Key Points
Background: Why This Research Matters
Epidemiology: How Common Is Thyroid Cancer?
Thyroid Cancer Subtypes
Genetics and Risk Factors
Ultrasound: The First Line of Defense
SPECT Scans: Tracking Iodine in the Body
CT Scans: Finding Incidental Nodules
PET/CT Scans: Detecting Aggressive Tumors
MRI: Detailed Soft Tissue Imaging
PET/MRI: Combining Two Powerful Technologies
Theranostics: Combining Diagnosis and Treatment
Clinical Implications for Patients
Limitations of This Review
Recommendations for Patients
Frequently Asked Questions
Source Information

Key Points

About 1.3% of people develop thyroid cancer, with a 98% five-year survival, but anaplastic thyroid cancer carries a median survival of 3–7 months.
Incidental thyroid nodules appear on up to 65% of chest CT scans; about 5% are malignant, so suspicious ones need ultrasound follow-up.
TI-RADS scoring helps decide which nodules need biopsy: TR5 lesions 1 cm or larger generally warrant fine needle aspiration.
FDG PET/CT is preferred for aggressive, de-differentiated thyroid cancers that are invisible on iodine scans, though infection and inflammation can cause false positives.
Theranostics, like radioactive iodine, combines imaging and therapy in one agent, enabling diagnosis and treatment of differentiated thyroid cancer.

Background: Why This Research Matters

Thyroid cancer is the most common endocrine (hormone-gland) cancer and the 12th most common cancer among all cancer types. The past decade has brought a major shift in how this disease is detected. Doctors now find thyroid cancers not only when a patient feels a lump in the neck or during a routine physical exam, but increasingly as an "incidental" finding—a suspicious nodule discovered on a CT scan of the chest, a carotid ultrasound, or a PET scan that was originally ordered for an unrelated health problem.

Once a suspicious nodule is found, patients typically undergo a diagnostic work-up that includes laboratory blood tests, additional imaging, and often a biopsy (tissue sampling). Accurate diagnosis is essential for clinical staging and designing the best treatment plan for each patient.

This review article, published in the Journal of Thoracic Disease, was written by a team of radiologists, surgeons, and imaging specialists. Their goal was to explain the utility of various imaging modalities in thyroid cancer diagnosis and management, and to highlight emerging diagnostic techniques that improve diagnostic specificity and accuracy. The ultimate aim is to pave the way for precision medicine—care that is tailored to each individual patient's tumor characteristics.

Epidemiology: How Common Is Thyroid Cancer?

Thyroid cancer affects 1.3% of the population, and the numbers are growing. The incidence of thyroid cancer is almost double what it was in the year 2000, now accounting for 2.1% of all cancer diagnoses worldwide. Over the last decade, the rate of new cases has increased by approximately 2% per year.

The median 5-year survival rate for thyroid cancer was 98% between 2009 and 2015. However, this encouraging statistic masks a troubling trend: there has been a slow but steady increase in the rate of deaths associated with thyroid cancer—approximately 0.7% per year over the last decade.

Certain groups face different risks and outcomes. Between 1974 and 2013, the mean age of thyroid cancer diagnosis was 48 years old (with a standard deviation of 16 years). Women are more commonly affected than men, accounting for 75% of all diagnoses. The geriatric (elderly) population has an increased incidence of thyroid cancer and also tends to have a worse prognosis, in part because they experience increased treatment-related complications and mortality.

One of the challenges doctors face is the high recurrence rate. Thyroid cancer comes back in approximately 20% of patients. The ability to distinguish between a true recurrence and treatment-related tissue changes is critical to improving survival. This is exactly where precision imaging plays a vital role.

Thyroid Cancer Subtypes

There are four major subtypes of thyroid cancer:

Papillary thyroid cancer (PTC) — the most common, accounting for about 85% of all thyroid cancers
Follicular thyroid cancer (FTC)
Anaplastic thyroid cancer (ATC) — rare but extremely aggressive
Medullary thyroid cancer (MTC)

Less common subtypes include Hurthle cell carcinoma (HTC) and poorly differentiated thyroid cancer (PDTC). PTC, FTC, and HTC are known as "well-differentiated" subtypes, and together they account for approximately 95% of all thyroid cancers. These subtypes generally have a much better prognosis than PDTC and ATC.

