Recurrent missense variant identified in two unrelated families with MPZL2-related hearing loss, expanding the variant spectrum associated with DFNB111.

MPZL2-related hearing loss is a rare form of autosomal recessive hearing loss characterized by progressive, mild sloping to severe sensorineural hearing loss. Thirty-five previously reported patients had biallelic truncating variants in MPZL2, with the exception of one patient with a missense variant of uncertain significance and a truncating variant. Here, we describe the clinical characteristics and genotypes of five patients from four families with confirmed MPZL2-related hearing loss. A rare missense likely pathogenic variant [NM_005797.4(MPZL2):c.280C>T,p.(Arg94Trp)] located in exon 3 was confirmed to be in trans with a recurrent pathogenic truncating variant that segregated with hearing loss in three of the patients from two unrelated families. This is the first recurrent likely pathogenic missense variant identified in MPZL2. Apparently milder or later-onset hearing loss associated with rare missense variants in MPZL2 indicates that some missense variants in this gene may cause a milder phenotype than that resulting from homozygous or compound heterozygous truncating variants. This study, along with the identification of truncating loss of function and missense MPZL2 variants in several diverse populations, suggests that MPZL2-related hearing loss may be more common than previously appreciated and demonstrates the need for MPZL2 inclusion in hearing loss testing panels.

Surgical outcomes in survivors of childhood cancer undergoing thyroidectomy: A single-institution experience.

BACKGROUND: Childhood cancer survivors (CCS) are at increased risk for thyroid disease, and many require definitive management with thyroid surgery. Despite this, there is limited evidence on surgical outcomes among CCS. We sought to evaluate postoperative outcomes at our institution among CCS undergoing thyroid surgery compared to patients without a history of primary childhood malignancy. PROCEDURE: Medical records were reviewed for 638 patients treated at the Children's Hospital of Philadelphia Pediatric Thyroid Center between 2009 and 2020. Rates of surgical complications, including recurrent laryngeal nerve (RLN) paralysis and hypoparathyroidism, among CCS were compared to patients with sporadic/familial thyroid cancer, Graves' disease, and other benign thyroid conditions. Operative time and intraoperative parathyroid hormone levels were also evaluated. RESULTS: There were no significant differences in long-term surgical complication rates, such as permanent RLN paralysis and hypoparathyroidism, between CCS and patients without a history of primary childhood malignancy (all p > .05). For all surgical outcomes, there were no significant differences in complication rates when CCS were compared to those undergoing surgery for sporadic/familial thyroid cancer or Graves' disease (all p > .05). CCS with benign final pathology had significantly higher rates of transient hypoparathyroidism compared to patients with benign thyroid conditions (p < .001). CONCLUSIONS: Our study suggests that CCS are not at higher risk of long-term complications from thyroid surgery when treated by high-volume surgeons within a multidisciplinary team.

Consensus Statement by the American Association of Clinical Endocrinology (AACE) and the American Head and Neck Society Endocrine Surgery Section (AHNS) on Pediatric Benign and Malignant Thyroid Surgery.

OBJECTIVES: To provide a clinical disease state review of recent relevant literature and to generate expert consensus statements regarding the breadth of pediatric thyroid cancer diagnosis and care, with an emphasis on thyroid surgery. To generate expert statements to educate pediatric practitioners on the state-of-the-art practices and the value of surgical experience in the management of this unusual and challenging disease in children. METHODS: A literature search was conducted and statements were constructed and subjected to a modified Delphi process to measure the consensus of the expert author panel. The wording of statements, voting tabulation, and statistical analysis were overseen by a Delphi expert (J.J.S.). RESULTS: Twenty-five consensus statements were created and subjected to a modified Delphi analysis to measure the strength of consensus of the expert author panel. All statements reached a level of consensus, and the majority of statements reached the highest level of consensus. CONCLUSION: Pediatric thyroid cancer has many unique nuances, such as bulky cervical adenopathy on presentation, an increased incidence of diffuse sclerosing variant, and a longer potential lifespan to endure potential complications from treatment. Complications can be a burden to parents and patients alike. We suggest that optimal outcomes and decreased morbidity will come from the use of advanced imaging, diagnostic testing, and neural monitoring of patients treated at high-volume centers by high-volume surgeons.

