Illustration of thyroid gland with immune cells and DNA, representing thyroid nodule diagnosis.

Thyroid Nodules: Can Immune Cell Analysis Replace Genetic Testing?

Jordan Keane in Health & Wellness December 2025 • 5 min read.

"Emerging research suggests that analyzing immune cell infiltration in thyroid nodules could offer a simpler, more reliable diagnostic approach than current molecular tests."

Thyroid nodules are common, and determining whether they are benign or malignant is a frequent clinical challenge. Current diagnostic methods often rely on fine needle aspiration (FNA) followed by cytological analysis. However, when FNA results are indeterminate, molecular testing is often employed to further assess the risk of malignancy.

While molecular tests have become increasingly sophisticated, they can sometimes yield ambiguous or conflicting results. This has led researchers to explore alternative approaches, including the analysis of immune cells within the nodule microenvironment. The rationale is that the presence and distribution of specific immune cell types, such as dendritic cells (DCs) and regulatory T cells (Tregs), may reflect the underlying nature of the nodule.

Two recent studies presented in this article explore the potential of using immune cell markers, specifically CD1a for DCs and FoxP3 for Tregs, to predict malignancy in thyroid nodules. By examining the presence and distribution of these immune cells, researchers aim to refine diagnostic accuracy and potentially reduce the reliance on complex molecular testing.

Immune Cell Infiltration: A Novel Diagnostic Marker?

Illustration of thyroid gland with immune cells and DNA, representing thyroid nodule diagnosis.

One study investigated the immune cell composition of both cancerous and non-cancerous thyroid tissue samples. The researchers found that malignant thyroid tissues, specifically papillary thyroid carcinoma (PTC), follicular variant PTC (FVPTC), and follicular carcinoma (FC), exhibited significantly higher levels of DC infiltration compared to benign thyroid tissues. Moreover, the combined presence of both DCs and Tregs was even more strongly associated with malignancy.

To assess the diagnostic potential of these findings, the researchers analyzed FNA samples from indeterminate thyroid nodules. They found that the presence of both CD1a+ DCs and FoxP3+ Tregs was highly specific for malignancy. While the sensitivity of this approach was modest (55%), the specificity was high (88-92%), indicating that when both cell types are present, the likelihood of malignancy is substantial. The positive predictive value (PPV) ranged from 67-75%, and the negative predictive value (NPV) was 82%.

High Specificity: Immune cell markers show strong ability to rule out malignancy when absent.
Improved Accuracy: Combining DC and Treg markers enhances diagnostic precision.
Potential for Reduced Molecular Test Usage: Refined risk assessment may decrease reliance on complex tests.

These results suggest that analyzing immune cell infiltration in thyroid nodules could provide valuable diagnostic information, potentially complementing or even replacing molecular testing in some cases. However, it's important to note that this approach is not without limitations. The sensitivity of immune cell markers alone may not be sufficient to rule out malignancy definitively, and further research is needed to optimize the technique and validate its clinical utility.

Refining Diagnostic Strategies for Thyroid Nodules

The findings presented in this article highlight the evolving landscape of thyroid nodule diagnosis. While molecular testing has undoubtedly improved our ability to identify malignant nodules, it is not a perfect solution. The analysis of immune cell infiltration offers a complementary approach that may enhance diagnostic accuracy and reduce the need for unnecessary surgeries.

Moreover, integrating immune cell data with molecular testing results could provide a more comprehensive assessment of malignancy risk. For example, a nodule with indeterminate cytology and borderline molecular test results could be further evaluated based on its immune cell profile. This integrated approach could lead to more personalized and effective management strategies for patients with thyroid nodules.

As research in this area continues to advance, it is likely that immune cell analysis will play an increasingly important role in the diagnosis and management of thyroid nodules. By combining traditional cytological methods with emerging molecular and immunological techniques, clinicians can strive to provide the most accurate and personalized care for their patients.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1016/j.jasc.2018.06.072, Alternate LINK

Title: Determining The Molecular Test Best Suited For Indeterminate Thyroid Nodules: A Quality Assurance Study

Subject: Pathology and Forensic Medicine

Journal: Journal of the American Society of Cytopathology

Publisher: Elsevier BV

Authors: Jennifer Maerki, Karen Chau, Melissa Klein, Cecilia Gimenez, Seema Khutti, Kasturi Das

Published: 2018-09-01

Everything You Need To Know

How might analyzing immune cells in thyroid nodules help determine if they're cancerous?

The studies suggest that analyzing the presence and distribution of specific immune cells, such as dendritic cells (DCs) identified by the marker CD1a and regulatory T cells (Tregs) identified by FoxP3, within thyroid nodules can indicate whether the nodule is likely to be benign or malignant. The presence of both CD1a+ DCs and FoxP3+ Tregs shows high specificity for malignancy, potentially improving diagnostic accuracy.

Why is there a need to explore immune cell analysis when molecular tests for thyroid nodules already exist?

Molecular tests, while advanced, can sometimes yield unclear or conflicting results, leading to diagnostic uncertainty. Analyzing immune cell infiltration, specifically looking at dendritic cells (DCs) and regulatory T cells (Tregs), offers a complementary approach. Studies have shown that the presence and distribution of these immune cells can reflect the nature of the nodule, potentially improving diagnostic accuracy and reducing the reliance on complex molecular testing.

How do CD1a+ dendritic cells and FoxP3+ regulatory T cells play a role in diagnosing indeterminate thyroid nodules?

The presence of CD1a+ dendritic cells (DCs) and FoxP3+ regulatory T cells (Tregs) in indeterminate thyroid nodules can improve diagnostic specificity. A study found that when both cell types are present, the likelihood of malignancy is substantial, with a high specificity (88-92%). However, the sensitivity was modest (55%), meaning that while the presence of these cells strongly suggests malignancy, their absence does not definitively rule it out.

What does analyzing 'immune cell infiltration' in thyroid nodules actually involve?

This method analyzes the presence and distribution of specific immune cell types within the thyroid nodule microenvironment. Specifically, it focuses on dendritic cells (DCs) identified by the marker CD1a and regulatory T cells (Tregs) identified by FoxP3. The premise is that the presence and interaction of these immune cells can indicate whether a nodule is benign or malignant. The combined presence of both DCs and Tregs has been strongly associated with malignancy, particularly in papillary thyroid carcinoma (PTC), follicular variant PTC (FVPTC), and follicular carcinoma (FC).

Are there any limitations to using immune cell analysis instead of genetic testing for thyroid nodules, and what further research is needed?

While analyzing dendritic cells (DCs) and regulatory T cells (Tregs) shows promise in improving diagnostic accuracy for thyroid nodules, especially in reducing unnecessary surgeries, it's not a standalone solution. The sensitivity of this method might not be sufficient to definitively rule out malignancy. Further research is needed to optimize the technique and validate its clinical utility. Also, this approach doesn't eliminate the need for initial fine needle aspiration (FNA) but rather refines the interpretation of indeterminate FNA results.