Clinical characteristics and long-term outcomes for parapharyngeal metastases of well-differentiated thyroid cancer during 131 I therapy and follow-up.

OBJECTIVE: Parapharyngeal metastases (PPM) are rarely observed in patients with well-differentiated thyroid cancer (WDTC). Radioiodine (131 I) therapy has been the main treatment for metastatic and recurrent DTC after thyroidectomy. This study was performed to evaluate the clinicopathological features and long-term outcomes associated with survival of patients with PPM at the end of follow-up. DESIGN: In total, 14,984 consecutive patients with DTC who underwent 131 I therapy after total or near-total thyroidectomy from 2004 to 2021 were retrospectively reviewed. Therapeutic efficacy was evaluated using the Response Evaluation Criteria in Solid Tumours v1.1 and logistic regression analysis. The disease status was determined using dynamic risk stratification. Disease-specific survival (DSS) was assessed using the Kaplan-Meier method and a Cox proportional hazards model. PATIENTS: Seventy-five patients with PPM from WDTC were enroled in this study. Their median age at the initial diagnosis of PPM was 40.2 ± 14.1 years, and the patients comprised 32 men and 43 women (male:female ratio, 1.00:1.34). Of the 75 patients, 43 (57.33%) presented with combined distant metastases. Fifty-seven (76.00%) patients had 131 I avidity and 18 had non-131 I avidity. At the end of follow-up, 22 (29.33%) patients showed progressive disease. Sixteen of the 75 patients died; of the remaining 59 patients, 6 (8.00%) had an excellent response, 6 (8.00%) had an indeterminate response, 10 (13.33%) had an biochemical incomplete response, and 37 (49.33%) had a structural incomplete response. Multivariate analysis confirmed that age at initial PPM diagnosis, the maximal size of PPM, and 131 I avidity had significant effects on progressive disease of PPM lesions (p = .03, p= .02, and p < .01, respectively). The 5- and 10-year DSS rates were 98.49% and 62.10%, respectively. Age of ≥55 years at initial diagnosis of PPM and the presence of concomitant distant metastasis were independently associated with a poor prognosis (p = .03 and p = .04, respectively). CONCLUSION: The therapeutic effect for PPM was closely associated with 131 I avidity, age at initial PPM diagnosis, and maximal size of PPM at the end of follow-up. Age of ≥55 years at initial diagnosis of PPM and the presence of concomitant distant metastasis were independently associated with poor survival.

Thyroid cancer, recent advances in diagnosis and therapy.

Over the past several decades, the approach to the diagnosis and management of patients with follicular cell-derived thyroid cancer has evolved based on improved classification of patients better matching clinical outcomes, as well as advances in imaging, laboratory, molecular technologies and knowledge. While thyroid surgery, radioactive iodine therapy and TSH suppression remain the mainstays of treatment, this expansion of knowledge has enabled de-escalation of therapy for individuals diagnosed with low-risk well-differentiated thyroid cancer; better definition of treatment choices for patients with more aggressive disease; and improved ability to optimize treatments for patients with persistent and/or progressive disease. Most recently, the advancement of knowledge regarding the molecular aspects of thyroid cancer has improved thyroid cancer diagnosis and has enabled individualized therapeutic options for selected patients with the most aggressive forms of the disease. Guidelines from multiple societies across the world reflect these changes, which focus on taking a more individualized approach to clinical management. In this review, we discuss the current more personalized approach to patients with follicular cell-derived thyroid cancer and point toward areas of future research still needed in the field.

Aspectos fundamentales del nódulo tiroideo y el cáncer bien diferenciado de tiroides para los médicos general y familiar.

The physician that has the first contact with the patient is the general or family doctor, on whose initial assessment patient treatment success often depends. National and international treatment guidelines are designed for specialists in the area, and the primary care physician often finds them difficult to interpret. The purpose of this document is to offer primary care physicians the fundamentals for the diagnostic and reference process of patients with thyroid nodules and possibly with well-differentiated thyroid cancer, from an objective and pragmatic point of view. Not all thyroid nodules require the same approach, and not all nodules are associated with cancer and neither should they be removed. The bases for a proper diagnosis of a thyroid tumor are patient history, physical examination and ultrasound. The results of these three initial assessment methods shall support the decision on the diagnostic-therapeutic process. This article explains the appropriate way to approach the diagnosis of a thyroid tumor, which studies are unnecessary, and which are the principles of thyroid cancer treatment.

