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The unobliterated portion of embryological thyroglossal duct may present as cystic swelling later in life and may contain functional thyroid follicles. This cyst requires excision along with the entire thyroglossal duct remnant and adjacent portion of hyoid bone. At times, the excised specimen could demonstrate a focus of carcinomatous change inside the cyst wall. Very rarely, this thyroglossal duct cyst carcinoma could be associated with malignancy of native thyroid gland. This case report illustrates an interesting case of synchronous carcinoma of thyroglossal duct cyst and native thyroid gland. It also sheds light on the controversies related to the pathophysiology of such association and the dilemmas surrounding the management of thyroglossal duct cyst carcinoma, with or without concurrent carcinoma of thyroid gland.

Thyroid mucoepidermoid carcinoma (MEC) is a rare thyroid malignancy first documented in 1977. The majority of thyroid MECs are indolent, low-grade tumours with excellent prognosis. A woman in her 60s presented with an ongoing sensation of a lump in the left neck. There were no swallowing, voice or airway concerns. Ultrasound of the neck showed an enlarged thyroid with U5 and U3 features on the right and left lobes, respectively. Right fine needle aspiration cytology (FNAC) demonstrated certain features of Hurthle cell or anaplastic carcinoma (Thy5). Left FNAC showed Hurthle cell changes with atypical cells and prominent nucleoli (Thy3a). Following total thyroidectomy, histopathology revealed synchronous right low-grade MEC and left papillary thyroid microcarcinomas (pT2(m) N0 M0) on a background of Hashimoto’s thyroiditis. This case adds to the literature and details the key histopathological features for a rare but important differential in patients with thyroid carcinoma due to synchronous histological types.

A woman in her 40s presented with a 3-month history of lower abdominal pain and intermenstrual bleeding. Ultrasound of the pelvis disclosed a 4 cm left adnexal mass. An MRI of the pelvis revealed a 2.2×3.6×2.4 cm solid, enhancing left ovarian mass. Due to high suspicion for malignancy, she underwent laparoscopic left salpingo-oophorectomy and resection of the tumour. Histopathology revealed papillary thyroid carcinoma in the background of struma ovarii as confirmed by thyroglobulin and thyroid transcription factor-1 positivity on immunohistochemistry. BRAF mutation analysis was negative. An ultrasound of the thyroid gland showed two low-risk nodules. An iodine-123 whole-body scan showed normal uptake in the thyroid gland. Thyroid-stimulating hormone (TSH) was 1.070 mcIU/mL (0.450–4.500), and thyroglobulin was 6.8 ng/mL (1.5–38.5). We risk-stratified this patient as low risk for recurrence. Risk stratification of malignant struma ovarii is essential to determine suitable thyroid targeting adjuvant therapy and reduce the risk of recurrence.

Struma ovarii (SO) is an uncommon monodermal teratoma predominantly composed of mature thyroid tissue. Approximately 5% of SO are malignant; however, metastases are rare. A single female in her 40s, with a medical history of Graves’ disease and bilateral cystectomy 10 years prior for right endometriotic cyst and left SO, presented with an enlarging abdominal mass for 4 months. Ultrasound pelvis showed a 13.8 cm left adnexal heterogeneous solid-cystic mass with internal septations and vascularity. She underwent open left salpingo-oophorectomy and resection of fibrous nodules from the right infundibulo-pelvic ligament and fallopian tube. Histology showed highly differentiated metastatic follicular carcinoma. She subsequently underwent total thyroidectomy, total hysterectomy, right salpingo-oophorectomy, tumour debulking and omentectomy followed by radioactive iodine treatment. Four-year follow-up did not show tumour recurrence or metastases. Due to its rarity, there are no well-established guidelines for the management and follow-up of metastatic follicular carcinoma arising from SO.

Follicular dendritic cell sarcoma is a rare low-grade sarcoma of mesenchymal origin. It involves the lymph nodes more commonly and rarely extranodal sites. The most common lymph node is cervical and usually presents as a painless asymptomatic mass. More often, it is a misdiagnosis, and there is a delay in treatment. It is rarely associated with Castleman disease, myasthenia gravis. Diagnosis of this condition is by histopathology and immunochemistry. Surgery is the primary modality of treatment, and adjuvant therapy has been tried with no definite trials due to the rarity of the disease. Here, we report a case of concomitant follicular dendritic sarcoma of the right cervical lymph node and papillary carcinoma of the thyroid managed in our institute. There was a line of investigations approaching towards a diagnosis, and she underwent total thyroidectomy and right modified radical neck dissection.

The elderly patient presenting with a neck lump often raises concerns regarding a malignancy. Thyroid gland malignancies are well recognised and subtype characteristics thoroughly researched, whereas rarer types of thyroid carcinoma are reported infrequently and often behave more aggressively. An 83-year-old woman was referred from the general practitioner (GP) to otolaryngology due to a 7-month history of an unexplained enlarging left-sided neck swelling. A fine-needle aspiration revealed cytology consistent with squamous cell carcinoma (SCC). Staging imaging failed to reveal evidence of a primary foci elsewhere. The definitive diagnosis was that of a primary thyroid SCC: a rare entity with limited citations in the literature. Surgical resection has been found to comprise the optimal treatment for this disease. Recognition of the possibility of primary thyroid SCC in elderly patients presenting with a neck lump, with prompt referral to a head and neck specialist permits a timely progression to potentially curative surgical management, a more promising prognosis and reduced mortality rates.

Thymosin beta-4 (TMSB4X) was recently identified as a differentially expressed gene between malignant and non-malignant thyroid cells via single-cell RNA sequencing. In the present study, we aimed to study the immunostaining pattern of TMSB4X in benign and malignant thyroid neoplasms. Immunohistochemical analysis revealed that normal thyroid tissue or benign thyroid disorders exhibited undetectable immunoreactivity against TMSB4X except for positive staining of inflammatory infiltrates and stromal cells associated with autoimmune thyroid disease. By contrast, overexpression of TMSB4X was observed in a variety of thyroid malignancies, including papillary, follicular, poorly differentiated, and undifferentiated thyroid cancer. Among 141 patients with differentiated thyroid cancer, higher TMSB4X expression was associated with papillary tumor type, extrathyroidal extension, lymph node metastasis, and BRAF V600E mutation. The results were consistent with those from the public transcriptomic datasets. In summary, TMSB4X expression was aberrantly increased in various types of thyroid cancer, and higher TMSB4X expression was correlated with advanced disease characteristics. Thymosin beta-4 may be a novel downstream effector of the BRAF V600E mutation.

