Malignancy Rates by Bethesda Subcategory in the Pediatric Population.

INTRODUCTION: While the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is the most widely used method for categorizing thyroid nodules, its applicability to children is often debated. We describe our institution's experience utilizing the TBSRTC and examine the rates of malignancy in our population. METHODS: We conducted a retrospective chart review of eligible patients undergoing primary thyroidectomy at a high-volume tertiary care pediatric hospital. All patients had pre-operative fine needle aspiration. RESULTS: Of the 112 patients in our cohort, 85 (76%) were female. The median age was 15.1 years. The patients were divided into groups based on the Bethesda categorization of the fine needle aspirations of their nodules. The percentages of patients whose resection specimens showed evidence of malignancy on the surgical pathology reports were recorded as follows: category I (n = 5): 20%, category II (n = 11): 0%, category III (n = 30): 17%, category IV (n = 13): 31%, category V (n = 17): 94% and category VI (n = 36): 100%. CONCLUSION: Our findings indicate that the malignancy rates at our institution are comparable to those reported by other high-volume studies. When compared with the 2017 TBSRTC data, we found that our results were similar in many categories, with the exception of categories I and V.

Integrated DNA and RNA sequencing reveals targetable alterations in metastatic pediatric papillary thyroid carcinoma.

BACKGROUND: Pediatric papillary thyroid carcinoma (PTC) is clinically and biologically distinct from adult PTC. We sequenced a cohort of clinically annotated pediatric PTC cases enriched for high-risk tumors to identify genetic alterations of relevance for diagnosis and therapy. METHODS: Tumor DNA and RNA were extracted from FFPE tissue and subjected to next-generation sequencing (NGS) library preparation using a custom 124-gene hybridization capture panel and the 75-gene Archer Oncology Research Panel, respectively. NGS libraries were sequenced on an Illumina MiSeq. RESULTS: Thirty-six pediatric PTC cases were analyzed. Metastases were frequently observed to cervical lymph nodes (29/36, 81%), with pulmonary metastases less commonly found (10/36, 28%). Relapsed or refractory disease occurred in 18 patients (18/36, 50%). DNA sequencing revealed targetable mutations in 8 of 31 tumors tested (26%), most commonly BRAF p.V600E (n = 6). RNA sequencing identified targetable fusions in 13 of 25 tumors tested (52%): RET (n = 8), NTRK3 (n = 4), and BRAF. Mutually exclusive targetable alterations were discovered in 15 of the 20 tumors (75%) with both DNA and RNA analyzed. Fusion-positive PTC was associated with multifocal disease, higher tumor staging, and higher American Thyroid Association risk levels. Both BRAF V600E mutations and gene fusions were correlated with the presence of cervical metastases. CONCLUSIONS: Targetable alterations were identified in 75% of pediatric PTC cases with both DNA and RNA evaluated. Inclusion of RNA sequencing for detection of fusion genes is critical for evaluation of these tumors. Patients with fusion-positive tumors were more likely to have features of high-risk disease.

miRNA expression can classify pediatric thyroid lesions and increases the diagnostic yield of mutation testing.

BACKGROUND: Genetic alterations in multiple cell signaling pathways are involved in the molecular pathogenesis of thyroid cancer. Oncogene mutation testing and gene-expression profiling are routinely used for the preoperative risk management of adult thyroid nodules. In this study, we evaluated the potential value of miRNA biomarkers for the classification of pediatric thyroid lesions. PROCEDURE: Double-blind case-control study with 113 resected pediatric lesions: 66 malignant and 47 benign. Quantitative and qualitative molecular data generated with a 10-miRNA expression panel (ThyraMIR) and a next-generation sequencing oncogene panel (ThyGeNEXT) were compared with clinicopathological parameters. RESULTS: miRNAs were differentially expressed in benign versus malignant tumors with distinct expression patterns in different histopathology categories. The 10-miRNA classifier identified 39 (59%) malignant lesions with 100% specificity. A positive classifier score was associated with lymph node metastasis, extrathyroidal extension and intrathyroidal spread. Genetic alterations associated with increased risk for malignancy were detected in 35 (53%) malignant cases, 20 positive for point mutations in BRAF, HRAS, KRAS, NRAS, PIK3CA, or TERT and 15 positive for gene rearrangements involving ALK, NTRK3, PPARG, or RET. The 10-miRNA classifier correctly identified 11 mutation-negative malignant cases. The performance of the combined molecular test was 70% sensitivity and 96% specificity with an area under the curve of 0.924. CONCLUSIONS: These data suggest that the regulatory miRNA pathways underlying thyroid tumorigenesis are similar in adults and children. miRNA expression can identify malignant lesions with high specificity, augment the diagnostic yield of mutation testing, and improve the molecular classification of pediatric thyroid nodules.