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.

Sclerosing Epithelioid Fibrosarcoma of the Bone With Rare EWSR1-CREB3L3 Translocation Driving Upregulation of the PI3K/mTOR Signaling Pathway.

Sclerosing epithelioid fibrosarcoma (SEF) is an uncommon neoplasm that rarely presents in bone. It is characterized by epithelioid cells arranged in nests and single-file cords within a sclerotic stromal background which may mimic neoplastic bone. SEF harbors an EWSR1 translocation, which may complicate its distinction from Ewing sarcoma in cases with histomorphologic overlap. We present a diagnostically challenging case of SEF in the mandible of a 16-year-old girl. Our experience highlights the lack of specificity of traditional morphology and EWSR1 break-apart fluorescent in situ hybridization. Open-ended RNA-based fusion gene testing coupled with MUC4 immunohistochemistry aided the eventual diagnosis in this case. Herein, we report the third case of SEF with EWSR1-CREB3L3 translocation and show that this fusion leads to aberrant upregulation of the phosphoinositide 3-kinase/mammalian target of rapamycin signaling pathway in heterologous cell models.

Complications of Surgery: Recognition and Management.

The middle ear and mastoid spaces contain delicate and functionally important structures. Safe cholesteatoma surgery requires mastery of otologic anatomy as well as thorough preoperative investigation. Cholesteatoma can damage otologic structures on its own; however, there is also an opportunity for an iatrogenic complication given the distortion of anatomy by the disease process. This article explores complications that can occur during cholesteatoma surgery, guidance on how to avoid intraoperative complications, and treatment of such complications.

Low-invasive somatic oncogenes and lymph node metastasis in pediatric papillary thyroid cancer: implications for prophylactic central neck dissection.

Objective: The American Thyroid Association (ATA) Pediatric Guidelines recommend selective, prophylactic central neck dissection (pCND) for patients with papillary thyroid carcinoma (PTC) based on tumor focality, tumor size, and the surgeon's experience. With the expansion of pre-surgical somatic oncogene testing and continued controversy over the benefits of pCND, oncogenic alteration data may provide an opportunity to stratify pCND. This study compared lymph node (LN) involvement in pediatric patients with PTC between tumors with low- and high-invasive-associated alterations to explore the potential utility of preoperative oncogenic alterations in the stratification of pCND. Methods: This is retrospective cohort study of pediatric patients who underwent somatic oncogene testing post thyroidectomy for PTC between July 2003 and July 2022. Results: Of 192 eligible PTC patients with postoperative somatic oncogene data, 19 tumors harbored somatic alterations associated with low-invasive disease (19/192, 10%), and 128 tumors harbored a BRAFV600E alteration (45/192, 23%) or an oncogenic fusion (83/192, 43%). Tumors with low-invasive alterations were less likely to present malignant preoperative cytology (2/18, 11%) than those with high-invasive alterations (97/124, 78%; P < 0.001). Twelve patients with low-invasive alterations had LNs dissected from the central neck (12/19, 63%) compared to 127 patients (127/128, 99%) with high-invasive alterations. LN metastasis was identified in two patients with low-invasive alterations (2/19, 11%) compared to 107 patients with high-invasive alterations (107/128, 84%; P < 0.001). Conclusion: Pediatric patients with low-invasive somatic oncogenic alterations are at low risk for metastasis to central neck LNs. Our findings suggest that preoperative knowledge of somatic oncogene alterations provides objective data to stratify pediatric patients who may not benefit from pCND.

Keratin-Positive Giant Cell Tumor of Bone and Soft Tissue With HMGA2::NCOR2 Fusion in Children Under 10 With Response to Imatinib Therapy: A Case Series.

