# Size-Specific Predictors for Malignancy Risk in Follicular Thyroid Neoplasms: Machine Learning Analysis

**Authors:** Xin Li, Wen-yu Yang, Fan Zhang, Rui Shan, Fang Mei, Shi-Bing Song, Bang-Kai Sun, Jing Chen, Run-ze Hu, Yang Yang, Yi-hang Yang, Jing-yao Liu, Chun-Hui Yuan, Zheng Liu

PMC · DOI: 10.2196/73069 · 2025-07-11

## TL;DR

This study uses machine learning to identify predictors of malignancy in follicular thyroid tumors based on their size, helping surgeons make preoperative decisions.

## Contribution

The study introduces size-specific predictors for malignancy risk in follicular thyroid neoplasms using machine learning.

## Key findings

- Macrocalcification and peripheral calcification are significant predictors for malignancy in small-sized follicular thyroid neoplasms.
- Lower thyroid-stimulating hormone levels and larger tumor size are associated with malignancy risk in both small- and large-sized tumors.
- Nodule-in-nodule appearance is a key predictor for malignancy in large-sized follicular thyroid neoplasms.

## Abstract

Surgeons often face challenges in distinguishing between benign and malignant follicular thyroid neoplasms (FTNs), particularly small tumors, until diagnostic surgery is performed.

This study aimed to identify the size-specific predictors for the malignancy risk of FTNs preoperatively.

A retrospective cohort study was conducted at Peking University Third Hospital in Beijing, China, from 2012 to 2023. Patients with a postoperative pathological diagnosis of follicular thyroid adenoma (FTA) or follicular thyroid carcinoma (FTC) were included. FTNs were classified into small- and large-sized categories based on the cutoff value of the tumor diameter derived from spline regression, which indicated the turning point of malignancy risk. We identified the 5 most important predictors from 22 variables including demography, sonography, and hormones, using machine learning methods. We also calculated the odds ratios (OR) with 95% CI for these predictors in both small- and large-sized FTNs.

Altogether, we included 1494 FTNs, comprising 1266 FTAs and 228 FTCs. FTNs with a maximum diameter less than 3.0 cm were grouped as small-sized tumors (n=715), while those with larger diameters were categorized as large-sized tumors (n=779). In the small-sized group, tumors with macrocalcification (OR 2.90, 95% CI 1.50-5.60), those with peripheral calcification (OR 4.50, 95% CI 1.50-13.00), and those in younger patients (OR 1.33, 95% CI 1.05-1.69) showed a higher malignancy risk. In the large-sized group, tumors presenting with a nodule-in-nodule appearance (OR 3.30, 95% CI 1.30-7.90) exhibited a higher malignancy risk. In both groups, lower thyroid-stimulating hormone levels (OR 1.49, 95% CI 1.20-1.85 for small-sized FTNs; OR 1.61, 95% CI 1.37-1.96 for large-sized FTNs) and a larger mean diameter (OR 1.40, 95% CI 1.10-1.70 for small-sized FTNs; OR 1.50 95% CI 1.20-1.70 for large-sized FTNs) were associated with the malignancy risk of FTNs.

This study identified size-specific predictors for malignancy risk in FTNs, highlighting the importance of stratified prediction based on tumor size.

## Linked entities

- **Diseases:** follicular thyroid adenoma (MONDO:0005032), follicular thyroid carcinoma (MONDO:0005034)

## Full-text entities

- **Diseases:** FTNs (MESH:D013964), Malignancy (MESH:D009369), FTA (MESH:D000236), FTC (MESH:D018263)
- **Chemicals:** FTAs (MESH:D005485)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12274017/full.md

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Source: https://tomesphere.com/paper/PMC12274017