Histologic Subtypes Of Thyroid Cancer Research Articles

7079 Analysis of the Association Between Recent Exposure to Pregnancy and the Histological Subtype of Thyroid Cancer

Abstract Disclosure: T.L. Danehy: None. A. Manavalan: None. C. Schechter: None. Y. Tomer: None. Objective: Thyroid cancer is the second most common cancer diagnosed in pregnancy (1). Both HCG and estrogen have been implicated in this increased risk (2). While the classic variant of papillary thyroid cancer is the most common subtype in non-pregnant women, the effect of exposure to pregnancy on histological subtype remains unclear and could have clinical implications. Methods: This is a retrospective cohort study conducted at Montefiore Medical Center. All women of childbearing age (18-45) with a diagnosis of thyroid cancer between the years of 2015 -2020 (n=152) were identified. 43 participants were excluded due to missing data. The remaining 114 participants were divided into 2 groups; Group 1 or the exposed (n=25) included those diagnosed with thyroid cancer during pregnancy or in the 2 years postpartum and had carried their pregnancy to term, and Group 2 or the unexposed (n =89) included those who were nulliparous or diagnosed with thyroid cancer prior to pregnancy or more than 2 years post-partum. Charts were reviewed to obtain data on the initial histopathology and were classified into Follicular Thyroid Cancer (FTC), Hurthle cell carcinoma (HCC), Medullary Thyroid Cancer (MTC), and Papillary Thyroid Cancer (PTC). Results: Women in the unexposed group were significantly younger than those exposed to pregnancy (28.7 vs 32.7 p=0.005). The distribution of histological types in the two groups was as follows:Group 1: FTC (13.0%), HCC (0%), MTC (0%), and PTC (87%). Group 2: FTC (5.7%), HCC (2.3%), MTC (3.4%), PTC (88.5%). Thus, the incidence of follicular thyroid cancer in the exposed group was > 2-fold that observed in unexposed group, but this difference did not meet statistical significance (p=0.594). Conclusions: Our study showed a non-statistically significant increased incidence of FTC in women who were diagnosed with thyroid cancer during pregnancy or 2 years postpartum compared to unexposed women. While this did not meet statistical significance, our study sample was small and may have been underpowered. Therefore, our findings merit further investigation given their potential clinical implications.

Circ-LDLRAD3/miR-655-3p/MAPK1 axis enhances cell migration and invasion in papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is a prevalent histological subtype of thyroid cancer, whose occurrence and development may be related to circRNA dysregulation. This research proposed to unravel circ-LDLRAD3-related mechanisms in PTC. First, circ-LDLRAD3, miR-655-3p .and MAPK1 levels in PTC were quantitatively measured. Then, plasmid vectors or oligonucleotides that interfere with circ-LDLRAD3, miR-655-3p, or MAPK1 were transfected into PTC cells, followed by the analysis of proliferation, apoptosis, migration, and invasion. Finally, the targeted binding sites between miR-655-3p and circ-LDLRAD3 or MAPK1 were predicted by starBase and experimentally verified. Statistically, PTC samples expressed high circ-LDLRAD3 and MAPK1 and low miR-655-3p. Knocking down circ-LDLRAD3 or enhancing miR-655-3p hindered PTC cell proliferation, migration, and invasion, and forced apoptosis. circ-LDLRAD3 bound to miR-655-3p to affect MAPK1 expression. Elevating MAPK1 rescued circ-LDLRAD3 knockdown-allowed obstruction of PTC cell growth. In conclusion, circ-LDLRAD3 stimulates PTC development by releasing miR-655-3p-targeted MAPK1.

The allelic regulation of tumor suppressor ADARB2 in papillary thyroid carcinoma.