El galeno de primer contacto con el paciente es el médico general o familiar, de cuya evaluación inicial muchas veces depende el éxito en el tratamiento de los pacientes. Las guías terapéuticas nacionales e internacionales están diseñadas para especialistas en el área y el médico de primer contacto suele encontrarlas difíciles de interpretar. El objetivo del presente documento es ofrecer al médico de primer contacto los fundamentos para el diagnóstico y proceso de referencia de los pacientes con nódulos tiroideos y eventualmente con cáncer bien diferenciado de tiroides, un punto de vista objetivo y pragmático. No todos los nódulos tiroideos requieren la misma aproximación diagnóstica y no todos los nódulos están asociados con cáncer ni deben ser retirados. Las bases para el adecuado diagnóstico de un tumor tiroideo son la historia clínica, la exploración física y el ultrasonido; los resultados de estos tres métodos iniciales de exploración serán los que orienten el proceso diagnóstico-terapéutico. En el presenta artículo se explica la forma adecuada para el diagnóstico de un tumor tiroideo, los estudios innecesarios y los principios del tratamiento del cáncer de tiroides.

Well-differentiated thyroid cancer and robotic transaxillary surgery at a North American institution.

BACKGROUND: Recent studies from Asia have reported the safety and feasibility of robotic-assisted thyroid surgery. In the United States, several small series and case reports have been published, mostly regarding treatment of benign disease. The aim of our study is to report the safety and feasibility of robotic surgery for well-differentiated thyroid cancer patients at a North American institution. MATERIALS AND METHODS: We performed a retrospective cohort study using a prospectively collected single-center clinical database at Tulane University Medical Center. We included all well-differentiated thyroid cancer patients who underwent robotic-assisted or conventional cervical approach thyroid surgery with or without lymph node dissections at our institution from January 2015 to June 2017. Patient demographics and perioperative data were collected and analyzed. RESULTS: A total of 144 surgeries for thyroid cancer were performed; 35 (24.3%) were robotic-assisted. There were no significant differences in estimated blood loss, operative times, complication rates, specimen sizes, positive microscopic margins, number of lymph nodes removed with associated lymph node dissections, patient follow-up duration, or clinical recurrence rates between the two groups. Overall length of stay was shorter for robotic-assisted surgery, at 0.6 ± 0.9 d, versus 1.1 ± 1.2 d for conventional open surgery (P = 0.009). For robotic-assisted surgery, 19 patients (54.3%) were discharged on the day of procedure, and only one patient was admitted as inpatient to the hospital (2.9%). CONCLUSIONS: Robot-assisted thyroid surgery is a safe, feasible, and oncologically sound approach for a select group of well-differentiated thyroid cancer patients. However, long-term studies are needed.

Thyroid cancer is more likely to be detected incidentally on imaging in private hospital patients.

BACKGROUND: The incidence of well-differentiated thyroid cancer (WDTC) is increasing. Patients with higher socioeconomic status have higher rates of WDTC, possibly due to increased imaging and overdiagnosis. We compared methods of WDTC diagnosis in patients treated at a public and an adjacent private university hospital. MATERIALS AND METHODS: Patients with WDTC at the two hospitals between 2004 and 2010 were included. Patients were categorized into having their WDTC discovered on physical examination or on unrelated imaging. Demographic and pathologic data were collected. T-test was used for quantitative variables, and chi-squared test was used for categorical values. Binomial logistic regression was used to asses for confounding. RESULTS: Among 473 patients, 402 (85%) were from the university hospital, and 71 (15%) were from the public hospital. Patients from the university hospital were older (mean age: 49 versus 44, P = 0.02) and had a different racial composition compared to those from the public hospital. The patients at the public hospital had larger tumors (23 versus 18 mm, P = 0.04). Patients from the university hospital were more likely to have WDTC detected by imaging than patients in the public hospital (46% versus 28%, P < 0.01) on univariate analysis. CONCLUSIONS: This study demonstrates that patients with WDTC treated at a university hospital are more likely to have their tumor detected on unrelated imaging than those treated at a public hospital. These data may support the hypothesis that patients with improved insurance are more likely to have WDTC detected by imaging.