The differences between subtypes matter enormously for patient outcomes:

Anaplastic thyroid cancer (ATC) accounts for less than 1% of all thyroid cancers, but its median survival is only three to seven months, and the 1-year survival rate is just 10–20%.
Papillary thyroid cancer most commonly spreads through lymph nodes (nodal metastasis). Prior radiation exposure is the most common risk factor, especially for PTC.
Follicular thyroid cancer is more likely to spread through the bloodstream (hematogenous spread), typically to the lungs and bones.
Poorly differentiated thyroid cancer is locally aggressive, invading adjacent structures such as the trachea (windpipe) and blood vessels, and can also spread through the bloodstream.
Medullary thyroid cancer develops from the parafollicular neuroendocrine cells in the thyroid and often metastasizes to the cervical (neck) lymph nodes.

Understanding how each subtype behaves locally and how it tends to spread is integral to planning diagnostic work-ups and treatment strategies. For instance, the review presents the case of an 82-year-old female diagnosed with metastatic medullary and classical papillary thyroid carcinoma, whose ultrasound showed microcalcifications—tiny calcium deposits that are a warning sign of malignancy.

Genetics and Risk Factors

Thyroid cancer is driven by specific genetic mutations, and identifying these mutations has become essential in the era of precision medicine. The most common mutations are found in the BRAF and RET genes, as well as in PAX8/PPARγ gene rearrangements. These mutations alter two critical cellular signaling pathways: the MAPK pathway and the PI3K-AKT pathway.

Here is what the research shows about how these mutations map to specific thyroid cancer subtypes:

A mutation in the BRAF gene occurs in 40–45% of de novo papillary thyroid cancers (cancers that arise without prior radiation exposure).
Patients with prior radiation exposure most commonly have RET mutations.
The most common mutation in follicular thyroid cancer (40–50%) and poorly differentiated thyroid cancer (20–40%) is in the RAS gene.
A mutation in the TP53 gene occurs in 50–80% of anaplastic thyroid cancers and is generally not seen in well-differentiated carcinomas like PTC and FTC.
Medullary thyroid cancer is unique: the RAS mutation is present in more than 95% of familial (inherited) forms, but only in about 25% of sporadic (non-inherited) forms.

Genetic testing is increasingly part of routine care at academic institutions. ThyroSeqv2™ is a next-generation sequencing (NGS) panel that is being used to diagnose thyroid neoplasms that were previously classified as "indeterminate cytology" (meaning the biopsy results were not clearly benign or malignant). The review also cites important research in this area:

Chudova et al. used algorithms to differentiate between benign and malignant tumors using gene expression profiles.
Wylie et al. utilized miRNA gene expression profiles and somatic gene alterations to develop molecular classifications of thyroid cancer.
Sanler et al. analyzed the connection between germline mutations (inherited changes) in DNA repair genes and the risk of developing thyroid cancer.

As precision medicine grows, diagnostic and treatment strategies built around genetic mutations will likely become standard practice in both academic and community settings.

Ultrasound: The First Line of Defense

Ultrasound is the initial imaging modality of choice to evaluate thyroid nodules and to distinguish benign (non-cancerous) from neoplastic (cancerous) nodules. It is cost-effective, readily available, and does not expose patients to ionizing radiation.

Thyroid nodules with suspicious features are often biopsied using ultrasound-guided fine needle aspiration (FNA). Ultrasound is not only useful for detecting the primary tumor; it also evaluates the lymph nodes in the neck (locoregional lymph nodes) for signs of metastasis. Surgeons frequently use ultrasound guidance during operative planning to ensure that all suspicious nodules and lymph nodes are removed.

