Papillary Thyroid Cancer Cases Research Articles

Zebra Case of Papillary Thyroid Cancer in MEN-2 Syndrome

Introduction: The occurrence of papillary thyroid cancer in patients with familial medullary thyroid cancer (FMTC) is extremely rare and underreported. Case Presentation: A 51-year-old caucasian female with no past medical history who presented to primary care physician for her annual visit. She denied any complaints. Vital signs were unremarkable. Physical examination was remarkable for large left thyroid nodule without cervical lymph nodes enlargements. Family history was significant for metastatic MTC of her two sisters (at the age of 55, 60) and her niece at age of 21. She previously declined genetic testing. Labs were unremarkable including serum calcium of 8.3 mg/dL. Thyroid function panel revealed a TSH of 2.1 μU/mL, Free T4 of 1.4 ng/dL, Thyroid peroxidase (TPO) antibody of <6 IU/mL. Neck ultrasonography revealed a mid-left thyroid hypoechoic nodule of 1.8 ×1.5 cm, without cervical lymph nodes enlargements. Fine needle biopsy revealed a papillary thyroid cancer, follicular variant. The diagnosis confirmed by two university pathologists, without any evidence of MTC. Genetic testing revealed a germline mutation in RET oncogene exons 13. Further labs revealed normal metanephrines of 12 pg/mL and normal normetanephrine of 31 pg/mL, normal serum calcitonin was less than 2 pg/mL (0-5), normal serum CEA was 2.5 ng/mL (0-5), elevated anti- thyroglobulin (anti-TG) antibodies of 1234 iu/mL (0-0.9), and elevated thyroglobulin of 50 ng/mL (1.5-38.5). The patient was referred to ENT for total thyroidectomy. Further, she was treated with radioactive iodine ablation by 155 mCi of iodine 131. Follow up whole body thyroid scan revealed no evidence of residual or recurrence. The patient was treated with 112 mcg levothyroxine with a target of TSH less than 0.1. On six months follow up, repeated neck ultrasonography revealed no remnant of thyroid tissue. Follow up Thyroglobulin (TG) was less than 0.1 ng/mL, TSH 0.05 μU/mL, FT4 of 1.98 ng/dL, and calcitonin was still less than 2 pg/ml. Genetic testing of her daughters (24, 31) revealed germline mutations in RET-oncogene exons 13 and was referred for prophylactic thyroidectomy. Discussion: FMTC is an inherited syndrome characterized by the presence of only MTC without hyperparathyroidism or pheochromocytoma and is considered a variant of MEN2A. Most cases of MEN2A have been attributed to mutations in the intracellular portion of RET, and somatic mutations in RET have been identified in 50% of cases of sporadic FMTC. We recommend in patients with germline RET mutations and a family history of MTC, the diagnosis of papillary thyroid cancer should be confirmed by two pathologists, and patients should be tested for serum calcitonin, serum calcium, and metanephrines/normetanephrine levels. Genetic testing of first-degree relatives of FMTC at an early age is essential in guiding major management decisions such as the timing of prophylactic thyroidectomy.

Management of Papillary Thyroid Cancer Metastatic to the Central Nervous System: A Narrative Review of the Literature

Abstract Introduction: Brain metastases (BM) associated with papillary thyroid cancer (PTC) occur with an approximate frequency of 0.15% to 1.3% of PTC cases. There is little evidence regarding the treatment of this association (PTC and BM). A narrative review of the literature is presented. We assessed multiple treatment options and its effectiveness in this vulnerable population. Methods: The data were collected using the PubMed search engine and Google Scholar. There were selected all studies that included: &amp;lt;&amp;lt; thyroid carcinoma &amp;gt;&amp;gt; &amp;lt;&amp;lt; brain metastases &amp;gt;&amp;gt; &amp;lt;&amp;lt; radiotherapy &amp;gt;&amp;gt; &amp;lt;&amp;lt; surgery &amp;gt;&amp;gt; &amp;lt;&amp;lt; iodine-131 &amp;gt;&amp;gt; &amp;lt;&amp;lt; papillary carcinoma &amp;gt;&amp;gt; &amp;lt;&amp;lt; differentiated carcinoma &amp;gt;&amp;gt;. Once the relevant works had been listed and compared, the main findings of each one were related and analyzed. Results: We found 15 studies between the years 1990 and 2019 that describe 187 patients with thyroid cancer and brain metastases; of which 138 presented PTC, and 62% (58/93) were women. The average age was 59 years. Patients who received multimodal treatment (association of 2 or more therapies; one of them, brain metastasis resection) had a longer survival, with an average of 54 months, compared to monotherapy. Discussion: Patients with PTC who also present BM require a multimodal therapy approach: when it is associated with brain metastasis resection, better results are evident; in contrast, when monotherapy is used, a limited performance is observed, with poor results. Conclusion: Patients with PTC who also present BM have better outcomes and higher survival rate with a multimodal therapy approach, including brain metastasis resection.

