Hee-Sung Ahn, Eyun Song, Chae A Kim, Min Ji Jeon, Yu-Mi Lee, Tea-Yon Sung, Dong Eun Song, Jiyoung Yu, Ji Min Shin, Yeon-Sook Choi, Kyunggon Kim, Won Gu Kim
Endocrinol Metab. 2025;40(4):623-636. Published online April 10, 2025
Background The preoperative diagnosis of follicular thyroid carcinoma (FTC) is challenging because it cannot be readily distinguished from follicular adenoma (FA) or benign follicular nodular disease (FND) using the sonographic and cytological features typically employed in clinical practice.
Methods We employed comprehensive proteomics and machine learning (ML) models to identify novel diagnostic biomarkers capable of classifying three subtypes: FTC, FA, and FND. Bottom-up proteomics techniques were applied to quantify proteins in formalin-fixed, paraffin-embedded (FFPE) thyroid tissues. In total, 202 FFPE tissue samples, comprising 62 FNDs, 72 FAs, and 68 FTCs, were analyzed.
Results Close spectrum-spectrum matching quantified 6,332 proteins, with approximately 9% (780 proteins) differentially expressed among the groups. When applying an ML model to the proteomics data from samples with preoperative indeterminate cytopathology (n=183), we identified distinct protein panels: five proteins (CNDP2, DNAAF5, DYNC1H1, FARSB, and PDCD4) for the FND prediction model, six proteins (DNAAF5, FAM149B1, RPS9, TAGLN2, UPF1, and UQCRC1) for the FA model, and seven proteins (ACTN4, DSTN, MACROH2A1, NUCB1, SPTAN1, TAGLN, and XRCC5) for the FTC model. The classifiers’ performance, evaluated by the median area under the curve values of the random forest models, was 0.832 (95% confidence interval [CI], 0.824 to 0.839) for FND, 0.826 (95% CI, 0.817 to 0.835) for FA, and 0.870 (95% CI, 0.863 to 0.877) for FTC.
Conclusion Quantitative proteome analysis combined with an ML model yielded an optimized multi‐protein panel that can distinguish FTC from benign subtypes. Our findings indicate that a proteomic approach holds promise for the differential diagnosis of FTC.
A 65-year-old woman presented with a dry cough and multiple various sized nodules in both lungs on chest X-ray. A CT scan showed a 9.5 cm sized hypervascular mass in the liver and a 5.5 cm sized intraabdominal mass. A percutaneous needle biopsy of one of the lung nodules revealed a metastatic follicular thyroid carcinoma. Therefore, thyroid ultrasonography was performed, which revealed a 1 cm sized nodule in the right thyroid lobe. Cytology, obtained by ultrasonography guided fine needle aspiration, revealed a follicular neoplasm. The tumor cells were weakly positive on galectin-3 immunostaining, which favored a follicular carcinoma. An ultrasonography guided biopsy of the liver and EUS (endoscopic ultrasonography)-guided biopsy of the intraabdominal mass revealed a metastatic follicular thyroid carcinoma in the liver and peritoneum. We report a very rare case of a follicular thyroid microcarcinoma, with multiple metastases to the lung, liver and peritoneum.
So Hun Kim, Ji Young Jung, Sung Jae Shin, So Young Park, Si Hoon Lee, Yoo Mee Kim, Yu Mie Rhee, Soon Won Hong, Bong Soo Cha, Chul Woo Ahn, Kyung Rae Kim, Sung Kil Lim, Hyun Chul Lee
J Korean Endocr Soc. 2004;19(4):411-418. Published online August 1, 2004
Pendred syndrome is an autosomal recessive genetic disorder, which is characterized by sensorineural hearing loss, goiter and a positive perchlorate discharge test. It is caused by mutations of the PDS gene, and its clinical characteristics vary widely. The thyroid function in most cases is normal, or shows only mild hypothyroidism. In Pendred syndrome, there is an organification defect that leads to defective thyroid hormone synthesis, followed by chronic TSH stimulation. Herein is reported a case of a follicular thyroid carcinoma associated with Pendred syndrome. To our knowledge, this is the first case reported in Korea. The patient presented with a huge anterior neck mass, sensorineural hearing loss and a positive perchlorate discharge test. Fine needle aspiration cytology suggested malignancy of the thyroid, and a total thyroidectomy, with central compartment node dissection, was performed. The pathology from the thyroid mass showed a poorly differentiated follicular thyroid carcinoma