On diagnostic ultrasound, thyroid nodules are characterized based on several key features:

Size
Margins (the border between the nodule and normal tissue)
Eccentric location of the solid portion
Hypoechogenicity (the nodule appears darker than surrounding thyroid tissue)
Microcalcification (tiny calcium deposits)
Irregular shape
Whether the tumor is "taller than it is wide" (a shape that suggests malignancy)

These features help doctors distinguish benign from malignant nodules. For example, irregular margins and microcalcifications are associated with malignant nodules, while small subcentimeter (less than 1 cm) spongiform avascular nodules are considered benign. The review illustrates this with the case of a 60-year-old female whose ultrasound revealed multiple micropapillary carcinomas with microcalcification and increased vascularity.

The Bethesda System for Reporting Thyroid Cytopathology

The Bethesda System (BSRTC) is a diagnostic classification system based on FNA cytology (the microscopic examination of cells obtained from a biopsy). It has six diagnostic categories:

Non-diagnostic or unsatisfactory
Benign
Atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS)
Follicular neoplasm or suspicious for a follicular neoplasm
Suspicious for malignancy
Malignant

Approximately 20% of FNA results fall into the "AUS/FLUS" category, which is a gray zone that can be challenging for doctors and stressful for patients. In these cases, additional imaging and sometimes molecular testing is needed to clarify the diagnosis.

TI-RADS: A Standardized Scoring System

The American College of Radiologists (ACR) has developed a management system called the Thyroid Imaging Reporting and Data System (TI-RADS). This system is increasingly used by radiologists and clinicians to plan the management of thyroid tumors, which may include FNA biopsy, surgery, or radiotherapy. TI-RADS criteria are based on five features: composition, echogenicity, shape, margins, and echogenic foci. Each criterion is scored based on risk levels, ranging from benign (TR1) to highly suspicious (TR5).

Here is how the five TI-RADS categories guide management decisions:

TR1 (Score 0) — Benign: No FNA required.
TR2 (Score 2) — Not suspicious: No FNA required.
TR3 (Score 3) — Mildly suspicious: Follow-up if nodule is ≥1.5 cm; FNA if ≥2.5 cm; follow-up at 1, 3, and 5 years.
TR4 (Score 4–6) — Moderately suspicious: Follow-up if ≥1.0 cm; FNA if ≥1.5 cm; follow-up at 1, 3, and 5 years.
TR5 (Score ≥7) — Highly suspicious: Follow-up if ≥0.5 cm; FNA if ≥1.0 cm; annual follow-up for up to 5 years.

The scoring system works as follows:

Composition: Cystic or almost completely cystic (0 points); spongiform (0 points); mixed cystic and solid (1 point); solid or almost completely solid (2 points).
Echogenicity: Anechoic (0 points); hyperechoic or isoechoic (1 point); hypoechoic (2 points); very hypoechoic (3 points).
Shape: Wider-than-tall (0 points); taller-than-wide (3 points).
Margin: Smooth (0 points); ill-defined (0 points); lobulated or irregular (2 points); extra-thyroidal extension (3 points).
Echogenic foci: None or large comet-tail artifacts (0 points); macrocalcifications (1 point); peripheral (rim) calcifications (2 points); punctate echogenic foci (3 points).

Research by Wu et al. compared the efficacy of the BSRTC system to the TI-RADS classification and BRAF mutation testing. The BRAF mutation was previously found to have low sensitivity (meaning it misses many cancers) but almost 100% specificity (meaning when it is present, cancer is almost certainly the cause). The BRAF mutation showed similar clinical value to TI-RADS in nodules classified as BSRTC III/V. Since BRAF mutations are found in 40–45% of papillary thyroid cancers—and PTC is the most common subtype—TI-RADS-derived diagnosis can provide a non-invasive "radiogenomic" approach that potentially predicts underlying common genomic alterations in these thyroid tumors.

