Papillary Thyroid Cancer Cases Research Articles

Association of exposure to multiple metals with papillary thyroid cancer risk in China.

Papillary thyroid cancer (PTC) has inflicted huge threats to the health of mankind. Metal pollution could be a potential risk factor of PTC occurrence, but existing relevant epidemiological researches are limited. The current case-control study was designed to evaluate the relationships between exposure to multiple metals and the risk of PTC. A total of 262 histologically confirmed PTC cases were recruited. Age- and gender-matched controls were enrolled at the same time. Urine samples were used as biomarkers to reflect the levels of environmental exposure to 13 metals. Conditional logistic regression models were adopted to assess the potential association. Single-metal and multi-metal models were separately conducted to evaluate the impacts of single and co-exposure to 13 metals. The increased concentration of urinary Cd, Cu, Fe, and Pb quartiles was found significant correlated with PTC risk. We also found the decreased trends of urinary Se, Zn, and Mn quartiles with the ORs for PTC. These dose-response associations between Pb and PTC were observed in the single-metal model and remained significant in the multi-metal model (OR25-50th=1.39, OR50-75th=3.32, OR>75th=7.62, p for trend <0.001). Our study suggested that PTC was positively associated with urinary levels of Cd, Cu, Fe, Pb, and inversely associated with Se, Zn, and Mn. Targeted public health policies should be made to improve the environment and the recognition of potential risk factors. These findings need additional studies to confirm in other population.

SUN-603 A Case of Papillary Thyroid Cancer and EXTRAOVARIAN Pelvic Teratoma

INTRODUCTION Teratomas comprise a spectrum of tumors that have striking imaging appearances and are commonly considered when evaluating a mass in the female pelvis. A subgroup of these tumors located in an extragonadal abdominopelvic location, in contrast, are extremely rare. Thyroid tissue in teratoma may demonstrate the same spectrum of pathological features as in the normal thyroid including benign and malignant changes. Herein, we describe a case of papillary thyroid cancer of the thyroid gland with incidentally diagnosed extraovarian pelvic teratoma. CASE 52 y.o. woman with locally-invasive, multifocal, papillary thyroid carcinoma (PTC) s/p radical thyroidectomy and left central neck dissection. She was treated with thyrogen stimulated 100 mCi I-131, and her post-therapy whole body scan showed uptake in thyroid bed and in the right lower quadrant, for which SPECT imaging was acquired to assess this region better. SPECT imaging showed a heterogeneous, solid lesion seemed to be arising from the left adnexa, which correlated with the region of tracer uptake. The lesion contained fat and dystrophic calcifications with differential considerations including ovarian teratoma/struma ovarii. Her thyrogen stimulated thyroglobulin level was 66 ng/ml. She underwent laparoscopic exploration of the pelvis. Interestingly, the pelvic mass was noted to be completely separate from the left ovary. Pathology result showed a dermoid cyst with thyroid tissue. DISCUSSION A dermoid cyst is a cystic teratoma, usually benign, that contains an array of developmentally mature, solid tissues. In most cases, thyroid tissues found in teratomas are ovarian, not extra-ovarian. There are some case reports of thyroid carcinoma arising in a struma ovarii (thyroid tissue in ovarian teratoma) and a few case reports of synchronous carcinoma in the thyroid gland and the struma ovary. For cases with incidentally found teratoma with thyroid tissue, the next step is to proceed with further work up to confirm the diagnosis and to explore the possibility of a malignant lesion in the mass- either primary or metastasis. For our case, suspicion for metastasis was low as thyrogen stimulated thyroglobulin level was not very high to suggest a distant metastasis. Another important clinical question is whether the iodine uptake in the thyroid tissue in the teratoma will interfere the radio-iodine uptake of the micrometastasis and the long-term outcome. CONCLUSION Radioiodine uptake in the pelvic mass raises the question of possible thyroid tissue- teratoma vs. metastasis. Although teratoma with thyroid tissue might be an incidental finding, this might change the long-term outcome of patients with thyroid cancer treated with radioiodine.