Papillary thyroid cancer (PTC) is one of the histological subtypes of thyroid cancer which is the most common endocrine malignancy in the world. The disrupted balance of the adenosine-to-inosine (A-to-I) RNA editing due to dysregulation of the editing genes exists in thyroid cancer. However, it is still largely unknown how functional single nucleotide polymorphisms (SNPs) in the A-to-I RNA editing genes contribute to PTC genetic susceptibility. In this study, we systematically annotated and investigated the role of 28 potential functional SNPs of ADAR, ADARB1, ADARB2 and AIMP2 in PTC. We identified ADARB2 rs904957 and rs1007147 genetic variants which are associated with significantly elevated PTC risk in two case-control sets consisting of 2020 PTC cases and 2021 controls. Further investigations disclosed that ADARB2 could inhibit cell viability and invasion capabilities of PTC cells as a novel tumor suppressor. The ADARB2 rs904957 T-to-C polymorphism in gene 3'-untranslated region enhances miR-1180-3p binding affinity and represses ADARB2 expression through an allele-specific manner. In line with this, carriers with the rs904957 C allele correlated with decreased tumor suppressor ADARB2 expression in tissue specimens showed notably increased risk to develop PTC compared to the T allele carriers. Our findings highlight that the A-to-I RNA editing gene ADARB2 SNPs confer PTC risk. Importantly, these insights would improve our understanding for the general roles of RNA editing and editing genes during cancer development.

Asporin Interacts With HER2 to Promote Thyroid Cancer Metastasis via the MAPK/EMT Signaling Pathway.

Approximately 85% of histological subtypes of thyroid cancer are papillary thyroid cancer (PTC), and the morbidity and mortality of PTC patients rapidly increased due to lymph node metastases or distant metastasis. Therefore, it needs to distill an enhanced understanding of the pathogenesis of PTC patients with lymph node metastases or distant metastasis. We employed the TMT-based quantitative proteomics approach to identify and analyze differentially expressed proteins in PTC with different degrees of lymph node metastases. Compared with paired normal tissues, asporin is overexpressed in PTC-N0, PTC-N1a, and PTC-N1b tumorous tissues via proteomics, western blotting, and immunohistochemistry assays. Functionally, asporin is mainly expressed in the extracellular matrix, cell membrane, and cytoplasm of PTC tumorous tissues, and promotes thyroid cancer cell proliferation, migration, and invasion. Mechanistically, asporin, interacting with HER2, co-localizes HER2 on the cell membrane and cytoplasm, and the asporin/HER2/SRC/EGFR axis upregulate the expression of EMT-activating transcription factors through the MAPK signaling pathway. Clinically, asporin can be regarded as a serological biomarker to identify PTC patients with or without lymph node metastasis, and high expression of asporin in PTC tumorous tissues is a risk factor for poor prognosis.

Indications of external beams radiation for thyroid cancer.

The use of external beam radiation therapy (EBRT) for the treatment of the different histologic subtypes of thyroid cancer is a matter of debate. This article provides an up-to-date review on the current evidence concerning the benefits of EBRT in thyroid cancer in specific indications. Based on retrospective studies, adjuvant EBRT lessens the risk of locoregional recurrence in locally advanced differentiated thyroid cancer (DTC) and medullary thyroid cancer (MTC) with high-risk features. The effect of EBRT on overall survival remains uncertain. EBRT should also be part of the multimodality treatment in anaplastic thyroid cancer (ATC), as it improves survival rates in incompletely resected ATC. The role of EBRT in thyroid cancer remains unclear. To date, no randomized control studies are available. Retrospective data showed improved outcomes in patients with high-risk features for locoregional recurrence.

Circ_0039411 promotes papillary thyroid carcinoma development through mediating the miR-423-5p/SOX4 signaling.