Ultrasound in Medullary Thyroid Cancer

Although FNA cytology can detect about half of medullary thyroid cancers, additional imaging is often necessary for an accurate diagnosis. Zhu et al. conducted a study to assess whether the standard ACR TI-RADS or a modified TI-RADS was better at diagnosing MTC. They analyzed the systems based on sensitivity, specificity, negative predictive value (the probability that a negative test truly means no disease), accuracy, and the Youden index (a measure of overall diagnostic effectiveness). Zhu et al. concluded that the modified TI-RADS was a better framework for diagnosing MTC than the standard ACR TI-RADS.

Ultrasound Limitations

Other ultrasound-based classification systems exist from the British Thyroid Association (BTA) and the American Association of Clinical Endocrinologists (AACE). These are used based on regional practice guidelines, which are influenced by geographic location and physician training. In the United States, radiologists mostly adhere to ACR and American Board of Radiology (ABR) guidelines, which has led to rapid adoption of TI-RADS.

Despite its many strengths, ultrasound is not always predictive of malignancy. Ram et al. showed that the sensitivity (ability to correctly identify cancer) and specificity (ability to correctly identify benign nodules) of ultrasound in predicting malignancy were 80% and 68%, respectively. Brito et al.'s meta-analysis further showed that studies quote variable levels of diagnostic accuracy for ultrasound, and the degree of accuracy depends heavily on the experience of the physician interpreting the images.

This is why, in patients with a high index of suspicion for primary or recurrent thyroid cancer, additional imaging modalities—including SPECT, CT, and MRI—should be used to rule out disease.

SPECT Scans: Tracking Iodine in the Body

123Iodine SPECT (single-photon emission computed tomography) has been an important diagnostic tool for over six decades. It is used to work up indeterminate or suspicious thyroid nodules and to stage thyroid cancer. The technique leverages a natural biological mechanism: sodium-iodide symporters (NIS) located on the basolateral plasma membrane of thyrocytes (thyroid cells) create a high affinity for iodine. This physiologic mechanism is exploited in both radioiodine imaging and therapy.

Whole-body scintigraphy (WBS) is commonly performed with 123Iodine to determine whether a suspicious or indeterminate thyroid nodule is "hot" (meaning it takes up iodine avidly) or "cold" (meaning it has diminished iodine uptake). Radioiodine scans are particularly useful in differentiated subtypes of thyroid cancer because these tumors preserve NIS, allowing radioactive iodine to accumulate preferentially in the tumor compared with normal thyroid tissue. The review cites a 39-year-old male patient with metastatic papillary thyroid carcinoma whose 131-Iodine SPECT scan showed uptake indicating follicular adenoma.

However, there is an important pitfall to understand. As thyroid neoplasms de-differentiate (become more aggressive and less like normal thyroid tissue), they lose their NIS ability, making them appear "occult" (hidden) on radioiodine SPECT scans. This is a critical false-negative finding that doctors must watch for.

131Iodine (131I) emits both beta and gamma particles, making it the perfect "theranostics" agent—a substance that can be used for both therapy and diagnosis. It is commonly administered after thyroidectomy (surgical removal of the thyroid), with or without lymph node dissection, to treat residual thyroid tissue and local or distant metastasis. Because of the gamma activity of 131I, SPECT can also be performed to evaluate the patient's response to 131Iodine radioablation. Post-ablation SPECT is usually performed within five to nine days after treatment because this timing improves the signal-to-noise ratio, increasing overall sensitivity for detecting distant metastases.

CT Scans: Finding Incidental Nodules

With the continual increase in the use of CT (computed tomography), unsuspected thyroid nodules are frequently detected on scans ordered for other reasons. The incidental thyroid nodule detection rate on CT of the chest ranges from 2–65%. Although the majority of these incidental nodules are benign, 5% are malignant.

Because of this, combined with the decade-long trend of increased thyroid cancer incidence, the ACR has published recommendations for managing incidental thyroid nodules found on CT. The review's Figure 4 outlines this clinical work-up:

For non-suspicious nodules in patients whose health is compromised by other medical conditions or limited life expectancy, no additional imaging assessment is warranted (nodules less than 1.5 cm, or 1.5 cm or larger depending on patient health).
For suspicious nodules, if the patient's health is similar to the general population and the patient is 35 years or older, nodules measuring 1 cm or larger should be investigated with ultrasound. For patients under 35 years of age, nodules measuring 1.5 cm or larger should be investigated. Smaller nodules in each category do not require immediate ultrasound.