SUN-613 Papillary Thyroid Carcinoma in a Pediatric Patient with Beta Thalassemia

Background: Beta thalassemia is characterized by the abnormal synthesis of β hemoglobin chains resulting in hemolytic anemia. Treatment involves frequent blood transfusions, which leads to the deposition of iron in many organs, including endocrine tissue such as the thyroid gland. Iron overload has been associated with various malignancies, most notably liver and hematological. To date, 7 cases of papillary thyroid cancer in patients with beta thalassemia have been reported in the adult literature, but none in pediatrics. Clinical Case: The patient is a 15 year 4 month old female with beta thalassemia requiring chronic red blood cell transfusions since the age of 5 months. She initially presented to us for evaluation of secondary amenorrhea. She underwent a splenectomy at the age of 10 years and received chelating therapy with deferasirox and deferiprone. Her ferritin levels had been stable around 1500ng/mL for the year prior to presentation; however, MRI revealed iron deposition in her pancreas, liver, kidneys, bone marrow and pituitary gland. On exam, her thyroid gland was asymmetric with the right lobe measuring 1cm larger than the left. The gland was firm in consistency with palpable lymph nodes along the right anterior cervical chain. A thyroid ultrasound was completed which revealed an enlarged right lobe containing 3 focal hypoechoic masses with calcific foci. Biopsy obtained via fine needle aspiration was consistent with papillary thyroid carcinoma. She underwent total thyroidectomy and histological examination confirmed the diagnosis. Her postoperative course was uncomplicated and she was started on replacement therapy with levothyroxine. Conclusion: To our knowledge this is the first case of papillary thyroid carcinoma in a pediatric patient with beta thalassemia. The incidence of thyroid cancer in patients with beta thalassemia is currently unknown, however there may be utility in routine surveillance of this patient population.

SUN-618 An Unusual Case of Papillary Thyroid Cancer within a Thyroglossal Duct Cyst

Background: During gestation, the thyroid gland arises from endodermal tissues, and starts at the foramen cecum, then descends into the neck through the thyroglossal duct, and disappears at 8-10 weeks of gestation. Thyroglossal duct cysts arise from incomplete obliteration of the thyroglossal duct, and may contain thyroid tissue. Although the incidence of thyroid cancer has been rising, it is still relatively uncommon compared to other cancers, with papillary thyroid carcinoma being the most common type. However, in rare cases, thyroid carcinoma can occur within the thyroglossal duct cyst. We present a rare case of a young female with papillary thyroid carcinoma within a thyroglossal duct cyst. Case Presentation: A 28-year old female noticed an enlarging midline neck mass over the course of 5 years. She was initially evaluated by otolaryngology. CT neck revealed a heterogeneous large midline neck mass, measuring 5.7 x 3.6 x 4.99cm, which was separate from the thyroid gland. Submandibular lymph nodes were also enlarged. Pathology of core tissue biopsy of the mass demonstrated papillary thyroid carcinoma. She underwent thyroglossal duct cyst resection and total thyroidectomy with neck dissection. Pathology report was positive for papillary thyroid carcinoma, arising from thyroglossal duct cyst measuring 4.2cm. Three out of 16 lymph nodes were positive for papillary thyroid carcinoma. Thyroid gland had no evidence of malignancy. Postoperatively, thyroid hormone suppression therapy was started and she was treated with radioactive iodine ablation. Discussion: Thyroglossal duct cysts are the most common abnormalities in thyroid gland development. They are usually managed with excision, specifically the Sistrunk procedure, where the cyst, along with the entire tract and part of the hyoid bone is excised. In rare cases, thyroid cancer can arise within the thyroglossal duct cyst. When this occurs, management can sometimes be controversial, as there are no specific guidelines, and severity of disease varies. It is important to recognize that evaluation of these type of patients should include the thyroid and regional lymph nodes, in order to ensure that the thyroglossal duct cyst carcinoma is primary, and not a metastasis from a primary thyroid carcinoma. In cases where the malignancy is confined to the cyst, the Sistrunk procedure alone can be done. If malignancy is found in the thyroid and regional lymph nodes, the Sistrunk procedure in addition to total thyroidectomy is completed, and then post-operative management is the same as for differentiated thyroid cancer including radioactive iodine ablation. References Pellegriti G, Lumera G, Malandrino P, et al., Thyroid Cancer in Thyroglossal Duct Cysts Requires a Specific Approach due to Its Unpredictable Extension, JCEM, Volume 98, Issue 2, 1 February 2013, Pages 458-465.