Effects of sorafenib and an adenylyl cyclase activator on in vitro growth of well-differentiated thyroid cancer cells.

Well-differentiated thyroid carcinomas have driver mutations involving growth factor receptor-tyrosine kinases (RTKs) or their intracellular signaling pathway, that is, the mitogen-activated protein kinase (MAPK) pathway. Sorafenib is a multikinase inhibitor of RTKs and the MAPK pathway and has recently been used for the treatment of unresectable well-differentiated thyroid carcinoma. In normal thyroid follicular cells, stimulation of the thyroid-stimulating hormone (TSH) receptor activates the cyclic adenosine monophosphate (cAMP) pathway and promotes cell growth as well as hormonal secretion. However, an adenylyl cyclase (AC) activator, forskolin, has been reported to suppress the growth of thyroid carcinoma cells. To clarify the roles of the MAPK and cAMP pathways in proliferation of well-differentiated thyroid carcinoma cells, we compared the effects of sorafenib and forskolin in in vitro models. Sorafenib inhibited constitutive activation of the MAPK pathway, cyclin-dependent kinase 4 (CDK4), and phosphorylated retinoblastoma protein (RB) in 3 well-differentiated carcinoma cell lines, but it did not show sufficiently effective suppression of cell growth. Forskolin significantly suppressed the growth of all 3 cell lines and also activated the cAMP pathway and inhibited expression of cyclin D1. Our results suggest that activation of the cAMP pathway could be more potent than activation of the MAPK pathway in suppressing proliferation of well-differentiated thyroid cancer cells. We postulate that the AC activator suppresses growth of thyroid carcinoma cells through undetermined mechanisms.

Impact of surgical resection extension on outcome for primary well-differentiated thyroid cancer-a retrospective analysis.

BACKGROUND: The surgical resection extension in well-differentiated thyroid cancer is controversially discussed with the possibility of an overtreatment on the one hand against the risk of local disease recurrence. The aim of this study is to evaluate how the surgical resection extension with the adjunction of radioiodine therapy affects postoperative morbidity and the oncologic outcome of patients primarily treated for well-differentiated thyroid cancer. METHODS: All patients undergoing primary surgery for a well-differentiated, non-recurrent thyroid cancer from January 2005 to April 2013 at Tuebingen University Hospital were retrospectively analyzed. RESULTS: Papillary thyroid cancer (PTC) was present in 73 patients (including 27 papillary microcarinoma) and follicular thyroid cancer in 14 patients. Fifty-six of 87 patients (64%) underwent one-stage surgery, of which 26 patients (30%) received simultaneous lymph node dissection (LND). The remaining 31 patients (36%) underwent a two-stage completion surgery (29 patients with LND). Only in three patients a single lymph node metastasis was newly detected during two-stage completion surgery. Patients with LND at either one-stage and two-stage completion surgery had a significant higher rate of transient postoperative hypocalcemia. Postoperative adjuvant radioiodine therapy was performed in 68 of 87 patients (78%). After a median follow-up of 69 months [range 9-104], one local recurrence was documented in a patient suffering from PTC 23 months after surgery. CONCLUSION: No prophylactic two-stage lymphadenectomy should be performed in case of well-differentiated thyroid cancer to avoid unnecessary complication without any proven oncologic benefit.

Radiation-Induced Thyroid Cancer: Gender-Related Disease Characteristics and Survival.

BACKGROUND: Radiation exposure is a well-known risk factor for well-differentiated thyroid cancer (WDTC). However, gender disparity in disease characteristics is not completely understood. The purpose of this study was to determine the behavior of radiation-induced thyroid cancer according to gender. METHODS: Charts of all patients diagnosed with WDTC after radiation exposure between the years 1985 and 2013 in a tertiary referral center were retrieved. RESULTS: Forty-three patients were reviewed, 29 females and 14 males. Mean age of exposure for women and men were 17.1 ± 19.5 and 15.5 ± 12.5 years, respectively (P = .78). Age at diagnosis were 47.5 ± 15.5 and 41.5 ± 15 years for women and men, respectively (P = .18). Mean disease-specific survival was 44.1 and 43.7 years for women and men, respectively (P = .50). CONCLUSIONS: Similar disease characteristics, tumor pathology, disease-free survival, and overall survival in both genders. In sporadic well-differentiated thyroid carcinoma, female gender is associated with better tumor behavior and prognosis. However, our results suggest that women are more affected by radiation than men and therefore have the same prognosis as men.