HMGA2::NCOR2 keratin-positive giant cell tumors in children with response to imatinib in an infant.

Comprehensive management and classification of first branchial cleft anomalies: An International Pediatric Otolaryngology Group (IPOG) consensus statement.

OBJECTIVE: First branchial cleft anomalies are rare congenital head and neck lesions. Literature pertaining to classification, work up and surgical treatment of these lesions is limited and, in some instances, contradictory. The goal of this work is to provide refinement of the classification system of these lesions and to provide guidance for clinicians to aid in the comprehensive management of children with first branchial cleft anomalies. MATERIALS AND METHODS: Delphi method survey of expert opinion under the direction of the International Pediatric Otolaryngology Group (IPOG) was conducted to generate recommendations for the definition and management of first branchial cleft anomalies. The recommendations are the result of expert consensus and critical review of the literature. RESULTS: Consensus recommendations include evaluation and diagnostic considerations for children with first branchial cleft anomalies as well as recommendations for surgical management. The current Work classification system was reviewed, and modifications were made to it to provide a more cogent categorization of these lesions. CONCLUSION: The mission of the International Pediatric Otolaryngology Group (IPOG) is to develop expertise-based recommendations based on review of the literature for the management of pediatric otolaryngologic disorders. These consensus recommendations are aimed at improving care of children presenting with first branchial cleft anomalies. Here we present a revised classification system based on parotid gland involvement, with a focus on avoiding stratification based on germ layer, in addition to guidelines for management.

Thyroid Ultrasound Screening in Childhood Cancer Survivors following Radiotherapy.

INTRODUCTION: Childhood cancer survivors (CCS) are at risk for radiotherapy (RT) late effects, including second malignancies. Optimal screening for differentiated thyroid cancer (DTC) in CCS post-RT remains controversial. We assessed the outcome of thyroid ultrasound (US) surveillance in CCS exposed to RT. METHODS: 306 CCS were surveilled with thyroid US between 2002-2021. Surveillance was dependent on age at the time of primary diagnosis, interval from receipt of RT, and individual provider. Thyroid US, clinicopathologic features, and outcomes were described. Cutpoints of CCS RT age associated with varying risk of nodule presentation were explored. The selected cutpoints were used to define age categories, which were then used to compare thyroid nodule-related outcomes. Risk factors for thyroid nodule(s) were evaluated using multivariate logistic regression (odds ratio [OR] [95% confidence interval]). RESULTS: The most common CCS diagnoses were leukemia (32%), CNS tumor (26%), and neuroblastoma (18%). Patients received TBI (45%) and/or RT to craniospinal (44%), chest (11%), and neck regions (6%). About 49% (n = 150) of patients had thyroid nodule(s). Forty-four patients underwent surgery, and 28 had DTC: 19 with American Thyroid Association (ATA) low-risk classification, 2 with ATA intermediate-risk, and 7 with ATA high-risk disease. Age cutpoint analyses identified cutpoints 3 and 10; hence, ≤3, >3 to ≤10, and >10 years were used. Of the 9 patients with intermediate- or high-risk disease, 8 were ≤10 years and 1 was >10 years at the time of RT. Female sex (OR = 1.62 [1.13-2.12] p = 0.054) and greater interval between RT and first US (OR = 1.10 [1.04-1.16] p = 0.001) were independent risk factors for nodule presentation. CONCLUSIONS: Thyroid US surveillance may be beneficial for CCS exposed to RT at younger ages (≤10 years) for earlier detection of DTC, prior to developing advanced metastatic disease.

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.

Impact of Definitive Surgery for Graves' Disease on Adolescent Disease-Specific Quality of Life and Psychosocial Functioning.

