Preoperatively detected PTEN alterations in thyroid nodules correlate with a 32.4% risk of invasive malignancyMolecular testing helps identify risk in thyroid nodules

Human pathology Published September 12, 2026 Study authors: Straccia Patrizia, Fiorentino Vincenzo, Urtueta Belen Padial, Zhang Qianqian, Piermattei Alessia, Ci… PubMed ↗ DOI ↗ Editorial oversight: Dr. Lars van Dijk, PhD · Surgical, Procedural & Diagnostic

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Key Takeaway

Interpret preoperatively detected PTEN alterations as a moderate-risk finding for follicular or oncocytic neoplasia.

This meta-analysis evaluates the risk of malignancy (ROM) in patients with Bethesda III/IV thyroid nodules who have preoperatively detected PTEN alterations via FNA molecular testing. The analysis included 87 patients to determine the prevalence of invasive and noninvasive malignancies associated with these specific genetic alterations.

The primary finding indicates a 32.4% risk of invasive malignancy (28 out of 87 cases; 95% CI 23.4-42.9) in the study population. When including noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), the risk of malignancy was 37.7% (95% CI 23.9-53.9).

The authors note that the reported risk of malignancy is modulated by two factors: the selection of patients for surgery based on pathway-related factors and the specific way PTEN alteration is operationalized, such as sequence variants versus protein loss. Furthermore, PTEN alterations are not as high-specific as BRAF V600E.

Clinically, a preoperatively detected PTEN alteration should be communicated as a moderate-risk molecular finding. While these alterations frequently map to follicular or oncocytic neoplasia, they also include differentiated carcinomas and rare high-grade disease. The results provide a framework for interpreting molecular findings in the context of thyroid nodule management.

How this fits prior evidence

This meta-analysis addresses a gap in characterizing the specific risk associated with PTEN alterations in thyroid nodules. While prior coverage noted that BRAF V600E analysis can rectify histopathological misdiagnosis of cervical lymph node metastasis, this study clarifies that PTEN alterations are not high-specific like BRAF V600E. It provides specific risk percentages for invasive malignancy (32.4%) and broader malignancy (37.7%) in the presence of PTEN alterations, offering a more nuanced view of molecular risk than previous reports on thyroid cancer markers.

When a patient finds a lump on their thyroid, the next step is often a needle biopsy. However, some results can be hard to interpret. New data shows that testing for a specific genetic change called a PTEN alteration can help doctors better understand the risk of cancer in these nodules.

In a review of 87 cases, researchers found that patients with these specific genetic changes had a 32.4 percent risk of invasive cancer. When including a specific type of noninvasive growth, that risk rose to 37.7 percent. This finding helps doctors categorize these cases as moderate risk, which helps them decide on the best path forward.

It is important to note that these results can vary based on how the test is performed and the specific type of genetic change found. While this test is helpful for identifying certain types of growths, it is not as specific as other common tests. Patients should talk to their doctors to understand what these results mean for their specific situation.

What this means for you:

PTEN genetic testing helps identify a moderate risk of cancer in thyroid nodules.

Common questions

What does a PTEN alteration mean for my thyroid nodule?

A PTEN alteration is a specific genetic change found in some thyroid nodules. When this change is detected before surgery, it is considered a moderate risk finding. It often points toward certain types of growths, including both common types and rarer, more serious cases of cancer.

What is the risk of cancer if a PTEN alteration is found?

The study found that patients with these specific genetic changes had a 32.4 percent risk of invasive cancer. If the calculation includes a specific noninvasive growth called NIFTP, the risk of malignancy is reported at 37.7 percent.

Is this test as accurate as other thyroid tests?

While this test is useful for identifying certain types of growth, it is not as specific as other common markers like BRAF V600E. Because results can vary based on how the test is performed, you should discuss these specific findings with your doctor.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedSep 2026

PMID41865773

View Original Abstract ↓

AIMS: Phosphatase and tensin homolog (PTEN) alterations are increasingly encountered on molecular testing of thyroid fine-needle aspiration (FNA) specimens in Bethesda III/IV nodules. Unlike high-specificity alterations (e.g., BRAF V600E), PTEN alterations can map to a broad morphologic spectrum and are influenced by the diagnostic pathway determining which nodules proceed to surgery. We performed a systematic review and meta-analysis to define risk of malignancy (ROM) for PTEN-altered thyroid nodules detected preoperatively. METHODS: Studies (2020-2025) reporting PTEN alterations detected preoperatively on FNA-based testing with surgical histopathology were reviewed. The primary meta-analysis included Bethesda III/IV-predominant cohorts with PTEN-altered nodules undergoing surgery. We pooled invasive malignancy ROM using random-effects meta-analysis and performed a sensitivity analysis counting noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) as an event. RESULTS: Three cohorts comprised 87 resected PTEN-altered nodules with 28 invasive malignancies. Pooled ROM for invasive malignancy was 32.4% (95% confidence interval (CI) 23.4-42.9; I = 0%). Malignant outcomes included follicular thyroid carcinoma, papillary thyroid carcinoma (including variants), and rare poorly differentiated or anaplastic thyroid carcinoma. Counting NIFTP as an event increased pooled ROM to 37.7% (95% CI 23.9-53.9). CONCLUSIONS: PTEN alterations detected preoperatively confer an intermediate ROM (∼32%) in surgically followed cohorts, but ROM is modulated by pathway-related selection for surgery and by how PTEN alteration is operationalized (sequence variant vs protein loss). A PTEN-altered preoperative result should be communicated as a moderate-risk molecular finding that frequently maps to follicular/oncocytic neoplasia yet includes differentiated carcinomas and rare high-grade disease, supporting integrated pathology-radiology-molecular decision-making.

Preoperatively detected PTEN alterations in thyroid nodules correlate with a 32.4% risk of invasive malignancyMolecular testing helps identify risk in thyroid nodules

How this fits prior evidence

Common questions

Study Details

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Preoperatively detected PTEN alterations in thyroid nodules correlate with a 32.4% risk of invasive malignancyMolecular testing helps identify risk in thyroid nodules

How this fits prior evidence

Common questions

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