DNA methylation profiling of well-differentiated thyroid cancer uncovers markers of recurrence free survival.

Thyroid cancer is a heterogeneous disease with several subtypes characterized by cytological, histological and genetic alterations, but the involvement of epigenetics is not well understood. Here, we investigated the role of aberrant DNA methylation in the development of well-differentiated thyroid tumors. We performed genome-wide DNA methylation profiling in the largest well-differentiated thyroid tumor series reported to date, comprising 83 primary tumors as well as 8 samples of adjacent normal tissue. The epigenetic profiles were closely related to not only tumor histology but also the underlying driver mutation; we found that follicular tumors had higher levels of methylation, which seemed to accumulate in a progressive manner along the tumorigenic process from adenomas to carcinomas. Furthermore, tumors harboring a BRAF or RAS mutation had a larger number of hypo- or hypermethylation events, respectively. The aberrant methylation of several candidate genes potentially related to thyroid carcinogenesis was validated in an independent series of 52 samples. Furthermore, through the integration of methylation and transcriptional expression data, we identified genes whose expression is associated with the methylation status of their promoters. Finally, by integrating clinical follow-up information with methylation levels we propose etoposide-induced 2.4 and Wilms tumor 1 as novel prognostic markers related to recurrence-free survival. This comprehensive study provides insights into the role of DNA methylation in well-differentiated thyroid cancer development and identifies novel markers associated with recurrence-free survival.

Neck Surgery for Non-Well Differentiated Thyroid Malignancies: Variations in Strategy According to Histopathology.

Lymph node metastases in non-well differentiated thyroid cancer (non-WDTC) are common, both in the central compartment (levels VI and VII) and in the lateral neck (Levels II to V). Nodal metastases negatively affect prognosis and should be treated to maximize locoregional control while minimizing morbidity. In non-WDTC, the rate of nodal involvement is variable and depends on the histology of the tumor. For medullary thyroid carcinomas, poorly differentiated thyroid carcinomas, and anaplastic thyroid carcinomas, the high frequency of lymph node metastases makes central compartment dissection generally necessary. In mucoepidermoid carcinomas, malignant peripheral nerve sheath tumors, sarcomas, and malignant thyroid teratomas or thyroblastomas, central compartment dissection is less often necessary, as clinical lymphnode involvement is less common. We aim to summarize the medical literature and the opinions of several experts from different parts of the world on the current philosophy for managing the neck in less common types of thyroid cancer.

Association of Neutrophil-to-Lymphocyte Ratio and Lymphocyte-to-Monocyte Ratio with Clinicopathological Features and Short-Term Outcome in Well-Differentiated Thyroid Cancer.

Purpose of the Study: To assess the association of inflammatory markers with known risk factors and short-term outcome of well-differentiated thyroid cancer. Materials and Methods: Well-differentiated nonmetastatic thyroid cancer patients diagnosed and treated between September 2015 and December 2019 at Kasturba Hospital, Manipal, India, were retrieved for the study. Patients' presurgical blood parameters were noted, and neurtrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) were calculated. Clinicopathological details along with tumor markers at baseline and at 6 months' follow-up were tabulated. Patients were categorized as complete disease clearance if their clinical examination was normal, stimulated thyroglobulin (Tg) was <1 ng/ml, Anti-thyroglobulin antibodies <65 IU/L or showing a decreasing trend, and follow-up I-131 whole-body scan was negative. The association of the inflammatory markers with known risk factors and short-term outcomes were compared. Results: A total of 272 patients were analyzed in the study. The median NLR in our study cohort was 2.55 (mean = 3.96 with standard deviation [SD] =4.20) and the median LMR was 3.72 (mean = 3.79 with SD = 1.94). The disease clearance rate of our study cohort was 73.9%. The median NLR (2.4 vs. 3.1) and LMR (3.13 vs. 3.93) were significantly different among the patients with complete disease clearance and those with persistent disease (P = 0.008 and P = 0.003, respectively). The known risk factors such as multifocality (P = 0.04), tumor size (P = 0.013), lymph node metastases (P = 0.001), and baseline Tg (P ≤ 0.001) were significantly associated with persistent disease at 6 months. The NLR showed a positive correlation and LMR had a negative correlation with the known risk factors, however, the associations were not statistically significant. Conclusions: The NLR and LMR are simple yet potential prognostic tools in well-differentiated thyroid cancer.

