C250T (7.0%), which were mutually exclusive. Moreover, 11 (61.1%) cases also harbored the BRAF V600E mutation, which was not associated with gender, age, tumor size, lymph node metastasis, and recurrence risk stratification (P &gt;0.05). The rate of TERT promoter mutation was higher in males, age ≥45, and in the middle/high-risk group (P &lt;0.05), and the rate of simultaneous BRAF V600E and TERT promoter mutations were higher in the middle/high-risk group (P &lt;0.05). In addition, NIS positive rate in the concurrent BRAF V600E and TERT promoter mutation group (45.5 %) was lower than in other groups (that is, the DTC group with BRAF V600E or TERT promoter mutations (55.1%), the DTC group with no BRAF V600E or TERT promoter mutation (57.5%), the nodules and normal group (75.9%); | r | = 0.171, P = 0.002). Conclusion TERT promoter mutations were lower in patients with DTC, with the C250T mutation being the most common. The detection of BRAF V600E mutation combined with TERT promoter mutations was instructive for the prognosis assessment and treatment of DTC.

Preoperative diagnostics in differentiated thyroid carcinoma

The preoperative diagnosis of differentiated thyroid carcinomas (DTC) is particularly challenging in view of the high prevalence of thyroid nodules in the general population. Incidental diagnosis of DTC, on the other hand, can lead to reoperations and increased risk of morbidity. This study aimed to assess the prediction value of preoperative DTC dignity assessment and it's impact on surgical approaches. We retrospectively reviewed 107 cases of DTC and subdivided them in three groups based on the preoperative dignity assessment: suspected malignancy (SM), unclear dignity (UD), and incidental findings (IF). The group differences were investigated in terms of diagnostic methods, findings, and impact on the subsequent surgical approach. The patient groups consisted of n = 51 (SM), n = 32 (UD), and n = 24 (IF). The tumor size, T staging, and ultrasound (US) assessment had the largest impact on the dignity classification (each p < 0.001). Scintigraphy was performed in 80 % of the patients, fine-needle aspiration cytology (FNAC) in 28 %. Hypofunction at scintigraphy (p < 0.001) and cytology results (p < 0.01) were identified as significant predictors for group assignment. Other significant factors were the frequency of the US documentation of nodule characteristics (p < 0.001) and malignancy criteria (p < 0.01) as well as reduced thyroid-stimulating hormone (TSH) levels (p < 0.01). Frozen section (p < 0.001) and total thyroidectomy (p < 0.01) at initial surgery were performed significantly more often in the MV group. Reoperations were significantly more frequent in the IF group (p < 0.001). A relevant number of DTC cases was diagnosed incidentally, leading to significantly more frequent reoperations. A more systematic diagnostic approach with complete documentation of the findings according to current guidelines should be pursued.

Risk factors and stratification for recurrence of patients with differentiated thyroid cancer, elevated thyroglobulin and negative I-131 whole-body scan, by restaging 18F-FDG PET/CT.

In nearly 20%-30% of patients with differentiated thyroid carcinoma (DTC) relapse and 7% of them die during the next 10 years after initial diagnosis. In 10%-30% of patients with DTC after ablation therapy during the follow-up show a negative iodine-131 (131I) whole-body screening test (131I WBS) and increased serum thyroglobulin (Tg) level. Loss of ability of DTC metastatic lesions to trap 131I is associated with pure survival and often aggressive disease. Several studies have shown that in DTC cases non trapping 131I, fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET) can detect recurrence or metastases with high sensitivity (80%-90%). The purpose of this study was to investigate the clinicopathologic features and other related risk factors of patients with DTC having elevated Tg levels and negative 131I WBS in which recurrence was detected by 18F-FDG PET/CT. We tried to study and stratify patients in this grey zone who could benefit from 18F-FDG PET/CT for the detection of metastases/recurrence according to predefined risk factors not investigated by other researchers. We studied retrospectively 165 DTC patients with elevated Tg levels and a negative 131I WBS during their follow-up between 2004-2015. Metastases/recurrence was found in 49% of the patients on restaging with 18F-FDG PET/CT and were compared with nonmetastatic group according to predefined risk factors. These factors were also evaluated in true positive and false negative cases. The sensitivity and specificity of 18F-FDG PET/CT for detecting recurrent/metastatic disease were 90% and 98.5%, respectively. No apparent predefined risk factor impacting a false negative 18F-FDG PET/CT was found. Findings in follicular carcinoma, Hürtle cell carcinoma and papillary carcinoma were not different from positive PET findings. The variants of papillary carcinoma also had no statistically difference with regard to 18F-FDG results. The most important factors affecting a true positive 18F-FDG PET/CT study were: ETE, high total 131I dose and the SUVmax values over 4.5.