Influence Factors for Lymph Node Metastasis in Papillary Thyroid Carcinoma: Hashimoto's Thyroiditis Has a Weak Effect on Central or Lateral Lymph Node Metastasis.

PurposeTo analyze the effect of Hashimoto’s thyroiditis (HT) concurrent with papillary thyroid cancer (PTC) on cervical lymph node metastasis (LNM).MethodsTwo thousand nine hundred twenty-six patients who underwent thyroidectomy and lymph node dissection between January 2015 and December 2018 were enrolled in this study. Patient demographics and clinicopathologic features were analyzed.ResultsOf the total enrolled patients, 598 (20.4%) had concurrent HT. There were 1482 PTC cases with N0, 1033 cases with N1a, and 411 cases with N1b. Patients with HT had lower frequency of extrathyroidal extension (ETE), lymphatic vascular (LV) invasion, high pathological T stage (III+IV) and central LNM rate. Stratifying central LNM by non-ETE or without intrathyroidal spreading, it was further found that central LNM rate in patients with HT was lower than that of patients without HT. However, there was no significant difference in the central LNM rate in patients with PTC stratified by ETE or intrathyroidal spreading. HT with PTC played a weak protective role in N1a, reducing the risk of N1a by 16.4%. Conversely, HT is a risk factor for N1b, increasing the risk by 1.336 times compared to patients without HT. TgAb is an independent risk factor for N1b, which appears related to the promotion of N1b by HT.ConclusionIn PTC, HT has a protective effect on central LNM and a risk effect on lateral LNM, although the difference was not significant. This weak protective effect on N1a is more obvious in PTC with less aggressive clinicopathologic characteristics. The risk effect of HT on N1b may be associated with TgAb.

Неповоротний гортанний нерв, обумовлений аномальним ходом правої підключичної артерії (arteria lusoria), у пацієнтки з рецидивуючим папілярним тиреоїдним раком: перший в Україні документований клінічний випадок

Актуальність. Аберантна права підключична артерія (аrteria lusoria, AL) є рідкісною судинною аномалією дуги аорти в людини, що спостерігається з частотою 0,1–2,5 % та має важливе клінічне значення через поєднану аномалію ходу нижнього гортанного нерва (неповоротний гортанний нерв, НГН), імовірність пошкодження якого в тиреоїдній хірургії різко зростає. Уперше в Україні детально описаний клінічний випадок передопераційної діагностики AL, інтраопераційної ідентифікації НГН та проаналізований сучасний стан розробки питання. Мета: на прикладі історії пролікованої пацієнтки з папілярним тиреоїдним раком та аналізу світової літератури показати важливість дослідження анатомії дуги аорти з імовірним утворенням AL, що, у свою чергу, викликає ембріональне аномальне формування НГН із високим ризиком його пошкодження при операціях на щитоподібній залозі. Матеріали та методи. Наведений випадок рецидивуючого папілярного раку щитоподібної залози в молодої жінки, яка була двічі оперована (тотальна тиреоїдектомія з лівобічною радикальною дисекцією шиї, правобічна латеральна та центральна редисекція шиї), перед другою операцією при комп’ютерній томографії виявлена аномалія правої підключичної артерії. Запідозрена наявність правобічного НГН, що було підтверджено під час операції за допомогою електрофізіологічного нейромоніторингу. Аналіз відповідної світової літератури засвідчив актуальність питання, відсутність вітчизняних аналогів. Результати. На підставі отриманих при комп’ютерній томографії (із 3D-реконструкцією великих судинних структур шиї) зображень було встановлене аберантне відгалуження правої підключичної артерії від дистальної частини дуги аорти— AL. Було припущене існування нервової аномалії— НГН праворуч. Шляхом застосування електронейромоніторингу та дисекції правого блукаючого нерва під час операції судинно-нервова аномалія була підтверджена, що дозволило уникнути хірургічних ускладнень у вигляді порушення функції гортані, успішно провести хірургічне лікування шийних метастазів тиреоїдного раку. Висновки. Плануючи операції на щитоподібній залозі, слід мати на увазі можливість існування судинної аномалії дуги аорти з відповідним ризиком пошкодження нижнього гортанного нерва, що має неповоротний хід. Рентгенологічне або сонографічне обстеження може виявити аберантне розташування правої підключичної артерії, а застосування електронейромоніторингу— знайти НГН для уникнення його пошкодження при операціях на шиї.

Papillary Thyroid Cancer Association with the Use of Infertility Drugs Case Report and Literature Review

Recently, the incidence of papillary thyroid cancer increases rapidly than any other type of cancer worldwide, without the age and gender discrimination. Environmental or therapeutic exposure of radiation is main culprit of papillary thyroid cancer, but there is limited research available to support that to the usage of infertility drug associated with papillary thyroid cancer. We presented the rare and interesting case of papillary thyroid cancer while patient was on clomiphene citrate for the management of infertility. We found few studies which showed pathophysiology connection between in CC and papillary cell carcinoma.