Introduction: Pediatric Graves' disease (GD) is associated with hyperthyroid symptoms that impact psychosocial and physical functioning. Total thyroidectomy (TT) is a definitive treatment option that replaces antithyroid medication. While studies have examined health-related quality of life (QOL) in adults, there are no data describing impacts of TT in pediatrics. In this prospective longitudinal study, we explored the impact of TT on disease-specific QOL and satisfaction with TT and scar appearance in adolescent patients with GD undergoing TT. Methods: Patients 12-19 years old pursuing TT for GD and their parents were recruited to complete surveys before and at least 6 months after TT. Surveys assessed motivations for pursuing TT, QOL, perceived stigmatization, self-esteem, scar appearance, and surgery satisfaction. Paired scores were compared using Wilcoxon signed-rank tests, and subscore associations were assessed using Spearman association tests. Results: Thirty-seven patient-parent dyads completed baseline surveys, including 20 patient-parent dyads completing pre- and post-TT surveys. At baseline, patients reported physical and cognitive symptomology, including tiredness, anxiety, and emotional susceptibility through ThyPRO. Psychosocial functioning at school was low through PedsQL. Disease-specific QOL significantly improved after TT, with notable improvements associated with resolution of goiter (median change = -26.14, p = 0.003), hyperthyroid symptoms (median change = -43.75, p = 0.002), tiredness (median change = -26.79, p = 0.017), cognitive impairment (median change = -14.58, p = 0.035), anxiety (median change = -33.33, p = 0.010), and emotional susceptibility (median change = -28.99, p = 0.035). Physical (median change = 18.75, p = 0.005) and school-related functioning (median change = 30.00, p = 0.002) also significantly improved post-TT. Reported GD-associated eye symptomology (thyroid eye disease) was the second lowest scoring ThyPRO subscore at baseline and improved after surgery (median change = 14.06, p = 0.03). Families reported median recovery by two months, high satisfaction with the outcomes of TT, and minimal concerns over scar appearance. No permanent surgical complications (i.e., recurrent laryngeal nerve damage or hypoparathyroidism) were sustained. Conclusions: In the setting of a high-volume surgeon with low complication rates, TT for GD in pediatric populations may have substantial beneficial effects on disease-specific QOL and psychosocial functioning, with minimal adverse complaints about scar appearance.

Clinicopathologic Characteristics of Pediatric Follicular Variant of Papillary Thyroid Carcinoma Subtypes: A Retrospective Cohort Study.

Introduction: Follicular patterned thyroid nodules with nuclear features of papillary thyroid carcinoma (PTC) encompass a range of diagnostic categories with varying risks of metastatic behavior. Subtypes include the invasive encapsulated follicular variant of PTC (Ienc-fvPTC) and infiltrative fvPTC (inf-fvPTC), with tumors lacking invasive features classified as noninvasive follicular thyroid neoplasms with papillary-like features (NIFTPs). This study aimed to report the clinical and histological features of pediatric cases meeting criteria for these histological subtypes, with specific focus on Ienc-fvPTC and inf-fvPTC. Methods: In this retrospective cohort study, pediatric patients with thyroid neoplasms showing follicular patterned growth and nuclear features of PTC noted on surgical pathology between January 2010 and January 2021 were retrospectively reviewed and classified according to the recent 2022 World Health Organization (WHO) criteria. Clinical and histopathologic parameters were described for NIFTP, Ienc-fvPTC, and inf-fvPTC subtypes, with specific comparison of Ienc-fvPTC and inf-fvPTC cases. Results: The case cohort included 42 pediatric patients, with 6 (14%), 25 (60%), and 11 (26%) patients meeting criteria for NIFTP, Ienc-fvPTC, and inf-fvPTC, respectively. All cases were rereviewed, and 5 patients originally diagnosed with Ienc-fvPTC before 2017 were reappraised as having NIFTPs. The NIFTP cases were encapsulated tumors without invasive features, lymph node or distant metastasis, or disease recurrence. Ienc-fvPTC tumors demonstrated clearly demarcated tumor capsules and capsular/vascular invasion, while inf-fvPTC tumors displayed infiltrative growth lacking a capsule. inf-fvPTC cases had increased prevalence of malignant preoperative cytology, lymph node metastasis, and distant metastasis (p < 0.01). These cases were treated with total thyroidectomy, lymph node dissection, and subsequent radioactive iodine therapy. Preliminary genetic findings suggest a predominance of fusions in inf-fvPTC cases versus point mutations in Ienc-fvPTC (p = 0.02). Conclusions: Pediatric NIFTP and fvPTC subtypes appear to demonstrate alignment between clinical and histological risk stratification, with indolent behavior in Ienc-fvPTC and invasive features in inf-fvPTC tumors.