Radiation-Induced Differentiated Thyroid Cancer Is Associated with Improved Overall Survival but Not Thyroid Cancer-Specific Mortality or Disease-Free Survival.

Radiation is a well-described risk factor for differentiated thyroid carcinoma (DTC). Although the natural history of DTC following nuclear disasters and in healthcare workers with chronic radiation exposure (RE) has been described, little is known about DTC following short-term exposure to therapeutic medical radiation for benign disease. This study compares DTC morphology and outcomes in patients with and without a prior history of therapeutic external RE. A retrospective review was performed of patients with DTC treated at The University of Chicago between 1951 and 1987, with a median follow-up of 27 years (range 0.3-60 years). Patients were classified as either having (RE+) or not having (RE-) a history of therapeutic RE. Variables examined included sex, age at RE, dose of RE, indication for RE, DTC histology, and outcome. Morphology was determined by blinded retrospective review of all available histologic slides. Outcomes were assessed using Cox proportional hazards model and Kaplan-Meier curves. Of 257 DTC patients, 165 (64%) were RE- and 92 (36%) were RE+, with males comprising a greater proportion of the RE+ group (43.5% vs. 27.3%; p = 0.01). A total of 94.2% of DTC cases were classic papillary cancers; histology did not differ between RE+ and RE- cohorts (p = 0.73). RE was associated with an increased median overall survival (OS; 43 years vs. 38 years; hazard ratio [HR] = 0.55 [confidence interval (CI) 0.34-0.89]; p = 0.01). Survival for males in the RE- group was significantly worse than it was for RE- females (HR = 1.78 [CI 1.05-3.03]; p = 0.03) or RE+ males (HR = 2.98 [CI 1.39-6.38]; p = 0.01). Recurrence did not differ between the RE+ and RE- groups (HR = 0.85 [CI 0.52-1.41]; p = 0.54), nor did DTC-specific mortality (HR = 0.54 [CI 0.21-1.37]; p = 0.20). While DTC following RE has historically been considered a more aggressive variant than DTC in the absence of RE, the present data indicate that RE+ DTC is associated with better OS than RE- DTC, especially for males. Additionally, recent reports are confirmed of equivalent rates of thyroid cancer recurrence. These results warrant further investigation into the factors underlying this unexpected finding.

Does chronic lymphocytic thyroiditis influence the staging of differentiated thyroid carcinoma?

AbstractThe association between differentiated thyroid carcinoma (DTC) and chronic lymphocytic thyroiditis (CLT) has been reported in literature.Aim: To evaluate the incidence of this association and to determine whether the CLT may influence on the early initial staging of DTC when associated with other variable risks.Study design: Historical (retrospective) cohort.Materials and Methods: Fifty two patients with DTC were evaluated from 1999 to 2009. They were divided into two groups. The first group had 35 patients with DTC without DLT; the second had 17 patients with CLT. Total thyroidectomy was the treatment chosen for all patients. Similarities shared in both groups such as age, gender, histological tumor type, tumor diameter, regional only or with distant metastases, extrathyroidal invasion, multifocality and presence of tumor capsule were considered. T-Student tests and Chi-square tests were applied to analyze the data.Results: The incidence of DTC without CLT was higher that of DTC+CLT (p=0.0126). We noticed no statistic differences between the common variables analyzed.Conclusions: CLT occurred in 33% of the patients with DCT. All cases of DTC were in the early stages.

Common variants at the 9q22.33, 14q13.3 and ATM loci, and risk of differentiated thyroid cancer in the Cuban population.