Papillary thyroid carcinoma is the most frequent histological subtype of thyroid cancer with a high incidence. We aimed to explore the function of circular RNA_0039411 (circ_0039411) and its associated mechanism in papillary thyroid carcinoma progression. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were conducted to determine the expression of RNA and protein, respectively. The colony formation ability, migration, invasion, and apoptosis were analyzed by colony formation assay, transwell migration assay, transwell invasion assay, and flow cytometry. Cell glycolytic metabolism was analyzed using fluorescence-based glucose assay kit and fluorescence-based lactate assay kit. Dual-luciferase reporter assay and RNA-Pull-Down Assay were performed to validate the binding between microRNA-423-5p (miR-423-5p) and circ_0039411 or SRY-box transcription factor 4 (SOX4). The xenograft tumor model was used to assess the role of circ_0039411 in the tumor growth in vivo. Circ_0039411 was highly expressed in papillary thyroid carcinoma tissues and cell lines compared with adjacent normal tissues and NTHY-ORI3.1 cells. Circ_0039411 interference suppressed the colony formation ability, migration, invasion, and glycolysis but promoted the apoptosis of papillary thyroid carcinoma cells. MiR-423-5p was a target of circ_0039411 in papillary thyroid carcinoma cells. Circ_0039411 knockdown-mediated effects in papillary thyroid carcinoma cells were largely overturned by the silence of miR-423-5p. MiR-423-5p bound to the 3' untranslated region (3'UTR) of SOX4. SOX4 overexpression largely reversed circ_0039411 silencing-mediated effects in papillary thyroid carcinoma cells. Circ_0039411 positively regulated SOX4 expression by sponging miR-423-5p in papillary thyroid carcinoma cells. Circ_0039411 silencing notably suppressed the growth of xenograft tumors in vivo. Circ_0039411 promoted the malignant behaviors of papillary thyroid carcinoma cells partly depending on the regulation of the miR-423-5p/SOX4 axis.

MON-507 A Descriptive Study of Clinical and Surgical Characteristics of Patients with Thyroid Cancer: A 10-Year Retrospective Study from UAE

Introduction: Thyroid cancer is the sixth most common type of cancer in the UAE. It has been observed that the incidence of thyroid cancer has been steadily increasing worldwide. However, limited studies about thyroid cancer has been reported from the Arab gulf region.Objective: The objective of this study was to describe the clinical and surgical characteristics of patients with thyroid cancer in the UAE population.Methods: Retrospective analysis was performed on all adult patients attending thyroid cancer clinic at Sheikh Khalifa Medical City (SKMC) in Abu Dhabi, UAE over ten years from 2008 to 2018. All patients with a confirmed histological diagnosis of thyroid cancer who had surgical intervention with long-term follow up data on cancer outcome have been included. Categorical variable analysis and descriptive analysis were used to identify factors associated with increased risk of developing thyroid cancer.Results: Total number of 203 patients with confirmed diagnosis of thyroid cancer were included. Most of the patients were female (72.9 %, n=148). Mean age at the time of diagnosis was 40±13 years. Papillary thyroid carcinoma was the most common thyroid cancer observed (95.6%, n=194) followed by follicular thyroid carcinoma (2%), medullary thyroid carcinoma (1.5%) and mixed medullary-papillary (0.9%). Classical variant and follicular variant of papillary thyroid carcinoma were the two most commonly observed histological subtypes of thyroid cancer with prevalence of 54.7 % and 21.7 % respectively. 91.1% (n=185) of patients had total thyroidectomy and 8.9%(n=18) had hemithyroidectomy. Female gender has been observed to be associated with higher prevalence of thyroid cancer (OR 2.78, 95% CI 1.18–4.50, p=0.001). Smoking status did not show any significant association with developing thyroid cancer. Recurrent thyroid cancer was observed in 9.4%(n=19). Most of recurrence happened as local metastasis 89.5%(n=17). The mean time of recurrence was 24 months (range, 7–64 months).Conclusions: Our data demonstrate that in the UAE population, papillary thyroid cancer is the most common type of thyroid cancer. Female gender is observed to be associated with higher risk of thyroid cancer. Recurrence rate of thyroid cancer noted to be 9.4%. Further studies are required to investigate factors associated with recurrence and cancer free survival rates.