Indeterminate Thyroid Fine-Needle Aspirations in Pediatrics: Exploring Clinicopathologic Features and Utility of Molecular Profiling.

INTRODUCTION: The diagnostic utility of molecular profiling for the evaluation of indeterminate pediatric thyroid nodules is unclear. We aimed to assess pediatric cases with indeterminate thyroid fine-needle aspiration (FNA) alongside clinicopathologic features and mutational analysis. METHODS: A retrospective review of 126 patients with indeterminate cytology who underwent FNA between January 2010 and December 2021 at the Children's Hospital of Philadelphia was performed. Indeterminate cases defined by The Bethesda System for Reporting Thyroid Cytopathology (AUS/FLUS or TBSRTC III; FN/SFN or TBSRTC IV; SM or TBSRTC V) were correlated to clinicopathologic and genetic characteristics. RESULTS: Of the 114 surgical cases, 48% were malignant, with the majority of malignant cases diagnosed as follicular variant of papillary thyroid carcinoma (28/55). Risk of malignancy increased with TBSRTC category: 23% for AUS/FLUS, 51% for FN/SFN, and 100% for SM nodules. There were significant differences in surgical approach (p < 0.01), performance of lymph node dissection (p < 0.01), histological diagnosis (p < 0.01), primary tumor focality/laterality (p = 0.04), and lymphatic invasion (p = 0.02) based on TBSRTC classification, with resultant differences in post-surgical risk stratification per American Thyroid Association (ATA) Pediatric Guidelines (p = 0.01). Approximately 89% (49/55) of cases were classified as ATA low risk, and 5 of 6 patients with ATA intermediate- or high-risk disease had SM cytology. Somatic molecular testing was performed in 40% (51/126) of tumors; 77% (27/35) of malignant cases and 38% (6/16) of benign cases harbored driver alteration(s). Of the driver-positive malignant cases, 52% (14/27) were associated with low risk (DICER1, PTEN, RAS, and TSHR mutations), 33% (9/27) were associated with high risk (BRAF mutations and ALK, NTRK, and RET fusions), and 15% (4/27) had unreported risk for invasive disease (APC, BLM, and PPM1D mutations and TG-FGFR1 fusion). Incidence of high-risk drivers increased with TBSRTC category. Approximately 23% (8/35) of patients harboring thyroid malignancy did not have an identifiable driver alteration. CONCLUSIONS: Molecular analysis is useful to discriminate benign and malignant thyroid nodules with indeterminate cytology. Patients with driver genetic alteration(s) and indeterminate cytology should consider surgical management secondary to the high incidence (82%; 27/33) of thyroid malignancy in these patients.

Fusion Oncogenes Are Associated With Increased Metastatic Capacity and Persistent Disease in Pediatric Thyroid Cancers.