Complete remission after primary single dose of radioactive iodine in metastatic papillary thyroid carcinoma: a case report

Background: Papillary thyroid cancer (PTC) accounts for 90% of the thyroid malignancies with predominance in females. Distant metastasis is usually seen in lungs and bones. The treatment of metastatic papillary cancer thyroid is total/near total thyroidectomy followed by radioactive iodine (RAI) ablation. Lung metastasis shows good response to RAI therapy. Case Presentation: We describe a case of 22-year-old female, referred to nuclear medicine department after surgery for RAI ablation. Patient was diagnosed case of PTC. First dose of 100 mCi of RAI under steroid cover was given. Post-therapy scan showed bilateral pulmonary metastasis. However, follow up I-131 whole body imaging after 2 years showed no evidence of functioning thyroid tissue/metastasis. Conclusion: PTC with lung metastasis has good prognosis and better survival in young patients treated with RAI. A single dose of RAI (I-131) may cure extensive lung metastasis.

Study of BRAF and RAS Mutations in Thyroid Nodules with Indeterminate Cytology and Papillary Thyroid Cancer

OBJECTIVES Thyroid cancer Treatment decision-making is often guided by tumor tissue molecular analysis. The aim of this study was the detection of BRAF, NRAS and HRAS mutations in Georgian patients with thyroid cancer and determination of the frequency of these mutations in the respective populations. SETTING Diagnostic molecular laboratory located in Tbilisi, Georgia. PARTICIPANTS 116 patients with thyroid cancer participated in the study. PRIMARY AND SECONDARY OUTCOME MEASURES Genetic change is the main force of thyroid tumor development, based on new methods of managing thyroid cancer. The latest significant genetic discovery in thyroid cancer is the BRAF-T1799A (V600E) transformation (the gene for B-type RAF kinase, BRAF). Since the initial report of this breakthrough in thyroid cancer years ago, rapid progress has been made. The BRAF mutation is the most common genetic change in thyroid cancer. BRAF and NRAS mutations are frequent genetic alterations found in thyroid nodules. These molecular markers establish a differential diagnosis and facilitate clinical decision-making. Prevalence of thyroid nodule-associated mutations has not been studied in Georgia. We evaluated BRAF, NRAS and HRAS mutations in Georgian patients with indeterminate cytology or diagnosed with papillary thyroid cancer (PTC). RESULTS BRAF (V600E), NRAS (G12C, G12D, Q61R, and Q61K) and HRAS (G12C, G13R, and Q61R) were determined in the DNA extracted from fine needle aspirate specimens. In total, 116 patient samples were analyzed using competitive-specificTaqMan PCR (Cast PCR TM). In these samples, 36 were diagnosed as papillary thyroid carcinoma, and 80 were indeterminate by Bethesda system for reporting thyroid cytopathology (BSRTC III-V). BRAF (V600E) mutation was the most frequent genetic alteration found in 31% of all analyzed samples. Specifically, this mutation was present in 61% of PTC cases and 18% of cases classified as indeterminate (BSRTC III-V). NRAS mutations were present in 16% of PTC and 30% of indeterminate cytology samples. NRAS G12D and Q61R were most prevalent at 36.6% and 40% of all NRAS mutations. BSRTC IV category of indeterminate cytology had the highest frequency of NRAS mutations at 43%. From analyzed samples, HRAS (Q61R) mutation was present in only one PTC case.

Short-term Outcome of T1bN0M0 Papillary Thyroid Cancer after Ultrasonography-guided Radiofrequency Ablation

Objective To investigate the short-term outcome of T1bN0M0 papillary thyroid cancer after ultrasonography-guided radiofrequency ablation(RFA). Methods Eighty-nine patients with T1bN0M0 papillary thyroid cancer who were treated with ultrasonography-guided RFA in our center from April 2014 to January 2019 were retrospectively analyzed.Trans-isthmus approach and moving shot technique were used during the RFA procedure.Ultrasonography and contrast-enhanced ultrasonography were performed before ablation,and immediately,1,3,6 and 12 months after ablation and then every 6 months thereafter. Results RFA was performed in 89 cases of papillary thyroid cancer,and no major complications were observed during the RFA.The mean follow-up was(18.8±7.3)months.The ablation zones decreased gradually during follow-up,and 38 ablation zones(42.7%)completely disappeared.The volume reduction rate was(99.2±2.3)% 30 months after ablation.During follow-up,2 patients(2.2%)developed tumor recurrence and 1 patient(1.1%)developed cervical lymph node metastasis. Conclusion Ultrasonography-guided RFA may be a safe and effective method for patients with T1bN0M0 papillary thyroid cancer.

