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Updated: Jul 15, 2025

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Indeterminate Thyroid Nodules: From Cytology to Molecular Testing.

Paola Vignali1, Elisabetta Macerola1, Anello Marcello Poma1

  • 1Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Via Savi 10, 56126 Pisa, Italy.

Diagnostics (Basel, Switzerland)
|September 28, 2023
PubMed
Summary

Thyroid nodules are often indeterminate, posing a diagnostic challenge. Molecular testing of these indeterminate thyroid nodules can help classify them, guiding better patient management and treatment strategies.

Keywords:
BRAF-likeRAS-likefine-needle aspiration (FNA)molecular teststhyroid cytology

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Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • Thyroid cancer is the most common endocrine malignancy.
  • Fine-needle aspiration (FNA) biopsy is the standard for thyroid nodule evaluation.
  • A significant percentage (10-30%) of thyroid nodules are classified as indeterminate by FNA, complicating patient management.

Purpose of the Study:

  • To review recent molecular findings in indeterminate thyroid nodules.
  • To highlight the utility of molecular tests in managing patients with indeterminate thyroid nodules.

Main Methods:

  • Review of current literature on thyroid nodule molecular profiling.
  • Analysis of identified molecular profiles in thyroid tumors.

Main Results:

  • Two main molecular profiles identified: RAS-like and BRAF V600E-like.
  • RAS-like profile includes NRAS, HRAS, KRAS mutations, EIF1AX mutations, BRAF K601E mutation, and PPARG/THADA fusions.
  • BRAF V600E-like profile includes BRAF V600E mutation and RET/BRAF fusions.

Conclusions:

  • Molecular profiling offers a pathway to better classify indeterminate thyroid nodules.
  • Molecular tests are crucial for optimizing patient management strategies in cases of indeterminate thyroid nodules.