AGK-BRAF is associated with distant metastasis and younger age in pediatric papillary thyroid carcinoma.

BACKGROUND: The incidence of thyroid carcinoma has increased in most populations, including pediatric patients. The increase is almost exclusively due to an increase in the incidence of papillary thyroid carcinoma (PTC). Genetic alterations leading to mitogen-activated protein kinase (MAPK) pathway activation are highly prevalent in PTC, with BRAF V600E mutation being the most common event in adult PTC. Although a lower prevalence of BRAF V600E had been reported among pediatric patients, a higher prevalence of BRAF fusion has been identified in both radiation-exposed and sporadic pediatric PTC. However, little is known about the prognostic implications of BRAF fusions in pediatric PTC. PROCEDURE: In this study, we investigated the prevalence of BRAF alterations (AGK-BRAF fusion and BRAF V600E mutation) in a large set of predominantly sporadic pediatric PTC cases and correlate with clinicopathological features. Somatic AGK-BRAF fusion was investigated by RT-PCR and confirmed by FISH break-apart. The BRAF V600E mutation was screened using Sanger sequencing. RESULTS: AGK-BRAF fusion, found in 19% of pediatric PTC patients, was associated with distant metastasis and younger age. Conversely, the BRAF V600E, found in 15% of pediatric PTC patients, was correlated with older age and larger tumor size. CONCLUSION: Collectively, our results advance knowledge concerning genetic bases of pediatric thyroid carcinoma, with potential implications for diagnosis, prognosis, and therapeutic approaches.

Risk of second malignancies among survivors of pediatric thyroid cancer.

BACKGROUND: Thyroid carcinoma is a very rare tumor in the pediatric age group, accounting for only 1.5-3% of childhood carcinomas in the United States and Europe. We aimed to identify the risk of a second malignancy among pediatric thyroid cancer survivors. METHODS: The cohort analysis consisted of pediatric cancer patients aged less than 20 years, diagnosed with a primary thyroid cancer, identified by site code ICD-0-3: C739, and reported to the SEER 9 database between 1973 and 2013. They were followed up until December 31, 2013; the end of the study period, or up to death if earlier. RESULTS: Out of 1769 patients diagnosed primarily with thyroid carcinoma, 42 patients had a total of 45 incidences of subsequent malignancies. The mean age of patients at the initial diagnosis of thyroid cancer was 16 years. Females (90.5%) had a significantly higher incidence of second malignancies (SM) than males (9.5%). The overall Standardized Incidence Ratio (SIR) of SM in the study patients was higher than expected (SIR = 1.48). Some specific sites showed significantly higher incidences: the salivary glands (SIR = 33.95), the gum and other parts of the mouth [excluding the lips, tongue, salivary glands and floor of the mouth] (SIR = 24.53)*** and the kidneys (SIR = 5.72). The overall risk of SM in patients who had received radioactive iodine was higher than expected (SIR = 4.41). The cumulative incidence of SM after treatment of thyroid cancer in children increases steadily over 40 years (11.92%). CONCLUSIONS: Race, gender, histological subtypes, and radioactive iodine are potentially significant prognostic factors for the development of SM among pediatric thyroid cancer survivors. Identification of underlying mechanisms that raise the risk of SM is important for both treatment and follow-up strategies.

