2022 European Thyroid Association Guidelines for the management of pediatric thyroid nodules and differentiated thyroid carcinoma

Diagnostics/stagingClinical question 1. What is the sensitivity and specificity of thyroid ultrasound for distinction of thyroid cancer from a benign thyroid nodule of a child?P (Population):Children diagnosed with a thyroid noduleI (etiologic/risk factor):Thyroid ultrasound characteristics of thyroid cancer; i.e. solid composition, microcalcifications, irregular margins, taller-than-wide shape, hypoechogenicity C (comparison):Thyroid ultrasound characteristics of a benign noduleO (outcome):Ultrasound characteristics compared to histopathological resultT (type of question): EtiologyS (study design):Cohort studyInclusion/exclusion criteria studies:English language Children <21 years of age Study population of at least N=20Type of search:Extensive systematic search (PubMed)Clinical question 2.What is the sensitivity/specificity of different suspicious US findings for presence of DTC metastasis to a lymph node?P (Population):Children or young adolescents diagnosed with a thyroid noduleI (etiologic/risk factor):Suspicious thyroid ultrasound findings in a child or young adolescent with lymph node metastasesC (comparison):Thyroid ultrasound findings in a child or young adolescent without lymph node metastasesO (outcome):Study describing sensitivity/ specificity for US findings of a suspicious lymph node to be DTCT (type of question): DiagnosticS (study design):Cohort studyInclusion/exclusion criteria studies:English language Children <21 years of age Study population of at least N=20Type of search:Extensive systematic search (PubMed)
Clinical question 3. Will molecular testing in a FNB specimen of a thyroid nodule in a child help you to distinguish from a benign nodule?

## P (population):
Children diagnosed with a thyroid nodule(s) by ultrasound with an indeterminate FNA result (AUS, SFN, SFM)

## I (etiologic/risk factor):
Genetic testing of FNA sample for specific mutation (e.g. BRAF 600E, NRAS, RET/PTC and cancer predisposition syndromes such as PTEN, DICER-1)

## C (comparison):
Benign thyroid nodule

## O (outcome):
Genetic analyses in FNA specimen related to histopathology

## T (type of question): diagnosis

## S (study design):
Cohort study

## Inclusion/exclusion criteria studies:
English language Children <21 years of age Study population of at least N=20

## Type of search: extensive systematic search (pubmed)
Clinical question 4. Does genetic testing in thyroid carcinoma tissue in a child or young adolescent alter its management?

## P (population):
Histopathological tissue of children with thyroid carcinoma

## I (etiologic/risk factor):
Genetic testing for specific mutations (e.g. BRAF 600E,NRAS, RET/PTC, and/or cancer predisposition syndromes such as PTEN , DICER-1)

## C (comparison):
No genetic testing

## O (outcome):
Genetic analyses in thyroid tissue related to outcome of disease Clinical question 17. What is the difference in outcome in children or young adolescents with recurrent disease/progressive thyroid cancer treated with additional RAI/surgery/other versus a wait-and-see approach?
? P (Population): Recurrent disease/progressive thyroid cancer or young adolescents in children

## I (intervention):
Additional RAI/surgery/ other

## C (comparison):
Wait-and-see

## O (outcome):
Thyroid cancer related morbidity or mortality

## T (type of question): treatment

## S (study design):
Cohort study

## Inclusion/exclusion criteria studies:
English language Children <21 years of age Study population of at least N= 20 ?

## P (population):
Children or young adolescents treated for DTC I (etiologic/risk factor) -

## C (comparison): -

## O (outcome):
Thyroid cancer related cardiac, salivary gland, female fertility, bone or psychosocial morbidity/mortality

## T (type of question): diagnosis

## S (study design):
Cohort study

## Inclusion/exclusion criteria studies:
English language Children or young adolescents <21 years of age Study population of at least N=20

## Type of search:
Extensive systematic search (PubMed)
Clinical question 22. Is presentation, outcome and/or disease course of DTC in children or young adolescents with genetic syndromes different than in children without genetic syndromes for which treatment and/or follow up should be adjusted?
?

## P (population):
Children or young adolescents treated for DTC I (etiologic/risk factor) Genetic syndromes (Cowden, DICER, Li Fraumeni, Lynch syndrome, FAP, Carney complex).

## C (comparison):
Patients without genetic syndromes

## O (outcome):
Thyroid cancer recurrence / thyroid cancer related mortality

## T (type of question): etiology

## S (study design):
Cohort study (multi-variate analysis)

## Inclusion/exclusion criteria studies:
English language Children <21 years of age

## Type of search:
Extensive systematic search (PubMed)
Clinical question 23. Is presentation, outcome and/or disease course of DTC in children with a history of radiation exposure different than in children without a history of radiation exposure for which treatment and/or follow up should be adjusted?
?

## P (population):
Children or young adolescents treated for DTC I (etiologic/risk factor) History of radiation exposure

## C (comparison):
Patients with no history of radiation exposure

## O (outcome):
Thyroid cancer recurrence/thyroid cancer related mortality

## T (type of question): etiology

## S (study design):
Cohort study (multi-variate analysis)

## Inclusion/exclusion criteria studies:
English language Children <21 years of age Study population of at least N= 20

## Type of search:
Extensive systematic search (PubMed)