MON-560 Thyroid Cancer and Iodine Nutritional Status in Asturias (Spain)

INTRODUCTION Iodine deficiency may play a role in thyroid cancer carcinogenesis. Because Spain has region-specific historical iodine deficiency, it is ideal to evaluate the potential impact of recent national iodine supplementation policies on thyroid cancer incidence trends. In Asturias there have been several population studies of iodine nutritional status (in 1983, 1992, 2000 and 2010), showing a progressive and significant increase in urinary iodine concentration, probably due to promotion of iodized salt use. OBJECTIVES Evaluate the potential impact of iodine nutrition status changes in the last 30 years in subtypes thyroid cancer distribution trends MATERIAL AND METHODSDescriptive, observational study of the different histological subtypes of thyroid cancer in a tertiary referral hospital. Cases were divided into 3 periods of time (1981-1990, 1991-2000, and 2001-2010), according with our epidemiological studies on iodine nutrition. For the statistical analysis SPSS v17 was used. RESULTSA total of 697 patients with histologic report were included. Proportion of papillary cancer has significantly increased (group 1 1981-1990 44.8%, [95%CI 36.6-53], group 3 2001-2010 66.2%, [95%CI 61.2-71.1] p < 0.001) whereas follicular cancer significantly decreased between 1981 and 2010 (group 1 1981-1990 43.8% [95%CI 35.3-51.6], group 3 2001-2010 27% [95%CI 22.3-31.6] p < 0.001). Anaplastic cancer also significantly decreased (group 1 1981-1990 7.6% [95%CI 3.2-11.9], group 3 2.6% [95%CI 0.9-4.2] p < 0.001. These changes occurred in a historically iodine deficient region. Median urinary iodine concentration increased from 63 µg/L in the 80’s until 181 µg/L in the last study in 2010. CONCLUSIONSTrends among different histological subtypes of thyroid cancer change as the nutritional status of iodine improves, with a greater proportion of papillary thyroid cancer compared to the follicular and anaplastic subtypes.

Global DNA methylation profile in medullary thyroid cancer patients

BackgroundChanges in global DNA methylation have been suggested to cause genomic instability leading to increased risk of cancer. The accumulation of epigenetic changes is believed to contribute to tumorigenesis and dedifferentiation, but the effects of such changes in thyroid cancer are still yet defined. ObjectiveTo evaluate the global DNA methylation levels in thyroid cancer patients. MethodsTotal DNA was extracted from peripheral blood leukocytes of the medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC) patients and the methylation pattern was evaluated using the Imprint Methylated DNA Quantification kit (Sigma-Aldrich). ResultsA total of 42 patients were analyzed (24 MTC, 12 PTC, and 6 controls). For MTC, the mean age was 41 ± 20 years, 54% were women and 12 cases were sporadic. The median calcitonin level at diagnosis was 1692 (637–8865), 65% of the MTC patients had local metastases and 23% distant metastases. For PTC, the median age was 43 ± 15 years, 58% were women and 50% had local metastases. The percentage of overall methylation differed according to the tumor subtype. Patients with MTC had a higher level of DNA methylation when compared to individuals with PTC (35 (24–48) vs. 17 (6.5–20.5); P = 0.002, respectively). Interestingly, among patients with MTC, individuals with the sporadic form of the disease had a higher level of methylation when compared to the hereditary form (25 (16–37) vs. 43 (33–52); P = 0.025, respectively). No association was observed between global methylation levels and clinical and/or oncological characteristics of the disease. ConclusionGlobal methylation levels were higher in MTC as compared to PTC patients. These results suggest the overall DNA methylation profile may be influenced by the histological subtype of thyroid cancer.

EZH2 Overexpression as a Useful Prognostic Marker for Aggressive Behaviour in Thyroid Cancer.