Up-regulated lipocalin-2 in pediatric thyroid cancer correlated with poor clinical characteristics.

BACKGROUND: The incidence of thyroid cancer is fast increasing in both adults and children. The pediatric thyroid cancer had often already progressed to a more advanced stage of the disease at diagnosis. Early detection of pediatric thyroid cancer has been a problem for many years. Lipocalin-2 (Lcn2) has been reported to be over-expressed in cancers of diverse histological origin and it facilitates tumorigenesis by promoting survival, growth, and metastasis. METHODS: The plasma Lcn2 concentration of 28 Chinese papillary thyroid cancer (PTC) children and 24 healthy controls was measured. Immunostaining for Ki-67 of tumor tissue from PTC children was performed. The expression levels of Lcn2 and NFκB in PTC tissue and peri-carcinoma tissue of PTC children were measured through Western blot. RESULTS: The plasma concentration of Lcn2 was significantly elevated in pediatric PTC patients compared with healthy controls. Besides, the plasma Lcn2 concentration significantly correlated with clinical characteristics, NFκB level, and Ki-67 positive rate of nucleus in tissue of PTC. CONCLUSION: This is the first study to evaluate the plasma Lcn2 in pediatric PTC patients. It is possible that the plasma Lcn2 may be a new biomarker of pediatric thyroid cancer. Further studies are needed to explore the definite role and mechanism of Lcn2 in thyroid cancer, which will help to explore novel diagnostic or therapeutic strategies.

Anaplastic Carcinoma Thyroid in a Young Child - an Extremely Rare Occurrence.

Anaplastic thyroid carcinoma (ATC), one of the most aggressive malignancies, is extremely rare in childhood. We present a case of 5-yearold child who presented with rapidly progressing thyroid swelling and stridor, for which she underwent emergency tracheostomy and biopsy. Histopathological features were suggestive of ATC and the patient died within two months after diagnosis. ATC, though very rare in childhood, should be kept in the differential diagnoses of rapidly enlarging neck masses in children. To the best of our knowledge, this is the youngest case of ATC reported in literature.

Surgical management of papillary thyroid carcinoma in childhood and adolescence: an Italian multicenter study on 250 patients.

PURPOSE: The extent of surgery for pediatric papillary thyroid carcinoma is debatable. The aim of this study was to evaluate the feasibility of offering pediatric patients a tailored surgical approach based on certain clinical features. METHODS: A national multicenter retrospective review of 250 pediatric patients treated for papillary thyroid carcinoma in a 14-year period was performed. Outcomes of interest included tumor-related features, type of surgery, surgical morbidity, disease-free and overall survival rates. Recurrence was thoroughly analyzed with particular focus on how it correlated with certain patient- and tumor-related features. RESULTS: The majority of patients (58.8 %) had tumors >2 cm in size. Nodal involvement occurred in 115/250 (46 %) patients and distant metastasis in 4 % (10/250). Total thyroidectomy and lobectomy were performed in 90.4 % (226/250) and 9.6 % (24/250) of patients, respectively. The overall rate of surgical complications was 20.8 % (52/250). These included transient and permanent hypoparathyroidism (13.6 and 4.4 %, respectively), and vocal fold palsy (2.8 %). All surgical complications occurred exclusively in the total thyroidectomy group. The rate of recurrent disease was 12 % (30/250) with the vast majority of recurrences (96.6 %) occurring in the total thyroidectomy group. The risk of recurrence correlated significantly with certain tumor-related features (size > 2 cm, multifocality, extrathyroidal invasion, nodal positivity, and distant metastasis). However, it did not correlate with the patient's age or sex. Overall survival was 100 %. CONCLUSION: Pediatric patients are likely to benefit from a tailored surgical strategy. Uniformly offering patients total thyroidectomy seems to be an overly radical approach.

