Assessing Thyroid Nodules: A Clinician's Guide

Mark A. Lupo, MD; Zsofia Geck, MD


December 11, 2020

Editorial Collaboration

Medscape &

Thyroid Cytopathology

The Bethesda system categorizes thyroid cytopathology into the following:

  • Nondiagnostic

  • Benign. A benign diagnosis carries a 0%-3% risk for thyroid cancer. These can be monitored with ultrasound, unless they have high-suspicion ultrasound characteristics, in which case a repeat biopsy is indicated.

  • Atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS)

  • Follicular neoplasm. Indeterminate results include the AUS/FLUS and follicular neoplasm categories, and carry a 10%-40% risk for thyroid cancer. The next step in diagnosis is either molecular marker testing or a diagnostic lobectomy.

  • Suspicious for malignancy. The suspicious-for-malignancy category carries a cancer risk of 45%-60%. The recommendation is to proceed with surgery, lobectomy, or total thyroidectomy.

  • Malignant. A malignant result carries a 94%-99% risk for thyroid cancer. The recommendation is the same as for the previous category: lobectomy or total thyroidectomy.

Our patient prefers to avoid surgery and decides to proceed with molecular marker testing. The results are indeed negative, rendering a very high probability of a benign nodule, similar to benign cytopathology. The patient is very pleased to have avoided surgery and is happy to be monitored periodically with ultrasound.

An Enlarged Nodule With Discomfort

Your last patient of the day is a 47-year-old man with a history of a thyroid nodule that was noted on physical exam over 10 years ago. He thinks he had a biopsy at that time but was told that it was insufficient (not enough thyroid cells) for evaluation. The biopsy was painful, so he avoided follow-up until now.

He is concerned because the nodule has enlarged, and he now has discomfort with swallowing and when he turns his neck. He denies radiation exposure. He is not on thyroid medications. He denies a family history of thyroid disease. Your exam notes a 2-cm right thyroid nodule that is firm and mobile.

His ultrasound notes a 2.1-cm partially cystic nodule with eccentric and irregular mural components containing microcalcifications (Figure 11).

Figure 11. Right cystic thyroid nodule with solid component showing microcalcifications. Slight Doppler flow is noted in the transverse view (right panel).

These are high-suspicion ultrasound characteristics, and you persuade him to have a biopsy despite his previous negative experience. His pathology returns with papillary thyroid cancer. He proceeds with a total thyroidectomy.


In the cases above, we used the ATA pattern-based risk stratification — a common practice among thyroid clinicians. However, the ACR TI-RADS point-based system, introduced in 2017, is increasingly being used by radiologists. Similar to the ATA's, ACR TI-RADS uses a system of five risk categories and offers advice on whether to proceed with fine-needle aspiration biopsy or surveillance.  

Other factors, in addition to sonographic characteristics and nodule size, should be considered when evaluating a nodule for biopsy vs surveillance. Patient preference after informed discussion, other medical illnesses, and age all factor into this decision.

For small, very low-risk, or benign nodules, ultrasound follow-up may not be required. Low- and intermediate-risk nodules as well as carefully selected small high-suspicion nodules may be offered active surveillance in the appropriate setting.

As with ultrasound itself, the optimal use of any risk-classification system is highly user-dependent. Additionally, there is fairly low interobserver agreement in assigning a nodule to a risk category. Ideally, thyroid nodule evaluation is performed in expert centers where real-time ultrasound is performed by the clinician or thyroid-focused radiologist. In this paradigm, many unnecessary biopsies can be avoided, and higher-risk features such as invasion or lymph node involvement can be detected sooner, resulting in best patient outcomes.

Mark A. Lupo, MD, is the founder and medical director of the Thyroid & Endocrine Center of Florida. He lectures nationally and internationally on the topic of thyroid nodules and teaches neck ultrasound in the evaluation of nodules and cancer to other endocrinologists and surgeons.

Zsofia Geck, MD, is an endocrinologist with a subspecialty focus in thyroid and parathyroid disorders.

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