This review discusses the current literature regarding low-value thyroid care in older adults, summarizing recent findings pertaining to screening for thyroid dysfunction and management of hypothyroidism, thyroid nodules and low-risk differentiated thyroid cancer.Despite a shift to a "less is more" paradigm for clinical thyroid care in older adults in recent years, current studies demonstrate that low-value care practices are still prevalent. Ineffective and potentially harmful services, such as routine treatment of subclinical hypothyroidism which can lead to overtreatment with thyroid hormone, inappropriate use of thyroid ultrasound, blanket fine needle aspiration biopsies of thyroid nodules, and more aggressive approaches to low-risk differentiated thyroid cancers, have been shown to contribute to adverse effects, particularly in comorbid older adults.Low-value thyroid care is common in older adults and can trigger a cascade of overdiagnosis and overtreatment leading to patient harm and increased healthcare costs, highlighting the urgent need for de-implementation efforts.

Background. Metastatic clear cell renal cell carcinoma (RCC) is one of the most common secondary thyroid malignancies. Diagnosis can be challenging, particularly if presenting many years after initial diagnosis. We reviewed clinicopathologic features and immunoprofile of metastatic clear cell RCC in thyroid. Design. We identified 17 patients from 2003-2021. Clinical data were obtained from medical records, and slides were retrieved and reviewed. Results. Seventeen patients (12 male and 5 female) included 12 thyroidectomies, 3 core biopsies, 1 excisional biopsy, and 1 fine-needle aspiration. The average patient age was 68.7 years (range, 45-88 years). Sixteen patients had history of clear cell RCC, and in 1 patient, the clear cell RCC was discovered after the thyroid metastasis was found. Thyroid gland metastases were on average diagnosed 90.7 months after the diagnosis of the renal primary (range, 24-240 months). Patients presented with a new palpable mass (n = 11) or dyspnea/stridor (n = 1). Five tumors were incidentally found via surveillance imaging. In 2 patients, metastases occurred within follicular thyroid neoplasms. All metastases showed conspicuous sinusoidal vasculature between the tumor nests and areas of myxoid degeneration. A prominent thick fibromuscular pseudocapsule was evident in 10 resections. Immunohistochemistry (n = 5) showed that the metastases were positive for PAX8, CA9, and CD10, while negative for keratin 7, thyroglobulin, and TTF1. Conclusions. Metastatic clear cell RCC involving the thyroid gland is infrequent and typically occurs remotely after the initial diagnosis. Cytologic and histologic features may show significant overlap with primary thyroid lesions. Immunohistochemistry can help reliably distinguish metastases from primary thyroid neoplasms.

lt;bgt;lt;igt;Background:lt;/igt;lt;/bgt; Oncogenic BRAF mutations are commonly found in advanced differentiated thyroid cancer (DTC), and reports have shown efficacy of BRAF inhibitors in these tumors. We investigated the difference in response between dabrafenib monotherapy and dabrafenib + trametinib therapy in patients with BRAF-mutated radioactive iodine refractory DTC.lt;bgt;lt;igt;Methods:lt;/igt;lt;/bgt; In this open-label randomized phase 2 multicenter trial, patients aged ≥18 years with BRAF-mutated radioactive iodine refractory DTC with progressive disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 within 13 months before enrollment were eligible. Patients were randomly assigned to receive dabrafenib alone or dabrafenib + trametinib. The primary endpoint was objective response rate by modified RECIST (minor response of -20% to -29%, partial and complete response) within the first 24 weeks of therapy. Trial Registration Number: NCT01723202.lt;bgt;lt;igt;Results:lt;/igt;lt;/bgt; A total of 53 patients were enrolled. The objective response rate (modified RECIST) was 42% (11/26 [95% confidence interval {CI} 23-63%]) with dabrafenib versus 48% (13/27 [CI 29-68%]) with dabrafenib + trametinib (lt;igt;plt;/igt; = 0.67). Objective response rate (RECIST 1.1) was 35% (9/26 [CI 17-56%]) with dabrafenib and 30% (8/27 [CI 14-51%]) with dabrafenib + trametinib. Most common treatment-related adverse events included skin and subcutaneous tissue disorders (17/26, 65%), fever (13/26, 50%), hyperglycemia (12/26, 46%) with dabrafenib alone and fever (16/27, 59%), nausea, chills, fatigue (14/27, 52% each) with dabrafenib + trametinib. There were no treatment-related deaths.lt;bgt;lt;igt;Conclusions:lt;/igt;lt;/bgt; Combination dabrafenib + trametinib was not superior in efficacy compared to dabrafenib monotherapy in patients with BRAF-mutated radioiodine refractory progressive DTC.

An 85-year-old woman who lived in Kanuma, Tochigi prefecture, Japan, presented to the emergency department of a hospital with dyspnoea, which developed 3 hours before the visit. At the time of presentation, she was in respiratory distress, with a blood pressure of 171/88 mm Hg, heart rate of 105