SUN-605 A Case of Metastatic Papillary Thyroid Cancer Presenting as a Skin Lesion

Introduction: The most common sites of thyroid cancer metastases include the lymph nodes, lungs, bone, and occasionally the brain. Skin metastases are rare and the most common location that has been reported is the scalp (1-3). When they do occur, skin metastases usually occur in the setting of locally invasive thyroid cancer or widely disseminated neoplastic disease (4). Case: A 69 year old male with a history of coronary artery disease and thyroid surgery (done for an unknown, benign condition, as per patient) presented to our dermatology clinic with an exophytic, violaceous skin lesion (1 x 0.5 cm) below his left clavicle. He noticed the lesion 3 years ago and noted that it had enlarged over the 3 months prior to presentation. An excisional biopsy of the lesion was consistent with papillary thyroid carcinoma positive for TTF, CK7, and thyroglobulin. The patient was subsequently evaluated in our endocrine clinic at which time a thyroid ultrasound revealed a 4 mm right thyroid nodule and confirmed prior history of a left hemithyroidectomy. He underwent completion thyroidectomy and radioactive iodine ablation therapy with 80 mci of I-131. Surgical pathology showed no carcinoma of the right thyroid lobe. A post-RAI whole body scan demonstrated no evidence of metastatic disease and a neck ultrasound did not reveal any thyroid remnant tissue or abnormal lymph nodes. An initial pre-operative Tg level was 31.5 ng/ml that decreased to 3.2 ng/ml five months post-RAI. The Tg Ab remains undetectable. Currently, he is without structural evidence of disease. We have recommended a TSH goal of less than 0.5 uIU/mL and plan to monitor the Tg levels with a 1 year follow-up whole body scan. Conclusion: We present an unusual case of metastatic papillary thyroid cancer manifesting as a dermatologic lesion in the absence of local concurrent or advanced metastatic disease. It is important to consider thyroid carcinoma in the differential diagnosis of atypical skin lesions.

Expression of serum microRNA-34 in papillary thyroid cancer and clinical significance

Objective To investigate the relationship between serum microRNA (miRNA, miR)-34 level and clinical characteristics in patients with thyroid papillary carcinoma, and to analyze the value of serum miR-34 in the diagnosis and prognosis evaluation of thyroid papillary carcinoma. Methods The clinical data of 84 cases of papillary thyroid cancer, 45 cases of nodular goiter and 30 cases of normal thyroid in our department were analyzed. The serum levels of miR-34 in all subjects were detected by fluorescence quantitative PCR. The correlation between serum miR-34 level and clinical features of thyroid cancer patients was analyzed, and the diagnostic efficacy of serum miR-34 for thyroid cancer was also analyzed by receiver operating characteristic (ROC) curve method. The correlation between the expression of serum miR-34 and overall survival (OS) and progression-free survival (PFS) in patients with thyroid papillary cancer was analyzed, and the predictive value of serum miR-34 in prognosis of patients with thyroid papillary cancer was evaluated by Kaplan-Meier analysis. Results The relative expression level of serum miR-34 in patients with papillary thyroid cancer was significantly lower than that in patients with nodular goiter and normal persons (P 0.05). Spearman correlation coefficient test showed that the relative expression level of serum miR-34 was closely related to karnofsky performance status (KPS) score, World Health Organization (WHO) pathological grade and extraglandular infiltration (P<0.05). The area under the ROC curve (AUC) was 0.912 [95% confidence interval (CI): 0.831-0.973]; when the AUC <0.48 was used as the criterion for the diagnosis of papillary thyroid cancer, the sensitivity, specificity and Yoden index were 96.67%, 79.54% and 76.21%, respectively. The median PFS and median OS were 39.5 (95% CI: 37.916-41.655) months and 50.3 (95% CI: 43.143-56.651) months in the high-level group, 28.3 (95% CI: 24.146-32.618) months and 32.6 (95% CI: 28.781-37.765) months in the low-level group, respectively. PFS and OS in the low-level group were significantly longer than those in the high-level group (P<0.01). Conclusion Serum miR-34 level has good accuracy in the diagnosis of thyroid papillary carcinoma, and has a significant correlation with the prognosis of thyroid papillary carcinoma. Key words: Thyroid papillary carcinoma; MicroRNA-34; Diagnosis; Prognosis

Leukocyte Telomere Length and Risk of Papillary Thyroid Carcinoma.