Pattern of Nodal Metastasis in Relation to Size of the Primary Tumour in Well-Differentiated Thyroid Carcinoma.

This study was conducted to see the pattern of neck node metastasis in relation to the size of primary tumour in Well-differentiated thyroid cancer. A prospective study on 50 patients was carried out in the Department of Head and Neck Surgery, Dr B. Borooah Cancer Institute from 1st August, 2018 to 31st July, 2019. All new cases who had not previously received treatment were included which were histopathogically proven. Residual and recurrent cases were not taken into account. Most common age-group affected was 21-30 years (24%). It was more common in females (84%). Papillary thyroid cancer has been found to be the most common histological type of WDTC (88%), out of which the classical variant of PTC constitute 72%. 46% of them had tumour size > 4 cm 88% cases had cervical neck node metastases, out of which 72% were unilateral and 16% were bilateral. The commonest level involved was level VI. There is a definite correlation (clinical and histological) between increased involvement of positivity of lymph node in relation to size of the primary tumour in well-differentiated thyroid carcinoma.

Prevalence and Predictors of Malignancy in Contralateral Thyroid Lobe in Patients Undergoing Completion Thyroidectomy.

(1) To determine prevalence of malignancy in contralateral lobe (CL) in patients undergoing completion thyroidectomy (CT) and to study complications of CT. (2) To analyze clinical, ultrasonography(USG) findings and histopathological features of the tumor in ipsilateral lobe (IL) that could predict malignancy in CL. Retrospective chart review of 40-patients who first underwent hemi-thyroidectomy for fine-needle-aspiration (FNA) diagnosed benign lesions followed by CT between September-2017 and November-2019. Histopathology reports from both surgeries, along with patient characteristics and USGfeatures of initial hemi-thyroid lobe were reviewed. Thirty-two (80%) of the 40 patients were female. Mean age of presentation was 38.2 years (Range = 19-61years). Malignancy was found in 22(55%) contralateral-lobes of 40 completion thyroidectomies performed. Multi-focality of tumor in first surgery was only factor with significant association with presence of malignancy in CL (OR = 5.53, 95% CI 1.01-30.35, p = 0.048).In terms of USG-findings, most common suspicious feature in IL was peripheral/rim calcification, with TIRADS ≥ 4 was present in 19 patients but none of features could significantly predict bilateral disease. Three (7.5%) patients developed permanent unilateral recurrent-laryngeal-nerve (RLN) palsy (2-following initial surgery and 1-following CT). Fourteen (35%) patients developed hypoparathyroidism following CT of whom 12 were symptomatic and 4(10%) proceeded to permanent hypoparathyroidism. There were no other major complication following CT. Multifocality in initial hemithyroidectomy specimen was most frequently associated with malignancy in CL. Preoperative TIRADS ≥ 4 of IL may be considered a risk factor for bilateral malignancy. CT may be performed in FNA misdiagnosed thyroid cancers as there is high prevalence(56%) of disease in CL. CT is safe and it eradicates disease in CL.

Nuances in the Surgical Management of Thyroid Cancer.

The incidence of thyroid cancer is rapidly rising, primarily due to the increased use of imaging studies and incidentalomas. In the USA, the incidence has quadrupled. The last decades have seen remarkable advances in diagnosis and surgery for thyroid cancer. We will discuss the surgical advances in this manuscript. The American Thyroid Association and many other organizations around the world have been quite instrumental in developing the guidelines for the management of thyroid cancer, which have streamlined the treatment approaches. There have also been advances made in the management of medullary and anaplastic thyroid cancer, which will be a different subject not included in this manuscript. The major surgical advances include the following: impact of molecular markers, risk group stratifications, de-escalation in surgery, nerve monitoring, and endoscopic surgery. We will discuss some of these surgical nuances in this review article.