The RET oncogene in papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is the most common form of thyroid cancer, accounting for greater than 80% of cases. Surgical resection, with or without postoperative radioiodine therapy, remains the standard of care for patients with PTC, and the prognosis is generally excellent with appropriate treatment. Despite this, significant numbers of patients will not respond to maximal surgical and medical therapy and ultimately will die from the disease. This mortality reflects an incomplete understanding of the oncogenic mechanisms that initiate, drive, and promote PTC. Nonetheless, significant insights into the pathologic subcellular events underlying PTC have been discovered over the last 2 decades, and this remains an area of significant research interest. Chromosomal rearrangements resulting in the expression of fusion proteins that involve the rearranged during transfection (RET) proto-oncogene were the first oncogenic events to be identified in PTC. Members of this fusion protein family (the RET/PTC family) appear to play an oncogenic role in approximately 20% of PTCs. Herein, the authors review the current understanding of the clinicopathologic role of RET/PTC fusion proteins in PTC development and progression and the molecular mechanisms by which RET/PTCs exert their oncogenic effects on the thyroid epithelium.

Recurrence and survival for patients with thyroid carcinoma in the pediatric age group in the Emirate of Abu Dhabi: retrospective analysis of a multicentre cohort.

OBJECTIVES: Pediatric thyroid cancer represents 2.3 % of thyroid cancers, and its long-term outcome data are sparse. There have not been studies in the UAE delineating its epidemiology, clinical and histological characteristics, and follow-up outcomes. We aimed to evaluate the clinical-pathological behavior, recurrence and survival rates in pediatrics with all types of thyroid cancer in the UAE. METHODS: Multicentre retrospective chart review analysis of pediatric patients with thyroid carcinoma from January 2010 to December 2020 in Abu Dhabi, UAE. RESULTS: Thirty-four patients were included, 85 % being females. Papillary thyroid carcinoma (PTC) was the commonest type of thyroid cancer (88 %) vs. follicular thyroid carcinoma (FTC) (11.8 %). Almost half of our patients had a multifocal disease, 26 % had lymphovascular invasion (LVI), and 21 % had extrathyroidal extension (ETE). There were no mortalities during follow-up. 85 % of patients exhibited complete remission, while 15 % of patients showed evidence of progressive residual or recurrent disease. One patient had metastasis to lymph nodes and lungs. CONCLUSIONS: There were similar trends of incidence, sex prevalence, and histopathological patterns as the ones observed internationally. Potential risk factors in our population include a family history of thyroid cancer and obesity. The lower rate of ETE, LVI, metastasis, and recurrence indicates a possibly less aggressive disease.

Serum anti-Müllerian hormone is lower in patients with multiple radioiodine dose for treatment of pediatric thyroid cancer.

Introduction: Treatment of patients with pediatric differentiated thyroid cancer (DTC) often involves radioiodine (RAI), which is associated with increased risks of short- and long-term adverse outcomes. The impact of RAI treatment on the female reproductive system remains uncertain. Anti-Müllerian hormone (AMH) is a marker of ovarian reserve and is related to fertility. Objective: The aim was to analyze the association between RAI and serum AMH level in women treated with RAI. Methods: We evaluated women with pediatric DTC treated with RAI at the age of ≤19 years. Serum AMH was measured. Results: The study included 47 patients with a mean age of 25.1 years (12.4-50.8) at AMH measurement and follow-up of 11.8 ± 8.4 years. The mean RAI administered was 235 mCi (30-1150). Sixteen (34%) received multiple RAI doses (471 ± 215 mCi). Mean AMH level was 2.49 ng/mL (0.01-7.81); the level was 1.57 ng/mL (0.01-7.81) after multiple RAI doses and 2.99 ng/mL (0.01-6.63) after a single RAI dose (P = 0.01). Patients who received a cumulative RAI lower than 200 mCi had higher AMH levels (2.23 ng/mL, 0.39-7.81) than those who received more (1.0 ng/mL, 0.01-6.63; P = 0.02). In patients with similar cumulative RAI activities, administration of multiple RAI doses was significantly and independently associated with AMH level lower than the reference range for age (HR: 5.9, 1.55-52.2, P = 0.014) after age adjustments. Conclusion: Levels of AMH were lower after multiple RAI doses, especially after a cumulative RAI dose above 200 mCi. More studies are needed to clarify the impact of RAI on fertility considering its cumulative activity and treatment strategy.

