Aug 2026· iScience· Vol 29, pp. 117167· 0 citations· 42 references
Medicine
TL;DR
It is suggested that Hashimoto’s thyroiditis reshapes both epithelial transcriptional states and the intratumoral microbial environment, potentially contributing to a less aggressive tumor phenotype.
Abstract
Summary Hashimoto’s thyroiditis is associated with reduced lymph node metastasis in papillary thyroid carcinoma, suggesting that the autoimmune microenvironment may influence tumor progression. We utilized single-cell RNA sequencing and intratumoral 16S ribosomal RNA gene sequencing to investigate malignant epithelial cell states and microbial features in PTC with and without Hashimoto’s thyroiditis. Tumors with Hashimoto’s thyroiditis exhibited malignant epithelial populations enriched for innate immune signaling programs and showed increased intratumoral microbial diversity with reduced abundance of several Gram-negative bacteria, particularly Pseudomonas. Within the Hashimoto’s thyroiditis subgroup, lymph node metastasis was associated with increased Gram-negative bacterial abundance. Functional experiments further showed that Pseudomonas-derived lipopolysaccharide enhanced thyroid cancer cell migration in vitro and in vivo. These findings suggest that Hashimoto’s thyroiditis reshapes both epithelial transcriptional states and the intratumoral microbial environment, potentially contributing to a less aggressive tumor phenotype.
Background: Sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) is an extremely rare thyroid tumor that frequently arises in association with chronic lymphocytic thyroiditis. We report a rare case of SMECE and mucosa-associated lymphoid tissue (MALT) lymphoma diagnosed simultaneously in the same thyroid gland. Case report: A man in his 60s with serological findings suggestive of Hashimoto’s thyroiditis was referred to our hospital after a thyroid nodule was incidentally detected on carotid ultrasonography. Fine-needle aspiration cytology revealed clusters of intermediate-type epithelial cells with an eosinophil-rich inflammatory background. Left thyroid lobectomy was performed to establish a diagnosis. Results: Histologically, the tumor showed dense stromal sclerosis with nests of squamoid cells, intermediate-type cells, and mucin-producing cells, accompanied by marked eosinophilic infiltration. Immunohistochemistry demonstrated positivity for CK5/6, p63, and CK19 and negativity for thyroglobulin and TTF-1. Fluorescence in situ hybridization analysis revealed no MAML2 gene rearrangement. Chronic lymphocytic thyroiditis was present in the surrounding thyroid tissue, along with extranodal marginal zone lymphoma of the MALT. Conclusion: This case suggests that chronic inflammatory conditions associated with Hashimoto’s thyroiditis may have contributed to the tumorigenesis of both the epithelial and lymphoid components. Recognizing this rare coexistence is important for accurate pathological diagnosis.
Yutaka Nakamura, T. Murata, Yuichi Fujita et al.· Journal of Rural Medicine· 0 citations
Papillary thyroid carcinoma (PTC) is less aggressive when associated with lymphocytic thyroiditis (LT), even in the presence of oncogenic BRAF, including smaller tumours, less lymph node involvement, and reduced extrathyroidal extension (1). To investigate possible immune mechanisms underlying this association, we compared the tumour microenvironment of PTC-BRAF with and without LT using single-cell RNA sequencing (scRNA-seq). Single-cell libraries were generated from fresh and fixed tumour samples with post-dissociation viability >70% using the 10x Genomics Chromium platform and sequenced on an Illumina NovaSeq 6000. We analysed scRNA-seq data from 11 PTC-BRAF tumours, including four with LT (one publicly available sample) and seven without LT. Downstream analyses included quality control, batch correction, dimensionality reduction, and differential gene expression analysis. We found neutrophils were the predominant myeloid cell type in PTCs without LT. Thyrocytes without LT showed significant expression of the neutrophil recruitment chemokine ECRG4. In the absence of LT, neutrophils expressed oncogenic genes with poor clinical outcomes. In contrast, thyrocytes from tumours with LT showed increased expression of MHC-II antigen presentation, consistent with effective immune surveillance. Thyrocytes and macrophages in the presence of LT showed enrichment of interferon gamma response pathways. Our data suggests LT in thyroid cancer is associated with enhanced antigen presentation and fewer features of pro-tumorigenic innate immune activity. These results identify previously under recognized innate immune cell population and associated transcriptomic features which suggests new mechanisms to target immune treatments in PTC refractory to other therapies.
S. Perampalam, M. Gild, Sey Adwoa Amoakowa et al.· Endocrine-Related Cancer· 0 citations
This study comprehensively maps the coevolution of malignant thyrocyte plasticity and the immunosuppressive metastatic niche in thyroid cancer and provides a robust molecular rationale for developing next-generation immunotherapeutic strategies tailored to thyroid cancer.