Thyroid nodules with suspicious features on CT are followed up with ultrasound and may require ultrasound-guided FNA biopsy to determine whether the lesion is benign or malignant. Although CT is not the initial modality of choice for evaluating primary thyroid cancer, it is extremely useful for staging—specifically, detecting metastasis (spread of disease). In cases where the primary thyroid lesion extends below the sternum (substernal extension) or there is concern for airway compromise, CT is the preferred diagnostic modality. The review illustrates this with the case of a 39-year-old male with metastatic papillary thyroid carcinoma whose CT showed a heterogeneously enhancing nodule eroding through the thyroid capsule.

PET/CT Scans: Detecting Aggressive Tumors

PET/CT (positron emission tomography/computed tomography) is widely used for staging and restaging of malignancies because it simultaneously acquires structural (anatomical) and functional (metabolic) information. The logic for using PET/CT in thyroid cancer follows directly from the biology we discussed earlier:

Differentiated thyroid neoplasms preserve NIS and are adequately assessed on SPECT scans.
De-differentiated or poorly differentiated thyroid neoplasms are "occult" on radioiodine SPECT because they lose NIS.
However, these aggressive neoplasms have increased metabolic activity, which makes them visible on 18Fluorodeoxyglucose (FDG) PET/CT.

In patients with high levels of thyroglobulin (a protein produced by thyroid cells, used as a tumor marker) and a negative iodine scan, PET/CT can assess the extent of metastatic disease, assist in radiotherapy planning, and evaluate the patient's response to treatment. The quantitative measurements from FDG-PET/CT have been shown to have predictive and prognostic value. As such, FDG PET/CT is the preferred modality for restaging patients with de-differentiated thyroid neoplasms for whole-body assessment.

The review provides two illustrative cases:

A 66-year-old female with poorly differentiated thyroid carcinoma whose FDG PET/CT showed increased FDG uptake in the thyroid nodule, along with FDG-avid metastasis to an ipsilateral cervical chain lymph node.
A 74-year-old female with anaplastic thyroid carcinoma whose PET/CT showed increased FDG uptake within an enlarged thyroid with irregular margins encasing the trachea (windpipe).

However, PET/CT has important limitations:

False positives: FDG PET/CT has increased rates of false positives when there is co-existing infection and/or inflammation. It is often difficult to distinguish radiation-related inflammation from residual tumor, especially after treatment.
Equivocal cases may require further evaluation with other modalities (MRI, PET/MRI) and/or biopsy to improve diagnostic specificity.
Limited resolution for small lung metastases: Whole-body PET/CT has larger slice thickness, which limits assessment of pulmonary micrometastasis (very small lung deposits). In such cases, dedicated high-resolution CT of the chest is the best diagnostic modality.
Limited soft tissue resolution: If there is concern for central nervous system (CNS) or spinal metastasis, MRI or PET/MRI are the preferred diagnostic modalities.

MRI: Detailed Soft Tissue Imaging

Because of its cost and limited availability compared to other modalities, MRI (magnetic resonance imaging) is most frequently used as a second-line tool for characterizing suspicious regions. Ultrasound remains the modality of choice for initial diagnosis and follow-up, but when recurrence or relapse is suspected, MRI is utilized because of its superior soft tissue resolution relative to ultrasound, CT, PET/CT, and SPECT.

MRI is the modality of choice for surveying recurrence in high-risk patients, including those with a family history of thyroid cancer (familial neoplasms) or aggressive initial cancers with positive surgical margins. Improved contrast and soft tissue resolution on newer MRI techniques provide more precise evaluation of tumor extent and infiltration of surrounding tissues such as blood vessels, nerves, and bones.

