What is the gold standard for diagnosing thyroid cancer?

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Last updated: July 6, 2025View editorial policy

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From the Guidelines

The gold standard for diagnosing thyroid cancer is a fine needle aspiration (FNA) biopsy followed by histopathological examination, as it provides high sensitivity and specificity for detecting malignant thyroid nodules. This procedure involves inserting a thin needle into the thyroid nodule to extract cells, which are then examined under a microscope by a pathologist 1. FNA biopsy is typically performed on thyroid nodules that are suspicious based on ultrasound characteristics, size (usually greater than 1 cm), or growth pattern. The procedure is minimally invasive, can be done in an outpatient setting, and usually takes only a few minutes to complete. Local anesthesia may be used to minimize discomfort.

The extracted cells are analyzed using cytological criteria such as the Bethesda System for Reporting Thyroid Cytopathology, which categorizes findings into six diagnostic categories ranging from benign to malignant 1. While FNA biopsy has high sensitivity and specificity, in some cases with indeterminate results, additional molecular testing of the biopsy sample or a surgical biopsy may be necessary for definitive diagnosis. The accuracy of FNA diagnosis is enhanced when performed under ultrasound guidance, which helps ensure the needle is placed precisely within the suspicious area of the thyroid.

Some key points to consider when performing FNA biopsy include:

  • Using ultrasound guidance to ensure accurate needle placement
  • Considering molecular diagnostic testing to detect individual mutations or pattern recognition approaches using molecular classifiers for indeterminate FNA samples 1
  • Evaluating FNA samples using the Bethesda System for Reporting Thyroid Cytopathology
  • Performing FNA biopsy on thyroid nodules that are suspicious based on ultrasound characteristics, size, or growth pattern.

It's worth noting that other diagnostic methods, such as measurement of serum calcitonin, may be useful in specific cases, such as medullary thyroid cancer, but FNA biopsy remains the gold standard for diagnosing thyroid cancer in general 1.

From the Research

Diagnosing Thyroid Cancer

The gold standard for diagnosing thyroid cancer involves fine-needle aspiration biopsy (FNAB) [(2,3,4,5,6)]. This method has proven to be accurate for the detection of thyroid cancer.

Fine-Needle Aspiration Biopsy (FNAB)

  • FNAB is an accurate, slightly invasive, and safe method for the preoperative diagnosis of thyroid nodules 3.
  • The diagnostic accuracy of FNAB can be enhanced with ultrasound guidance 3.
  • Ultrasound-guided FNAB allows for a more precise and adequate sampling of thyroid nodular lesions and is associated with a lower rate of false-negatives 3.

Molecular Testing

  • Molecular testing of cytology specimens from thyroid nodules has the potential to play a major role in the evaluation of indeterminate thyroid lesions 5.
  • Several commercially available tests, including the Afirma Gene Expression Classifier, ThyGenX, and ThyroSeq, can be used to assess the risk of malignancy 5.
  • These tests have excellent negative predictive value (NPV) and positive predictive value, allowing them to be used as "rule out" and "rule in" tests 5.

Indeterminate Cytology Diagnoses

  • Indeterminate cytology diagnoses remain a diagnostic challenge 5.
  • Integration of new molecular markers is opening new perspectives in order to increase the diagnostic precision of thyroid nodules with an indeterminate cytology 6.
  • Repeat aspiration is often successful and should be the standard approach to such nodules, given their risk of malignancy 2.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Assessment of nondiagnostic ultrasound-guided fine needle aspirations of thyroid nodules.

The Journal of clinical endocrinology and metabolism, 2002

Research

Diagnostic accuracy of conventional versus sonography-guided fine-needle aspiration biopsy of thyroid nodules.

Thyroid : official journal of the American Thyroid Association, 1998

Research

[Next generation sequencing].

Revue medicale de Bruxelles, 2016

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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