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

Thiesmeyer, Jessica W.; Egan, Caitlin E.; Greenberg, June; Beninato, Toni; Zarnegar, Rasa; Fahey, Thomas J.; Finnerty, Brendan M.

doi:10.1089/thy.2022.0098

Cited by 8 publications

(10 citation statements)

References 41 publications

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“…In our study, however, we found that AIT was observed in 50% of operated children, but we could not confirm the association of AIT with the PTC stage in relation to LNM or ETE. The only association involving the extent of the disease was found in relation to the age, tumour diameter, and TPOAb, similarly as observed in other recent paediatric studies ( 59 – 61 ). In paediatric patients, Huang et al.…”

Section: Discussionsupporting

confidence: 89%

Ultrasound evolution of parenchymal changes in the thyroid gland with autoimmune thyroiditis in children prior to the development of papillary thyroid carcinoma – a follow-up study

et al. 2023

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BackgroundFollicular cell-derived thyroid carcinoma represents the vast majority of paediatric thyroid cancers (TCs). Papillary thyroid carcinoma (PTC) accounts for over 90% of all childhood TC cases, and its incidence in paediatric patients is increasing. The objective of this follow-up study was to present the outcome of ultrasound (US) and laboratory monitoring of paediatric patients with autoimmune thyroiditis (AIT) prior to the development of PTC.Patients and methodsThis prospective study included 180 children and adolescents (132 females; 73.3%) with a suspicion of thyroid disorder referred to the Outpatient Endocrine Department. The patients were divided into four groups: 1) 28 patients with a mean age of 10.7 [standard deviation (SD), 3.1] y, in whom PTC was detected during the active surveillance of AIT [AIT(+), PTC(+) follow up (F)]; 2) 18 patients with a mean age of 12.8 (SD, 3.4) y, in whom PTC and AIT were detected upon admission (A) [AIT(+), PTC(+) A]; 3) 45 patients with a mean age of 13.0 (SD, 3.4) y, in whom PTC was detected upon admission and AIT was excluded [AIT(-), PTC(+) A]; and 4) an age- and sex-matched control group of 89 patients with AIT and with a mean age of 9.4 (SD, 3.0) y. The analysis included clinical, US, and laboratory assessment results of children on admission (groups 1–4) and during follow-up (groups 1 and 4) in the Paediatric Endocrine Outpatient Department.ResultsUpon admission of those in group 1, the US evaluation revealed a hypoechogenic thyroid gland in 12 and an irregular normoechogenic gland in 16 patients. US monitoring revealed an increase in thyroid echogenicity and an increased irregularity of the thyroid structure during the follow-up period of all of the patients from group 1. Such changes were not noticed in group 4. PTC was diagnosed at the mean time of 3.6 y (3 mo–9 y) since AIT confirmation in group 1. The mean maximum PTC diameter as per the US was significantly smaller in group 1 than in groups 2 and 3 [13.2 (10.8) mm vs. 22.2 (12.8) and 22.05 (15.4) mm]. Fewer patients in group 1 were referred to 131I than in groups 2 and 3 (71.4% vs. 94.4 and 93.3%). Interestingly, significant differences were observed in the thyroglobulin antibody (TgAb)/thyroid peroxidase antibody (TPOAb) ratio between groups 2 and 3, as opposed to group 4, at the beginning of observation [15.3 (27.6) and 3.5 (8.8] vs. 0.77 (1.9)]. In group 1, after the follow-up, an increase in the TgAb/TPOAb ratio was observed [1.2 (9.8) to 5.2 (13.5)]. There were no significant differences between groups 1–3 in labeling index Ki67, lymph nodes metastasis, extrathyroidal extension, and angioinvasion. There were no associations between thyroid-stimulating hormone, TgAb, and the extent of the disease.ConclusionThe use of thyroid US focused on the search for developing tumours in the routine follow-up of patients with AIT may not only help in the early detection of thyroid malignancies that are not clinically apparent but may also influence the invasiveness of oncological therapy and reduce the future side effects of 131I therapy. We propose that the repeat evaluation of TPOAb and TgAb warrants further exploration as a strategy to determine TC susceptibility in paediatric patients with AIT in larger multicentre studies.

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Section: Discussionsupporting

confidence: 89%

Ultrasound evolution of parenchymal changes in the thyroid gland with autoimmune thyroiditis in children prior to the development of papillary thyroid carcinoma – a follow-up study

et al. 2023

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“…and Thiesemeyer et al. ( 47 , 48 ). In most cases of PTC, thyroid function tests are within normal limits ( 9 , 18 ).…”

Section: Discussionmentioning

confidence: 90%

“…Thiesmeyer et al., in the largest study of paediatric PTC so far, also reported that prepubertal children presenting with the most extensive disease were most likely to have lymph node metastasis, extrathyroidal extension, nodal, and distant metastases at the time of diagnosis, even in the setting of small-diameter PTC ( 47 ). Prepubertal age compared to adolescent age is an independent predictor of nodal and distant metastatic disease ( 47 ).…”

Section: Discussionmentioning

confidence: 99%

“…Nonetheless, the paediatric population is not homogeneous, considering the influence of puberty ( 36 , 37 , 45 , 47 , 48 ). Few studies have compared differences in the biology of paediatric PTC between age groups.…”