Several advanced MRI techniques are improving diagnostic accuracy:

Diffusion weighted imaging (DWI), coupled with changes in other sequences (T1- and T2-weighted), can help discriminate between benign and malignant thyroid lesions.
Perfusion MRI, which evaluates the degree of tumor vascularity (blood vessel supply) and tumoral blood flow relative to normal tissue, has also been shown to help distinguish benign from malignant lesions.

The review includes the case of a 37-year-old female diagnosed with papillary thyroid carcinoma whose MRI showed a heterogeneously enhancing nodule in the anterior aspect of the left thyroid lobe, with well-circumscribed borders and no evidence of lymph node involvement or tracheal invasion.

Historically, implantable cardiac devices and other metallic implants were a limitation of MRI. However, because of the clinical need for accurate diagnosis, manufacturers have developed MRI-compatible devices, and newer MRI protocols have been developed by the American College of Radiology to overcome these limitations.

PET/MRI: Combining Two Powerful Technologies

PET/MRI is a hybrid modality that provides simultaneous acquisition of PET and MRI data. It combines the individual strengths of both technologies, allowing it to overcome many of the limitations of PET/CT.

Research by Binse et al. demonstrated several advantages of PET/MRI in thyroid cancer:

PET is more accurate in diagnosing the spatial extent of disease.
It provides better morphologic (structural) characterization, especially in the operative bed (the area where surgery was performed).
It shows improved detection of disease in the brain, bones, and spinal canal.
The PET detectors in PET/MRI are more sensitive and can detect more lesions than conventional PET/CT detectors.

In the postoperative and post-ablative setting, MRI is better than CT at assessing residual and/or recurrent disease in the treatment region. Because the MRI component of PET/MRI does not require ionizing radiation, there is overall decreased radiation exposure from PET/MRI compared to PET/CT.

In a study by Jentzen et al., the quantitative performance of 124I PET/MRI and 124I PET/CT was compared directly. The study showed comparable quantitative PET performance between the two modalities, further suggesting that PET/MRI can be reliably used for evaluation of thyroid cancer in both initial staging and follow-up settings.

Theranostics: Combining Diagnosis and Treatment

Theranostics is a term that combines "therapy" and "diagnostics." It incorporates diagnostic methods and therapeutics to develop precision medicine techniques that give patients personalized treatments. Radiotheranostics is the subset that uses radioactive components, which can serve both diagnostic imaging and therapeutic purposes.

One of the first radiotheranostic agents ever used was radioiodine (131I) for the treatment of thyroid cancer. The presence of NIS in differentiated thyroid neoplasms allows tumors to be both imaged and ablated (destroyed) with the same agent. This dual capability is the essence of theranostics.

The authors explain this concept using a compelling clinical example: a 39-year-old male patient diagnosed with metastatic papillary thyroid carcinoma presented with 131-Iodine uptake on SPECT scan, indicating follicular adenoma. The same molecular mechanism that allows iodine to be taken up by thyroid cells for imaging also allows radioactive iodine to be delivered as therapy directly to the cancer cells.

This approach is a natural fit for thyroid cancer care because the thyroid gland's unique iodine-avid biology provides a built-in targeting mechanism. As more molecular targets are identified, theranostic approaches are likely to expand beyond radioiodine to include other radioactive agents coupled to tumor-specific molecules.

Clinical Implications for Patients

So what does all of this mean for patients? Several key takeaways emerge from this review:

First, incidental findings are increasingly common. If you have a CT scan of the chest for an unrelated reason (such as a cough, chest pain, or trauma) and the radiologist spots a thyroid nodule, this does not mean you have cancer. The vast majority of these incidental nodules are benign. However, the 5% malignancy rate means that follow-up ultrasound is warranted for suspicious nodules according to the ACR guidelines—especially in younger patients (under 35) and when nodules are 1 cm or larger.

Second, the diagnostic work-up is now highly standardized. The TI-RADS system gives doctors a clear, evidence-based framework for deciding which nodules need biopsy and which can be safely monitored. The Bethesda system standardizes how biopsy results are reported, reducing ambiguity and helping patients understand their results.

