Incidence and malignancy rates of indeterminate pediatric thyroid nodules

Abstract

Background The American Thyroid Association guidelines task force currently recommends definitive thyroidectomy or lobectomy after an indeterminate thyroid biopsy in children. This recommendation is based on evidence of a greater incidence and a higher risk of malignancy compared with adults in earlier pediatric studies. Such management may lead to overtreatment and unnecessary surgery for many children in the United States. Methods The objective of the current study was to re‐evaluate pediatric thyroid nodules and assess the overall percentages and malignancy rates for indeterminate thyroid biopsies in children. In total, 302 pediatric thyroid fine‐needle aspirations (FNAs) were analyzed retrospectively (2001‐2018). Distribution percentages and malignancy rates were calculated for each category of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). Results Two indeterminate TBSRTC groups (atypia of undetermined significance/follicular lesion of undetermined significance and follicular neoplasm/suspicious for a follicular neoplasm) had much lower distribution percentages and malignancy rates compared with earlier pediatric series and American Thyroid Association guidelines. A meta‐analysis further supported these findings and demonstrated distinctly different malignancy rates for the indeterminate groups (atypia of undetermined significance/follicular lesion of undetermined significance, follicular neoplasm/suspicious for a follicular neoplasm, and suspicious for malignancy), suggesting the need for TBSRTC category‐specific management recommendations rather than a nondiscriminatory, up‐front surgical approach. Conclusions Adult patients with indeterminate preoperative thyroid cytopathology are followed by repeat biopsy and possibly molecular testing before undergoing definitive surgery. However, in children, the guidelines are considerably more aggressive and recommend definitive surgery after the first indeterminate thyroid biopsy. Here, the largest pediatric cohort to date with meta‐analysis is presented, and the authors propose a re‐evaluation of this up‐front approach to pediatric thyroid care.

Thyroid Cancer in the Pediatric Population

“…Although there is significant variability between studies, the risk of malignancy in non-diagnostic (Bethesda I), benign (Bethesda II), and suspicious/malignant (Bethesda V/VI) mirror adult risk assessment at 0% (range 0–10%), 5–8% (range 0–16%), and 100% respectively (Bethesda V range: 40–100%, Bethesda VI range: 100%). [42]. Several studies suggest that Bethesda III (atypia of uncertain significance/follicular lesion of uncertain significance; AUS/FLUS) and Bethesda IV (follicular neoplasm/suspicious for follicular neoplasm; FN/SFN) categories account for up to 40% (range: 13–43%) of all pediatric FNA diagnoses [42].…”

“…[42]. Several studies suggest that Bethesda III (atypia of uncertain significance/follicular lesion of uncertain significance; AUS/FLUS) and Bethesda IV (follicular neoplasm/suspicious for follicular neoplasm; FN/SFN) categories account for up to 40% (range: 13–43%) of all pediatric FNA diagnoses [42]. Further, these indeterminate aspirate diagnoses are associated with increased risk of malignancy in children versus adults (28% in children vs. 6–30% in adults for AUS/FLUS and 58% in children vs. 10–40% in adults for FN/SFN lesions) [42].…”

“…Several studies suggest that Bethesda III (atypia of uncertain significance/follicular lesion of uncertain significance; AUS/FLUS) and Bethesda IV (follicular neoplasm/suspicious for follicular neoplasm; FN/SFN) categories account for up to 40% (range: 13–43%) of all pediatric FNA diagnoses [42]. Further, these indeterminate aspirate diagnoses are associated with increased risk of malignancy in children versus adults (28% in children vs. 6–30% in adults for AUS/FLUS and 58% in children vs. 10–40% in adults for FN/SFN lesions) [42]. However, more recent studies indicate lower percentages of indeterminate FNA groups than previously reported (13–18% for indeterminate diagnoses combined) and a lower risk of malignancy after histologic resection within these groups (11–20% for AUS/FLUS; 25–28% for FN/SFN) [42].…”

“…Further, these indeterminate aspirate diagnoses are associated with increased risk of malignancy in children versus adults (28% in children vs. 6–30% in adults for AUS/FLUS and 58% in children vs. 10–40% in adults for FN/SFN lesions) [42]. However, more recent studies indicate lower percentages of indeterminate FNA groups than previously reported (13–18% for indeterminate diagnoses combined) and a lower risk of malignancy after histologic resection within these groups (11–20% for AUS/FLUS; 25–28% for FN/SFN) [42].…”

“Predictive Factors of Malignancy in Pediatric Patients with Thyroid Nodules and Performance of the Italian Classification (SIAPEC 2014) in the Outcome of the Cytological FNA Categories”

“…For the adult population, some Italian Authors have studied national cohorts affected by thyroid nodules and reported signi cantly higher sensitivity of the Italian system than the Bethesda one, validating the TIRa/TIR3b subclassi cation for the individuation of benign nodules and malignant tumors, with a rate of malignancy of 4-20.8% and 28-60.3%, respectively [33][34][35][36][37][38][39][40][41][42][43][44]. Pediatric studies based on the BSRTC system indicate a higher ROM for indeterminate nodules (39.5% for AUS/FLUS category and 41.5% for the SFN category) compared to adults (30.5% and 28.9% respectively), with no substantial differences in ROM between the two indeterminate categories in both pediatric and adult age [46][47][48][49][50][51][52][53][54][55][56][57][58][59].…”