ImportanceSeveral less-invasive staging procedures have been proposed to replace axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC) in patients with initially clinically node-positive (cN+) breast cancer, but these procedures may fail to detect residual disease. Owing to the lack of high-level evidence, it is not yet clear which procedure is most optimal to replace ALND.ObjectiveTo determine the diagnostic accuracy of radioactive iodine seed placement in the axilla with sentinel lymph node biopsy (RISAS), a targeted axillary dissection procedure.Design, Setting, and ParticipantsThis was a prospective, multicenter, noninferiority, diagnostic accuracy trial conducted from March 1, 2017, to December 31, 2019. Patients were included within 14 institutions (general, teaching, and academic) throughout the Netherlands. Patients with breast cancer clinical tumor categories 1 through 4 (cT1-4; tumor diameter 5 cm or extension to the chest wall or skin) and pathologically proven positive axillary lymph nodes (ie, clinical node categories cN1, metastases to movable ipsilateral level I and/or level II axillary nodes; cN2, metastases to fixed or matted ipsilateral level I and/or level II axillary nodes; cN3b, metastases to ipsilateral level I and/or level II axillary nodes with metastases to internal mammary nodes) who were treated with NAC were eligible for inclusion. Data were analyzed from July 2020 to December 2021.InterventionPre-NAC, the marking of a pathologically confirmed positive axillary lymph node with radioactive iodine seed (MARI) procedure, was performed and after NAC, sentinel lymph node biopsy (SLNB) combined with excision of the marked lymph node (ie, RISAS procedure) was performed, followed by ALND.Main Outcomes and MeasuresThe identification rate, false-negative rate (FNR), and negative predictive value (NPV) were calculated for all 3 procedures: RISAS, SLNB, and MARI. The noninferiority margin of the observed FNR was 6.25% for the RISAS procedure.ResultsA total of 212 patients (median [range] age, 52 [22-77] years) who had cN+ breast cancer underwent the RISAS procedure and ALND. The identification rate of the RISAS procedure was 98.2% (223 of 227). The identification rates of SLNB and MARI were 86.4% (197 of 228) and 94.1% (224 of 238), respectively. FNR of the RISAS procedure was 3.5% (5 of 144; 90% CI, 1.38-7.16), and NPV was 92.8% (64 of 69; 90% CI, 85.37-97.10), compared with an FNR of 17.9% (22 of 123; 90% CI, 12.4%-24.5%) and NPV of 72.8% (59 of 81; 90% CI, 63.5%-80.8%) for SLNB and an FNR of 7.0% (10 of 143; 90% CI, 3.8%-11.6%) and NPV of 86.3% (63 of 73; 90% CI, 77.9%-92.4%) for the MARI procedure. In a subgroup of 174 patients in whom SLNB and the MARI procedure were successful and ALND was performed, FNR of the RISAS procedure was 2.5% (3 of 118; 90% CI, 0.7%-6.4%), compared with 18.6% (22 of 118; 90% CI, 13.0%-25.5%) for SLNB (P P = .03).Conclusions and RelevanceResults of this diagnostic study suggest that the RISAS procedure was the most feasible and accurate less-invasive procedure for axillary staging after NAC in patients with cN+ breast cancer.

Superior mediastinal lymph node metastases in papillary thyroid cancer are uncommon. The clinical characteristics and surgical strategy of superior mediastinal lymph node metastases remain unclear. Superior mediastinal lymphadenectomy can be accomplished either by a transcervical or transsternal approach. Transsternal approach for superior mediastinal lymphadenectomy can cause great damage; transcervical approach sometimes results in inadequate exposure. Here we report our experience of a papillary thyroid cancer patient with superior mediastinal lymph node metastases who underwent video-assisted superior mediastinal lymphadenectomy. A 49-year-old woman diagnosed with papillary thyroid cancer in left thyroid underwent unilateral lobectomy and ipsilateral central and lateral node dissection in the local hospital 4 years ago. Currently lymph node metastases were found in mediastinum and the right neck, some of which were adjacent to the right innominate vein. Unilateral lobectomy, ipsilateral central and lateral node dissection, and video-assisted superior mediastinal lymphadenectomy were successfully performed by transcervical approach. Subsequently, the patient received thyroxine suppression therapy and adjuvant radioiodine treatment. Video-assisted superior mediastinal lymphadenectomy, providing adequate exposure for a complete superior mediastinal lymphadenectomy, is proved to be safe and feasible.

There is a recent proliferation of clinical studies about the minimally invasive scarless thyroid surgery. The transoral endoscopic thyroidectomy vestibular approach (TOETVA) carries a great potential for being scarless surgery via a short dissection flap. However, TOETVA has limitations in extracting larger thyroid tumours via the transoral vestibular incision and due to its potential damage to the branches of the mental nerve. The rapidly evolving surgical innovations have now introduced transoral and submental thyroidectomy (TOaST) approach that allows extraction of large thyroid tumours with less flap dissection and minimal postoperative pain. We present a 39-year-old man with a large multinodular goitre. The patient was euthyroid with moderate to severe compression symptoms of difficulty in breathing and swallowing. We performed a TOaST procedure using intraoperative neuromonitoring and indocyanin green fluorescence imaging with an uneventful recovery. This is a first case report from the middle east region that will pave the way to large clinical trials to determine the efficacy and safety of TOaST.

Significant genotype-phenotype variability among multiple endocrine neoplasia type 2A patients with a RET V804M mutation has been reported.Patients with a RET V804M mutation treated at a single center were identified (January 1996-December 2020). The baseline characteristics, operative details, pathology, biochemical, and long-term data were analyzed.There were 79 patients; none developed pheochromocytoma or hyperparathyroidism or died in the study period. The mean age was 41.5 years (range = 1.0-81.0 years); 46.8% were men. Of 68 surgical patients, 53 (77.9%) underwent total thyroidectomy and 15 (22.1%) underwent total thyroidectomy with central neck dissection with or without lateral neck dissection. Twenty-four patients had elevated preoperative calcitonin, of whom 12 underwent total thyroidectomy (median = 7.5; range = 5.0-237.0 pg/mL), 10 underwent total thyroidectomy + central neck dissection (median = 27.6; range = 5.1-147.0 pg/mL), and 2 underwent total thyroidectomy + central neck dissection + lateral neck dissection (median = 3182.0; range = 361.0-6003.0 pg/mL). Pathology was benign (27.9%), papillary thyroid cancer alone (1.5%), C-cell hyperplasia (23.5%), and medullary thyroid cancer (47.1%; median tumor size = 3.0 mm). Three patients had elevated calcitonin postoperatively (median follow-up time = 60.0 months). In adjusted modeling, a preoperative calcitonin5 pg/mL was associated with having medullary thyroid cancer on final pathology (odds ratio = 13.3; 95% confidence interval, 3.2-56.3; P.001).In this large United States cohort of surgical patients with a RET V804M mutation, most had indolent disease and were without classic multiple endocrine neoplasia type 2A features. Calcitonin5 pg/mL may serve as a meaningful value to guide surveillance and timing of surgery.

Thyroid surgery at high-quality hospitals is associated with fewer complications. We evaluated the impact of referring older adults with thyroid cancer to higher-performing local hospitals.We performed a simulation study of Surveillance, Epidemiology, and End Results-Medicare patients, aged ≥66 years, who underwent a thyroidectomy for well-differentiated thyroid cancer (2013-2017). An 80% sample was used to calculate each hospital's risk-standardized 30-day serious adverse event rate, dividing hospitals into quartiles by performance. Hospitals located ≤30 miles of the remaining 20% of patients were compared, and 30-day serious adverse event rates and costs were simulated as if patients were treated at higher-quality hospitals using logistic regression with each alternative hospital's fixed-effect.We identified 8,946 patients who underwent thyroid resection at 843 hospitals. Average risk-adjusted serious adverse event rates ranged from 13.9% to 52.9% between quartile 1 and 4 hospitals (P.001). We identified higher-quality hospitals for 43.7% of patients. Simulating care at the best local hospital reduced predicted serious adverse event rates from 25.6% (95% confidence interval, 24.7-26.4) to 16.2% (95% confidence interval, 15.5-16.8; P.001), while modestly lowering average costs from $12,883 (95% confidence interval, 12,500-13,267) to $12,679 (95% confidence interval, 12,304-13,056; P = .029).Simulated care at higher-performing hospitals decreased serious adverse event rates after thyroid resection. Optimizing hospital selection may reduce postoperative morbidity without compromising preferences for local treatment.

