Evolving approaches in paediatric thyroid cytopathology: A review.

The guidelines for the workup of thyroid nodules have been established in adult populations and secondarily applied to paediatric populations. In particular, The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is commonly applied to both adult and paediatric thyroid nodules. However, as paediatric nodules have distinct molecular drivers and behavioural trajectories, there is renewed interest in diagnostic and management strategies that are paediatric specific. Here, we review key differences between paediatric and adult thyroid cancer and recent literature evaluating the use of TBSRTC in paediatric populations.

Evaluation and application of American College of Radiology Thyroid Imaging Reporting and Data System for improved malignancy detection in paediatric thyroid nodules.

OBJECTIVE: The American College of Radiology Thyroid Imaging Reporting and Data System (TI-RADS) is a widely used method for the management of adult thyroid nodules. However, its use in paediatric patients is controversial because adult fine needle aspiration biopsy (FNAB) recommendations may lead to delayed diagnoses of cancer in children. The objectives of this study were to evaluate the performance of TI-RADS in paediatric thyroid nodules and to tailor FNAB recommendations for children. METHODS: Consecutive surgically resected paediatric thyroid nodules from two tertiary care centres between 2003 and 2021 were reviewed. Ultrasounds were blindly scored by radiologists according to TI-RADS. Management recommendations based on TI-RADS were evaluated. Various modelling methodologies were used to determine the optimal cutoff for FNAB in children. RESULTS: Of the 96 patients, 79 (82%) were female and the median age at surgery was 16.1 years. Fifty (52%) nodules were malignant on surgical pathology. The area under the receiver operating characteristic curve of TI-RADS for predicting malignancy was 0.78. Adult TI-RADS recommendations would have resulted in 4% of cancerous nodules being lost to follow-up. Modifications to TI-RADS (FNAB of all TR3 nodules ≥1.5 cm, FNAB of TR4 and TR5 nodules ≥0.5 cm, surveillance of nodules ≥1 cm, consider surgery for nodules >4 cm) reduced this missed malignancy rate to 0%. CONCLUSIONS: TI-RADS can risk-stratify paediatric thyroid nodules. However, the system requires modifications to reduce the missed malignancy rate in paediatric thyroid nodules. Our data suggest that lower size thresholds for FNAB are warranted in children.

Impact of comorbidities on immediate post-operative complications in oral cavity free flap patients.

PURPOSE: To examine the relationship between comorbidities and the development of immediate post-operative complications in patients undergoing oral cavity composite resection (OCCR) with free flap (FF) reconstruction. MATERIALS AND METHODS: Retrospective analysis was completed on all consecutive OCCRs with FF reconstruction performed at a single quaternary care facility between 1999 and 2020. Comorbidities, immediate post-operative complications, patient demographics, and tumor characteristics were collected. Odds ratios (OR) with 95 % confidence intervals were calculated for associations between comorbidities and immediate post-operative complications. RESULTS: 320 patients who underwent OCCR with FF reconstruction were included. One hundred twenty-one (37.8 %) patients developed a post-operative complication during their initial hospital admission. The most common complications were non-pneumonia cardiopulmonary events (14.1 %), pneumonia (9.4 %), and wound infection (8.4 %). Other complications included flap compromise, bleeding, and fistula. On multivariate analysis, patients without comorbid conditions were less likely to develop a post-operative complication (OR 0.64; 0.41-0.98). Atrial fibrillation (OR 2.94; 1.17-7.39) and cerebrovascular disease (OR 2.28; 1.08-4.84) were associated with increased odds of developing any complications. Furthermore, cerebrovascular disease (OR: 2.33; 1.04-5.39) and peripheral vascular disease (OR: 2.7; 1.2-6.08) were independently associated with pneumonia. CONCLUSION: In this retrospective review of patients undergoing OCCR with FF reconstruction for oral cavity SCC, lack of identifiable comorbidities appeared to be protective for post-operative complications while atrial fibrillation and cerebrovascular disease were associated with increased odds of any complication. Pre-existing vascular disease was also associated with an increased risk of pneumonia.

Patient Perceptions of Audio and Video Recording in the Operating Room.