Thyroid Receptor Antagonism of Chemicals Extracted from Personal Silicone Wristbands within a Papillary Thyroid Cancer Pilot Study.

Research suggests that thyroid cancer incidence rates are increasing, and environmental exposures have been postulated to be playing a role. To explore this possibility, we conducted a pilot study to investigate the thyroid disrupting bioactivity of chemical mixtures isolated from personal silicone wristband samplers within a thyroid cancer cohort. Specifically, we evaluated TRβ antagonism of chemical mixtures extracted from wristbands (n = 72) worn by adults in central North Carolina participating in a case-control study on papillary thyroid cancer. Sections of wristbands were solvent-extracted and analyzed via mass spectrometry to quantify a suite of semivolatile chemicals. A second extract from each wristband was used in a bioassay to quantify TRβ antagonism in human embryonic kidney cells (HEK293/17) at concentrations ranging from 0.1 to 10% of the original extract (by volume). Approximately 70% of the sample extracts tested at a 1% extract concentration exhibited significant TRβ antagonism, with a mean of 30% and a range of 0-100%. Inhibited cell viability was noted in >20% of samples that were tested at 5 and 10% concentrations. Antagonism was positively associated with wristband concentrations of several phthalates, organophosphate esters, and brominated flame retardants. These results suggest that personal passive samplers may be useful in evaluating the bioactivities of mixtures that people contact on a daily basis. We also report tentative associations between thyroid receptor antagonism, chemical concentrations, and papillary thyroid cancer case status. Future research utilizing larger sample sizes, prospective data collection, and measurement of serum thyroid hormone levels (which were not possible in this study) should be utilized to more comprehensively evaluate these associations.

Patient-Derived Papillary Thyroid Cancer Organoids for Radioactive Iodine Refractory Screening.

Simple SummaryOver the past three decades, the incidence of thyroid cancer has been rising, with 90% being the well-differentiated thyroid cancer subtype. After diagnosis and surgical removal of the thyroid gland, radioactive iodine is administered to induce a localized post-operative radiation treatment. However, in 15-33% of papillary thyroid cancer cases, the cells are unable to take up radioactive iodine, resulting in an ineffective treatment which sometimes has severe side effects. Pre-treatment diagnosis of non-responding patients would prevent ineffective and toxic iodine treatment. Therefore, in this study, we developed a patient-derived papillary thyroid cancer organoid model. Patient-derived organoids responding or not responding to radioactive iodine clearly resembled the tumor of origin, but showed clear differences in sodium/iodide symporter expression. Our results indicate that thyroid cancer organoids might be a suitable tool for the early diagnosis of non-responding patients, in order to eventually reduce radioactive iodine overtreatment and its many side effects for thyroid cancer patients.Patients with well-differentiated thyroid cancer, especially papillary thyroid cancer (PTC), are treated with surgical resection of the thyroid gland. This is followed by post-operative radioactive iodine (I131), resulting in total thyroid ablation. Unfortunately, about 15-33% of PTC patients are unable to take up I131, limiting further treatment options. The aim of our study was to develop a cancer organoid model with the potential for pre-treatment diagnosis of these I131-resistant patients. PTC tissue from thirteen patients was used to establish a long-term organoid model. These organoids showed a self-renewal potential for at least five passages, suggesting the presence of cancer stem cells. We demonstrated that thyroid specific markers, a PTC marker, and transporters/receptors necessary for iodine uptake and thyroid hormone production were expressed on a gene and protein level. Additionally, we cultured organoids from I131-resistant PTC material from three patients. When comparing PTC organoids to radioactive iodine (RAI)-refractory disease (RAIRD) organoids, a substantial discordance on both a protein and gene expression level was observed, indicating a treatment prediction potential. We showed that patient-derived PTC organoids recapitulate PTC tissue and a RAIRD phenotype. Patient-specific PTC organoids may enable the early identification of I131-resistant patients, in order to reduce RAI overtreatment and its many side effects for thyroid cancer patients.

Exposure to Polychlorinated Biphenyls and Organochlorine Pesticides and Risk of Thyroid Cancer in Women