Thyroid carcinoma (THCA) is a common malignancy of the endocrine system. Further understanding of the molecular mechanism underlying THCA is crucial to develop effective diagnostic therapy and improve its treatments. In this study, we intended to provide novel direction for THCA targeted therapy from the aspect of lncRNA-miRNA-mRNA interaction. We aimed to investigate the function and molecular mechanism of lncRNA ATP1A1-AS1 in THCA.Gene expression was assessed by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Cell growth was detected by CCK-8 and EdU assays. Flow cytometry was applied for analyzing cell apoptosis. The binding of ATP1A1-AS1 or IRF2BP2 to miR-620 was validated by RNA pulldown and luciferase reporter assays. The protein levels were examined by western blotting.ATP1A1-AS1 was decreased in THCA cells and tissues. ATP1A1-AS1 overexpression attenuated cell growth and promoted apoptosis. MiR-620, which was upregulated in THCA, was identified as a direct target of ATP1A1-AS1. Furthermore, IRF2BP2 was discovered to be a target of miR-620, which displayed low expression in THCA cells and tissues. Importantly, IRF2BP2 knockdown reversed the influence of ATP1A1-AS1 overexpression on THCA cell proliferation and apoptosis.LncRNA ATP1A1-AS1 inhibited cell growth and promotes apoptosis in THCA via the miR-620/IRF2BP2 axis.

Background: Cross-talk between mitogen-activated protein kinase and estrogen has been reported; however, the role of BRAFV600E in the estrogen responsiveness of thyroid cancer is unknown. We elucidated the effect of BRAFV600E on the estrogen-induced increase in metastatic potential in thyroid cancer.Methods: Using a pair of cell lines, human thyroid cell lines which harbor wild type BRAF gene (Nthy/WT) and Nthy/BRAFV600E (Nthy/V600E), the expression of estrogen receptors (ERs) and estrogen-induced metastatic phenotypes were evaluated. Susceptibility to ERα- and ERβ-selective agents was evaluated to confirm differential ER expression. ESR expression was analyzed according to BRAFV600E status and age (≤50 years vs. >50 years) using The Cancer Genome Atlas (TCGA) data.Results: Estradiol increased the ERα/ERβ expression ratio in Nthy/V600E, whereas the decreased ERα/ERβ expression ratio was found in Nthy/WT. BRAFV600E-mutated cell lines showed a higher E2-induced increase in metastatic potential, including migration, invasion, and anchorage-independent growth compared with Nthy/WT. An ERα antagonist significantly inhibited migration in Nthy/V600E cells, whereas an ERβ agonist was more effective in Nthy/WT. In the BRAFV600E group, ESR1/ESR2 ratio was significantly higher in younger age group (≤50 years) compared with older age group (>50 years) by TCGA data analysis.Conclusion: Our data show that BRAFV600E mutation plays a crucial role in the estrogen responsiveness of thyroid cancer by regulating ER expression. Therefore, BRAFV600E might be used as a biomarker when deciding future hormone therapies based on estrogen signaling in thyroid cancer patients.

This real-world retrospective database study quantified the costs of biomarker testing in a US population of patients with lung or thyroid cancers.The commercial claims IBM Marketscan database, a de-identified real-world dataset, was used to identify patients diagnosed with lung or thyroid cancer between 1/2015 and 12/2019. Eligible patients were 18 years or older with two or more lung or thyroid diagnosis codes. Patients were excluded who had evidence of prior cancer diagnoses. Subgroup analyses evaluated eligible patients with metastatic disease. Descriptive statistics were used to evaluate commercial insurance plan payer and patient out-of-pocket costs for diagnostic testing overall as well as by test procedure code and payer type. Costs were adjusted to 2020 US dollars.A total of 23,633 patients with lung cancer were eligible, 13,320 of whom had metastatic disease. There were 36,867 patients with thyroid cancer, 2,241 of whom had metastatic disease. Biomarker codes were observed among 68.4/75.8% (lung/metastatic lung) and 18.2/42.3% (thyroid/metastatic thyroid). Few patients had codes for comprehensive biomarker tests (5.2/6.7% lung/metastatic lung, 0.3/2.2% thyroid/metastatic thyroid) Among those with biomarker tests, the median per-patient total payer lifetime costs of all biomarker testing were $394/$462 (lung/metastatic lung) and $148/$232 (thyroid/metastatic thyroid). Total lifetime biomarker costs for payers ranged from a median of $128 (consumer-driven health plans) to $477 (preferred provider organizations). Median lifetime patient out-of-pocket costs were $0.00 for both tumor types and all payer types except for consumer-driven health plans ($12 for thyroid and $10 for metastatic lung).While comprehensive testing adds to the cost of biomarker testing, these data suggest the relatively low lifetime cost of biomarker testing for both payers and patients. Costs for biomarker testing should not be a limitation to access among these populations with commercial insurance plans in the US.This real-world retrospective database study found that there is a relatively low lifetime total cost of biomarker testing for the care of patients with lung or thyroid cancers. While comprehensive testing adds to the cost of biomarker testing, these data suggest the relatively low lifetime cost of biomarker testing for both payers and patients. Payer costs for biomarker testing do not appear to be limitation to access among populations with commercial insurance plans in this study.

After the first-round (Preliminary Baseline Survey) ultrasound-based examination for thyroid cancer in response to the accident at the Fukushima Daiichi Nuclear Power Plant in 2011, two rounds of surveys (Full-scale Survey) have been carried out in Fukushima Prefecture. Using the data from these surveys, the geographical distribution of thyroid cancer incidence over 6 or 7 years after the disaster was examined.Children and adolescents who underwent the ultrasound-based examinations in the second- and/or third-round (Full-scale) survey in addition to the first-round survey were included. With a discrete survival model, we computed age, sex, and body mass index standardized incidence ratios (SIRs) for municipalities. Then, we employed spatial statistics to assess geographic clustering tendency in SIRs and Poisson regression to assess the association of SIRs with the municipal average absorbed dose to the thyroid gland at the 59-municipality level.Throughout the second- and third-round surveys, 99 thyroid cancer cases were diagnosed in the study population of 252,502 individuals. Both flexibly shaped spatial scan statistics and maximized excess events test did not detect statistically significant spatial clustering (P = 0.17 and 0.54, respectively). Poisson regression showed no significant dose-response relationship: the estimated relative risks of lowest, middle-low, middle-high, and highest areas were 1.16 (95% confidence interval [CI], 0.52-2.59), 0.55 (95% CI, 0.31-0.97), 1.05 (95% CI, 0.79-1.40), and 1.24 (95% CI, 0.89-1.74).There was no statistical support for geographic clustering or regional association with radiation dose measures of the thyroid cancer incidence in the cohort followed up to the third-round survey (fiscal years 2016-2017) in Fukushima Prefecture.

