Julia Baran

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. 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. 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 ( < 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 ( = 0.02). 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.

DOI

10.1089/thy.2022.0239

Alternate Title

Thyroid

PMID

36103376

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Title

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

Year of Publication

2022

Author

Date Published

07/2022

ISSN Number

1663-2826

Abstract

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.