Section: Introductionmentioning

confidence: 99%

“…The most common genetic alterations in paediatric PTC are RET-PTC and NTRK fusions, whereas mutations in BRAF, V600E, and RAS are less frequent than in adults (45,46). Nonetheless, the paediatric population is not homogeneous, considering the influence of puberty (36,37,45,47,48). Few studies have compared differences in the biology of paediatric PTC between age groups.…”

Section: Introductionmentioning

confidence: 99%

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Ultrasound, laboratory and histopathological insights in diagnosing papillary thyroid carcinoma in a paediatric population: a single centre follow-up study between 2000-2022

et al. 2023

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BackgroundPapillary thyroid carcinoma (PTC) often coincides with autoimmune thyroiditis (AIT); whether this association is incidental or causal remains debated.ObjectiveTo evaluate the ultrasonographic, laboratory, and histopathological features of PTC in paediatric patients with and without AIT and its relationship to puberty.DesignA retrospective cohort study.Patients and methodsA retrospective analysis of medical records of 90 patients (69; 76.7% females). The mean age at PTC diagnosis was 13.8 years [range 6-18]. All patients were evaluated ultrasonographically before thyroid surgery. Thyroid nodules were categorised using the European Thyroid Imaging Reporting and Data System (EU-TIRADS PL), and cytopathology was assessed using Bethesda criteria. Neck ultrasound results and thyroid and autoimmune status were correlated with histopathological PTC assessment.ResultsThe coexistence of PTC and AIT was found in 48.9% (44/90) of patients. The percentage of AIT was increasing with age; AIT was present only in 1/3 of prepubertal, close to 50% in pubertal, and over 60% in adolescent patients. The youngest patients (aged <10 years old) presented more often with goitre and lymphadenopathy and less often with AIT than adolescents (15-18 years of age). There were no differences in TPOAb, TgAb, and TSH levels between the age subgroups. Presurgical TgAb levels were higher than those of TPOAb in the youngest patients. Histopathological analysis revealed that the solid subtype was observed more often in prepubertal children and diffuse sclerosing in children below 14 years of age, whereas the classic subtype dominated in late pubertal. Univariate and multivariate analyses revealed that lymph nodes metastases (LNM) were associated with PTC diameter and fT4 level, whereas extrathyroidal extension with age and angioinvasion with PTC diameter and age. The correlations between age and fibrosis, and the presence of psammoma bodies in malignant tissues were close to significant. We did not observe an association between TSH levels and the presence of autoimmunity and PTC variables.ConclusionsIn paediatric patients the natural course of PTC may be less aggressive in adolescent patients than in younger children (especially < 10 years of age). We suggest that pre-operative evaluation of paediatric patients with thyroid nodules could include apart from assessment of thyroid hormones, evaluation of TPOAb, TgAb, and TRAb together with comprehensive neck ultrasonography.

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Age Stratification and Prognostic Factor Analysis in Pediatric Differentiated Thyroid Cancer

Winder,

Lazar,

Hod

et al. 2024

The Laryngoscope

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ObjectivesDifferentiated thyroid cancer (DTC) is rare in the pediatric population. It remains unclear whether younger children are at greater risk of more aggressive disease. We aimed to identify prognostic factors for aggressive pediatric DTC and to define an appropriate age stratification.MethodsThis retrospective cohort study included all patients aged 18 years or less who were treated for DTC between 1985 and 2021 in a tertiary medical center and were followed up for a minimum of 1.5 years after treatment.ResultsSeventy‐eight patients were included, all diagnosed with papillary thyroid carcinoma: 30 (38.5%) low‐risk, 21 (26.9%) intermediate‐risk, and 27 (34.6%) high‐risk according to the American Thyroid Association (ATA) risk stratification. The mean duration of follow‐up was 11.8 ± 7.8 years. No evidence of disease was documented in 52 patients (66.7%) at 1‐year post‐treatment and 64 patients (82.1%) at the end of follow‐up. On analysis by age, evidence of disease at 1‐year post‐treatment was found in 66.7% of children younger than 11 years, compared to 25.4% of older children (p = 0.002). There was no significant difference by age in evidence of disease at the last follow‐up (p = 0.453). Patients aged <11 years at diagnosis were associated with more aggressive disease features on histopathologic examination, metastatic disease, and high ATA risk level. Patients aged <8 years were associated with more frequent bilateral disease and extrathyroidal extension.ConclusionPediatric DTC patients who are younger than 11 years at diagnosis have more aggressive disease features and a lower early remission rate than older patients. Nevertheless, their long‐term outcome is satisfactory.Level of Evidence4‐retrospective cohort study Laryngoscope, 2024

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

Cited by 8 publications

References 41 publications

Ultrasound evolution of parenchymal changes in the thyroid gland with autoimmune thyroiditis in children prior to the development of papillary thyroid carcinoma – a follow-up study

Ultrasound evolution of parenchymal changes in the thyroid gland with autoimmune thyroiditis in children prior to the development of papillary thyroid carcinoma – a follow-up study

Ultrasound, laboratory and histopathological insights in diagnosing papillary thyroid carcinoma in a paediatric population: a single centre follow-up study between 2000-2022

Age Stratification and Prognostic Factor Analysis in Pediatric Differentiated Thyroid Cancer

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