The Fukushima Health Management Survey (FHMS) was established in response to the Fukushima Daiichi Nuclear Power Plant accident on March 11, 2011. The primary objectives of the study are to monitor residents' long-term health and promote their future well-being, and to determine the health effects of long-term low-dose radiation exposure. This special issue summarizes the results and current status of the FHMS and discusses the challenges and future directions of the FHMS. The FHMS, a cohort study of all people who were residents in Fukushima Prefecture at the time of the accident, consists of a Basic Survey, Thyroid Ultrasound Examination, Comprehensive Health Check, Mental Health and Lifestyle Survey, and Pregnancy and Birth Survey. The radiation exposure was estimated based on the behavioral records examined using the Basic Survey. Although the response rate was low in the Basic Survey, the representativeness of the radiation exposure data was confirmed using additional surveys. There appears to be no relationship between the radiation exposure and risk of thyroid cancer, although more thyroid cancer cases were detected than initially expected. The ongoing Comprehensive Health Check and Mental Health and Lifestyle Survey have provided evidence of worsening physical and mental health status. The Pregnancy and Birth Survey showed rates of preterm delivery, low birth weight, and congenital abnormalities similar to the national average. Considering the above evidence, the Fukushima Prefectural Government decided to end the Pregnancy and Birth Survey at the end of March 2021, as recommended by the Prefectural Oversight Committee. The framework of the FHMS has not changed, but the FHMS needs to adapt according to the survey results and the changing needs of the eligible residents and municipalities.

Quercetin, a flavonoid with anti-inflammatory and anticancer properties, is expected to be an innovative anticancer therapeutic agent for papillary thyroid carcinoma (PTC). However, the downstream signaling pathways that mediate quercetin-dependent anticancer properties remain to be deciphered. Herein, potential targets of quercetin were screened with several bioinformatic avenues including PharmMapper, Gene Expression Omnibus (GEO) database, protein–protein interaction (PPI) network, and molecular docking. Besides, western blot, CCK-8 transwell analysis of migration and invasion, flow cytometric analysis, and colony formation assays were performed to investigate the underlying mechanism. We found four core nodes (MMP9, JUN, SPP1, and HMOX1) by constructing a PPI network with 23 common targets. Through functional enrichment analysis, we confirmed that the above four target genes are enriched in the TNF, PI3K-AKT, and NF-κB signaling pathways, which are involved in the inflammatory microenvironment and inhibit the development and progression of tumors. Furthermore, molecular docking results demonstrated that quercetin shows strong binding efficiency with the proteins encoded by these 4 key proteins. Finally, quercetin displayed strong antitumor efficacy in PTC cell lines. In this research, we demonstrated the application of network pharmacology in evaluating the mechanisms of action and molecular targets of quercetin, which regulates a variety of proteins and signaling pathways in PTC. These data might explain the mechanism underlying the anticancer effects of quercetin in PTC.

BACKGROUND Many patients with papillary thyroid cancer (PTC) demonstrate satisfactory outcomes. However, 8%-28% of patients with PTC show tumor recurrence, which may affect prognosis. Therefore, identifying factors associated with tumor recurrence in patients with PTC may be helpful to refine therapeutic strategies. PATIENTS AND METHODS To identify factors associated with PTC recurrence, we retrospectively reviewed demographic features (sex and age), operation method, image character, serum thyroglobulin (Tg), accumulated radioactive iodine (I-131) therapeutic dose, I-131 uptake, and metastases at diagnosis in 829 patients with PTC. Patients were grouped into early (stage I and II; n = 698) and advanced (stage III and IV; n = 131) tumor-node-metastasis (TNM) stages. Recurrence rate, mortality rate, risk factors of recurrence, recurrent free survival and overall survival curve were compared between two groups. RESULTS Patients in the early stage demonstrated a lower recurrence rate (7.2%) than did those in the advanced stage (28.2%, p < 0.05). The mortality rate of patients with recurrence in the advanced stage was higher than that of those in the early stage (51.4% vs. 12.0%). The major impact factors on tumor recurrence in early TNM stage were distant metastasis and lymph node metastasis, while in advanced TNM stage were distant metastasis, male gender, total thyroidectomy with limited lymph node dissection, and a high serum Tg level. CONCLUSIONS Strategies to monitor tumor recurrence might be refined according to the TNM stages of PTC patients.

To identify factors associated with radioactive iodine (RAI)-acquired nasolacrimal duct obstruction (NLDO).Retrospective chart review and telephone surveys of patients who received RAI therapy for thyroid carcinoma at an academic institution were conducted. Telephone surveys were used to screen for post-RAI NLDO diagnoses. Databases were reviewed for documented NLDO, demographics, RAI dose, total number of RAI treatments, and sialadenitis. Routine post-RAI whole-body scintigraphy (WBS) images were analyzed for the presence or absence ofOf the 209 patients who completed the survey, 15 (7%) had NLDO diagnoses. Increased intranasal I-131 activity on WBS, presence of nasolacrimal I-131 WBS activity, presence of documented post-RAI sialadenitis, and history of1 RAI treatment were associated with the development of NLDO from univariate analyses (P ≤ .013). After adjusting for the administered dose of I-131, the presence of sialadenitis and nasolacrimal I-131 activity on WBS were the remaining 2 factors significantly associated with NLDO development (P .001 and P = .01, respectively).The presence of sialadenitis and nasolacrimal I-131 activity on WBS are I-131 dose-independent correlative factors for RAI-associated NLDO. Patients with these characteristics should be counseled on their increased risk of NLDO after RAI therapy for thyroid carcinoma.