Background: Both polychlorinated biphenyls (PCB) and organochlorine pesticides (OCP) have been associated with thyroid hormone disruption, but their relationship to thyroid cancer is not known. Methods: We investigated the relationship between serum PCB and OCP concentrations and papillary thyroid cancer (PTC) in 250 incident female PTC cases and 250 female controls frequency-matched on age, all residing in Connecticut. Interviews and serum samples were collected from 2010-2013. Samples were analyzed for 32 different chemicals using gas chromatography with isotope dilution high resolution mass spectrometry. We calculated odds ratios (OR) and 95% confidence intervals (CI) using single pollutant logistic regression models for concentrations (per interquartile range) of individual PCB/OCP and summed groups of structurally or biologically similar PCB/OCP, adjusted for education, family history of cancer, alcohol consumption, and body mass index. Sub-analyses included stratification by tumor size (&lt;=1 cm and &gt;1 cm) and birth cohort (born before or in 1960 and born after 1960). We also applied three multi-pollutant approaches (standard multi-pollutant regression, hierarchical Bayesian modeling, principal components regression analysis) to investigate associations with exposures to multiple PCB/OCPs. Results: No PCB/OCPs were positively associated with PTC risk in primary analyses. Statistically significant associations were observed for 9 of the 32 chemicals and 3 summed groups of similar chemicals in the younger birth cohort based on single-pollutant models. Multi-pollutant analyses suggested null associations overall. Conclusions: Our results using single and multi-pollutant modeling do not generally support an association between PCB or OCP exposure and PTC risk, but some associations in the younger birth cohort suggest that additional investigation into early-life exposures and subsequent thyroid cancer risk may be warranted.

Exposure to polychlorinated biphenyls and organochlorine pesticides and thyroid cancer in connecticut women

BackgroundThyroid cancer incidence has increased substantially over the past decades, and environmental risk factors have been suggested to play a role. Polychlorinated biphenyls (PCB) and organochlorine pesticides (OCP) are established thyroid hormone disruptors, but their relationship to thyroid cancer is not known. MethodsWe investigated the relationship between serum PCB and OCP concentrations and papillary thyroid cancer (PTC) in 250 incident female PTC cases and 250 female controls frequency-matched on age, all residing in Connecticut. Interviews and serum samples were collected from 2010 to 2013. Samples were analyzed for 32 different chemicals using gas chromatography with isotope dilution high resolution mass spectrometry. We calculated odds ratios (OR) and 95% confidence intervals (CI) using single pollutant logistic regression models for concentrations (per interquartile range) of individual PCB/OCP and summed groups of structurally or biologically similar PCB/OCP, adjusted for education, family history of cancer, alcohol consumption, age, and body mass index. Sub-analyses included stratification by tumor size (≤ and >1 cm) and birth before or during peak PCB production (born in 1960 or earlier and born after 1960), as exposures during early life may be important. We also applied three multi-pollutant approaches (standard multi-pollutant regression, hierarchical Bayesian modeling, principal components regression analysis) to investigate associations with co-exposures to multiple PCB/OCPs. ResultsNo PCB/OCPs were positively associated with PTC in primary analyses. Statistically significant associations were observed for 9 of the 32 chemicals and 3 summed groups of similar chemicals in the those born during peak production based on single-pollutant models. Multi-pollutant analyses suggested null associations overall. ConclusionsOur results using single and multi-pollutant modeling do not generally support an association between PCB or OCP exposure and PTC, but some associations in those born during peak production suggest that additional investigation into early-life exposures and subsequent thyroid cancer risk may be warranted.

Birth Characteristics and Risk of Pediatric Thyroid Cancer: A Population-Based Record-Linkage Study in California.

Background: Incidence rates of thyroid cancer in children and young adults (age 0-19 years) have nearly doubled over a recent 15-year period in the United States. Children with thyroid cancer may require long-term therapy and surveillance and are at greater risk for second primary malignancies. High-dose exposure to ionizing radiation is the only known nongenetic risk factor; the vast majority of cases have an unknown etiology. Methods: We conducted a population-based nested case-control study to evaluate the relationship between a range of birth characteristics and the risk of pediatric thyroid cancer. Using linked birth records and cancer registry data from California, we included 1012 cases who were diagnosed with first primary thyroid cancer at the age of 0-19 years from 1988 to 2015 and 50,600 birth-year matched controls (1:50 case to control ratio). We estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) by using multivariable logistic regression models applied to the full population and stratified by thyroid cancer subtypes (papillary and follicular), race/ethnicity (white and Hispanic), and age at diagnosis (0-14 and 15-19 years). Results: Hispanic ethnicity (OR: 1.20 [CI 1.01-1.42]), higher birth weight (OR: 1.11 [CI 1.04-1.18] per 500g), and higher maternal education (13-15 years OR: 1.35 [CI 1.09-1.68], 16+ years OR: 1.35 [CI 1.07-1.71]) were associated with an increased risk of pediatric thyroid cancer, while male sex (OR: 0.21 [CI 0.18-0.25]) and higher birth order (third or higher OR: 0.81 [CI 0.68-0.98]) were associated with a decreased risk. Some heterogeneity was observed across subtype, most notably an elevated OR with higher birth order for follicular thyroid cancer, in contrast to the reduced risk for this category among papillary thyroid cancer cases (p-value for interaction = 0.01). Hispanic ethnicity was a risk factor for papillary, but not follicular thyroid cancer (p-value for interaction = 0.07). Conclusions: In this population-based study of birth characteristics and pediatric thyroid cancer, we identified several important risk factors for pediatric thyroid cancer, including female sex, Hispanic ethnicity, higher birth weight, higher maternal educational attainment, and lower birth order. Our data provide new areas for replication and investigation of biological mechanisms for this poorly understood malignancy.