PURPOSE: In 2014, data from a comprehensive multiplatform analysis of 496 adult papillary thyroid cancer samples reported by The Cancer Genome Atlas project suggested that reclassification of thyroid cancer into molecular subtypes, RAS-like and BRAF-like, better reflects clinical behavior than sole reliance on pathologic classification. The aim of this study was to categorize the common oncogenic variants in pediatric differentiated thyroid cancer (DTC) and investigate whether mutation subtype classification correlated with the risk of metastasis and response to initial therapy in pediatric DTC. METHODS: Somatic cancer gene panel analysis was completed on DTC from 131 pediatric patients. DTC were categorized into RAS-mutant (H-K-NRAS), BRAF-mutant (BRAF p.V600E), and RET/NTRK fusion (RET, NTRK1, and NTRK3 fusions) to determine differences between subtype classification in regard to pathologic data (American Joint Committee on Cancer TNM) as well as response to therapy 1 year after initial treatment had been completed. RESULTS: Mutation-based subtype categories were significant in most variables, including age at diagnosis, metastatic behavior, and the likelihood of remission at 1 year. Patients with RET/NTRK fusions were significantly more likely to have advanced lymph node and distant metastasis and less likely to achieve remission at 1 year than patients within RAS- or BRAF-mut subgroups. CONCLUSION: Our data support that genetic subtyping of pediatric DTC more accurately reflects clinical behavior than sole reliance on pathologic classification with patients with RET/NTRK fusions having worse outcomes than those with BRAF-mutant disease. Future trials should consider inclusion of molecular subtype into risk stratification.

Outcomes in Pediatric Thyroidectomy: Results From a Multinational, Multi-institutional Database.

OBJECTIVE: Traditionally, data regarding thyroidectomy were extracted from billing databases, but information may be missed. In this study, a multi-institutional pediatric thyroidectomy database was used to evaluate recurrent laryngeal nerve (RLN) injury and hypoparathyroidism. STUDY DESIGN: Retrospective multi-institutional cohort study. SETTING: Tertiary care pediatric hospital systems throughout North America. METHODS: Data were individually collected for thyroidectomies, then entered into a centralized database and analyzed using univariate and multivariable regression models. RESULTS: In total, 1025 thyroidectomies from 10 institutions were included. Average age was 13.9 years, and 77.8% were female. Average hospital stay was 1.9 nights and 13.5% of patients spent at least 1 night in the pediatric intensive care unit. The most frequent pathology was papillary thyroid carcinoma (42%), followed by Graves' disease (20.1%) and follicular adenoma (18.2%). Overall, 1.1% of patients experienced RLN injury (0.8% permanent), and 7.2% experienced hypoparathyroidism (3.3% permanent). Lower institutional volume (odds ratio [OR], 3.57; 95% CI, 1.72-7.14) and concurrent hypoparathyroidism (OR, 3.51; 95% CI, 1.64-7.53) correlated with RLN injury on multivariable analysis. Graves' disease (OR, 2.27; 95% CI, 1.35-3.80), Hashimoto's thyroiditis (OR, 4.67; 95% CI, 2.39-9.09), central neck dissection (OR, 3.60; 95% CI, 2.36-5.49), and total vs partial thyroidectomy (OR, 7.14; 95% CI, 4.55-11.11) correlated with hypoparathyroidism. CONCLUSION: These data present thyroidectomy information and complications pertinent to surgeons, along with preoperative risk factor assessment. Multivariable analysis showed institutional volume and hypoparathyroidism associated with RLN injury, while hypoparathyroidism associated with surgical indication, central neck dissection, and extent of surgery. Low complication rates support the safety of thyroidectomy in pediatric tertiary care centers.

Pediatric intraoperative nerve monitoring during thyroid surgery: A review from the American Head and Neck Society Endocrine Surgery Section and the International Neural Monitoring Study Group.

Children are more likely to experience recurrent laryngeal nerve (RLN) injury during thyroid surgery. Intraoperative nerve monitoring (IONM) may assist in nerve identification and surgical decision making. A literature review of pediatric IONM was performed and used to inform a monitoring technique guide and expert opinion statements. Pediatric IONM is achieved using a variety of methods. When age-appropriate endotracheal tubes with integrated surface electrodes are not available, an alternative method should be used. Patient age and surgeon experience with laryngoscopy influence technique selection; four techniques are described in detail. Surgeons must be familiar with the nuances of monitoring technique and interpretation; opinion statements address optimizing this technology in children. Adult IONM guidelines may offer strategies for surgical decision making in children. In some cases, delay of second-sided surgery may reduce bilateral RLN injury risk.

Clinical Course of Early Postoperative Hypothyroidism Following Thyroid Lobectomy in Pediatrics.