Patients with slowly progressive and/or symptomatic oligometastatic radioactive iodine refractory (RAIR) differentiated thyroid carcinomas (DTCs) are candidates to receive locoregional treatment to delay the start of systemic therapy with multikinase inhibitors. Information provided by the recent literature has not been extensively reviewed in previous published works, thus we aim to bridge this gap.We present for each metastatic site the different locoregional treatment options, contraindications and potential adverse events. Some techniques can be combined together, whereas others are discouraged in certain situations, requiring a high level of expertise and multidisciplinarity in the treatment algorithm.Different techniques of radiation therapy and interventional radiology allow to control the metastatic spread. However, as no clinical trials are available to compare the treatment schemes in terms of safety and potential impact on the prognosis, the most appropriate option for each patient should be selected within a multidisciplinary decision making, taking into account the clinical conditions and the pattern/rapidity of metastatic disease.

DICER1 mutated thyroid nodules are commonly seen in pediatric populations often, as part of DICER1 syndrome. We seek to evaluate DICER1 mutated thyroid nodules in adult populations to assess whether there exists distinctive clinical, cytologic, histologic, and molecular characteristics that underline our institutional cohort.Retrospective analysis was performed on all fine-needle aspiration (FNA) specimens with a corresponding ThyroSeq panel, to select a cohort of cases with DICER1 mutations. Clinical, radiologic, and cytology materials were reviewed, and histology was reviewed for corresponding resection cases were available. ThyroSeq panel was further scrutinized for additional molecular alterations and variant allele frequency.DICER1 mutated thyroid nodules (n = 8), more commonly occurred in younger adults (P = 0.01) with larger (P = 0.01) nodules and only in female patients in our cohort. FNA commonly demonstrates cellular specimens with banal cytomorphologic cues including regular nuclei, inconspicuous nucleoli, smooth nuclear membranes, and abundant colloid. On retrospective review by 2 cytopathologists, the lesions were frequently diagnosed as Bethesda II (5 of 8) by both reviewers. Histology, when available, showed that all nodules were categorized as follicular adenomas (5 of 5), often demonstrating macrofollicles with papillary excrescences demonstrating bland nuclei (4 of 5). DICER1 mutational profile revealed a variant allele frequency ofgt;40% in 25% of cases (2 of 8) andgt;30% in an additional 4 cases, highlighting a possible germline association.DICER1 mutated nodules may be under-reported due to banal cytomorphologic features and may be associated with an underlying germline alteration.

BACKGROUND: Thyroid carcinoma is one of the most common malignancies worldwide. More than 70%-80% are papillary thyroid carcinoma (PTC). Many factors influence the PTC pathway of development such as genetic mutations, growth factors, and radiation. More biological understanding of the genetic and molecular pathways is needed in PTC to determine tumor behavior, and initial clinical assessment. OBJECTIVES: Investigate the relation of COX-2 immunostaining in thyroid carcinoma with clinicopathological parameters to assess whether immunostaining results have prognostic significance. DESIGN: Retrospective study SETTING: Pathology department, tertiary care center METHODS: Records of PTC were retrieved and tissue microarrays were constructed. Tissue sections were stained using anti-human COX-2 monoclonal antibody. Immunostaining results were recorded and analysed. MAIN OUTCOME MEASURES: Relationship of COX-2 immunostaining in thyroid carcinoma with clinicopathological parameters. SAMPLE SIZE: 139 tissue samples from 139 patients RESULTS: High versus low COX-2 immunostaining showed no significant differences for most clinicopathological parameters. However, high COX-2 immunostaining showed borderline association with tumor multifocality ( P =.05), lower overall (log-rank=8.739 and P =.003), and disease-free survival (log-rank=7.033, P =.008). CONCLUSION: The study showed a positive association of high COX-2 immunostaining with lower survival outcomes in PTC. COX-2 immunostaining could be a potential prognostic factor for survival in PTC. Additional molecular and clinical investigations are needed for further understanding the molecular pathways of COX-2 in PTC and the feasibility of using inhibitors of COX-2 as adjuvant therapy along with current chemotherapy. LIMITATIONS: Relatively low number of PTC variants, and no testing of other thyroid carcinomas. CONFLICT OF INTEREST: None.

Background Fine-needle aspiration cytology (FNAC) is an integral part of thyroid nodule assessment. Nodules with an indeterminate cytology (THY3a–f) require formal histological assessment to confirm benign or malignant pathology. This study aimed to provide data for an evidence-based approach for management of patients with THY3f nodules. Methods Retrospective review of patients who had a thyroid FNAC reported as suspicious of follicular neoplasm (THY3f) or showing atypia (THY3a) were identified, and clinical, operative and outcomes data were analysed. Results Between 2018 and 2020, 200 patients (167F:33M, median age 51 years (range:18–86 years)) had a THY3f cytology. Most presented with a palpable nodule (n=104; 68.4%). Overall, 152 (76.0%;130F:23M) underwent surgery and 31 (20.4%) were found to have a thyroid carcinoma (22 follicular carcinomas, 7 papillary carcinomas, 1 medullary thyroid carcinoma and 1 metastatic renal carcinoma). An additional incidental carcinoma (size: 0.7–13mm) was found in seven (4.6%). Among those with cancer, a completion thyroidectomy and radioactive iodine treatment was indicated in nine (4cm) or age, were not found to be associated with increased risk. During the same period, THY3a cytology was reported in 53 patients, of whom 29 underwent diagnostic surgery and 4 patients were found to have a thyroid cancer (follicular, n=3 and medullary, n=1). Conclusion One in five patients with features suspicious of a follicular neoplasm (THY3f) has a thyroid carcinoma. This risk is much lower for THY3a. This study reinforces the current recommendation for thyroid surgery in all patients with a reliable THY3f cytology, as no further stratifying risk factors could be identified.

Thyroglobulin antibodies (TgAb) trend may be considered a surrogate marker for thyroglobulin in differentiated thyroid carcinoma. The aim of this study is to analyse, in cases with positive TgAb, trend over time and its relationship with response to treatment.Retrospective and descriptive study of 100 patients with differentiated thyroid carcinoma and positive TgAb (measured by electrochemoluminiscense) after thyroidectomy. Assessment of response to initial treatment was performed 6-24 months after surgery. Status at last follow-up was evaluated.After the first year nearly half of the patients showed a reduction in TgAb levels ≥50%, in 91% of these patients, status at last follow up was excellent response (65%) or indeterminate response due to decreasing TgAb levels (26%). At first assessment, indeterminate responses were found in 49% of cases, without significant differences among initial risk of recurrence category or whether radioiodine ablation was performed. At last evaluation (median 53.5 months), 15% of ablated low-risk patients had an indeterminate response (due to declining TgAb), vs 62% in the non-ablated low-risk group (p 0.03). Median time to negativization for post-surgical TgAb levels100UI/ml was 11 months [3-94] vs 31 months [8-119] for patients with TgAb≥100UI/ml (p 0.0003).A reduction of ≥50% in TgAb levels during the first year correlated with favourable outcomes. Non-ablated patients and patients with higher levels of post-surgical TgAb may need a longer time to achieve negative conversion.