Enhancer of zeste homolog 2 (EZH2) is a member of the polycomb group of genes, which are key factors in the regulation of cell proliferation and differentiation. EZH2 is overexpressed in many malignancies. We analyzed EZH2 protein expression levels in different histological subtypes of thyroid cancer to examine its utility as a prognostic factor. We examined EZH2 protein expression by immunohistochemistry in tissue samples from 67 cases of poorly differentiated (PDTC) and 48 cases of anaplastic thyroid carcinoma (ATC), and in samples of adjacent normal and differentiated thyroid carcinoma (DTC). We examined differences in expression of EZH2 among various histological types of thyroid cancer, and the relationship between EZH2 expression and patient outcome. EZH2 protein was expressed in PDTC and ATC, but not in normal thyroid gland or DTC. EZH-positivity increased in the order of DTC, PDTC, and ATC (p<0.01). Higher EZH2 expression correlated with poorer survival in PDTC (p=0.004), and a similar but non-significant trend was observed in ATC (p=0.166). Multivariate analysis identified EZH2 as an independent prognostic factor similar to metastatic status in the Japanese Society of Thyroid Surgery (JSTS) classification of PDTC. EZH2 overexpression is associated with malignant potential in thyroid cancer, and may thus be a useful prognostic marker of aggressive thyroid cancer.

MicroRNA-144 inhibits proliferation by targeting WW domain-containing transcription regulator protein 1 in papillary thyroid cancer.

Papillary thyroid carcinoma (PTC), the most common histological subtype of thyroid cancer, accounts for between 80 and 90% of all thyroid cancer cases. Previous studies have suggested that microRNAs (miRNAs/miRs) are involved in the development of PTC. The aim of the present study was to investigate whether miR-144 inhibits cellular proliferation in PTC. The expression of miR-144 was detected in PTC and corresponding adjacent non-cancerous tissues, and in the PTC cell line IHH4, using reverse transcription-quantitative polymerase chain reaction. Associations between miR-144 expression levels and the clinicopathological characteristics were analyzed. Receiver operating characteristic (ROC) curves were used to assess the diagnostic value of miR-144 expression, and the potential function of miR-144 was investigated in IHH4 cells using a Cell Counting Kit-8 and colony formation assays. Western blotting was applied to analyze the expression level of WW domain-containing transcription regulator 1 (WWTR1) in PTC tissues. miR-144 was significantly downregulated in PTC tissues and the PTC cell line. Low expression of miR-144 was associated with larger tumor sizes (P<0.001). The ROC curves demonstrated that miR-144 may be a potential biomarker for identifying PTC and non-cancerous diseases (sensitivity, 58.7%; specificity, 87.3%) as well as to differentiate PTC with tumor sizes ≥2 cm (sensitivity, 79.2%; specificity, 69.2%). Upregulation of miR-144 significantly suppressed proliferation in IHH4 cells. WWTR1 was overexpressed in PTC tissues compared with in adjacent non-cancerous tissues, and the ectopic expression of miR-144 downregulated WWTR1 in IHH4 cells. Co-transfection with pcDNA-WWTR1 and miR-144 ‘rescued’ the proliferation inhibition. The results of the present study collectively demonstrated that miR-144 is downregulated in PTC, that low expression levels of miR-144 are associated with larger tumor sizes and that miR-144 inhibits cellular proliferation in PTC by targeting WWTR1.

Intérêt de la TEP/TDM au 18FDG dans les sous-types histologiques agressifs de cancers thyroïdiens (oncocytaire et peu différencié)

IntroductionThe objective of our study was to evaluate the performance of 18FDG PET/CT in aggressive histological subtypes of differentiated cancer of the thyroid and its therapeutic impact. MethodThirty-three patients (22 Hürthle cell carcinoma and 11 poorly differentiated carcinoma) who underwent FDG PET/CT were retrospectively included. Nine scans have been performed for initial staging, 16 for suspicion of recurrence (with 11 having a rising Tg), 3 for the reassessment of metastatic disease under systemic treatment and 30 systematically during follow-up. The results of PET/CT were confronted with histological data and follow-up results. ResultsThirteen out of 18 positive scans were confirmed (8 locoregional recurrences and 5 distant metastases). The majority of them were performed for a suspicion of recurrence (8) or for initial staging (2). The sensitivity, specificity, PPV, and NPV were respectively 81.2%, 88.1%, 72.2% and 92.5%. For Hürthle cell carcinoma and poorly differentiated carcinoma, the sensitivity and specificity were respectively 100% vs. 57% and 86% vs. 93%. Systematic PET scans were most of the time negative (26/30) and in accordance with histological and follow-up results. It was the same in case of scans performed for undetectable initial Tg (16/22). PET/CT modified patient management in 14% of the cases. ConclusionThis study confirms the good performances of 18FDG PET/CT for initial staging and in case of elevated Tg during the follow-up of aggressive histological subtypes of thyroid cancer. It does not seem relevant in the absence of a suspicion of recurrence or in the case of undetectable initial Tg.