OBJECTIVE: The goal of this study was to determine surgical patients' perceptions of hypothetical continuous audio-video OR recording (ORR). SUMMARY OF BACKGROUND DATA: Continuous audio-video recording of the operating room (OR), akin to the aviation industry's black box, has been proposed as a means to enhance training, supplement the medical record, and allow large-scale analysis of surgical performance and safety. These recordings would include patients' bodies; yet, understanding of patient perceptions regarding such technology is limited. METHODS: Semi-structured interviews were conducted during elective surgery preoperative appointments during a 2-week period in August 2018 at a quaternary care center. Deidentified transcripts were analyzed using thematic analysis. RESULTS: Forty-nine subjects were interviewed. Subjects recognized the potential for recording to improve surgical quality, safety and training. Subjects also desired access to an objective record of their own surgery, for the purposes of future care, medical-legal evidence, and to satisfy their own curiosity and understanding. Subjects had mixed perceptions regarding OR decorum and thus, differing views on the potential effect of ORR on OR behavior; some imagined that ORR would discourage bad behavior and others worried that it would cause unnecessary anxiety to the surgical team. CONCLUSIONS: Patients have a diverse set of views about the potential benefits, risks, and uses for OR data and consider themselves to be important stakeholders. Our study identifies pathways and potential challenges to implementation of continuous audio/video recording in ORs.

Delayed Upper Aerodigestive Tract Perforation from Anterior Cervical Spine Hardware: Treatment and Swallowing Outcomes.

Delayed upper aerodigestive tract (UADT) perforation is a rare complication of anterior cervical spinal hardware. The purpose of this study was to investigate swallowing outcomes between treatment approaches for delayed UADT perforation. A retrospective chart review was performed on patients with anterior cervical hardware and delayed UADT perforation who were treated at a single tertiary care center between 2000 and 2020. Of the twelve patients identified, most patients presented with dysphagia (n = 9, 75%) and/or neck pain (n = 7, 58%). Perforations generally occurred at the level of C6 (n = 6, 50%) and C7 (n = 4, 33%) and spanned only one spinal level (n = 8, 67%). The majority (n = 8, 67%) of patients were past or current cigarette users. Operative approaches included primary repair (n = 5, 42%) and rotational flap (n = 4, 33%); the rotational flap harvest sites included supraclavicular fasciocutaneous (n = 2), infrahyoid muscle (n = 1), and sternocleidomastoid muscle (n = 1). While most patients demonstrated penetration and/or aspiration on first post-operative swallow study (n = 6), this resolved completely within a median time of 31 days. There were no differences in swallowing outcomes between repair approaches. Patient smoking history appears to be a clear risk factor for the development of delayed UADT perforation from anterior cervical spine hardware. A variety of techniques can be used to repair these perforations, and there were no differences in swallowing outcomes between repair approaches.

Established, emerging and elusive molecular targets in the treatment of lung cancer.

Although histological subtype still underlies tumour classification and treatment, the recognition that lung cancer is, largely, a genetic disease has prompted a push to reconfigure cancer taxonomies according to molecular criteria. In this review, we discuss established (e.g. EGFR, ALK, ROS1, and programmed cell death 1/programmed death-ligand 1), emerging (e.g. MET, RET, and NTRK) and elusive (e.g. TP53, KRAS, and MYC) molecular targets in the treatment of lung cancer. We synthesize a large and rapidly growing body of literature regarding the discovery and therapeutic inhibition of these targets in lung cancer. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Same-Day Discharge for Pediatric Hemithyroidectomy Patients: Evaluating Safety and Barriers to Discharge.

