Ultrasound and histopathological assessment of benign, borderline, and malignant thyroid tumors in pediatric patients: an illustrative review and literature overview

Abstract

Background: The risk of malignancy in thyroid nodules is higher in children than in adults, often necessitating a more aggressive endocrine and surgical approach. However, given that not all solid thyroid nodules are malignant, a more conservative approach may also be appropriate in certain cases.

Objective: This study aims to present an illustrative analysis of the pathological foundations underlying the sonographic appearance of benign, borderline, and malignant thyroid nodules in the pediatric population at a single tertiary thyroid center.

Methods: A total of 47 well-documented pediatric patients referred for thyroid surgery between 2010 and 2023 were analyzed. This retrospective assessment included an examination of demographic data, hormonal profiles, ultrasound findings, and histopathology reports.

Results: Ultrasound and histopathology of thyroid nodules provided insights into subgroup differentiation. Benign nodules like dyshormonogenetic goiter showed solid hypoechoic features on ultrasound and dense fibrosis on histopathology, while thyroid follicular nodular disease exhibited isoechoic nodules with halos, histologically revealing dilated follicles. In borderline tumors, well-differentiated tumor of uncertain malignant potential (WDT-UMP) nodules were hypo/hyperechoic with occasional capsular invasion, resembling papillary thyroid carcinoma (PTC) features histologically. Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) appeared as well-defined hypoechoic nodules with a hypoechoic rim, with histology showing follicular architecture and PTC nuclear features, but no invasion. Follicular tumor of uncertain malignant potential (FT-UMP) displayed hypo/hyperechoic patterns and indistinct borders, with uncertain capsular invasion and no PTC nuclear features. Malignant lesions showed distinct patterns: PTC as hypoechoic, irregular nodules with mixed vascularization, follicular thyroid carcinoma as large, hyperechoic nodules with invasive features, and poorly differentiated thyroid carcinoma (PDTC) as heterogeneous hypoechoic masses.

Conclusion: Because of the significant overlap in sonographic features among benign, borderline, and certain malignant thyroid lesions in pediatric patients, ultrasonography alone is insufficient for accurate risk stratification. This overlap necessitates referrals for fine-needle aspiration biopsy (FNAB) in children more frequently than in adults. Future studies utilizing artificial intelligence (AI) to predict clinical outcomes in thyroid nodule diagnostics may offer new advancements, particularly given the increasing number of pediatric patients with solid thyroid lesions.

Keywords: FT-UMP; NIFTP; WDT-UMP; follicular thyroid carcinoma; papillary thyroid carcinoma.

Figure 1

Dyshormonogenetic thyroid goiter (DHG). Columns represent: US and HE (magnification: A1, B1 ×5; A2, B2 ×50; A3, B3 ×1,000; and A4, B4 ×5,000). (A) Eighteen-year-old female patient; (B) 8-year-old female patient. US reveals a hypoechogenic nodule with well-defined borders and with hyperechogenic areas inside the nodule. In HE fibrosis, hemorrhages and inflammatory granulation tissue are seen. The structure is microfollicular and the nuclei are slightly enlarged and rarely overlap (A4, B3).

Figure 2

Thyroid follicular nodular disease (TFND). Columns represent US and HE (magnification A1–E1 ×5; A2–E2 ×50; and A3–E3 ×5,000). (A) Sixteen-year-old male patient with euthyroid goiter; (B) 14-year-old male patient with euthyroid goiter; (C) 18-year-old female patient with euthyroid goiter; (D) 18-year-old female patient with euthyroid goiter; (E) 15-year-old female patient with euthyroid goiter. In US, TFND is usually seen as a well-defined hyperechogenic nodule, surrounded by a hypoechogenic “halo” rim with mixed hypervascularity. In HE, macrofollicular (large follicles filled with pink colloid), medium-sized, and microfollicular structures are seen. Focally small fibrosis, hemorrhages, and papillary-like features are seen. The nuclei are a mixture of normotypical, slightly enlarged, and elongated, and they rarely have grooves. In patient (E), ischemia (shrunk cells partially detached from the tissue matrix) in the central area of the nodule and clear-cell change are seen.

Figure 3

Thyroid follicular nodular disease (TFND) in patients with DICER1 syndrome. Columns represent US and HE (magnification: A1, B1 ×5; A2, B2 ×50; and A3, B3 ×5,000). (A) Seventeen-year-old female patient with euthyroid TFND; (B) 12-year-old male patient with euthyroid TFND. US shows multinodular goiter composed of hyper/isoechogenic solid-cystic nodules with macrocalcifications, especially in patient (A) In HE, the whole thyroid is built up by many hypocellular nodules filled with pink colloid. The hyperplastic nodules present a small, medium, and large vesicular structure and focally papillary arrangement (intrafollicular centripetal growth). Some of the nodules show areas of non-specific granulation, fibrosis, single calcifications, and a mixed-cellular inflammatory infiltrate with foamy macrophages containing hemosiderin. The remaining thyroid parenchyma is slightly congested.