Expression of glutamine metabolism-related proteins in thyroid cancer

PurposeThis study aimed to investigate the expression of glutamine metabolism-related protein in tumor and stromal compartments among the histologic subtypes of thyroid cancer.ResultsGLS1 and GDH expression in tumor and stromal compartments were the highest in AC than in other subtypes. Tumoral ASCT2 expression was higher in MC but lower in FC (p < 0.001). In PTC, tumoral GLS1 and tumoral GDH expression was higher in the conventional type than in the follicular variant (p = 0.043 and 0.001, respectively), and in PTC with BRAF V600E mutation than in PTC without BRAF V600E mutation (p<0.001). Stromal GDH positivity was the independent factor associated with short overall survival (hazard ratio: 21.48, 95% confidence interval: 2.178-211.8, p = 0.009).MethodsWe performed tissue microarrays with 557 thyroid cancer cases (papillary thyroid carcinoma [PTC]: 344, follicular carcinoma [FC]: 112, medullary carcinoma [MC]: 70, poorly differentiated carcinoma [PDC]: 23, and anaplastic carcinoma [AC]: 8) and 152 follicular adenoma (FA) cases. We performed immunohistochemical staining of glutaminolysis-related proteins (glutaminase 1 [GLS1], glutamate dehydrogenase [GDH], and amino acid transporter-2 [ASCT-2]).ConclusionGlutamine metabolism-related protein expression differed among the histologic subtypes of thyroid cancer.

High Prevalence of Agent Orange Exposure Among Thyroid Cancer Patients in the National Va Healthcare System

Thyroid cancer is the most common endocrine malignancy and the most rapidly increasing cancer in the U.S. Little is known regarding the epidemiology and characteristics of patients with thyroid cancer within the national Veterans Health Administration (VHA) integrated healthcare system. The aim of this study was to further understand the characteristics of thyroid cancer patients in the VHA population, particularly in relation to Agent Orange exposure. This is a descriptive analysis of the VA (Veterans Affairs) Corporate Data Warehouse database from all U.S. VHA healthcare sites from October1, 1999, to December 31, 2013. Information was extracted for all thyroid cancer patients based on International Classification of Diseases-ninth revision diagnosis codes; histologic subtypes of thyroid cancer were not available. There were 19,592 patients (86% men, 76% white, 58% married, 42% Vietnam-era Veteran) in the VHA system with a diagnosis of thyroid cancer within this 14-year study period. The gender-stratified prevalence rates of thyroid cancer among the Veteran population during the study period were 1:1,114 (women) and 1:1,023 (men), which were lower for women but similar for men, when compared to the U.S. general population in 2011 (1:350 for women and 1:1,219 for men). There was a significantly higher proportion of self-reported Agent Orange exposure among thyroid cancer patients (10.0%), compared to the general VHA population (6.2%) (P<.0001). Thyroid cancer patients, in this sample, have a higher prevalence of self-reported Agent Orange exposure compared to the overall national VA patient population. T4 = thyroxine TCDD = 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin TSH = thyroid-stimulating hormone VA = Veterans Affairs VHA = Veterans Health Administration.

Incidental cancer in multinodular goitre post thyroidectomy.

