Risk of malignancy in PTEN-altered thyroid nodules detected on preoperative FNA molecular testing: a systematic review and meta-analysis.
Patrizia Straccia, Vincenzo Fiorentino, Belen Padial Urtueta et al.
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In 30 seconds
This systematic review and meta-analysis assessed malignancy risk in thyroid nodules with PTEN alterations detected by preoperative fine-needle aspiration molecular testing. The primary analysis included three predominantly Bethesda III/IV cohorts, comprising 87 surgically resected PTEN-altered nodules. Pooled risk of invasive malignancy was 32.4% (95% confidence interval 23.4-42.9; I 2 = 0%). Outcomes included follicular and papillary thyroid carcinomas, with rare poorly differentiated or anaplastic carcinomas. Counting NIFTP as an event raised the pooled estimate to 37.7% (95% CI 23.9-53.9).
Key findings
- Across three cohorts, 28 of 87 resected PTEN-altered nodules were invasive malignancies.
- Pooled invasive malignancy risk was 32.4% (95% confidence interval 23.4-42.9; I 2 = 0%).
- Including NIFTP as an event increased pooled risk to 37.7% (95% CI 23.9-53.9).
- Malignant outcomes included follicular and papillary thyroid carcinomas, as well as rare poorly differentiated or anaplastic carcinomas.
Why it matters
PTEN alterations do not indicate a single tumour type, and the pooled estimate suggests a meaningful but intermediate malignancy risk in surgically followed nodules. Recognising the range of possible outcomes can support clear communication of molecular results and interpretation alongside cytology, imaging, and pathology, rather than treating PTEN alteration as equivalent to a highly specific molecular marker.
What to keep in mind
The estimate is based on only three cohorts and surgically followed nodules; selection for surgery may influence the observed risk. Risk also depends on how PTEN alteration is defined.