Third, imaging is not a one-size-fits-all approach. Different imaging modalities serve different purposes:

Ultrasound is the first step—it's safe, cheap, and excellent for characterizing nodules in the neck.
SPECT tells doctors whether the tumor takes up iodine, which predicts whether radioiodine therapy will work.
CT is best for staging and for evaluating airway involvement or substernal extension.
PET/CT is the go-to for aggressive, de-differentiated tumors that don't show up on iodine scans, and for patients with rising thyroglobulin levels but negative iodine imaging.
MRI provides the best soft tissue detail for evaluating recurrence, especially in high-risk patients, and for assessing spread to the brain or spine.
PET/MRI combines the strengths of PET and MRI with less radiation exposure, and is emerging as a powerful tool for both staging and follow-up.

Fourth, genetics are changing the game. Knowing whether a tumor has a BRAF, RAS, RET, or TP53 mutation can help predict behavior and guide treatment decisions. Molecular testing panels like ThyroSeqv2™ are helping doctors diagnose indeterminate nodules and choose targeted therapies where appropriate.

For the 98% of patients with well-differentiated thyroid cancer, the prognosis remains excellent. But for the small but real group with aggressive subtypes—particularly anaplastic thyroid cancer, where median survival is only 3–7 months—accurate, rapid diagnosis and the right imaging tools can make a meaningful difference in treatment planning and outcomes.

Limitations of This Review

As with any review article, there are important limitations to keep in mind. First, ultrasound accuracy varies significantly depending on the experience of the interpreting physician, as documented in Brito et al.'s meta-analysis. A test that is 80% sensitive and 68% specific (per Ram et al.) means that ultrasound will miss some cancers and will also flag some benign nodules as suspicious.

Second, PET/CT has a notable false-positive rate in the setting of infection or inflammation. This means that a positive PET scan after radiation therapy could reflect treatment-related inflammation rather than residual cancer—a scenario that creates diagnostic uncertainty and sometimes leads to unnecessary biopsies.

Third, the standard TI-RADS system may be suboptimal for certain tumor types, such as medullary thyroid cancer, where a modified TI-RADS framework appears to perform better (per Zhu et al.). This suggests that the one-size-fits-all approach to imaging interpretation may need refinement for less common subtypes.

Fourth, this is a review article, not a prospective clinical trial. It synthesizes existing evidence rather than presenting new patient data. Some of the cited studies are small or were conducted at single institutions. The field is evolving rapidly, and some of the technologies discussed (particularly PET/MRI) may not be widely available in all clinical settings.

Finally, the cost and availability of advanced imaging (MRI, PET/CT, PET/MRI) remain barriers. MRI is used second-line "due to cost and limited availability," and PET/MRI is not yet a standard tool in most community practices.

Recommendations for Patients

Based on this review, here are practical steps patients can take:

Know your risk factors. If you have a history of radiation exposure (especially to the head or neck), a family history of thyroid cancer (particularly medullary thyroid cancer), or are over 60, talk to your doctor about appropriate screening.
Don't panic over incidental nodules. If a CT scan performed for another reason finds a thyroid nodule, follow your doctor's guidance. Most incidental nodules are benign. The ACR has clear criteria for which nodules need further evaluation based on size, suspicious features, and your age.
Understand your TI-RADS score. If you have an ultrasound, ask your radiologist or doctor what your TI-RADS category was (TR1 through TR5). Higher scores mean higher suspicion and more aggressive follow-up is warranted.
Ask about molecular testing. If your FNA biopsy comes back as "indeterminate" (such as atypia of undetermined significance), ask whether next-generation sequencing panels like ThyroSeqv2™ could help clarify whether your nodule is benign or malignant.
Expect a multi-modality approach for aggressive disease. If you have poorly differentiated or anaplastic thyroid cancer, or if you have rising thyroglobulin with a negative iodine scan, ask whether FDG PET/CT is appropriate for restaging. For brain or spine concerns, MRI or PET/MRI is preferred.
Know the signs of recurrence. Because thyroid cancer recurs in approximately 20% of patients, ongoing surveillance is critical. Based on this review, high-risk patients (those with familial neoplasms or aggressive initial cancers with positive margins) should be monitored with MRI as the modality of choice.
Participate in shared decision-making. The choice of imaging modality depends on many factors, including tumor type, stage, treatment history, and your overall health. Ask your care team why they are recommending a particular scan and what they hope to learn from it.