OBJECTIVE: Hemithyroidectomy is often performed in the pediatric population for indeterminate or benign thyroid nodules. Prior studies confirmed the safety of same-day discharge for adults undergoing hemithyroidectomy or total thyroidectomy, but this has not been studied thoroughly in the pediatric population. Our goal was to determine differences in pediatric patients undergoing hemithyroidectomy who were admitted versus discharged for complications or factors to support same-day discharge. STUDY DESIGN: Retrospective cohort. SETTING: Pediatric tertiary care hospital. METHODS: This was a retrospective study of pediatric patients (0-18 years of age) undergoing hemithyroidectomy at a pediatric tertiary care hospital from 2003 to 2022. Perioperative variables and outcomes were gathered via manual chart review. RESULTS: One hundred five pediatric patients who underwent hemithyroidectomy were identified. Ninety (86%) patients were admitted postoperatively, and 15 (14%) were discharged the same day. There were no differences in patient demographics, including age (P = 0.29) distance from the hospital (P = 0.08) or benign versus malignant pathology (P = 0.93). Surgical time in same-day discharges was significantly shorter (P = 0.0001; 138.6 minutes, SD = 66.0) versus admitted patients (204.2 minutes, SD = 48.6) Hemostatic agents were used more in same-day discharges at 53.3% versus 4.5% (P = 0.0001). Perioperative complications occurred in 2 (2.2%) admitted patients compared to none in the same-day discharge (P = 1.0). There were no readmissions within 30 days for same-day discharges. CONCLUSION: In pediatric patients undergoing uncomplicated hemithyroidectomy, same-day discharge appears appropriate for those with shorter surgical times and intraoperative use of hemostatic agents with no readmissions or complications in those discharged the same day.

Establishing a role for the oral microbiome in infectious complications following major oral cavity cancer surgery.

Surgery forms the backbone of treatment for most locoregional or advanced oral cavity squamous cell carcinoma. Unfortunately, infectious complications (including orocutaneous fistulas) are common following such extensive surgery and can afflict over half of patients. These complications can lead to delays in adjuvant treatment, prolonged hospitalization, reconstructive failure, and decreased quality of life. The frequency and morbidity associated with infectious complications has led to the search for pre-disposing risk factors; and, several have been identified, including both patient (e.g. diabetes) and surgical (e.g. operative time) factors. However, these findings are inconsistently reproduced, and risk factor modification has had a limited impact on rates of infectious complications. This is striking given that the likely contaminant-the oral microbiome-is a well-studied microbial reservoir. Because many oral cavity cancer surgeries involve violation of oral mucosa and the spillage of the oral microbiome into normally sterile areas (e.g. the neck), variance in oral microbiome composition and function could underly differences in infectious complications. The goal of this perspective is to highlight 1) this knowledge gap and 2) opportunities for studies in this domain. The implication of this line of thought is that the identification of oral microbial dysbiosis in patients undergoing surgery for oral cavity cancer could lead to targeted pre-operative therapeutic interventions, decreased infectious complications, and improved patient outcomes.

Disparities in pediatric parotid cancer treatment and presentation: A National study.

OBJECTIVES: Although parotid gland malignancies are uncommon, they nevertheless represent a cause of morbidity and mortality in the pediatric population. Few studies have sought to identify disparities related to their presentation, treatment, and survival. There is a need to understand these variations to improve care for historically underrepresented groups. STUDY DESIGN: Retrospective Cohort Study. SETTING: Surveillance, Epidemiology, and End Results (SEER) Program Database. METHODS: Analysis of pediatric patients with parotid gland malignancies between 2000 and 2019. Race and ethnicity were classified as Non-Hispanic White, Non-Hispanic Black, Asian, and Hispanic for multivariable analysis. Outcomes included tumor size and stage at diagnosis, survival, and need for facial nerve sacrifice. Kaplan-Meier analysis was used to analyze survival. Multivariable logistic regression was conducted to identify predictors of outcomes. RESULTS: 149 patients met the criteria for inclusion. Stratified by race/ethnicity, Non-Hispanic Black (Median 23 mm, IQR 15-33), Asian (30 mm, 14-32), and Hispanic (23 mm, 20-28) patients had larger tumors at presentation than Non-Hispanic White patients (18 mm, 12-25, p = 0.017). Disease-specific survival differed by time-to-treatment (log-rank, p = 0.01) and overall survival differed by income (p < 0.001). On multivariable analysis, Hispanic patients were more likely to experience facial nerve sacrifice (OR 3.71, 95%CI 1.25-11.6, p = 0.020), and Non-Hispanic Black (OR 3.37, 0.95-11.6, = 0.053) and Asian (OR 5.67, 1.46-22.2, p = 0.011) patients presented with larger tumors compared to Non-Hispanic White patients. CONCLUSIONS: Variations in presentation and treatment exist across race and ethnicity in pediatric parotid cancer. Identifying these disparities may help improve access and outcomes for underserved patient populations. LEVEL OF EVIDENCE: III.