A TIGHT COLLAR: A UNIQUE PRESENTATION OF PAPILLARY THYROID CANCER

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Carotid sinus hypersensitivity (CSH) can be caused by a multitude of clinical syndromes. Rarely, head and neck tumors can also present with symptoms of CSH due to excessive stimulation of the carotid sinus. Diagnosis in such cases may be delayed because of the rarity of this presentation. It is crucial to recognize the underlying cause of CSH to prevent lethal outcomes. We present a case of papillary thyroid cancer with an unusual clinical presentation. CASE PRESENTATION: 27-year old female with no significant past medical history presented to our hospital with syncopal episodes. The patient reported that she has been experiencing several episodes of dizziness and loss of consciousness for ten days. These episodes reportedly occur when she gets up from a sleeping position. The patient denied having diarrhea, vomiting, decreased oral intake, or using any medications. On presentation, she had positive orthostatic vital signs with a drop in systolic blood pressure by 55 mm Hg and diastolic blood pressure by 40 mm Hg on standing up from a sleeping position. Physical examination was notable for a left thyroid nodule. Laboratory investigations were unremarkable. Electrocardiogram demonstrated bradycardia with a heart rate of 55 beats/minute with no evidence of conduction abnormalities. She subsequently underwent a computerized tomography scan of the neck that revealed a left-sided thyroid nodule that was further confirmed on the ultrasound as being a hypoechoic mass lateral to the left carotid artery. Since the findings were concerning for a malignant lesion, she underwent fine-needle aspiration biopsy that demonstrated papillary thyroid cancer. She subsequently underwent thyroidectomy with a complete resolution of symptoms. The syncopal episodes were attributed to carotid sinus hypersensitivity in the presence of a thyroid mass in an otherwise young female. DISCUSSION: The compression of the carotid sinus by malignant neoplasms in the neck can potentially cause cardio-inhibition and vaso-depression leading to syncope and presyncope. The pathogenesis is attributed to autonomic dysregulation and increased baroreceptor sensitivity. Although most cases of CSH are self-limiting, some might lead to conduction abnormalities and necessitate pacemaker placement. Early diagnosis and treatment are vital to prevent lethal outcomes such as atrioventricular blocks or sinus pauses due to excess vagal stimulation. Hence, a thorough history and physical examination, and a broad differential is the key to manage this condition appropriately. CONCLUSIONS: Unexplained abrupt episodes of bradycardia and syncope should alert the physician of the possibility of carotid sinus compression. This may be caused by a neck mass and should warrant a detailed physical examination and thorough workup for obstructive head and neck masses. Reference #1: Toscano M, Cristina S, Alves A (February 19, 2020) Carotid Sinus Syndrome in a Patient with Head and Neck Cancer: A Case Report. Cureus 12(2): e7042. DOI:10.7759/cureus.7042 Reference #2: Korkmaz, Ö., Göksel, S., Özlü, H., & Berkan, Ö. (2014). Papillary thyroid cancer located in the carotid bifurcation mimicking carotid body tumors. Ulusal cerrahi dergisi, 31(1), 52–54. https://doi.org/10.5152/UCD.2014.2658 DISCLOSURES: No relevant relationships by Ayesha Azmeen, source=Web Response No relevant relationships by Dimitrios Drekolias, source=Web Response No relevant relationships by Naga Vaishnavi Gadela, source=Web Response No relevant relationships by Sana Hyder, source=Web Response No relevant relationships by Srimathi Manickaratnam, source=Web Response No relevant relationships by Mahati Paravathaneni, source=Web Response

Risk factors for papillary thyroid cancer in obesity and diabetes mellitus

Obesity and resulting diabetes mellitus are being two of the most prevalent pathological conditions worldwide accounting almost 2 billion adults and 340 million children affected. In the same time, global cancer statistics rises each year showing the growth in the umber of cases of papillary thyroid cancer. Relationship between thesediseases has created strong interest among scientists and discovered ew directions in prevention and therapy. Moreover, obesity usually leads to the disturbance in gut microbiota. Accordingly, the aim of our research was to summarize the evidence of the impact of these risk factors on the possible development of papillary thyroid cancer. Current article reflects ewest achievements in the understanding of pathological mechanisms underlying the epidemiological trends connecting adiposity, hyperglycemia, diabetes mellitus, antidiabetic therapy and microbiota changes. Wide range of evidences testify in favor that obesity is one of the factors for the possible development of oncological processes in the body due to hormonal imbalance and the development of chronic inflammation, which stimulate mitogenic cell division. Complete chronicinflammation, often found in obese people, predisposesto a particular type of cancer, creating a tissueenvironment that creates oxidative stress, stimulatesDNA damage, increases cell proliferation, and inhibitsapoptosis.Talking about diabetes mellitus, recent studies suggested that when culturing follicular cells, their quantity increases significantly in the presence of insulin and TSH as compared to thepresence of only TSH. This phenomenon occurs due insulinstructural similarity to insulin-like growth factor 1. Same mechanism is also related to increase in thyroid cancer risk in diabetic patients prescribed with sulfonylurea and injectable insulins. Other points are still partly unclear and eed further investigations and therapeutic implications.