Thyroid Cancer and Telemedicine During the COVID-19 Pandemic.

The COVID-19 pandemic has forced endocrinologists to utilize telemedicine to care for their patients. There is limited information on the experience of endocrinologists in managing patients with thyroid cancer virtually. We sent a 9-item questionnaire to endocrinologists and endocrine surgeons at our institution to better understand the barriers and benefits of caring for patients with thyroid cancer via telemedicine, as well as how we can incorporate telemedicine into our future care of patients with this malignancy. Among the 9 physicians who responded, the majority listed technological issues with the virtual platform as a challenge in caring for patients with thyroid cancer remotely. Additional barriers included difficulty in expressing empathy, decreased ability to coordinate care with the interdisciplinary team, and lack of the physical examination. Benefits included compliance with social distancing measures and convenience for patients with American Thyroid Association (ATA) low-risk thyroid cancer who presented for follow-up visits. Overall, physicians were satisfied or strongly satisfied with caring for patients with thyroid cancer remotely, especially low-risk patients on long-term follow-up. That said, they recommend that some patients be seen in person after the pandemic, including symptomatic patients and ATA high-risk patients. While the COVID-19 pandemic has allowed endocrinologists to manage patients with thyroid cancer remotely, the providers have faced challenges, some of which can be improved upon. Further studies will help determine how telemedicine affects patient outcomes, including satisfaction, disease progression, and survival, which will inform how we may incorporate this practice into our future care of patients with thyroid cancer.

Predictors of Response to Therapy Among Post Thyroidectomy Adult Filipino Patients with Papillary Thyroid Carcinoma Based on the 2015 American Thyroid Association Guidelines.

OBJECTIVE: To identify factors independently associated with incomplete response to therapy based on the 2015 ATA guidelines in surgically treated Filipino patients with papillary thyroid carcinoma (PTC). METHODOLOGY: This is a retrospective cohort study of adults aged 21-74 years with papillary thyroid carcinoma (PTC) treated with surgery with or without radioactive iodine therapy (RAI) in Makati Medical Center from 2013 to 2017. We collected the following factors through a review of charts: age at diagnosis, gender, family history of thyroid cancer, date of surgery, tumor size, capsular/lymphovascular invasion, lymph node/distant metastases, stage, risk of recurrence, dose of post-surgical RAI therapy, initial post-treatment serum Thyroglobulin (Tg) and anti-Tg antibody levels (Negative Tg level: suppressed non-stimulated Tg <0.2 ng/mL or TSH-stimulated Tg <1 ng/mL; Positive Tg level: suppressed Tg ≥1 ng/mL or a TSH-stimulated Tg ≥10 ng/mL or rising anti-Tg antibody levels), thyroid stimulating hormone suppression, post-operative imaging studies and levothyroxine dose. Response to therapy was checked 6-24 months post-therapy. RESULTS: We analyzed a total of 115 patients with PTC who underwent thyroidectomy. Patients who had family history of thyroid cancer were less likely to have an incomplete or indeterminate response (p=0.045). None of the patients with excellent response had lymphovascular invasion. Having a positive Tg (p=0.001) and positive anti-Tg post-operatively (p<0.001) were strongly associated with incomplete or indeterminate response. CONCLUSION: Patients who were positive for thyroglobulin and anti-thyroglobulin post-operatively were strongly associated with incomplete or indeterminate response to therapy in PTC.

Metastatic thyroid carcinoma to the parapharyngeal and retropharyngeal spaces: Systematic review with seven newly reported cases describing an uncommon presentation of a common disease.

BACKGROUND: Metastatic thyroid carcinoma to retropharyngeal and parapharyngeal (RP/PP) lymph nodes is rare. Literature suggests previous lateral neck dissection (LND) may alter patterns of lymphatic drainage in the neck, predisposing to these less common sites of spread. METHODS: PRISMA-guided systematic search for all published cases detailing RP/PP metastases of well-differentiated thyroid carcinoma from 1970 to 2019. RESULTS: Seventy articles were identified and 44 were included, along with seven cases treated at our institution, totaling 239 cases. Cases represented both retropharyngeal (60.7%) and parapharyngeal (39.3%) metastases identified in the initial (27.6%) and recurrent (72.4%) setting. CONCLUSION: RP/PP metastases generally present in the recurrent setting. RP/PP metastases often represent high-risk disease, and surgical treatment is recommended.

