Exploring the Molecular Features and Clinicopathological Correlations of Diffuse Sclerosing Papillary Thyroid Carcinoma

IF 2.4 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Clinical Endocrinology Pub Date : 2025-08-11 DOI:10.1111/cen.70013

Yanhui Zhang, Tingting Ding, Runfen Cheng, Ying Wang, Jianghua Wu

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Abstract

Objective

The diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) is a rare, aggressive subtype with distinct clinicopathological features. This study aimed to characterize its molecular alterations and evaluate their clinical associations.

Methods

A retrospective analysis of 51 DSV-PTC cases was conducted. Clinicopathological data were reviewed, and molecular profiling was performed using fluorescent PCR to detect mutations and gene fusions across 12 thyroid cancer-related genes.

Results

This study included eight paediatric cases (15.7%) and 43 adult cases (84.3%) of DSV-PTC. The most common alteration was BRAF mutation (39.2%), followed by RET fusions (25.5%; including CCDC6-RET in 23.5% and NCOA4-RET in 2.0%), ETV6-NTRK3 fusion (5.9%) and TERT promoter mutations (2.0%). Compared with BRAF-mutated tumours, RET fusion-positive cases showed significantly larger primary tumours (p = 0.016), larger metastatic nodes (p = 0.009) and higher T stages (p = 0.046). Paediatric patients exhibited more aggressive features, such as higher rates of lateral neck metastasis and extrathyroidal extension, but had fewer BRAF mutations. The overall recurrence rate was 15.7%, with earlier recurrence in RET fusion cases. One patient with coexisting ETV6-NTRK3 fusion and TERT mutation progressed to anaplastic thyroid carcinoma and died of disease.

Conclusion

DSV-PTC demonstrates substantial molecular heterogeneity. RET fusions are linked to more aggressive behaviour, and paediatric cases often show extensive locoregional spread. Coexisting NTRK and TERT alterations may signal high-risk progression, highlighting the value of molecular stratification in management.

Abstract Image

查看原文本刊更多论文

探讨弥漫性硬化性甲状腺乳头状癌的分子特征及临床病理相关性。

目的：弥漫性硬化型甲状腺乳头状癌（DSV-PTC）是一种罕见的侵袭性亚型，具有独特的临床病理特征。本研究旨在表征其分子改变并评估其临床相关性。方法：对51例DSV-PTC病例进行回顾性分析。回顾临床病理资料，利用荧光PCR进行分子谱分析，检测12个甲状腺癌相关基因的突变和基因融合。结果：本研究包括8例儿童（15.7%）和43例成人（84.3%）DSV-PTC。最常见的变异是BRAF突变（39.2%），其次是RET融合（25.5%）；其中CCDC6-RET占23.5%，nco4a - ret占2.0%)，ETV6-NTRK3融合（5.9%）和TERT启动子突变（2.0%）。与braf突变的肿瘤相比，RET融合阳性病例原发肿瘤较大（p = 0.016），转移淋巴结较大（p = 0.009）， T分期较高（p = 0.046）。儿科患者表现出更强的侵袭性特征，如更高的侧颈转移率和甲状腺外展，但BRAF突变较少。总复发率为15.7%，RET融合病例复发率较早。1例同时存在ETV6-NTRK3融合和TERT突变的患者进展为间变性甲状腺癌并死于疾病。结论：DSV-PTC具有明显的分子异质性。RET融合与更具攻击性的行为有关，儿科病例通常表现出广泛的局部区域扩散。同时存在的NTRK和TERT改变可能预示着高风险的进展，这突出了分子分层在治疗中的价值。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Endocrinology 医学-内分泌学与代谢

CiteScore

6.40

自引率

3.10%

发文量

192

审稿时长

1 months

期刊介绍： Clinical Endocrinology publishes papers and reviews which focus on the clinical aspects of endocrinology, including the clinical application of molecular endocrinology. It does not publish papers relating directly to diabetes care and clinical management. It features reviews, original papers, commentaries, correspondence and Clinical Questions. Clinical Endocrinology is essential reading not only for those engaged in endocrinological research but also for those involved primarily in clinical practice.