Consideration of Antifungal Coverage in Treating Infections Related to Delayed Esophageal Perforation from Anterior Cervical Spine Hardware.

(1) Background/Objectives: Delayed esophageal perforation following anterior cervical (spine) discectomy and fusion (ACDF) is rare but can lead to serious infectious complications. The treatment usually involves hardware explanation and prolonged intravenous antibiotics; however, there are scarce reports about the microbiology of these infections and corresponding targeted therapy. (2) Methods: Patients diagnosed or treated for delayed esophageal perforation after anterior cervical fusion between 2000-2020 at a tertiary medical center were studied. (3) Results: Seven patients with delayed esophageal perforation following ACDF were identified. The most common bacteria isolated included Streptococcus, Haemophilus, and Mycobacterium species. The cultures from five patients grew fungal species, including Candida albicans and C. glabrata. All the patients received several weeks of broad-spectrum antibiotics, and, notably, 5/7 patients received antifungal therapy targeting Candida. (4) Conclusions: Although the incidence of delayed esophageal perforation following ACDF is low, providers should remain aware of this entity due to the serious infectious complications. Most infections are polymicrobial in nature, and providers should consider empiric antifungal coverage specifically targeting Candida species when treating patients with this complication.

Comparative Outcomes for Microvascular Free Flap Monitoring Outside the Intensive Care Unit.

OBJECTIVE: There is a trend towards nonintensive care unit (ICU) or specialty ward management of select patients. Here, we examine postoperative outcomes for patients transferred to a general ward following microvascular free flap (FF) reconstruction of the head and neck. STUDY DESIGN: Retrospective quality control study. SETTING: Single tertiary care center. METHODS: Consecutive patients who underwent FF of the head and neck before and after a change in protocol from immediate postoperative monitoring in the ICU ("Pre-protocol") to the general ward setting ("Post-protocol"). Outcomes included overall length of stay (LOS), ICU LOS, FF compromise, and postoperative complications. RESULTS: A total of 150 patients were included, 70 in the pre-protocol group and 80 in the post-protocol group. There were no significant differences in age, sex, comorbidities, tumor stage, or type of FF. Mean LOS decreased from 8.18 to 7.68 days (P = .4), and mean ICU LOS decreased significantly from 5.2 to 1.7 days (P < .01). There were no significant differences in postoperative or airway-related complications (P = .6) or FF failure rate (2.9% vs 2.6%, P > .9). There was a non-significant increase in ancillary consults in the post-protocol group (45% vs 33%, P = .13) and a significant increase in rapid response team calls, a nurse-driven safety net for abnormal vitals or mental status (19% vs 3%, P = .003). CONCLUSION: We show the successful implementation of a protocol shifting care of FF patients from the ICU to a general ward postoperatively, suggesting management on the floor with less frequent flap monitoring is safe and conserves ICU beds. Additional teaching and familiarity with these patients may over time reduce the rapid response calls.

Surgical Management and Outcomes of Pediatric Congenital Head and Neck Teratomas: A Scoping Review.

Objective: To perform a scoping review to characterize postoperative outcomes of pediatric patients (ages 0-18) with a history of congenital head and neck teratomas. Data Sources: PubMed, EMBASE, Web of Science, Cochrane, Clinicaltrails.gov. Review Methods: A search of multiple databases was performed. Studies were included if they detailed the surgical management and outcomes of pediatric patients with a history of congenital head and neck teratomas. Results: One hundred and eight studies totaling 137 patients were identified. The median gestational age at birth was 37 weeks. Respiratory distress, prompting emergent endotracheal intubation or tracheostomy, was present in most patients (58%). The ex utero intrapartum treatment (EXIT) procedure was utilized for 21 (15%) patients. The teratomas were resected after a median duration of 4 days from birth. The most common postsurgical complications were vocal cord paralysis (3%), hemorrhage (2%), and tracheomalacia (2%). Death occurred perioperatively in 2 patients (2%). Twenty-six patients (19%) required additional surgery, and 5 patients (4%) needed adjuvant chemotherapy. Patients were monitored for a median duration of 24 months with a recurrence rate of 6%. Four recurrent cases (50%) had intracranial extension, and 88% of the recurrent cases were mature teratomas at initial histopathological diagnosis. Conclusion: Most patients with congenital head and neck teratomas require emergent airway management perinatally. Excisional and surgical complications are rare, and most patients are cured of their disease with a single operation. Recurrent teratomas tend to have an intracranial extension and are likely to be of mature pathology at the time of initial diagnosis.