The risk of malignancy in patients with multinodular goitre (MNG) is approximately 7.2%. The gold standard for diagnosis of thyroid cancer is fine-needle aspiration biopsy (FNAB). Unsuccessful, inconclusive or suspicious results mandate further investigations. The concern is that with a benign FNAB result there is no indication for surgery unless the patient has compression symptoms or cosmetic issues, but the risk of missed malignancy is nevertheless present. To determine the prevalence and histological features of incidental cancers in patients who had thyroidectomy for MNG. Records of patients who underwent thyroidectomy between January 2005 and December 2010 at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa, were retrospectively reviewed. Data retrieved included demographic characteristics of the patients, type of thyroidectomy, thyroid function test results, FNAB cytology and final histology results. A total of 166 thyroidectomies were performed on 162 patients, the majority (139) of whom were females. The mean age was 46 years (range 15 - 79 years). A total of 120 pre-operative FNABs were available for analysis, 78 of which were suggestive of benign nodular goitre; 70 benign FNAB results were histologically confirmed to be MNG after thyroidectomy. Incidental malignancy was found in four of 70 cases of MNG (5.7%); all were papillary carcinomas, predominantly (75.0%) the follicular variant. The risk of missing cancer in patients with MNG was 5.7%. The commonest histological subtype of thyroid cancer found in MNG was papillary carcinoma.

Diagnostic Challenge in Papillary Thyroid Carcinoma With Cervical Lymphadenopathy, Metastasis, or Tuberculous Lymphadenitis

Papillary thyroid carcinoma (PTC) is the most frequent histological subtype of thyroid cancer. Total thyroidectomy with neck dissection is recommended for treatment. Tuberculous adenitis is a common cause of lymphadenopathy in endemic areas. Therefore, tuberculous lymphadenitis should be considered in the etiology of enlarged lymph nodes when PTC patients with risk factors such as tuberculosis present with cervical lymph node enlargement. Detailed evaluation of the neck metastasis of patients with PTC is necessary to avoid postoperative complications due to neck dissection. We present a 55-year-old female patient with tuberculous lymphadenitis mimicking metastatic lymph nodes from PTC.

The role of fluorine-18-fluorodeoxyglucose positron emission tomography in aggressive histological subtypes of thyroid cancer: an overview.

Aggressive histological subtypes of thyroid cancer are rare and have a poor prognosis. The most important aggressive subtypes of thyroid cancer are Hürthle cell carcinoma (HCTC) and anaplastic and poorly differentiated carcinoma (ATC and PDTC). The American Thyroid Association recently published guidelines for the management of patients with ATC, but no specific guidelines have been done about HCTC. We performed an overview of the literature about the role of Fluorine-18-Fluorodeoxyglucose positron emission tomography or positron emission tomography/computed tomography (FDG-PET or PET/CT) in aggressive histological subtypes of thyroid cancer. Only few original studies about the role of FDG-PET or PET/CT in HCTC, PDTC, and ATC have been published in the literature. FDG-PET or PET/CT seems to be useful in staging or followup of invasive and metastatic HCTC. FDG-PET or PET/CT should be used in patients with ATC in initial staging and in the followup after surgery to evaluate metastatic disease. Some authors suggest the use of FDG-PET/CT in staging of PDTC, but more studies are needed to define the diagnostic use of FDG-PET/CT in this setting. Limited experience suggests the usefulness of FDG-PET or PET/CT in patients with more aggressive histological subtypes of DTC. However, DTC presenting as radioiodine refractory and FDG-PET positive should be considered aggressive tumours with poor prognosis.

Distribution of Thyroid Cancer in the Eastern Part of Turkey 27 Years After the Chernobyl Accident.

BackgroundThe Chernobyl accident caused widespread effects across Europe and huge areas where radiocontaminated. The effects of the Chernobyl accident on thyroid cancer have been investigated in most European countries. According to the data of the Turkish Atomic Energy Authority, the eastern part of the Black Sea region was the most radiocontaminated area in Turkey at the time of Chernobyl accident. We therefore aimed to examine the data of thyroid cancers at our center, Rize city which is located in the eastern Black Sea region.MethodsThis retrospective study included the patients with histologically proven thyroid cancer at our center between January 2008 and May 2012. Pathologic examinations of thyroidectomy materials were reviewed. We evaluated patients’ age, gender, size of the primary tumor (all sizes, < 1 cm, 1 - 2.9 cm, 3 - 3.9 cm and ≥ 4 cm), multicentricity, histologic subtypes of thyroid cancer, the presence of lymphatic, vascular, capsule and the extrathyroidal invasion.ResultsFive hundred and forty-seven of the 3,556 patients were diagnosed with thyroid cancer. The mean age of the patients was 49.31 ± 0.49 years. The histopathologic diagnosis of patients was papillary carcinoma in 533 (97.4%) and the tumor size was < 1 cm in 53.6% of the patients. The presence of multicentricity was detected in 47% of the patients.ConclusionThe portion of thyroid carcinomas in all thyroidectomies was 15.4% in our institution 27 years after the Chernobyl accident.