PTEN is one of the most commonly inactivated tumour suppressor genes in sporadic cancer. Germline heterozygous PTEN gene alterations also underlie PTEN hamartoma tumour syndrome (PHTS), a rare human cancer-predisposition condition. A key feature of systemic PTEN deregulation is the inability to adequately dampen PI3-kinase (PI3K)/mTORC1 signalling. PI3K/mTORC1 pathway inhibitors such as rapamycin are therefore expected to neutralise the impact of PTEN loss, rendering this a more druggable context compared with those of other tumour suppressor pathways such as loss of TP53. However, this has not been explored in cancer prevention in a model of germline cancer predisposition, such as PHTS. Clinical trials of short-term treatment with rapamycin have recently been initiated for PHTS, focusing on cognition and colon polyposis. Here, we administered a low dose of rapamycin from the age of 6 weeks onwards to mice with heterozygous germline Pten loss, a mouse model that recapitulates most characteristics of human PHTS. Rapamycin was well tolerated and led to a highly significant improvement of survival in both male and female mice. This was accompanied by a delay in, but not full blockade of, the development of a range of proliferative lesions, including gastro-intestinal and thyroid tumours and endometrial hyperplasia, with no impact on mammary and prostate tumours, and no effect on brain overgrowth. Our data indicate that rapamycin may have cancer prevention potential in human PHTS. This might also be the case for sporadic cancers in which genetic PI3K pathway activation is an early event in tumour development, such as endometrial cancer and some breast cancers. To the best of our knowledge, this is the first report of a long-term treatment of a germline cancer predisposition model with a PI3K/mTOR pathway inhibitor. © 2022 The Authors. The Journal of Pathology published by John WileySons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Thyroid nodules are very common. Most of them are benign non-secerning incidentally found nodules - thyroid incidentalomas. Ultrasound (US) is an essential initial diagnostic tool in thyroid nodules management. Based on the US character, thyroid nodules should be classified to one of the US risk categories (TIRADS - Thyroid Imaging Reporting and Data System). Based on the US risk category and size, some nodules should be referred to fine needle aspiration with cytological evaluation of the sample (FNAC), some should be followed just by US, and some require no follow-up. Further management depends on the FNAC (Bethesda category) and US risk category. In most nodules (Bethesda category II, repeatedly Bethesda category I, some of the nodules of Bethesda category III), just defensive management is recommended (US and/or clinical follow-up, or no follow-up). Usually, only few cases require diagnostic (Bethesda categories III, IV and V) or therapeutic (Bethesda V and VI) surgery. In decision-making of management of nodules Bethesda category III and V, molecular testing for mutations associated with thyroid cancer and serum calcitonin could be useful.

The effectiveness of using serum thyroglobulin (TG) to predict thyroid cancer recurrence after a thyroid lobectomy is unknown. This study aimed to evaluate the predictive nature of serum TG and TG trends after thyroid lobectomies.We analyzed 514 papillary thyroid cancer (PTC) patients. The pre-, low-, high, and last-TG levels were reviewed and stratified into three groups. An ascending TG trend was defined if the last-TG level was more than 200% as high as the value of low-TG level. A descending trend was defined if the last-TG level decreased by more than 50% and a flat trend as between them.During a median follow-up period of 73.0 months, there were 21 (4.1%) recurrences. Most patients showed a descending (54.1%) or flat (35.6%) TG trend, but 10.3% of patients showed an ascending TG trend. Overall and lateral recurrences were significantly higher in the ascending TG group, indicating that an ascending TG trend was a good predictor for recurrence. Other factors such as positive node ratio (PNR), patient risk, age, and sex were not significant risk factors. In a Kaplan-Meier analysis, ascending TG trend was a good predictor of lateral recurrence.TG levels as a predictor of papillary cancer recurrence after thyroid lobectomy were found to be poor classifiers, and optimal cut-off values were not verified. An ascending TG trend was a good predictor of lateral recurrence. Further studies are warranted to investigate whether an ascending TG trend was due to an incomplete thyroid lobectomy or if the cancer had already metastasized to the lateral compartment.

Some pediatric papillary thyroid carcinoma (PPTC) cohorts have suggested a preliminary correlation with respect to DICER1 mutation status and histomorphology in both benign and malignant follicular cell-derived nodules; however, the data regarding correlates of DICER1-related sporadic PPTCs subtyped based on the 2022 WHO classification criteria are largely unavailable. The current study investigated the status of hotspot DICER1 mutations with clinical, histological and outcome features in a series of 56 patients with PPTCs with no clinical or family history of DICER1-related syndromic manifestation. Fifteen (27%) PPTCs harbored BRAF p.V600E. Eight (14%) cases of PPTCs harbored DICER1 mutations with no associated BRAF p.V600E. DICER1 mutations were identified in exons 26 and 27. A novel D1810del (c.5428_5430delGAT) mutation was also detected. We also confirmed the absence of hotspot DICER1 mutations in the matched non-tumor tissue DNA in all 8 DICER1-related PPTCs. The mean age of DICER1-harboring PPTCs was 15.1 (range: 9-18) years whereas the rest of this cohort had a mean age of 14.8 (range 6-18) years. With the exception of one PPTC, all DICER1-related PPTCs were seen in females (female-to-male ratio: 7). The female to male ratio was 3.8 in 48 DICER1-wild type PPTCs. In terms of histological correlates, 5 of 8 (63%) DICER1-mutant PPTCs were invasive encapsulated follicular variant papillary thyroid carcinomas (FVPTCs) including 4 minimally invasive FVPTCs and 1 encapsulated angioinvasive FVPTC, whereas the remaining 3 PPTCs were infiltrative classic papillary thyroid carcinomas (p 0.05). The incidence of DICER1 mutations was 19.5% in BRAF p.V600E-wild type PPTCs. Sixty-three percent of DICER1 hotspot mutations occurred in invasive encapsulated FVPTCs, and this figure represents 38% of invasive encapsulated FVPTCs. Only one (12%) patient with DICER1-related disease showed a single lymph node with micro-metastasis. Unlike DICER1-wild type patients, no distant metastasis is identified in patients with DICER1-related PPTCs. The current series expands on the surgical epidemiology of somatic DICER1-related PPTCs by correlating the mutation status with the clinicopathological variables. Our findings underscore that female gender predilection and enrichment in low-risk follicular-patterned PTCs are characteristics of DICER1-related PPTCs.