Two Decades of Thyroid Nodule Cytology in Children: Malignancy Risk Assessment at a Tertiary Care Center.

INTRODUCTION: Pediatric thyroid nodules exhibit higher malignancy rates compared to adults and are associated with increased incidences of metastases and recurrences. The American Thyroid Association recommends surgery for indeterminate thyroid biopsies in children based on these higher malignancy risks, though this approach may lead to overtreatment. However, there remains a lack of comprehensive pediatric data to inform clinical decisions. This study examines the risk of malignancy (ROM) in pediatric thyroid nodules using the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) and assesses the diagnostic accuracy of fine-needle aspiration (FNA) biopsy compared to histological outcomes. METHODS: A retrospective cross-sectional analysis was performed on patients under 19 years with thyroid nodules who underwent FNA and thyroidectomy at a tertiary care center. The sensitivity, specificity, positive predictive value, negative predictive value, and ROM of cytological biopsies were evaluated using TBSRTC criteria, with histology serving as the gold standard. Two analyses were conducted to assess diagnostic accuracy: (a) TBSRTC II as negative and TBSRTC VI as positive and (b) TBSRTC II as negative with TBSRTC V and VI as positive. For neoplasia detection, TBSRTC II was deemed negative, while TBSRTC IV, V, and VI were considered positive. TBSRTC categories III and I were excluded from the performance analysis and evaluated separately. Follicular neoplasm or lesions suspicious for follicular neoplasm (FN/SFN) were treated as positive outcomes, correlated with the presence of adenoma or carcinoma in the surgical specimen. RESULTS: Of 75 nodules from 73 patients, 28 (37.3%) were benign and 47 (62.6%) malignant. No significant differences in gender or age were noted between groups. The ROM in each TBSRTC was Bethesda I 0/2, 0%; II 0/13, 0%; III 2/7, 29%: IV 6/14, 43%; V 10/10, 100%, and VI 29/29, 100%. A sensitivity of 78.38% and specificity of 100% for FNA in detecting malignancy was found, with an even higher sensitivity (100%) for detecting neoplasia in TBSRTC IV. CONCLUSIONS: This study reveals that indeterminate thyroid nodules in pediatric patients exhibit a higher rate of malignancy compared to adults, yet align with rates previously reported in the pediatric population. These findings highlight the critical need for guidelines tailored specifically to the management of thyroid nodules and thyroid cancer in children.

Changing Clinical Presentation of Pediatric Differentiated Thyroid Cancer in Poland: A Retrospective Cohort Study Spanning 45 Years.