Introduction: Thyroid lobectomy reduces risks of surgical complications and need for levothyroxine (LT4). We aimed at identifying the clinical course and risk factors for postlobectomy hypothyroidism to optimize surgical counseling and management in pediatric patients undergoing lobectomy. Methods: Clinical and biochemical presentations pre- and postlobectomy were retrospectively reviewed for 110 patients who underwent thyroid lobectomy between 2008 and 2020 at the Children's Hospital of Philadelphia. Results: Approximately 28.2% of patients (31/110) developed postlobectomy hypothyroidism defined by an elevated thyrotropin (TSH) level, including 24.5% (27/110) with subclinical hypothyroidism (TSH >4.5 and <10.0 mIU/L) and 3.6% (4/110) with overt hypothyroidism (TSH >10.0 mIU/L). LT4 was initiated in 12.7% (14/110) of cases. Most patients (81.6%; 84/103) recovered euthyroidism within 12 months postlobectomy. When excluding patients with autonomous nodule(s), median preoperative TSH was 1.09 (interquartile range [IQR] = 0.70-1.77) mIU/L and 1.80 (IQR = 1.02-2.68) mIU/L in euthyroid and hypothyroid patients, respectively, with multivariate logistic regression confirming the association between an increased preoperative TSH and postlobectomy hypothyroidism (odds ratio = 1.8 [confidence interval 1.08-3.13], p = 0.024). Of the patients who underwent thyroid lobectomy and developed postoperative hypothyroidism (n = 31), 38.7% (12/31) had a preoperative diagnosis of an autonomously functioning thyroid nodule. Conclusions: Thyroid function should be evaluated postlobectomy to assess the need for LT4. LT4 should be considered if the TSH remains elevated, especially if an upward trend is observed or TSH is >10.0 mIU/L. Suppressed preoperative TSH associated with autonomous nodules is an independent risk factor for postlobectomy hypothyroidism.

Prevalence and Risk Factors for Multifocality in Pediatric Thyroid Cancer.

Importance: Current guidelines recommend total thyroidectomy for the majority of pediatric thyroid cancer owing to an increased prevalence of multifocality. However, there is a paucity of information on the exact prevalence and risk factors for multifocal disease-knowledge that is critical to improving pediatric thyroid cancer management and outcomes. Objective: To determine the prevalence and risk factors for multifocal disease in pediatric patients with papillary thyroid carcinoma (PTC). Design, Setting, and Participants: This multicenter retrospective cohort study included patients 18 years or younger who underwent thyroidectomy for PTC from 2010 to 2020 at 3 tertiary pediatric hospitals and 2 tertiary adult and pediatric hospitals in the US. Main Outcomes and Measures: Demographic and clinical variables, including age, family history of thyroid cancer, autoimmune thyroiditis, prior radiation exposure, cancer predisposition syndrome, tumor size, tumor and nodal stage, PTC pathologic variant, and preoperative imaging, were assessed for association with presence of any multifocal, unilateral multifocal, and bilateral multifocal disease using multiple logistic regression analyses. Least absolute shrinkage and selection operator analysis was performed to develop a model of variables that may predict multifocal disease. Results: Of 212 patients, the mean age was 14.1 years, with 23 patients 10 years or younger; 173 (82%) patients were female. Any multifocal disease was present in 98 (46%) patients, with bilateral multifocal disease in 73 (34%). Bilateral multifocal disease was more accurately predicted on preoperative imaging than unilateral multifocal disease (48 of 73 [66%] patients vs 9 of 25 [36%] patients). Being 10 years or younger, T3 tumor stage, and N1b nodal stage were identified as predictors for multifocal and bilateral multifocal disease. Conclusions and Relevance: This large, multicenter cohort study demonstrated a high prevalence of multifocal disease in pediatric patients with PTC. Additionally, several potential predictors of multifocal disease, including age and advanced T and N stages, were identified. These risk factors and the high prevalence of multifocal disease should be considered when weighing the risks and benefits of surgical management options in pediatric patients with PTC.