Hashimoto's Thyroiditis and the Risk of Papillary Thyroid Cancer in Children.

The association between Hashimoto's thyroiditis (HT) and pediatric thyroid cancer is controversial. Most studies examining this connection have been based on adults, and larger studies in children are lacking. We performed a retrospective study of all sequential pediatric patients who underwent a thyroidectomy for a neoplasm at our institution over a twenty-year period in order to explore the link between HT and pediatric thyroid cancer. A total of 153 patients, median age 16.5 (interquartile range [IQR] 14.2-18.3) years, underwent thyroid surgery for a neoplasm. Patients were mainly female (80%) and White (84%). Median follow-up was 58.6 (IQR 20.7-105.4) months. Thirty-five (23%) patients had HT. Patients who underwent thyroid surgery and had HT were more likely to harbor a malignant neoplasm (p = 0.05); specifically, papillary thyroid carcinoma (PTC, p = 0.02). There was a difference in the distribution of HT among the subtypes of PTC (p = 0.03). Despite this, there was no difference in terms of survival between patients with/without HT. In conclusion, children with a thyroid malignancy, specifically, PTC, are more likely to have HT. The association between HT and pediatric PTC appears to be subtype-specific but does not seem to affect patient survival.

Identifying Parathyroids in Pediatric Thyroid/Parathyroid Surgery by Near Infrared Autofluorescence.

OBJECTIVES: Compared to adult patients undergoing thyroid surgery, pediatric patients have higher rates of hypoparathyroidism often related to parathyroid gland (PG) inadvertent injury or devascularization. Previous studies have shown that near-infrared-autofluorescence (NIRAF) can be reliably used intraoperatively for label-free parathyroid identification, but all prior studies have been performed in adult patients. In this study, we assess the utility and accuracy of NIRAF with a fiber-optic probe-based system to identify PGs in pediatric patients undergoing thyroidectomy or parathyroidectomy. METHODS: All pediatric patients (under 18 years of age) undergoing thyroidectomy or parathyroidectomy were enrolled in this IRB-approved study. The surgeon's visual assessment of tissues was first noted and the surgeon's confidence level in the tissue identified was recorded. A fiber-optic probe was then used to illuminate tissues-of-interest with a wavelength of 785 nm and resulting NIRAF intensities from these tissues were measured while the surgeon was blinded to results. RESULTS: NIRAF intensities were measured intraoperatively in 19 pediatric patients. Normalized NIRAF intensities for PGs (3.63 ± 2.47) were significantly higher than that of thyroid (0.99 ± 0.36, p < 0.001) and other surrounding soft tissues (0.86 ± 0.40, p < 0.001). Based on the PG identification ratio threshold of 1.2, NIRAF yielded a detection rate of 95.8% (46/48 pediatric PGs). CONCLUSION: Our findings indicate that NIRAF detection can potentially be a valuable and non-invasive technique to identify PGs during neck operations in the pediatric population. To our knowledge, this is the first study in children to assess the accuracy of probe-based NIRAF detection for intraoperative parathyroid identification. LEVEL OF EVIDENCE: Level 4 Laryngoscope, 133:3208-3215, 2023.

A Large Thyroid Goiter in a Newborn With Congenital Hypothyroidism: Timeline for Decrease in Size of Thyroid.