Telomere length may contribute to predisposition to papillary thyroid cancer (PTC). To test this hypothesis, we examined the association between leukocyte telomere length and PTC risk. Case-control study in a Chinese Han population. A total of 1200 PTC cases and 1201 age- and sex-matched healthy controls were included in the study. ORs and 95% CIs were calculated by logistic regression. Short relative telomere length (RTL) was significantly associated with elevated risk of PTC (OR = 1.61, 95% CI = 1.35 to 1.92; P = 1.30 × 10-7). Interestingly, when individuals were categorized into four groups on the basis of quartile distribution of relative telomere length (RTL) in controls, we observed a reverse U-shaped association between telomere length and PTC risk. Compared with those in the first (the longest) quartile as the reference group, ORs (95% CIs) were 5.61 (4.04 to 7.78) (P = 6.10 × 10-25), 9.33 (6.78 to 12.83) (P = 6.99 × 10-43), and 1.23 (0.83 to 1.81) (P = 0.300) for individuals in the second, third, and fourth (the shortest) quartiles, respectively. This reverse U-shaped relationship was more apparent in younger individuals. Our findings suggest that RTL is significantly associated with susceptibility to PTC. There is an obvious reverse U-shaped association between telomere length and PTC risk. Telomere length may be a potential pronouncing biomarker to identify individuals with a high risk of developing PTC.

Amalgamation of Central Lymph Node Dissection in Papillary Thyroid Carcinoma: Study from South Indian Population.

The aim of this study was to evaluate the correlation between central lymph node (CLN) metastasis and Clinicopathological characteristics of papillary thyroid cancer (PTC). In addition, we investigated the incidence and risk factors for ipsilateral and contra lateral CLN metastasis in unilateral PTC and the appropriate surgical extent for CLN dissection. A prospective study of 143 patients with unilateral PTC who underwent total thyroidectomy and prophylactic bilateral CLN dissection was conducted. Of 143 patients, 58 had CLN metastases. The rate of CLN metastasis was considerably higher in cases of maximal tumor size > 1cm (P < 0.0001; OR 5.81). Ipsilateral CLN metastasis was detected in 41% of cases of unilateral PTC, and contra lateral CLN metastases was found in 14% of cases where as bilateral CLN metastases in 8% of cases. The rate of contra lateral CLN metastasis was considerably higher in cases of PTC with a large tumor size (≥ 1cm) (P = 0.0003; OR = 0.144) and with ipsilateral CLN metastasis (P = 0.0002; OR 0.12). Tumor size > 1cm was independent risk factors for CLN metastasis. Maximal tumor size > 1cm and presence of ipsilateral CLN macro metastasis were independent risk factors for contra lateral CLN metastasis. Therefore, both ipsilateral and contra lateral CLN dissections should be considered for unilateral PTC with a maximal tumor size > 1cm or presence of ipsilateral CLN macro metastasis.

Fasting serum glucose, thyroid-stimulating hormone, and thyroid hormones and risk of papillary thyroid cancer: A case-control study.

This study was to investigate the association of fasting serum glucose (FSG), thyroid-stimulating hormone (TSH), and thyroid hormones with papillary thyroid cancer (PTC). A total of 649 participants were included in this case-control study. The associations of FSG, TSH, free triiodothyronine (FT3) and free thyroxine (FT4) with PTC were estimated using an unconditional logistic regression. Compared with the lowest quintile of TSH levels, odds ratios (ORs) and 95% confidence intervals (CIs) for association between PTC risk and highest quintile of TSH levels were 1.67 (95% CI, 0.99-2.83). However, this risk correlation was more significant in PTC cases with ≤1.0 cm tumor size (adjusted OR, 1.95; 95% CI, 1.08-3.54; adjusted P-trend, 0.05). The PTC risk was also inversely associated with the serum FT3 level in all participants (adjusted P-trend, 0.001), but positively associated with the serum FT4 (adjusted P-trend, 0.001) and FSG (adjusted P-trend, 0.01) levels. Among the participants without diabetes, the individuals with high FSG levels and abnormal TSH concentration had an increased PTC risk (adjusted OR, 3.38; 95% CI, 1.78-6.42). The current study provides evidence for the association of FSG, TSH, and thyroid hormones (FT3 and FT4) with PTC risk. However, larger relative studies are needed.

Prediction of Ipsilateral and Contralateral Cervical Lymph Node Metastasis in Unilateral Papillary Thyroid Carcinoma

