Clinicopathologic Characteristics of Pediatric Follicular Variant of Papillary Thyroid Carcinoma Subtypes: A Retrospective Cohort Study.

2022

1353-1361

11/2022

1557-9077

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.

10.1089/thy.2022.0239

Thyroid

36103376

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

2022

07/2022

1663-2826

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.

10.1159/000526116

Horm Res Paediatr

35871517

Clinicopathologic Characteristics of Pediatric Follicular Variant of Papillary Thyroid Carcinoma Subtypes: A Retrospective Cohort Study.

2022

09/2022

1557-9077

Follicular patterned thyroid nodules with nuclear features of papillary thyroid carcinoma encompass a range of diagnostic categories with varying risks of metastatic behavior. Subtypes include invasive encapsulated fvPTC (Ienc-fvPTC) and infiltrative fvPTC (inf-fvPTC) with tumors lacking invasive features classified as non-invasive follicular thyroid neoplasm with papillary-like features (NIFTP). This study aimed to report the clinical and histologic 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 papillary thyroid carcinoma 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 re-reviewed, and 5 patients originally diagnosed with Ienc-fvPTC prior to 2017 were reappraised as NIFTP. 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 pre-operative 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 ( < 0.01). 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.

10.1089/thy.2022.0239

Thyroid

36103376

Utility of Fine-Needle Aspirations to Diagnose Pediatric Thyroid Nodules.

2021

2021 Sep 01

1663-2826

10.1159/000519307

Horm Res Paediatr

34469888

Characteristics of Follicular Variant Papillary Thyroid Carcinoma in a Pediatric Cohort.

2018

1639-1648

2018 Apr 1

1945-7197

<p><strong>Context: </strong>In adults, non-invasive follicular variant papillary thyroid carcinoma (FVPTC) is considered low risk for metastasis and persistent/recurrent disease.</p>

<p><strong>Objective: </strong>The goal of this study was to assess the clinical, sonographic, and histopathological features of FVPTC in a pediatric cohort.</p>

<p><strong>Design: </strong>A retrospective review of subjects &lt; 19 years of age with papillary thyroid carcinoma (PTC) who underwent thyroidectomy between January 2010 and July 2015.</p>

<p><strong>Setting: </strong>Multidisciplinary, academic referral center.</p>

<p><strong>Patients: </strong>Patients with FVPTC, defined as a tumor ≥1.0 cm in largest dimension with predominant follicular growth, complete lack of well-formed papillae, and nuclear features of PTC.</p>

<p><strong>Main Outcome Measure: </strong>Tumor size and location, presence of a tumor capsule, capsule and vascular invasion, lymph node and distant metastasis.</p>

<p><strong>Results: </strong>Eighteen patients with FVPTC were identified from a case cohort of 110 patients with PTC. On histopathology, 13 (72%) had unifocal nodules and 14 (78%) were completely encapsulated. Capsule invasion was frequent (9/14; 64%) and vascular invasion was found in one third of patients (6/18; 33%). No lymph node metastases were found in the 13 (72%) patients who had a central neck lymph node dissection. One patient with vascular invasion had distant metastases.</p>

<p><strong>Conclusion: </strong>When strictly defined, FVPTC in pediatric patients has a low risk for bilateral disease and metastasis. Prospective studies are needed to confirm whether lobectomy with surveillance is sufficient to achieve remission in pediatric patients with low risk FVPTC.</p>

10.1210/jc.2017-02454

29438531

Molecular Testing for Oncogenic Gene Alterations in Pediatric Thyroid Lesions.

2018

60-67

2018 Jan

1557-9077

<p><strong>BACKGROUND: </strong>Thyroid nodules are less common in pediatric patients (≤18 years) than in adults. The Bethesda System for Reporting Thyroid Cytopathology allows for individual risk stratification, but a significant number of nodules are indeterminate. Incorporating gene mutation panels and gene expression classifiers may aid in pre-operative diagnosis. The overall aim of this study was to assess the prevalence of oncogene alterations in a representative pediatric population and across a broad-spectrum of thyroid tumor diagnoses.</p>

<p><strong>METHODS: </strong>Retrospective cross-sectional evaluation of 115 archived samples, including: 47 benign [29 follicular adenoma (FA), 11 diffuse hyperplasia, 4 thyroiditis, and 3 multinodular goiter], 6 follicular thyroid cancer (FTC), 24 follicular variant of papillary thyroid cancer (fvPTC), 27 classic variant of PTC (cPTC), 8 diffuse sclerosing variant of PTC (dsvPTC) and 3 other PTC. Molecular testing was performed by multiplex qualitative PCR followed by bead array cytometry. Oncogene results were analyzed for association with age, gender, histology, lymph node metastasis and intrathyroidal spread.</p>

<p><strong>RESULTS: </strong>A mutation in one of the 17 molecular markers evaluated was found in: 2/6 (33%) FTC, 8/24 (33%) fvPTC, 17/27 (63%) cPTC, and 4/8 (50%) dsvPTC. Mutations in RAS or PAX8-PPARG were exclusive to FTC and fvPTC, BRAF was the most common mutation in cPTC (12/17; 71%) and RET-PTC was the only mutation associated with dsvPTC. Overall, a mutation was found in 32/68 (47%) malignant specimens with a single FA positive for PAX8-PPARG. The relative distribution of gene alterations in pediatric lesions was similar to adults. Presence of BRAF mutation in pediatric cPTC did not predict a more invasive phenotype.</p>

<p><strong>CONCLUSIONS: </strong>. 32/33 nodules with genetic alterations were malignant. Mutations in RAS were most frequently associated with FTC, RET-PTC rearrangements with dsvPTC and invasive fvPTC, and BRAF with cPTC. These results suggest a clinical role for mutational analysis of pediatric nodules to guide the surgical approach.</p>

10.1089/thy.2017.0059

Thyroid

29108474