Congenital hypothyroidism rarely causes a clinically significant neck mass in newborns. We present the case of a newborn with congenital hypothyroidism and significantly enlarged goiter and discuss imaging considerations and medical and surgical management. This infant was prenatally discovered to have a midline neck mass on 28 week ultrasound measuring 6.0 cm × 3.4 cm × 5.8 cm. Diagnostic cordocentesis demonstrated elevated thyroid-stimulating hormone (TSH, 361 µIU/mL). Maternal evaluation for thyroid disease and antithyroid antibodies was negative. A Cesarean section at 38 weeks gestation was recommended due to hyperextension of the fetal neck. The infant was intubated for respiratory distress. Postnatal magnetic resonance imaging revealed a 5.5 cm × 4.4 cm × 7.6 cm goiter and laboratory studies confirmed the diagnosis of primary hypothyroidism (TSH 16.7 µIU/mL). Treatment was initiated with intravenous levothyroxine and transitioned to oral supplementation. Serial ultrasounds showed decreased goiter volume over several weeks, with recent volume per lobe being 22% and 44% of original volume. This case demonstrates the importance of prompt diagnosis and initiation of thyroid hormone replacement, allowing for significant goiter regression without surgical intervention and ensuring normal growth and neurodevelopmental outcome. Surgical management should be considered for those with persistent compressive symptoms despite optimal medical management.

Molecular signature incorporating the immune microenvironment enhances thyroid cancer outcome prediction.

Genomic and transcriptomic analysis has furthered our understanding of many tumors. Yet, thyroid cancer management is largely guided by staging and histology, with few molecular prognostic and treatment biomarkers. Here, we utilize a large cohort of 251 patients with 312 samples from two tertiary medical centers and perform DNA/RNA sequencing, spatial transcriptomics, and multiplex immunofluorescence to identify biomarkers of aggressive thyroid malignancy. We identify high-risk mutations and discover a unique molecular signature of aggressive disease, the Molecular Aggression and Prediction (MAP) score, which provides improved prognostication over high-risk mutations alone. The MAP score is enriched for genes involved in epithelial de-differentiation, cellular division, and the tumor microenvironment. The MAP score also identifies aggressive tumors with lymphocyte-rich stroma that may benefit from immunotherapy. Future clinical profiling of the stromal microenvironment of thyroid cancer could improve prognostication, inform immunotherapy, and support development of novel therapeutics for thyroid cancer and other stroma-rich tumors.

Neonatal Laryngotracheal Anomalies.

Respiratory distress in the neonate is one of the most common reasons for referral to a tertiary NICU, accounting for more than 20% of admissions. (1) The cause of respiratory distress can range from parenchymal lung disease to anomalies of any portion of the neonatal airway including the nose, pharynx, larynx, trachea, or bronchi. This review will focus on airway anomalies at or immediately below the level of the larynx. Although rare, those with such congenital or acquired laryngotracheal anomalies often require urgent evaluation and surgical intervention. This review describes 1) the pathophysiology associated with congenital and acquired laryngotracheal deformities in the neonate, 2) the clinical presentation and diagnostic evaluation of these anomalies, and 3) the current medical and surgical strategies available in the NICU and after discharge.

It Takes Two to Tango: A Review of Oncogenic Virus and Host Microbiome Associated Inflammation in Head and Neck Cancer.

While the two primary risk factors for head and neck squamous cell carcinoma (HNSCC) are alcohol and tobacco, viruses account for an important and significant upward trend in HNSCC incidence. Human papillomavirus (HPV) is the causative agent for a subset of oropharyngeal squamous cell carcinoma (OPSCC)-a cancer that is impacting a rapidly growing group of typically middle-aged non-smoking white males. While HPV is a ubiquitously present (with about 1% of the population having high-risk oral HPV infection at any one time), less than 1% of those infected with high-risk strains develop OPSCC-suggesting that additional cofactors or coinfections may be required. Epstein-Barr virus (EBV) is a similarly ubiquitous virus that is strongly linked to nasopharyngeal carcinoma (NPC). Both of these viruses cause cellular transformation and chronic inflammation. While dysbiosis of the human microbiome has been associated with similar chronic inflammation and the pathogenesis of mucosal diseases (including OPSCC and NPC), a significant knowledge gap remains in understanding the role of bacterial-viral interactions in the initiation, development, and progression of head and neck cancers. In this review, we utilize the known associations of HPV with OPSCC and EBV with NPC to investigate these interactions. We thoroughly review the literature and highlight how perturbations of the pharyngeal microbiome may impact host-microbiome-tumor-viral interactions-leading to tumor growth.