Background: Surgical therapy is the cornerstone of treatment in patients with papillary thyroid cancer (PTC). Surgical therapy in PTC includes hemithyroidectomy or total thyroidectomy (TT) and, in cases of lymph node metastases, cervical lymph node dissection (CLND). The inclusion of prophylactic central compartment neck dissection (pCCND) as a new approach in the management of patients with PTC with clinically negative cervical lymph nodes raised controversies among the endocrine surgeons and predictive factors for central lymph node (CLN) metastasis in unilateral PTC cases not well defined. Objectives: To investigate the risk factors associated with CLNM in clinical lateral cervical lymph node?negative (cN0) and analyze the rate of ipsilateral and contralateral CLN metastasis in unilateral PTC casesin Al Azhar University Hospitals in the period from May 2016 tillJune 2018. Patients and Methods: A prospective case-control descriptive study was performed to investigate the research questions during the period from the 1st of May 2016 till the end of June 2018 in Al-Azhar University Hospitals. A total of 40 selected patients suffering from papillary thyroid with clinically negative cervical lymph nodes who have received total thyroidectomy with bilateral CLND. The clinicopathological features of PTC patients with respect to sex, age, observation, tumor diameter, multifocality, extrathyroidal invasion, lymphovascular invasion and capsular invasion. The risk factors of CLNM were analyzed by Chi-squared test and multivariate logistic regression model. Results: Ipsilateral CLN metastasis were present in 47.5% (19/40).Results analysis showed that males patients with tumor size (>1 cm) (P=0.027; OR, 2.153), age <45 years old (P=0.017; OR, 2.009) and capsular invasion (P= 0.018; OR= 0.730) were the predictors of ipsilateral CLN metastasis.Contralateral CLN metastasis were present in 17.5% (7/40) and prelaryngeal lymph node (LN) metastasis (P=0.008; OR, 13.333) and ipsilateral CLN metastasis (P=0.051; OR, 9.231), pretracheal lymph nodes (P=0.051; OR, 9.231), lymphovascular invasion (P=0.043; OR, 5.113) and ETE (P=0.05; OR, 4.901) independently predicted contralateral CLN metastasis. Conclusion: For the high-risk PTC patients with CLNM, prophylactic CLND may be beneficial. Nevertheless, the present data was a single center prospective analysis, and the long-term prognostic factors including recurrence rate and mortality rate were lacking. Therefore, the results of this research may only serve as a tool in predicting CLNM.

The role of matrix metalloproteinase-9 as a prognostic biomarker in papillary thyroid cancer

BackgroundThe aim of the present study was to investigate the association between matrix metalloproteinase-9 (MMP-9) expression with BRAF V600E mutation and clinicopathological features, in Iranian papillary thyroid cancer (PTC) patients.MethodsIn total, 90 participants including 60 PTC patients (15 males and 45 females) and 30 individuals with benign multinodular goiter (MNG) (5 males and 25 females) which were confirmed by surgical pathology, were investigated. MMP-9 was evaluated at both mRNA and protein levels, using SYBR-Green Real-Time PCR and enzyme-linked immune sorbent assay (ELISA), respectively. BRAF V600E mutation was detected by sequencing.ResultsMean age of PTC and MNG patients was 37.6 ± 12.6 and 48.1 ± 13.3 years, respectively (P = 0.001). BRAF V600E mutation was found in 24 of the 60 (40%) PTC cases, with mean tumor size of 1.59 ± 1.20 cm. MMP-9 mRNA levels were elevated in tumoral compared to the adjacent non-tumoral tissues (P = 0.039); moreover, this rise was also observed in PTC patients compared to MNG patients (P = 0.001). The mRNA levels of MMP-9 increased in patients aged≥45 years (P = 0.015), those with lymphovascular invasion (P = 0.003), and higher tumor stages (III and IV) (P = 0.011). The protein level of MMP-9 increased in tumoral compared to adjacent non-tumoral tissues (P < 0.001); this increase was also found in PTC patients compared to MNG participants (P = 0.004). MMP-9 protein level was higher in patients aged≥45 years (P = 0.001), those with lymphovascular invasion (P = 0.036) and higher TNM stages (III and IV) (P = 0.001). Area under the ROC curve (AUC) was 0.70 (95%CI: 0.57–0.83, P = 0.003), with 91.4% sensitivity and 51.9% specificity at the cutoff value of 0.50.ConclusionThe mRNA and protein levels of MMP-9 had no association with BRAF V600E mutation in Iranian PTC patients. These levels were associated with age, TNM stages, and lymphovascular invasion, being defined as malignant factors. Thus, elevated levels of MMP-9 in PTC patients compared to MNG participants illustrated that it can be used as a potential biomarker to differentiate PTC patients from those with MNG.