Background: Differentiated thyroid carcinoma (DTC) in children is uncommon; clinical presentation over recent decades is incompletely characterized. Methods: This retrospective cohort study analyzed demographic and disease characteristics of consecutive juveniles with DTC treated from 1970 to 2015 at Poland's largest pediatric DTC referral center, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice, who had available records. Sex, age, histopathological characteristics, and DTC stage were documented. We aimed to identify changes in these variables over time and independent risk factors for lymph node or distant metastases. Trends in these variables were assessed using the Cochran-Armitage test and Spearman correlation. Multivariable logistic regression was performed to identify risk factors associated with lymph node or distant metastases. Results: 475 of 479 patients (99.2%) were included in the analysis; roughly half were age ≥15 years, 10%, <10 years. Papillary thyroid carcinoma (PTC) represented 88% of cases and follicular thyroid carcinoma (FTC) 11%. Tumors ≤2 cm constituted 56% of cases with relevant data; those >4 cm accounted for 12%. Multifocality was observed in 37% and extrathyroidal invasion in 22%. Lymph node metastases were noted in 59% and distant metastases in 16%. Over the observation period, significant trends among new cases included: increased proportion of adolescents >15 years; increased frequency of tumors ≤2 cm, decreased multifocality rates, and increased proportion of PTC versus FTC. Extrathyroidal invasion rates remained appreciable throughout, ranging from 17 to 28% during the 5-year study subperiods after 1990. Lymph node metastases significantly increased in frequency in the central neck, remaining consistently common in lateral sites; presence of distant metastases significantly decreased. In multivariable analysis, multifocality, extrathyroidal invasion, and tumor size were independently associated with lateral lymph node metastases and multifocality, larger tumor size, and N1b metastases with distant spread. Conclusions: Our observations of a rising proportion of diagnoses in adolescence, reductions in primary tumor size, and decreased frequency of multifocality and distant metastases may reflect increased detection of patients with less aggressive DTC at earlier disease stages. Nonetheless, we found persistently substantial rates of locoregionally advanced disease features (multifocality, extrathyroidal invasion, and lymph node metastases), which multivariable analyses suggested have significant associations with lateral lymph node and/or distant metastases.

Survival Trends in Pediatric Differentiated Thyroid Cancer: A Middle Eastern Perspective.

Pediatric Differentiated Thyroid Cancer (pedDTC) is a rare pediatric malignancy with an increasing incidence over time. To date, there is a paucity of literature specifically addressing pedDTC within the context of Middle Eastern ethnicity. This retrospective study aimed to assess the risk-stratifying factors for overall survival (OS) and event-free survival (EFS) in pediatric DTC patients from Iraq and Jordan. The medical records of 81 patients from two tertiary cancer institutes were retrieved. Kaplan-Meier analysis was employed to investigate OS and EFS, and the Cox proportional hazards model was employed to estimate hazard ratios. All patients underwent surgery and radioactive iodine therapy, with a median age of 14 and an interquartile range of 12-15. Lymph node involvement was observed in 55% of cases, while distant metastases were present in 13.5%. After a median follow-up period of 68 months, the 10-year survival rate was determined to be 94%, while the 10-year EFS rate was 58%. EFS was negatively impacted by cervical lymph node metastases and early age of diagnosis (p ≤ 0.01, each). Therefore, pediatrics with initial cervical lymph node metastases and those diagnosed before puberty tend to experience poorer EFS, which may justify the need for more aggressive management plans.

Validating the Modified McGill Thyroid Nodule Score for Assessment of Preoperative Risk of Pediatric Thyroid Malignancy.

OBJECTIVE: The McGill Thyroid Nodule Score (MTNS) is a preoperative tool used to predict the risk for well-differentiated thyroid cancer in adults. It was developed by a multidisciplinary team using established evidence-based risk factors for thyroid cancer. The modified McGill Thyroid Nodule Score (mMTNS) was developed to predict malignancy risk in children. A pilot study suggested the mMTNS was able to assess malignancy risk in children with indeterminate cytology on fine needle aspiration (FNA). This study seeks to validate these findings. METHODS: Retrospective chart review identified subjects who underwent FNA biopsy and subsequent resection. Each patient was assigned a score to compare to final pathology. Statistical analysis was performed with SPSS. All tests were 2-tailed and statistical significance defined p < 0.05. Logistic regression used to determine predictive values of scores. RESULTS: 46 patients ≤21 years of age underwent resection of a thyroid nodule. Female predominance of 85% (n = 39). 78% (n = 36) of patients had palpable nodule. 65% (n = 30) found to have benign pathology and 35% (n = 16) found to have malignancy. Malignant nodules associated with greater mean mMTNS compared to benign [13.63 vs 7.23]. An mMTNS greater >12 had sensitivity of 86.7%, specificity of 90.3%, positive predictive value of 81.3%, and negative predictive value of 93.3%. CONCLUSION: Our data suggests the mMTNS continues to be a useful adjunct in predicting malignancy risk of pediatric thyroid nodules. An mMTNS >12 has a high risk for malignancy, which can aid in counseling and clinical decision making, particularly when there is indeterminate cytology on FNA. LEVEL OF EVIDENCE: IV.

