Thyroid surgery outcomes at a children's hospital: The value of a multidisciplinary team approach.

BACKGROUND: Our purpose is to describe the structure, function and outcomes of our multidisciplinary pediatric thyroid program and to evaluate our experience in comparison to other high-volume centers. METHODS: We reviewed all thyroid operations performed 10/2012 through 09/2019, and examined number of cases per year, patient demographics, procedures, final diagnoses and results. Primary outcomes were hypoparathyroidism and recurrent laryngeal nerve (RLN) injury at 12 months. Data were analyzed using descriptive statistics and univariate analyses. RESULTS: We performed 294 thyroid operations on 279 patients. Seventy-nine percent were female. Median age was 15 years (IQR: 12-17). Operations included total thyroidectomy (65%), lobectomy (30%) and completion thyroidectomy (5%). Most common diagnoses were Graves' disease (35%), malignancy (29%), and benign nodule (20%). We developed an evidence-based clinical pathway and conducted weekly multidisciplinary meetings. A clinical data specialist reviewed process and outcome measures routinely. Overall, 6 patients (2.0%) had hypoparathyroidism and 2 (0.7%) had unilateral RLN injury at 12 months. Two of the patients with clinical suspicion of permanent hypoparathyroidism were ultimately weaned off calcium. Both patients with RLN injury had extensive locally advanced malignant disease involving the nerve. CONCLUSIONS: Our multidisciplinary team achieved excellent long-term outcomes for pediatric thyroid surgery comparable to other high-volume pediatric and adult centers.

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.

Prolonged Untreated Disease and Limited English Proficiency: A Case of Van Wyk-Grumbach Syndrome.

Children from families with limited English proficiency have worse health outcomes than those from English-speaking families, likely related to the impact of a variety of social determinants on an increased risk of delayed presentation, diagnosis, and loss to follow-up. Van Wyk-Grumbach syndrome (VWGS) is a result of prolonged untreated primary hypothyroidism and early diagnosis of hypothyroidism is critical to prevent VWGS from developing. Whether social determinants of health, particularly limited English proficiency, impact the development, diagnosis, and treatment of VWGS has not been discussed previously. Here, we describe the case of an adolescent girl diagnosed with VWGS whose primary caregiver is foreign-born and with limited English proficiency, explore factors that may have placed her at increased risk for delayed presentation of VWGS, and discuss ongoing challenges of her disease management. We briefly review the pathophysiology of VWGS, emphasize the importance of being sensitive to this atypical presentation of hypothyroidism, and explore the intersections of this case with limited English proficiency status.

Considerations for total thyroidectomy in an adolescent with PTEN mutation.

Individuals with PTEN Hamartoma Tumor Syndrome (PHTS) are at greatly increased risk for developing well-differentiated thyroid cancer. Specific circumstances in which total thyroidectomies should be considered have not been defined. A 14-year-old macrocephalic female with history of developmental delay and lipoma over her left flank presented with neck swelling and was found have multinodular goiter and auto-immune thyroiditis. Asymptomatic tracheal narrowing was also detected on her initial diagnostic imaging. Later on, she developed positional dyspnea during sleep. Genetic testing revealed a heterozygous pathogenic variant in the PTEN gene (c.463T>A). A total thyroidectomy was performed. In addition to addressing the symptomology in our case, a total thyroidectomy also fortuitously eliminated the thyroid cancer risk. This case spurred us on further to identify specific clinical scenarios where total thyroidectomy may be considered as a true prophylactic measure to manage thyroid cancer risk in PHTS patients.

High false-positive rate of human immunodeficiency virus rapid serum screening in a predominantly hispanic prenatal population.

OBJECTIVE: To identify the characteristics of the gravidas delivering at our birthing center that place them at risk for false-positive human immunodeficiency virus (HIV) enzyme-linked immunosorbent assay (ELISA). STUDY DESIGN: The medical records of all rapid HIV-ELISA-positive gravidas that delivered at our hospital between January 2000 and October 2001 were retrieved, and information was gathered regarding maternal demographics. The results of the Western blot tests were also retrieved and correlated to the ELISA results, across varying maternal characteristics. chi(2), Student's t-test and multivariate analysis were performed, as appropriate, using the SAS software; statistical significance was denoted by p<0.05. RESULTS: A total of 69 patients had a positive rapid HIV-ELISA out of 9,781 deliveries. Of those, 26 were confirmed as HIV infected by Western blot (overall HIV prevalence: 0.27%, ELISA-positive predictive value: 37.7%). The subgroup prevalence of HIV and positive predictive value of ELISA were 1.53 and 75% among Caucasians; 2.43 and 82.6% among African-Americans; and 0.05 and 9.8% among Hispanics, respectively (p<0.05 for the comparisons between Hispanics and non-Hispanics only). A history of multiple (> or =5 lifetime) sexual partners was elicited in the majority of HIV-infected patients. CONCLUSIONS: The positive predictive value of rapid HIV-ELISA during pregnancy varies widely, depending on maternal race/ethnicity and sexual behavior. The routine disclosure of rapid intrapartum HIV serum screening results prior to Western blot confirmation should be avoided in very low-risk populations.