POLE and POLD1 pathogenic variants in the proofreading domain in papillary thyroid cancer.

Thyroid cancer is the most frequent endocrine cancer with an increasing incidence rate worldwide and is the second most common malignancy among females in Saudi Arabia. Papillary thyroid cancer (PTC) is the most common subtype. Germline pathogenic variants in the proofreading domain of the POLE and POLD1 genes predispose to several types of cancers. However, the role of pathogenic variants of these two genes in PTC remains unknown. Capture sequencing, Sanger sequencing and immunohistochemistry were performed on 300 PTC cases from the Middle Eastern region. One germline pathogenic variant each of POLE (1/300, 0.33%) and POLD1 (1/300, 0.33%) genes was identified. Low expression of POLD1 was detected in 46.5% (133/286) of cases and was significantly associated with the follicular variant of PTC (P = 0.0006), distant metastasis (P = 0.0033) and stage IV tumours (P = 0.0081). However, no somatic pathogenic variant was detected in POLE gene. Furthermore, low expression of POLE was noted in 61.7% (175/284) of cases with no significant clinicopathological associations. Our study shows that pathogenic variant in the POLE and POLD1 proofreading domain is a cause of PTC and low expression of POLD1 is associated with poor prognostic markers in the Middle Eastern population. Further studies from different geographic populations are needed to determine the frequency and spectrum of proofreading domain pathogenic variants in POLE and POLD1 genes and in PTC from different ethnicities.

The Clinicopathological Results of Thyroid Cancer With BRAFV600E Mutation in the Young Population of Fukushima.

Thyroid ultrasound screening for children aged 0 to 18 years was performed in Fukushima following the accident at the Fukushima Daiichi Nuclear Power Plant. As a result, many thyroid cancer cases were detected. To explore the carcinogenic mechanisms of these cancers, we analyzed their clinicopathological and genetic features. We analyzed 138 cases (52 males and 86 females) who had undergone surgery between 2013 and 2016 at Fukushima Medical University Hospital. Postoperative pathological diagnosis revealed 136 (98.6%) cases of papillary thyroid cancer (PTC). The BRAFV600E mutation was detected using direct DNA sequencing in 96 (69.6%) of the thyroid cancer cases. In addition, oncogenic rearrangements were detected in 23 cases (16.7%). Regarding chromosomal rearrangements, 8 (5.8%) RET/PTC1, 6 (4.3%) ETV6(ex4)/NTRK3, 2 (1.4%) STRN/ALK, and 1 each of RET/PTC3, AFAP1L2/RET, PPFIBP/RET, KIAA1217/RET, ΔRFP/RET, SQSTM1/NTRK3 and TPR/NTRK1 were detected. Tumor size was smaller in the BRAFV600E mutation cases (12.8 ± 6.8 mm) than in wild-type BRAF cases (20.9 ± 10.5 mm). In the BRAFV600E mutation cases, 83 (86.5%) showed lymph node metastasis, whereas 26 (61.9%) of the wild-type BRAF cases showed lymph node metastasis. The BRAFV600E mutation was mainly detected in residents of Fukushima, which was different from post-Chernobyl PTC cases with RET/PTC3 rearrangement. PTC with the BRAFV600E mutation was smaller but was shown in the high rate of central cervical lymph node metastasis than the wild-type BRAF PTC in the young population of Fukushima.

Dynamin 2 Is Correlated with Recurrence and Poor Prognosis of Papillary Thyroid Cancer.

BackgroundPapillary thyroid cancer (PTC) is the most common histological type of thyroid cancer. Most PTC patients have favorable outcomes, but 10% of patients still have distant metastases at presentation or during follow-up. Dynamin 2 (DNM2) is the only DNM ubiquitously expressed in human tissues, but its expression and clinical significance in PTC is still unknown.Material/MethodsIn our study, we investigated the expression of DNM2 in 112 cases of PTC and classified the patients into low and high expression of DNM2. The clinical significance of DNM2 was evaluated by assessing its correlation with the clinicopathological parameters with the chi-square method. The correlations between DNM2 expression and the disease-free survival rate or overall survival rate were assessed with the Kaplan-Meier method and the log-rank test. The independent prognostic factors of PTC were determined by the Cox-regression hazard model.ResultsPatients with low and high DNM2 expression accounted for 75% and 25% respectively in the 112 patients with PTC. High DNM2 expression was significantly associated with recurrence (P=0.014) and poor prognosis (P=0.004). In addition to tumor stage, DNM2 expression was an independent prognostic biomarker of PTC, indicating an unfavorable prognosis.ConclusionsDNM2 was an independent PTC biomarker indicating more likely recurrence and poorer prognosis. Detecting DNM2 expression may help to select the high-risk patients for adjuvant therapy.