Racial, ethnic, and socioeconomic disparities in the presentation and management of pediatric thyroid cancer.

OBJECTIVES: Disparities across race and socioeconomic status (SES) in cancer treatment exist for many malignancies. Disadvantaged groups have repeatedly been shown to receive sub-optimal treatment. This study intends to analyze racial and SES disparities in the presentation and management of pediatric thyroid cancer. METHODS: A retrospective national database study of children who underwent thyroidectomy for thyroid papillary, medullary, and follicular carcinoma between 2007 and 2016 was conducted using the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. Multivariable logistic regression was conducted to identify predictors of 1) tumor stage/size at diagnosis and 2) treatment modalities. RESULTS: 1942 children were analyzed. The average tumor size at presentation was 20 mm for White patients, 26 mm for Non-White patients, and 27 mm for Hispanic patients (p < 0.001). Stage of disease differed significantly by race/ethnicity (p < 0.001) with Non-White and Hispanic patients having more distant disease than White patients at presentation. On multivariable regression, Hispanic patients (OR 1.41, 95%CI 1.06-1.87, p = 0.017) were more likely to be diagnosed at later stages. Non-White (OR 2.03, 1.50-2.73, p < 0.001) and Hispanic patients (OR 1.57, 1.19-2.07, p = 0.002) had larger tumors at diagnosis than White patients after controlling for other SES factors. CONCLUSIONS: SES disparities exist in pediatric thyroid cancer. Non-White and Hispanic patients are more likely to present with larger tumors and distant disease as compared to White patients. Understanding and intervening on these SES disparities is essential to improve outcomes.

Evaluation of the Molecular Landscape of Pediatric Thyroid Nodules and Use of a Multigene Genomic Classifier in Children.

Importance: Definitive diagnosis of a thyroid nodule in a child is obtained through diagnostic surgery. This is problematic because pediatric thyroid surgery is associated with higher rates of complications. In adults, preoperative molecular testing improves the management of thyroid nodules, but this has not been validated in children. Objective: To determine whether the molecular landscape of pediatric thyroid nodules is amenable to detection by a multigene genomic classifier (GC) test (ThyroSeq v3; Sonic Healthcare USA). Design, Setting, and Participants: This was a retrospective consecutive case series and GC testing of fine-needle aspiration (FNA) and formalin-fixed paraffin-embedded (FFPE) tissues from sequential pediatric thyroidectomies performed between January 2003 and December 2019 at a single tertiary academic medical center. The study included 95 patients (median [range] age, 16.3 [4.8 to 21.1] years; 75 [79%] female) who underwent surgery for a thyroid nodule. Interventions: A total of 118 thyroid nodule samples (95 FFPE, 23 companion FNAs) yielded informative next-generation sequencing data and multigene GC. Main Outcomes and Measures: The primary outcome was the determination of the pediatric thyroid molecular landscape. The secondary outcome was the diagnostic accuracy of the GC test for pediatric thyroid nodules. Results: Of the 95 patients, 75 (79%) were female, and the median (IQR) age was 16.3 (14.0-17.3) years. Next-generation sequencing confirmed the unique molecular landscape of malignant pediatric thyroid nodules (compared with adults), which is dominated by gene fusions (most commonly RET and NTRK), rare BRAF/RAS alterations, and no TP53 or TERT promoter pathogenic variants. Several poorly differentiated thyroid cancers harbored DICER1 variants. Benign nodules appeared to be almost exclusively associated with TSHR and DICER1 alterations. The test demonstrated a 96% sensitivity (95% CI, 87%-99%) and 78% specificity (95% CI, 64%-88%). The negative predictive value was 95% (95% CI, 88%-98%) and the positive predictive value was 83% (95% CI, 74-89%). The concordance of GC between 23 pairs of matched FFPE and FNA tissues was 96%. Conclusions and Relevance: The study results of this retrospective consecutive case series suggest that the molecular landscape of pediatric nodules is unique but remains amenable to molecular classification. The multigene GC test, with high sensitivity and reasonably high specificity, represents a potential addition to the diagnostic workup of children with thyroid nodules and may decrease the use of diagnostic surgery.