Sorafenib in metastatic thyroid cancer

Although thyroid cancer usually has an excellent prognosis, few therapeutic options are available in the refractory setting. Based on the recent results of phase II studies with tyrosine kinase inhibitors, we designed a retrospective analysis of patients with metastatic thyroid cancer treated with sorafenib in seven Spanish referral centers. Consecutive patients with progressive metastatic thyroid cancer (papillary, follicular, medullary, and anaplastic) not suitable for curative surgery, radioactive-iodine therapy, or radiotherapy were treated with sorafenib 400 mg twice a day. The primary end point was objective response rate (RR). Secondary end points included toxicity, median progression-free survival (mPFS), median overall survival (mOS), and correlation between tumor marker levels (thyroglobulin, calcitonin, and carcinoembryonic antigen) and efficacy. Between June 2006 and January 2010, 34 patients were included in the study. Sixteen patients presented differentiated thyroid carcinomas (DTC) of which seven (21%) were papillary, nine (26%) follicular, 15 (44%) medullary (MTC), and three (9%) were anaplastic (ATC). Eleven (32%) patients achieved partial response and 14 (41%) had stable disease beyond 6 months. Regarding histological subtype, RRs were 47% (seven of 15) for MTC, 19% (three of 16) for DTC, and 33% (one of three) for ATC. With a median follow-up of 11.5 months, mPFS were 13.5, 10.5, and 4.4 months for DTC, MTC, and ATC respectively. Tumor markers were evaluated in 22 patients, and a statistically significant association was observed between RR and decrease in tumor marker levels >50% (P=0.033). In this retrospective trial, sorafenib showed antitumor efficacy in all histological subtypes of thyroid cancer, warranting further development in this setting.

Quantitative High-Throughput Drug Screening Identifies Novel Classes of Drugs with Anticancer Activity in Thyroid Cancer Cells: Opportunities for Repurposing

Despite increased understanding of the pathogenesis and targets for thyroid cancer and other cancers, developing a new anticancer chemical agent remains an expensive and long process. An alternative approach is the exploitation of clinically used and/or bioactive compounds. Our objective was to identify agents with an anticancer effect in thyroid cancer cell lines using quantitative high-throughput screening (qHTS). We used the newly assembled National Institutes of Health Chemical Genomic Center's pharmaceutical collection, which contains 2816 clinically approved drugs and bioactive compounds to perform qHTS. Multiple agents, across a variety of therapeutic categories and with different modes of action, were found to have an antiproliferative effect. We found the following therapeutic categories were the most enriched categories with antiproliferative activity: cardiotonic and antiobesity agents. Sixteen agents had an efficacy of greater than 60% and a 50% inhibitory concentration (IC50) in the nanomolar range. We validated the results of the qHTS using two agents (bortezomib and ouabain) in additional cell lines representing different histological subtypes of thyroid cancer and with different mutations (BRAF V600E, RET/PTC1, p53, PTEN). Both agents induced apoptosis, and ouabain also caused cell cycle arrest. To our knowledge, this is the first study to use qHTS of a large drug library to identify candidate drugs for anticancer therapy. Our results indicate such a screening approach can lead to the discovery of novel agents in different therapeutic categories and drugs with nonclassic chemotherapy mode of action. Our approach could lead to drug repurposing and accelerate clinical trials of compounds with well-established pharmacokinetics and toxicity profiles.