Concomitant BRAF Mutation in Hairy Cell Leukemia and Papillary Thyroid Cancer

Hairy cell leukemia (HCL) is an uncommon but distinct form of mature B-cell neoplasm that originates from activated late B-cells. It represents only 2% of all adult lymphoid leukemia; patients are predominantly middle-aged to elderly males with a median age of 50 years and is characterized by pancytopenia, monocytopenia and usually associated with massive splenomegaly.HCL associated with BRAF mutation 100% of cases, it's associated with hematological and oncological malignancies such as melanoma and papillary thyroid cancer with positive BRAF in 40 % of cases.Although the association of both cancers (HCL & papillary thyroid cancer) with BRAF mutation is well established in the literature, up to our knowledge, this specific combination has not been previously reported in one patient.Here we report a case of 48-year old Lebanese male, who presented to with bilateral hip pain and found to have lytic bone lesions on both x-ray and MRI. HIS CBC were normal and abdominal US didn't show any splenomegaly. Work-up for myeloma were negative.Bone marrow examination and flow cytometry results confirmed the diagnosis of hairy cell leukemia. The patient treated with cladrabine.Patient responded but have continues fever, PUO included Piston tomography showed abnormal uptake in thyroid. Ultrasound and final needle aspiration diagnose him as case of papillary thyroid cancer. He was treated with total thyroidectomy and followed up with RAI 30 micori.We sent BRAF from both bone marrow biopsy and thyroid tissue which turn out positive in both. The mutation results in substitution of adenine for thymine at position 1799 in exon 15 of the BRAF that replaces Valine (V) by glutamate (E) at amino acid 600(BRAF V600E).Although the BRAF V600E mutation is frequently present in different neoplasms, such as melanoma, papillary thyroid cancer, non-small cell lung cancer, colorectal cancer and Langerhans cell histiocytosis (X), within the lymphoid neoplasms, the BRAFV600E mutation is found to be highly specific for HCL and testing for this mutation is particularly useful in differentiating classic HCL from other B- cell neoplasm with overlapping features, such as HCL variantMutation in BRAF (particularly V600E) in HCL remarkably increase the BRAF kinase activity renders the protein constitutively active, phosphorylating then ERK as a monomers independent from upstream regulatory signals or in a RAS-independent manner leading to constitutive activation of RAF-MEK-ERK signaling pathway and enhanced survival of leukemic hairy cells, similar to what occurs in other BRAF-mutated tumors as papillary thyroid carcinomasOther BRAF mutations outside exon 15 were rarely reported as exon 11 F468C and D449E mutations.We emphasize on the link of BRAF mutation in HCL and papillary thyroid cancer. The biology has been established but never in real clinical case. We recommend having high clinical suspicion and sending BRAF mutation in those types of cancers and link it with other possible abnormal findings, as might detect more cases of similar association. DisclosuresNo relevant conflicts of interest to declare.

MicroRNA-146b-5p as an oncomiR promotes papillary thyroid carcinoma development by targeting CCDC6

The microRNA-146b–5p (miR-146b-5p) is known to be involved in the development of papillary thyroid cancer (PTC); however, the underlying mechanism is unclear. Here we have investigated the biological functions and underlying molecular mechanisms of miR-146b-5p in PTC. The expression of miR-146b–5p was assessed in 92 pairs of PTC and adjacent normal tissues and showed correlation with the clinicopathological status such as the tumour size. Effects of miR-146b-5p and its direct target, coiled-coil domain containing 6 (CCDC6), on cell proliferation, migration, invasion, and cell cycle were evaluated through gain- and loss-of-function studies in vitro and in vivo. The expression of CCDC6 was further examined in 187 PTC cases and was found to be correlated with the clinicopathological status. Overexpression of miR-146b-5p was observed in PTC tissues that correlated with advanced PTC. miR-146b-5p promoted cell proliferation, migration, invasion, and cell cycle progression in vitro, whereas CCDC6 reversed this effect. miR-146b-5p promoted PTC growth in a subcutaneous mouse model in vivo, whereas overexpression of CCDC6 exerted the opposite effect. In conclusion, miR-146b-5p expression correlated with advanced PTC and promoted PTC development by targeting CCDC6 in vitro and in vivo; it could, therefore, serve as a promising target for PTC treatment.

Low Prevalence of TERT Promoter, BRAF and RAS Mutations in Papillary Thyroid Cancer in the Greek Population.