Outcomes of Differentiated Thyroid Cancer in Children and Adolescents at King Abdulaziz Medical City, Jeddah.

Objective Differentiated thyroid cancer (DTC) is rare in the pediatric population, with most data from the Western world. We aimed to describe the clinical presentation, treatment intervention, histopathological characteristics, complications, follow-up, and response to treatment in 17 patients with DTC at or below the age of 20 years. Interventions This was a retrospective cohort study at King Abdulaziz Medical City, Jeddah, Saudi Arabia. We included patients aged younger than 20 years with DTC. Total or near-total thyroidectomy was performed in 82% of the patients, central and/or lateral neck dissection in 35% of cases, and radioactive iodine (RAI) ablation in 76% of cases. Results The study included 17 patients (14 females), with a median age of 16 years at the time of diagnosis. Thyroid nodules were the main complaint in 88% of the patients. Thyroid ultrasonography was the main method for the initial evaluation. Papillary cancer was the most common type of tumor, and lymph node spread was found in 82% of the patients. Moreover, 40% of the patients exhibited excellent responses to therapy, with 35% showing indeterminate results. Only 23.5% of the patients developed hypocalcemia postoperatively. Conclusions Classical papillary thyroid carcinoma was the predominant histopathological type, and most patients showed excellent responses to therapy, followed by indeterminate in most of the cases. The most common presentation was a neck nodule, signifying the role of thorough physical neck examinations. Finally, recurrence occurred in a minority of patients. However, none of these patients died.

Differentiated thyroid carcinoma of children and adolescents: 27-year experience in the yonsei university health system.

Thyroid carcinomas are uncommon in childhood and adolescence. The aim of this study was to analyze clinical features and clinical outcomes of thyroid cancer in the pediatric population treated in the Yonsei University Health System. From September 1982 to June 2009, 90 patients (75 females, 15 males; female:male ratio of 5:1) with differentiated thyroid carcinoma were identified in our institute. The mean age at diagnosis was 15.8 yr old (range 4.8-19.9 yr). Cervical masses were most common clinical manifestations at diagnosis in 65 patients (72.2%). Forty-two patients underwent less than total thyroidectomy and 18 patients underwent total thyroidectomy. Thirty patients (33.3%) had lateral neck lymph node metastasis and seven patients (7.8%) had lung metastasis at the time of surgery. Among the 90 patients, recurrence occurred in 14 patients (15.5%). Mean follow-up period for patients with differentiated thyroid carcinoma was 81.6 months (13-324 months). No patients died of differentiated thyroid carcinoma. Patients with differentiated thyroid carcinoma who were < 20-yr-of-age were present with aggressive local disease and a high frequency of lymph node and distant metastasis. It is recommended that pediatric thyroid cancer should be managed mostly using proper surgical approach with thyroidectomy and lymph node dissection when indicated.

Varying impact of patient age on the rising rate of pediatric thyroid cancer: Analysis of NCDB database (2004-2017).

Pediatric thyroid carcinoma is on the rise. We sought to better characterize patient factors associated with this and evaluate for trends based on age groups. Additionally, we examined surgical management over time, and whether it aligns with recommendations made by the American Thyroid Association. Using the National Cancer Database (NCDB), we examined cases of thyroid cancer from 2004 to 2017, ages 1-18 years. We subdivided this cohort by age group: those <10y, 10-15y, and >15y. NCDB query yielded 5,814 cases. The annual proportion of total cases ranged from 3% to 8% for <10y, 31%-40% for 10-15y, and 52%-66% for >15y. 80-90% of cases in all age groups did indeed receive total thyroidectomy which is consistent with ATA guidelines. Our results verify an overall increase in pediatric thyroid cancer cases, occurring mostly in the 10-18 years old age range with the largest year-to-year increases in the >15y group.