Well-Differentiated Thyroid Cancer Invading the Trachea in a Pediatric Patient.

OBJECTIVES: Pediatric thyroid cancer is rare. Most cases are well-differentiated thyroid cancers (WDTCs). However, gross laryngotracheal invasion of WDTCs is unusual. This report details the first case in English medical literature of a pediatric WDTC invading the trachea. METHODS: Thyroid stimulating hormone, free triiodothyronine, free thyroxine, thyroglobulin, parathyroid hormone, calcitonin, thyroglobulin antibody, chest magnetic resonance imaging, neck ultrasound, neck computed tomography, and fine needle aspiration were performed. RESULTS: A 9-year-old boy with moderate persistent asthma presented with increasing upper respiratory symptoms. Spirometry suggested a fixed upper airway obstruction. Chest x-ray revealed a left tracheal shift, and chest magnetic resonance imaging identified a right thyroid mass. Thyroglobulin level was 809 ng/mL (normal, ≤33 ng/mL). Results of thyroid stimulating hormone, free triiodothyronine, free thyroxine, parathyroid hormone, calcitonin, and thyroglobulin antibody were normal. Neck ultrasound revealed 2 right thyroid lobe nodules. Neck computed tomography revealed tracheal compression. Fine needle aspiration of the largest nodule yielded atypia of undetermined significance. Bronchoscopy findings at his local hospital were concerning for tracheal invasion. He underwent total thyroidectomy, cricotracheal resection, reconstruction, and radioactive iodine therapy (220 mCi). Pathology demonstrated a well-differentiated papillary thyroid carcinoma without solid or diffuse sclerosing subtype components. Tumor cytogenetic and single nucleotide polymorphism microarray studies showed normal findings. One year postoperatively, neck ultrasound demonstrated no recurrence, and thyroglobulin levels were undetectable while on levothyroxine therapy. CONCLUSION: Pediatric WDTC invading the trachea has not been reported.

Novel Therapeutics in Radioactive Iodine-Resistant Thyroid Cancer.

Iodine-resistant cancers account for the vast majority of thyroid related mortality and, until recently, there were limited therapeutic options. However, over the last decade our understanding of the molecular foundation of thyroid function and carcinogenesis has driven the development of many novel therapeutics. These include FDA approved tyrosine kinase inhibitors and small molecular inhibitors of VEGFR, BRAF, MEK, NTRK and RET, which collectively have significantly changed the prognostic outlook for this patient population. Some therapeutics can re-sensitize de-differentiated cancers to iodine, allowing for radioactive iodine treatment and improved disease control. Remarkably, there is now an FDA approved treatment for BRAF-mutated patients with anaplastic thyroid cancer, previously considered invariably and rapidly fatal. The treatment landscape for iodine-resistant thyroid cancer is changing rapidly with many new targets, therapeutics, clinical trials, and approved treatments. We provide an up-to-date review of novel therapeutic options in the treatment of iodine-resistant thyroid cancer.

A Study of Artificial Sweeteners and Thyroid Cancer Risk.

BACKGROUND: In recent decades, data from certain observational studies have stirred controversy over artificial sweeteners by linking them with certain malignancies. As the incidences of artificial sweetener consumption and thyroid cancer are both increasing, our study aimed to determine any possible association between them. METHODS: This retrospective observational study enrolled 50 patients (group 1) with proven diagnosis of well-differentiated thyroid cancer (WDTC) and 50 control subjects (group 2) diagnosed as having benign thyroid nodule by fine-needle aspiration. The survey questionnaire included the total amount and duration of intake of artificial sweeteners. RESULTS: Increased consumption of artificial sweeteners was noted in group 1 as compared to group 2, which was statistically significant (76% vs. 24%, P < 0.01). This study suggested that the use of an average of four packets (4 g) per day of artificial sweetener for an average duration of 5 years is associated with WDTC. CONCLUSIONS: Our study emphasizes the significance of artificial sweetener consumption as a potential risk factor for WDTC and increase in public awareness regarding this association if other studies in future report similar findings.