Thyroid cancer is a common endocrine malignancy and displays a variety of histological patterns ranging from adenoma to malignant tumors. Molecular diagnostics have given significant insights into the genetic basis of thyroid tumorigenesis, known to be linked with signaling pathways affected by oxidative stress. We report for the first time a genotype study of TERT promoter combined with BRAF and RAS mutations in Papillary Thyroid Cancer (PTC) cases in the Greek population. Polymerase Chain Reaction and sequencing were used to identify TERT promoter (C228T, C250T, CC243-243TT) mutations, the BRAF (T1799A) mutation and mutations in codons 12, 13, 61 of the HRAS, KRAS and NRAS genes. The most common C228T TERT promoter mutation was identified in 2 PTC cases co-existing with the BRAF mutation. The BRAF T1799A mutation was detected in 10 PTC cases, while two different NRAS mutations in codon 61 (C181A and A182G) were found in 2 PTC cases. These mutations occur in a mutually exclusive manner. Our results indicate that despite the low frequencies, the study of the specific mutations should be encouraged because they are indicative of aggressive forms of thyroid cancer of the papillary histotype in this patient cohort, thus providing insights towards their therapeutic management.

ZNF703 is Overexpressed in Papillary Thyroid Carcinoma Tissues and Mediates K1 Cell Proliferation.

Zinc finger protein 703 (ZNF703), a member of the NET family of transcription factors, has recently emerged as an important player in the development of several types of cancers, though its role in papillary thyroid cancer (PTC) has not been characterized. We investigated the expression of ZNF703, its association with the most common genetic mutation in PTC, BRAF V600E, and its potential use as a therapeutic target. Real-time PCR, immunohistochemical staining, and western blot analysis of ZNF703 expression were performed for 36 cases of PTC and corresponding normal thyroid tissues. ZNF703 mRNA and protein expression was found to be significantly higher in PTC compared to normal thyroid tissues (P < 0.05). Furthermore, expression was associated with the tumor size, lymph node metastasis, and advanced disease stage. Immunohistochemical results showed that there was no correlation between ZNF703 protein levels and BRAF V600E mutation. The human PTC cell line K1, which has a BRAF V600E mutation, was selected for further investigation. Using small interfering RNA (siRNA), ZNF703 was shown to contribute to the proliferation, apoptosis, and invasion of K1 cells. ZNF703-siRNA downregulated E2F1 and MMP9 protein expression and enhanced the expression of p27 protein (P < 0.05), but had no effects on BRAF V600E protein levels. These results suggest that ZNF703 may be of potential use as a new marker for PTC prognosis and therapy that functions independent of BRAF V600E expression.

A case of papillary thyroid cancer with soft tissue metastasis

Papillary thyroid cancer is the most common thyroid malignancy, and although metastatic spread is typically confined to regional lymph nodes, there are rare documented cases of distant spread of disease. Distant metastases of differentiated thyroid cancer are unusual; lung and bones are the most frequently affected sites. Soft tissue metastases are extremely rare. Here we present an unusual case of soft tissue metastasis of papillary thyroid cancer to skeletal muscle. Soft tissue metastasis is rarely seen in differentiated thyroid carcinoma. Differentiated thyroid carcinoma, although generally clinically indolent, may occasionally develop distant metastases and even manifest itself as a metastatic tumour.

A case-control study of urinary levels of iodine, perchlorate and thiocyanate and risk of papillary thyroid cancer

BackgroundThe incidence of thyroid cancer has recently increased worldwide. With the exception of radiation exposure, the effects of potential risk factors on thyroid cancer incidence remain controversial. ObjectivesThe association between exposure to iodine, perchlorate, and thiocyanate and papillary thyroid cancer (PTC) incidence was evaluated and risk factors were predicted. MethodsA pair-matching case-control study was performed including 116 age- and sex-matched PTC cases and 116 non-PTC controls. Iodine, perchlorate, and thiocyanate concentrations in urine specimens were determined by inductively coupled plasma mass spectrometry and ultra-performance liquid chromatography–tandem mass spectrometry. The association between iodine, perchlorate, and thiocyanate urinary concentrations and PTC was evaluated using univariable conditional regression logistic analysis followed by multivariable conditional logistic regression analyses with backward stepwise selection to predict risk factors for PTC. ResultsAfter adjusting for confounders and creatinine standardization, urinary concentrations of iodine [odds ratio (OR) = 11.01, 95% confidence interval (CI): 1.97–30.52] and perchlorate (OR = 2.27, 95% CI: 1.03–5.03) were associated with the risk of PTC, whereas urinary thiocyanate concentration showed a negative association (OR = 0.24, 95% CI: 0.09–0.65). ConclusionsIncreased exposure to iodine and perchlorate may affect PTC development, whereas high thiocyanate exposure may have a beneficial effect.

Langerhans' Cell Histiocytosis Masquerading as Metastatic Papillary Thyroid Cancer on F-18 FDG PET/CT: Diagnostic Dilemma Solved by PET/CT-Guided Biopsy.