BackgroundThe incidence of differentiated thyroid carcinoma (DTC) in Cuba is low and the contribution of host genetic factors to DTC in this population has not been investigated so far. Our goal was to assess the role of known risk polymorphisms in DTC cases living in Havana. We genotyped five polymorphisms located at the DTC susceptibility loci on chromosome 14q13.3 near NK2 homeobox 1 (NKX2-1), on chromosome 9q22.33 near Forkhead factor E1 (FOXE1) and within the DNA repair gene Ataxia-Telangiectasia Mutated (ATM) in 203 cases and 212 age- and sex- matched controls. Potential interactions between these polymorphisms and other DTC risk factors such as body surface area, body mass index, size, ethnicity, and, for women, the parity were also examined.ResultsSignificant association with DTC risk was found for rs944289 near NKX2-1 (OR per A allele = 1.6, 95% CI: 1.2–2.1), and three polymorphisms near or within FOXE1, namely rs965513 (OR per A allele = 1.7, 95% CI: 1.2–2.3), rs1867277 in the promoter region of the gene (OR per A allele = 1.5, 95% CI: 1.1–1.9) and the poly-alanine tract expansion polymorphism rs71369530 (OR per Long Allele = 1.8, 95% CI: 1.3–2.5), only the 2 latter remaining significant when correcting for multiple tests. Overall, no association between DTC and the coding SNP D1853N (rs1801516) in ATM (OR per A Allele = 1.1, 95% CI: 0.7–1.7) was seen. Nevertheless women who had 2 or more pregnancies had a 3.5-fold increase in risk of DTC if they carried the A allele (OR 3.5, 95% CI: 3.2–9.8) as compared to 0.8 (OR 0.8, 95% CI: 0.4–1.6) in those who had fewer than 2.ConclusionsWe confirmed in the Cuban population the role of the loci previously associated with DTC susceptibility in European and Japanese populations through genome-wide association studies. Our results on ATM and the number of pregnancies raise interesting questions on the mechanisms by which oestrogens, or other hormones, alter the DNA damage response and DNA repair through the regulation of key effector proteins such as ATM. Due to the small size of our study and to multiple tests, all these results warrant further investigation.

Unusual case of hepatic metastasis in follicular thyroid carcinoma detected using I-131 whole body scintigraphy and single-photon emission computerized tomography/computerized tomography.

Papillary and follicular thyroid carcinomas, together known as differentiated thyroid carcinomas (DTC), are among the most curable of cancers. Distant metastases are rare events at the onset of DTC. Among these presentations, metastasis to the liver is even more unusual. Only 11 cases of DTC with liver metastasis were previously reported in the literature. We present a 55-year-old male on Iodine-131 whole body scintigraphy showed intense uptake in thyroid bed, metastasis in both lungs and right lobe of the liver. Radioiodine concentration in liver metastases made him amenable to high-dose radioiodine therapy patient.

Exploring the Association BetweenDICER1Mutations and Differentiated Thyroid Carcinoma

Carriers of germline DICER1 mutations are predisposed to a rare cancer syndrome, the DICER1 syndrome. Thyroid abnormalities are a common finding in DICER1 syndrome with multinodular goiter frequently present in many families in which a germline DICER1 mutation is segregating. Differentiated thyroid carcinoma (DTC) is infrequently seen in such pedigrees. In addition to germline DICER1 mutations, specific somatic mutations have been identified in the DICER1 ribonuclease IIIb catalytic domain in several tumor types. We aimed to determine whether such characteristic somatic DICER1 mutations are present in DTCs that arise within germline DICER1 mutation carriers. The study involved an opportunistic collection of 3 cases of DTC arising in individuals suspected to have DICER1 syndrome and hospital-based ascertainment and testing was implemented. We identified somatic DICER1 mutations in 3 DTCs arising in unrelated germline DICER1 mutation carriers, all of whom had been diagnosed in infancy with pleuropulmonary blastoma (PPB), were treated with chemotherapy, exposed frequently to diagnostic radiation, and subsequently developed DTC. The somatic mutations occurred within the DICER1 ribonuclease IIIb domain, affecting highly conserved amino acid residues central to the catalytic activity of the domain. This report of somatic DICER1 mutations in DTC strengthens the association between DTC and the DICER1 syndrome. The possible association between germline DICER1 mutations, PPB treatment, and the risk of subsequent DTC must be considered by clinicians when treating PPB.

Invasive capacity of differentiated thyroid carcinoma in pediatric and adolescent patients

To summarize the invasion features of differentiated thyroid carcinoma (DTC) in pediatric and adolescent patients. The clinical data of 32 DTC cases (≤18 years old) were retrospectively analyzed for the invasive capacity of DTC in terms of age and gender. Bilateral (P=0.023), multifoci (P=0.037), and extrathyroid invasions (P=0.041) were more often in patients younger than 12 years old. DTC in pediatric and adolescent patients tend to have a more aggressive pattern, especially in patients younger than 12 years.