Figure 4

Thyroid follicular adenoma (TFA). Columns represent US and HE (magnification: A1–D1 ×5, A2–D2 ×50, and A3–D3 ×5,000). (A) Sixteen-year-old female patient with nodule found on US; (B) 16-year-old male patient with a nodule found on US; (C) 16-year-old female patient with euthyroid goiter with hoarseness; (D) 18-year-old male patient with euthyroid goiter with hoarseness. On US, a solitary, solid, round to oval, hypo/hyper/isoechogenic nodule is seen with well-defined hypoechogenic “halo” borders. On HE, the nodule is encapsulated, and the capsule is focally thickened and irregular. Pathological examination reveals no invasion through the capsule, the follicles inside a nodule are tightly packed, and the thyroid follicles adjacent to the nodule are constricted, larger (containing more colloid), but elongated. The nuclei are enlarged, with clearing and often overlap.

Figure 5

Oncocytic cell adenoma (OCA; Hürthle cell adenoma). Columns represent US and HE (magnification: A1–D1 ×5, A2–D2 ×50, and A3–D3 ×5,000). (A) Seventeen-year-old male patient with goiter; (B) 16-year-old female patient with a nodule found on US; (C) 17-year-old male patient with a nodule found on US; (D) 16-year-old male patient with a nodule found on US. US (C, D with power doppler, C*-without power doppler) reveals hyperechogenic nodules with small foci of hypoechogenic areas and increased mixed-type vascularity. HE examination reveals densely packed eosinophilic cells, and the hypoechogenic foci represent granular inflammatory tissue. Some of the cases might present with advanced fibrosis or contain medium-sized vessels (HE) and hyperperfusion in US (A, C, particularly). Cells are pleomorphic, with enlarged nuclei with prominent nucleoli.

Figure 6

NIFTP. Columns represent US and HE (magnification: A1–C1 ×5, A2–C2 ×50, and A3–C3 ×5,000). (A) Fifteen-year-old male patient with a nodule found on US; (B) 12-year-old male patient with a nodule found on US; (C) 14-year-old male patient with a nodule found on US. US reveals a small, well-defined hypoechogenic nodule with acoustic (posterior) enhancement. HE reveals follicular structures, from micro- to macrofollicles; the nodule is round or oval, well-defined with or without fibrotic capsule, and there is an absence of capsular and vascular invasion. The nuclei have a set of PTC features (focally grade 3).

Figure 7

FT-UMP. Columns represent US and HE (magnification: A1–F1 ×5, A2–F2 ×50, and A3–F3 ×5,000). (A) Seventeen-year-old female patient; (B) 17-year-old female patient; (C) 18-year-old female patient; (D) 16-year-old female patient; (E) 16-year-old female patient; (F) 16-year-old male patient. In all patients, a nodule was found on US. US revealed small, foremost well-defined nodules with hypo- and hyperechogenic areas; however, focally the nodules’ borders are hard to define. Vascularization is mixed in the nodules. HE reveals follicular structures, from micro- to macrofollicles, and the nodule is round or oval with uncertain foci of capsule invasion. There is absence of PTC nuclear features.

Figure 8

WDT-UMP. Columns represent US and HE (magnification: A1–D1 ×5, A2–D2 ×50, and A3–D3 ×5,000). (A) Seventeen-year-old male patient; (B) 16-year-old male patient; (C) 15-year-old female patient; (D) 17-year-old female patient. US reveals a medium-sized, quite well-defined hypoechogenic nodule in some cases with additional hyperechogenic areas. HE reveals follicular structures, predominantly microfollicles (hypoechogenic), and the nodule is oval, foremost well-defined but with the presence of capsular and vascular invasion, and the nuclei have PTC features.

Figure 9

DTC and PDTC. Columns represent US and HE (magnification: A1–E1 ×5, A2–E2 ×50, and A3-E3 ×5,000). (A) Fifteen-year-old female patient with PTC; (B) 11-year-old female patient with FTC; (C) 16-year-old male patient with FTC; (D) 17-year-old female patient with PDTC; (E) 16-year-old female patient with PDTC. PTC (A). US shows an irregular contoured, hypoechogenic nodule. In HE, the mixture of different-sized follicles built up from polymorphic cells with nuclei of “glassy” clearing and with grooves, invading through the capsule. FTC (B, C) and PDTC (D, E). US shows large, hypo- and hyperechogenic nodules; however, although the outlines might seem to be well-defined, there are quite large areas of uncertain borders consisting of small hyperechogenic fragments. HE reveals follicular structures, from micro- to macrofollicles, which invade through the capsule and/or there is an angioinvasion (D). The cells are pleomorphic and have large, overlapping nuclei. In PDTC, a set of neuroendocrine differentiation (salt-and-pepper nuclei) and trabecular structures can be found.

Figure 10

Ultrasonographic spectrum of papillary thyroid carcinoma in pediatric patients. (A-A2) hypoechogenic lesions with irregular margins; no increased vascularization in (A) and (A2); no microcalcifications in (A-A2); the shape is irregular oval, composition is solid. All patients with autoimmune thyroiditis (AIT). (B-B2) iso- and hypoechogenic lesions with `halo`; increased mixed vascularization and no microcalcifications in (B-B2); the shape is taller than wider or wider than taller, composition is solid. Only (B1) with AIT. (C-C2) represents diffuse sclerosing variant of PTC. Extrathyroidal invasion is seen on (C1). Vascularisation was increased in all lesions. All patients with AIT. (D-D2) represents hypoechogenic lesions surrounded by hyperechogenic irregular margin (histopathologically reported as fibrosis) in patients with autoimmune thyroiditis. No microcalcifications were seen but vascularization was increased in all lesions.