We present a case of papillary thyroid cancer (post-thyroidectomy status) on regular treatment with suppressive Levothyroxine therapy. On follow-up at 6months after radioactive iodine ablation for remnant thyroid tissue, her thyroglobulin, and anti-thyroglobulin levels were 0.06ng/ml and 670IU/ml, respectively. Low-dose whole-body I-131 scan was negative. To look for the cause of isolated increased anti-thyroglobulin level, a whole-body 18F-FDG PET/CT was done which revealed multiple FDG-avid lytic skeletal lesions suggestive of metastases. For confirmation of diagnosis, 18F-FDG PET/CT-guided metabolic biopsy was done, which revealed Langerhans' cell histiocytosis on histopathological examination.

Diagnostic value and lymph node metastasis prediction of a custom‑made panel (thyroline) in thyroid cancer.

Differentiation of benign and malignant thyroid nodules is crucial for clinical management. Here, we explored the efficacy of next-generation sequencing (NGS) in predicting the classification of benign and malignant thyroid nodules and lymph node metastasis status, and simultaneously compared the results with ultrasound (US). Thyroline was designed to detect 15 target gene mutations and 2 fusions in 98 formalin-fixed, paraffin-embedded (FFPE) tissues, including those from 82 thyroid cancer (TC) patients and 16 patients with benign nodules. BRAF mutations were found in 57.69% of the papillary thyroid cancer (PTC) cases, while RET mutations were detected among all the medullary thyroid cancer (MTC) cases. Multiple mutations were positive but none showed dominance in anaplastic thyroid cancer (ATC) and follicular thyroid cancer (FTC). The sensitivity and specificity of NGS prediction in differentiation of benign and malignant thyroid nodules were 79.27 and 93.75%, respectively, and the positive predictive value (PPV) and negative predictive value (NPV) were 98.48 and 46.88%, respectively. The sensitivity and specificity of US were 76.83 and 6.25%, respectively, and the PPV and NPV were 80.77 and 5.00%, respectively. The area under curve (AUC) of NGS and US were 0.865 and 0.415, respectively. A total of 27 patients had ≥1 metastases to lymph nodes, 19 of which carried mutations, including BRAF, RET, NRAS, PIK3CA, TP53, CTNNB1 and PTEN. However, there was no correlation between the variant allele frequency of specific gene mutations and the number of metastatic lymph nodes. In conclusion, the prediction value of NGS was higher than the US-based Thyroid Imaging Reporting and Data System (TI-RADS). NGS is valuable for the accurate differentiation of benign and malignant thyroid nodules, and pathological subtypes in FFPE samples. The findings of the present study may pave the way for the application of NGS in analyzing fine-needle aspiration (FNA) biopsy samples.

RADIOIODINE THERAPY OF PAPILLARY THYROID CANCER, COMPLICATED BY A RADIAL MYELITIS. CLINICAL CASE

Over the past decades, there has been an increase in the incidence of thyroid cancer in most countries, and the most common form of thyroid cancer is papillary thyroid cancer. Application of radioiodine therapy for papillary thyroid cancer depends on the degree of postoperative risk of the disease recurrence. Radioactive iodine is recommended after radical thyroidectomy in case of intermediate or high risk of recurrence, that reduces the probability of disease progression and increases survival. The aim of radioiodine therapy is the ablation of thyroid tissue left after thyroidectomy and metastases, accumulating radioactive iodine. The recommended activity of the drug for radioablation is 30 mCi in the intermediate risk group and 30 to 150 mCi with a high risk of recurrence, but total doses and multiplicity of courses varies widely. The acute side effects of radioiodine therapy, the probability of which increases with a radioiodine dose of more than 100 mCi, include allergic reactions to iodine, post-radiation parotitis and sialadenitis, gastritis, cystitis, pulmonitis (with lung metastases), myelodepression, transient amenorrhea and hypo-spermia. The listed violations are transient and last from several days to several months. In the presented article the clinical case of papillary thyroid cancer with metastases in the lymph nodes of the neck was examined. The patient underwent thyroidectomy, central lymphadenectomy and radiotherapy. One year after the third course of radioiodine therapy the patient experienced the development of post-radiation gastritis, myelodepression and myelitis, manifested by a marked pain syndrome in the cervical spine and sensory and movement disorder of hands and legs. Pulse therapy with glucocorticoids in combination with drugs that improve microcirculation, neuromuscular conduction and reduce the severity of neuropathic disorders allowed to stop post-radiation complications.