Cancer screening activity results in overdiagnosis and overtreatment of papillary thyroid cancer: A 10-year experience at a single institution.

BackgroundIt is estimated that one of the potential cause of the increasing prevalence of thyroid cancer (TC) is the easier and widespread access to diagnostic tools. If an individual evaluates the thyroid gland due to a mentioned mechanism without considering TC risk factors or symptoms, we can describe this phenomenon as cancer screening activity (CSA).Aim of the studyWe 1) estimated what types of TC were diagnosed due to CSA, 2) analyzed what clinicopathological features were characteristic of TCs diagnosed by CSA, 3) determined if these features were characteristic of indolent cases, and finally we 4) assessed whether CSA could have resulted in the increasing incidence of potentially indolent papillary thyroid cancer (PTC).Materials and methodsA retrospective review of 4,701 medical records of patients admitted and surgically treated at one surgical center between 2008 and 2017 was performed. Among the enrolled patients, 569 (12.1%) had thyroid malignancy, and 514 (10.9%) were diagnosed with PTC. We divided these patients into two groups: 1) patients in whom TC diagnostics were performed without considering any TC risk factors or symptoms (CSA-yes) and 2) those in whom TC was diagnosed due to TC risk factors or symptoms (CSA-no). We then compared the clinicopathological features of these two groups.ResultsThe most common type of TC diagnosed in the CSA-group was PTC (p = 0.024). CSA-yes patients showed a significantly lower degree of Tumor-Node-Metastasis (TNM) staging and demonstrated a significantly lower rate of multifocality, but not of bilaterality (p<0.0001 and p = 0.198, respectively). In the CSA-yes group, the number of TC foci was significantly lower than that in the CSA-no group (p<0.0001). All clinicopathological features characteristic of aggressive cases of TC were absent in CSA-yes patients (p<0.0001), while all features observed in CSA-yes patients were characteristic of indolent cases (p<0.0001).ConclusionsThe use of CSA results in the diagnosis of indolent cases of PTC and may be one of the potential causes of overdiagnosis and overtreatment of this malignancy.

Intermixed medullary and papillary thyroid cancer in a patient with renal cell carcinoma.

SummaryWe report a rare case of concurrent medullary thyroid cancer (MTC) and papillary thyroid cancer (PTC) with intermixed disease in several of the lymph node (LN) metastases in a patient who was subsequently diagnosed with clear cell renal cell carcinoma (RCC). A 56 year old female presented with dysphagia and was found to have a left thyroid nodule and left superior cervical LN with suspicious sonographic features. Fine needle aspiration biopsy (FNAB) demonstrated PTC in the left thyroid nodule and MTC in the left cervical LN. Histopathology demonstrated multifocal PTC with 3/21 LNs positive for metastatic PTC. One LN in the left lateral neck dissection exhibited features of both MTC and PTC within the same node. In the right lobe, a 0.3 cm focus of MTC with extra-thyroidal extension was noted. Given persistent calcitonin elevation, a follow-up ultrasound displayed an abnormal left level 4 LN. FNAB showed features of both PTC and MTC on the cytopathology itself. The patient underwent repeat central and left radical neck dissection with 3/6 LNs positive for PTC in the central neck and 2/6 LNs positive for intermixed PTC and MTC in the left neck. There was no evidence of distant metastases on computed tomography and whole body scintigraphy, however a 1.9 x 2.5 cm enhancing mass within the right inter-polar kidney was discovered. This lesion was highly suspicious for RCC. Surgical pathology revealed a 2.5 cm clear cell RCC, Fuhrman grade 2/4, with negative surgical margins. She continues to be observed with stable imaging of her triple malignancies.Learning points:Mixed medullary-papillary thyroid neoplasm is characterized by the presence of morphological and immunohistochemical features of both medullary and papillary thyroid cancers within the same lesion. Simultaneous occurrence of these carcinomas has been previously reported, but a mixed disease within the same lymph node is an infrequent phenomenon.Prognosis of mixed medullary-papillary thyroid carcinomas is determined by the medullary component. Therefore, when PTC and MTC occur concurrently, the priority should be given to the management of MTC, which involves total thyroidectomy and central lymph node dissection.Patients with thyroid cancer, predominantly PTC, have shown higher than expected rates of RCC. To our knowledge, this is the first report describing the combination of MTC, PTC, and RCC in a single patient.