Shu-hang Xu, Yaorong Su, Senmin Zhang et al.· Oncoimmunology· 0 citations
Papillary thyroid carcinoma (PTC) shows heterogeneous clinical behavior, and current clinicopathologic factors do not fully capture epithelial aggressiveness or tumor microenvironment (TME) remodeling. We integrated single-cell RNA-sequencing (scRNA-seq) datasets from normal thyroid tissue, primary PTC, and lymph-node metastases to construct a cross-stage cellular atlas and to characterize epithelial and T/NK-cell heterogeneity. Guided by the malignant epithelial program identified at single-cell resolution, we developed a four-gene risk signature in the TCGA-THCA cohort using Cox and LASSO regression. We further evaluated pathway activity, immune and stromal features, T-cell receptor (TCR) diversity, and exploratory in silico drug-response patterns, and we performed small interfering RNA (siRNA)-mediated knockdown of TMEM45A and STC1 in PTC cell lines. The integrated atlas revealed stage-related remodeling of epithelial, immune, and stromal compartments and identified a malignant epithelial state enriched for proliferation-, stress-, and migration-related programs. The four-gene signature was associated with overall survival stratification in TCGA-THCA after adjustment for age, sex, and stage. The high-risk group showed reduced immune infiltration, stronger stromal and epithelial-mesenchymal transition (EMT) signals, lower TCR diversity, and distinct predicted drug-response patterns. In vitro, TMEM45A or STC1 silencing suppressed proliferation and migration and altered EMT-related markers in PTC cells. These findings indicate that a malignant epithelial program defined by single-cell analysis can be translated into a four-gene signature associated with epithelial aggressiveness and TME remodeling in PTC, although its clinical utility requires validation in independent cohorts.
Ziyuan Wang, Shu Xu, Xuechen Chen et al.· Endocrine-Related Cancer· 0 citations
BACKGROUND
The association between Hashimoto's Thyroiditis (HT) and the clinicopathological behavior of Differentiated Thyroid Cancer (DTC) remains controversial. In particular, whether coexisting autoimmune thyroiditis independently influences invasive tumor characteristics after adjustment for tumor-related factors remains unclear. This study aimed to evaluate the relationship between HT and clinicopathological features of DTC, with a focus on tumor size, lymph node metastasis, and pathological indicators of tumor aggressiveness.
METHODS
This retrospective observational study included 198 patients with histologically confirmed DTC who underwent thyroidectomy between June 2023 and March 2025. Patients were stratified according to the presence or absence of Hashimoto's Thyroiditis. Tumor size, lymph node metastasis, capsular invasion, and extrathyroidal extension were compared between groups. Tumor aggressiveness was defined as capsular invasion and/or extrathyroidal extension. Multivariate logistic regression analysis was performed to assess independent associations. Model performance was evaluated using receiver operating characteristic (ROC) analysis and nomogram visualization.
RESULTS
Patients with coexisting HT presented with significantly smaller tumors compared with those without HT (median tumor size: 9 mm vs. 12 mm; p = 0.003). Lymph node metastasis was observed less frequently in the HT group than in the non-HT group (4.1% vs. 46.8%; p < 0.001). In multivariate analysis, tumor size was independently associated with tumor aggressiveness (odds ratio [OR] = 1.49, 95% confidence interval [CI]: 1.11-1.99; p = 0.008), whereas HT was not independently associated with aggressive pathological features (OR = 1.10, 95% CI: 0.70-1.73; p = 0.692). The predictive model demonstrated limited discriminative ability (AUC = 0.587), although calibration was acceptable.
CONCLUSIONS
Hashimoto's Thyroiditis is associated with smaller tumor size and a lower prevalence of lymph node metastasis in patients with Differentiated Thyroid Cancer. However, HT is not an independent predictor of pathological tumor aggressiveness after adjustment for tumor size. These findings suggest that HT may influence disease presentation but should not be considered a standalone prognostic factor for invasive tumor behavior.
TRIAL REGISTRATION
Not applicable. This study was a retrospective observational cohort study and did not involve prospective clinical trial registration.
Syed Haseeb Zia, Li Ying, Wenwen Zhang et al.· BMC Endocrine Disorders· 0 citations
To investigate the impact of Hashimoto’s thyroiditis (HT) on central lymph node metastasis (CLNM) patterns and identify independent risk factors for CLNM in patients with papillary thyroid carcinoma (PTC).
This retrospective study enrolled 668 cN0 PTC patients who underwent initial surgery at Huizhou Central People’s Hospital between August 2024 and July 2025. Patients were stratified into an HT-PTC group (n = 117) and a PTC-only group (n = 551) based on postoperative histopathological findings. Clinicopathological features and CLNM characteristics were systematically compared. Multivariable logistic regression was utilized to identify independent risk factors for CLNM in patients with HT-PTC, and the predictive efficacy of the resulting model was validated using ROC curves.
The HT-PTC group exhibited significantly higher rates of multifocality and central lymph node dissection, alongside lower BMI and serum thyroglobulin (Tg) levels, compared with the PTC-only group (all
P
< 0.05). While the incidence of CLNM did not differ significantly between groups (35.0% vs. 33.9%,
P
= 0.819), the metastatic lymph node ratio (LNR) was significantly lower in the HT-PTC group (
P
< 0.001). Multivariate analysis identified tumor diameter > 1 cm as an independent risk factor for CLNM among HT-PTC patients (OR = 3.678; 95% CI: 1.587–8.520,
P
= 0.002). The predictive model demonstrated moderate efficacy (AUC = 0.649). Notably, the incidence of CLNM in HT-PTC patients with microcarcinoma (≤ 1 cm) was only 25.9%.
Concomitant HT is associated with a reduced metastatic burden rather than an increased prevalence of CLNM in patients with PTC. Tumor diameter > 1 cm serves as an independent predictor of CLNM. For HT-PTC patients with tumors ≤ 1 cm and no other high-risk factors, the necessity of prophylactic central lymph node dissection warrants individualized assessment combining clinical data and intraoperative observations to avoid overtreatment.