Anaplastic thyroid carcinoma (ATC) are highly aggressive malignant tumors with poor overall prognosis despite multimodal therapy. As ATC are extremely rare, no randomized controlled study has been published for metastatic disease. Thyrosine kinase inhibitors, especially lenvatinib and immune checkpoint inhibitors such as pembrolizumab, are emerging drugs for ATC. Few studies have reported the efficacity of pembrolizumab and lenvatinib association, resulting in its frequent off-label use. In this review, we discuss rationale efficacy and safety evidence for the association of lenvatinib and pembrolizumab in ATC. First, we discuss preclinical rationale for pembrolizumab monotherapy, lenvatinib monotherapy and synergistic action of pembrolizumab and lenvatinib in the metastatic setting. We also discuss clinical evidence for immunotherapy and pembrolizumab in ATC through the analysis of studies evaluating immunotherapy, lenvatinib and pembrolizumab lenvatinib association in ATC. In addition, we discuss the safety of this association and potential predictive biomarkers of efficiency.

Female thyroid cancer survivors are more likely to have a higher risk of breast cancer compared to the general population, and the underlying causes are yet to be understood. The potential role of I-131 treatment on this association remains controversial.We pooled individual data of women who were treated for differentiated thyroid cancer from 1934 to 2005 in France, Italy and Sweden. Standardized incidence ratios (SIRs) for breast cancer were estimated by comparison with age, sex and calendar-year expected values of the general population in each country. We estimated breast cancer risk in relation to I-131 treatment using time-dependent Poisson models.Of 8475 women (mean age at diagnosis: 45 years, range 2-90 years), 335 were diagnosed with breast cancer [SIR = 1.52, 95% confidence interval (CI): 1.36-1.69] during a median follow-up time of 12.7 years since diagnosis. Overall, breast cancer risk did not differ between women treated or not with I-131 (relative risk=1.07, 95% CI 0.84-1.35). However, breast cancer risk increased with increasing cumulative I-131 activity, without significant departure from linearity (excess relative risk per 100 mCi=17%, 95% CI: 2% to 38%). The higher risk associated with a cumulative I-131 activity of ≥100 mCi and ≥400 mCi was translated into 4 (95% CI -4 to 13) and 42 (95% CI -8 to 93) excess breast cancer cases per 10,000 person-years, respectively.An elevated risk was observed for the highest cumulative administered activity (=400 mCi), and a significant dose-dependent association was observed among thyroid cancer survivors who were treated with I-131. However, overall, I-131 treatment might only explain partly the increase in breast cancer risk among female thyroid cancer survivors.

Cancer progression is associated with metabolic reprogramming and causes significant intracellular stress; however, the mechanisms that link cellular stress and growth signalling are not fully understood. Here, we identified a mechanism that couples the mitochondrial stress response (MSR) with tumour progression. We demonstrated that the MSR is activated in a significant proportion of human thyroid cancers via the upregulation of heat shock protein D family members and the mitokine, growth differentiation factor 15. Our study also revealed that MSR triggered AKT/S6K signalling by activating mTORC2 via activating transcription factor 4/sestrin 2 activation whilst promoting leucine transporter and nutrient-induced mTORC1 activation. Importantly, we found that an increase insupmt/supDNA played an essential role in MSR-induced mTOR activation and that crosstalk between MYC and MSR potentiated mTOR activation. Together, these findings suggest that the MSR could be a predictive marker for aggressive human thyroid cancer as well as a useful therapeutic target.

This review focuses on patients with differentiated thyroid carcinoma (DTC) associated with multiple primary malignant neoplasm (MPMN) treated by multikinase inhibitors (MKIs) as systemic treatment for advanced disease. Despite the increasing frequency of MPMNs (many at an advanced stage) and the usefulness of MKIs for multiple metastatic cancers, published data on the management of MPMN and MKI therapies in this scenario are scarce. There are infrequent descriptions of patients with advanced MPMN treated with MKIs, but only a few have described advanced DTC. The management of MPMNs, including DTC and its particular circumstances, is reviewed, focusing on the evidence for MKI therapies. Some considerations for MPMN patients with advanced DTC are discussed, with the intention of helping physicians make decisions in these challenging situations and improving treatment and patient outcomes.

In this article, we focus on a variety of immunosuppression scenarios and whether multikinase inhibitors, as systemic therapy for advanced thyroid carcinoma (TC), could be useful for the treatment of immunocompromised patients with TC. Lenvatinib and sorafenib, among other MKIs, have become the standard of care for advanced TC based on their efficacy data and despite their adverse effects. Currently, published data on MKIs in immunosuppressed patients are scarce. Secondary malignancies can arise in immunosuppressed patients who have undergone solid organ transplantation, human immunodeficiency virus-infected patients, and hematopoietic stem cell transplant recipients. This review will explore different immunosuppression settings, the risk of secondary malignancies in immunosuppressed patients, and the special characteristics of this population. Some considerations regarding anticancer treatment in immunosuppressed patients with advanced malignancies are reviewed.

Lateral cervical lymph node metastases (LNM) for pediatric patients with papillary thyroid cancer (PTC) is a poor prognostic factor. We aimed to identify risk factors for lateral LNM.This retrospective study had included 48 pediatric patients with papillary thyroid cancer underwent total thyroidectomy and central cervical lymphadenectomy at K hospital from 2016 to 2020.The number of patients in each T stage was as follows: 24 (50.0%) in stage 1, 9 (18.7%) in Stage 2, 8 (16.7%) in Stage 3, and 7 (14.6%) in Stage 4. Most of the patients had LNM with N1a and N1b rates of 83.3% and 62.5%, respectively. Lung metastases were observed at presentation in three patients (6.3%). Univariate analysis revealed that age (p = 0.021), male (p = 0.011), tumor size10 mm (p = 0.002), multifocality (p0.001), extrathyroidal extension (p = 0.001) and central LNM (p0.001) were factors that increase the risk of metastasis to lateral LNM.Approximately 62.5% of pediatric patients with PTC exhibited lateral LNM at the time of diagnosis. Our study confirmed that multifocality, maximum tumor diameter, extrathyroidal extension and central LNM were independent risk factors for lateral LNM in pediatric PTC.Level IV.