The era of precision imaging has transformed thyroid cancer care. With the right combination of ultrasound, nuclear medicine scans, CT, MRI, and molecular testing, patients can receive more accurate diagnoses, more targeted treatments, and better overall outcomes.

Frequently Asked Questions

What is the survival rate for thyroid cancer?

The median 5-year survival rate for thyroid cancer was 98% between 2009 and 2015. However, this varies by subtype. Anaplastic thyroid cancer is much more aggressive, with a median survival of only 3 to 7 months and a 1-year survival rate of 10–20%. Women are more commonly affected, accounting for 75% of diagnoses.

How common is thyroid cancer and who is most likely to get it?

Thyroid cancer affects 1.3% of the population and accounts for 2.1% of all cancer diagnoses worldwide. The average age at diagnosis is 48 years. Women are three times more likely to be diagnosed than men. Elderly patients have a higher incidence and worse prognosis. About 20% of patients experience recurrence after initial treatment.

If a CT scan for another reason finds a thyroid nodule, what happens next?

Most incidental thyroid nodules are benign, but 5% are malignant. According to the American College of Radiology, suspicious nodules measuring 1 cm or larger in patients 35 or older should be investigated with ultrasound. For patients under 35, nodules 1.5 cm or larger need ultrasound. Some small non-suspicious nodules may not require any additional imaging, especially in patients with limited life expectancy.

What is TI-RADS and what does my score mean?

TI-RADS is a standardized scoring system used by radiologists to classify thyroid nodules from TR1 (benign) to TR5 (highly suspicious). It evaluates composition, echogenicity, shape, margins, and echogenic foci. Higher scores mean higher suspicion of cancer and usually lead to more frequent follow-up or biopsy. For example, TR5 nodules 1 cm or larger typically require fine needle aspiration biopsy.

What is a 'hot' or 'cold' nodule on an iodine SPECT scan?

A SPECT scan with radioactive iodine shows how much iodine the thyroid nodule takes up. A 'hot' nodule takes up iodine avidly and is more likely benign. A 'cold' nodule has diminished uptake. Well-differentiated thyroid cancers often preserve iodine uptake, making SPECT useful. However, aggressive, de-differentiated tumors lose this ability and may appear 'occult' or hidden on iodine scans.

When is a PET/CT scan more useful for thyroid cancer?

PET/CT is especially helpful for aggressive, de-differentiated thyroid cancers that do not show up on iodine scans. These tumors have increased metabolic activity and appear on FDG PET/CT. It is also used when thyroglobulin levels are high but an iodine scan is negative. However, PET/CT can have false positives from infection or inflammation and has limited resolution for very small lung metastases.

What are theranostics in thyroid cancer treatment?

Theranostics combines therapy and diagnostics. Radioiodine (131I) is a classic radiotheranostic agent. Because well-differentiated thyroid cancer cells take up iodine, the same substance can be used to image and also treat the cancer. This approach delivers radioactive iodine directly to cancer cells, allowing both diagnosis and therapy in one step. This is a key part of precision medicine for thyroid cancer.

Source Information

Original Article Title: Thyroid cancer diagnosis in the era of precision imaging

DOI: 10.21037/jtd.2019.08.37

Authors: Kimberley-Jane Bonjoc, Hannah Young, Susanne Warner, Thomas Gernon, Ellie Maghami, Ammar Chaudhry

Institutions: Departments of Imaging Administration, Surgery, and Diagnostic Radiology, City of Hope National Medical Center, Duarte, CA, USA

Journal: Journal of Thoracic Disease, Vol 12, No 9, September 2020, pages 5128–5139

Publication Dates: Submitted Jul 29, 2019; Accepted Aug 21, 2019