Outcomes of ATA Low-Risk Pediatric Thyroid Cancer Patients Not Treated With Radioactive Iodine Therapy.

CONTEXT: The American Thyroid Association (ATA) Pediatric Guidelines recommend patients not receive radioactive iodine therapy (RAIT) for differentiated thyroid cancer (DTC) confined to the thyroid. Since publication, there is ongoing concern whether withholding RAIT will result in a lower rate of remission. OBJECTIVE: This study explores whether ATA low-risk patients treated with and without RAIT achieved similar remission rates. METHODS: Medical records of patients <19 years old diagnosed with DTC and treated with total thyroidectomy between 2010 and 2020 were reviewed. Multivariate logistic regression was performed to evaluate factors influencing RAIT administration and remission rate. RESULTS: Ninety-five patients with ATA low-risk DTC were analyzed: 53% (50/95) and 47% (45/95) were treated with and without RAIT, respectively. RAIT was used to treat 82% of patients before 2015 compared with 33% of patients after 2015 (P < .01). No significant difference in 1-year remission rate was found between patients treated with and without RAIT, 70% (35/50) vs 69% (31/45), respectively. With longer surveillance, remission rates increased to 82% and 76% for patients treated with and without RAIT, respectively. Median follow-up was 5.8 years (IQR 4.3-7.9, range 0.9-10.9) and 3.6 years (IQR 2.7-6.6; range 0.9-9.3) for both cohorts. No risk factors for persistent or indeterminate disease status were found, including RAIT administration, N1a disease, and surgery after 2015. CONCLUSION: Withholding RAIT for pediatric patients with ATA low-risk DTC avoids exposure to radiation and does not have a negative impact on remission rates. Dynamic risk stratification at 1-year after initial treatment is a suitable time point to assess the impact of withholding RAIT for these patients.

Prepubertal Children with Papillary Thyroid Carcinoma Present with More Invasive Disease Than Adolescents and Young Adults.

Introduction: Pediatric papillary thyroid carcinomas (PTCs) are more invasive than adult PTCs. No large, contemporary cohort study has been conducted to determine whether younger children are at higher risk for advanced disease at presentation compared to adolescents. We aimed to describe pediatric PTC and contextualize its characteristics with a young adult comparison cohort. Methods: The National Cancer Database was interrogated for pediatric and young adult PTCs diagnosed between 2004 and 2017. Clinical variables were compared between prepubertal (≤10 years old), adolescent (11-18 years old), and young adult (19-39 years old) groups. Multivariable logistic regression modeling for independent predictors of metastases was conducted. A subanalysis of microcarcinomas (size ≤10 mm) was performed. Results: A total of 4860 pediatric (prepubertal n = 274, adolescents n = 4586) and 101,159 young adult patients were included. Prepubertal patients presented with more extensive burden of disease, including significantly larger primary tumors, higher prevalence of nodal and distant metastases, and increased frequency of features such as lymphovascular invasion, and extrathyroidal extension (ETE). Prepubertal age was an independent predictor of positive regional nodes (adjusted odds ratio [AOR] = 1.36 [95% confidence interval {CI} 1.01-1.84], p = 0.04) and distant metastatic disease (AOR = 3.12 [CI 1.96-4.96], p < 0.001). However, there was no difference in survival between groups (p = 0.32). Prepubertal age independently predicted lymph node metastases for microcarcinomas (AOR = 2.19 [CI 1.10-4.36], p = 0.03). Prepubertal (n = 41) versus adolescent (n = 937) patient age was associated with gross ETE (p = 0.004), even with primary tumors ≤1 cm in size. Conclusions: Patients aged <11 years old present with more advanced disease than adolescents, with a higher likelihood of nodal and distant metastatic disease at time of diagnosis, although survival is high. Prepubertal children undergo more extensive treatment, likely reflective of more invasive disease at the outset, even in the setting of a subcentimeter primary tumor.