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Thyroid cancer is the most common endocrine malignancy, affecting women more commonly than men. The incidence in the UK was 3.2 per 100,000 population in 2007, and it has been increasing steadily over the last 10 years. Nearly half of all cases occur in people aged less than 50-years (Office for National Statistics (2008), cited in Cassidy et al, 2010, p.356).
The most common types of thyroid cancer are follicular and papillary, known as differentiated, and anaplastic and medullary known as non-differentiated thyroid cancer. We will mainly focus on differentiated cancers in this review.
Prognosis of thyroid cancer is highly dependent on early and accurate diagnosis combined with appropriate management and monitoring. Imaging plays a key role in all of these, and when used effectively alongside medical and surgical interventions, prognosis for the most common thyroid cancer is favourable (average 10 year survival for papillary carcinoma >90% (Sia et al, 2010)).
The increased incidence may be partly attributed to improve imaging modalities and detection of incidentalomas found during more general scans of the patient (Sipos, 2009).
A brief overview of the relevant anatomy and physiology will also be discussed but we will concentrate primarily on the different imaging modalities providing a rationale for their use in diagnosis, staging and follow-up.
Anatomy and Physiology
The thyroid is a large butterfly-shaped endocrine gland composed of two lobes and a central portion called the isthmus. It is located in the neck deep to the skin and muscles just inferiorly to the laryngeal prominence. The main hormones secreted by the thyroid are Thyroxine and Triiodothyronine, which help regulate and control of metabolism.
The thyroid is commonly supplied by the superior thyroid arteries and inferior thyroid arteries and is drained by three pairs of veins into the internal jugular and brachiocephalic veins (Tortora and Derrickson, 2008).
Lymphatic drainage of the thyroid gland is extensive and includes many different levels of the cervical nodes and upper mediastinal nodes (King, 2008).
Common imaging modalities used for Thyroid cancer
There are four images modalities commonly available in the diagnosis and management of thyroid cancer:
Ultrasound (US) utilises ultra-high frequency sound waves (>20KHz) inaudible to the human ear to produce dynamic cross-sectional and real-time images.
Images are produced by measuring the returning echo from tissues in response to the sound generated by a piezoelectric transducer, held against the skin. Each type of tissue has a different acoustic impedance, which can be utilised to form an image.
Computed Tomography (CT) is an imaging technique whereby x-rays are used to generate cross-sectional images around the craniocaudal axis. The data acquired can be reconstructed to produce an image in 3D or desired plane.
Magnetic Resonance Imaging (MRI) is an imaging technique that uses magnetic fields in place of ionising radiation to generate cross-sectional images similar to CT. In MRI the magnetic properties of the hydrogen atom are manipulated to produce a signal detectable by the scanner.
In Radionuclide Imaging (RNI) a pharmaceutical agent labelled with a radionuclide is administered to patients and then gamma cameras are used to detect and measure gamma radiation emitted from the decaying radionuclide in the body (Chowdhury et al, 2010). It is an imaging technique used to look at function and physiology rather than anatomy.
A diagnosis provides information to the patient and to inform the medical team on the best management for the patient.
Thyroid cancer most commonly presents as a newly palpable nodule in the thyroid but may also be asymptomatic or have vague symptoms. Ultrasound is the main imaging modality used in diagnosis (British Thyroid Association (BTA), Royal College of Physicians (RCP), 2007), being used for characterising a palpable nodule, guiding of a fine-needle-aspiration for histological confirmation. Ultrasound is crucial in reducing the number of inadequate biopsies of nodes (International Atomic Energy Agency (IAEA), 2009), essentially taking the guesswork out of aiming for deeper lesions.
US is well suited for initial diagnosis as it is widely available, relatively cheap and as a quick and non-invasive procedure, it is well tolerated by patients.
Since the thyroid gland is superficial, problems of attenuation are reduced allowing high-frequencies to be used which enable high-resolution real-time images sensitive enough to detect >1mm fluid filled lesions and >2mm solid lesions and accurate measurements to be made (Kharchenko et al, 2010 p.3). Suspicious ultrasonographic features such as micro-calcifications, marked hypoechogenicity, or irregular margins also aid diagnosis (BMJ 2010).
In addition to being convenient, US has benefits over CT/RNI in that it does not use ionising radiation and is regarded as safe for children and pregnant women if used appropriately to avoid bioeffects (British Medical Ultrasound Society, 2007).
In terms of efficacy, the major disadvantages of US in that it is very much dependent on the equipment used and the experience of the operator, their familiarity with anatomy and suspected markers of pathology (Kharchenko et al, 2010 p.3).
Limitations of US include attenuation of high-frequency sound waves in deeper tissues, distortion by air filed structures (e.g trachea) and acoustic shadowing from overlying bones which makes retrotracheal and mediastinal lesions difficult or impossible for US investigation in which case other modalities must be used (IAEA, 2009). Another disadvantage of US over other imaging modalities is that accurate diagnosis can only be done while the patient is being examined. Interpretation of stored images snapshots can be very difficult after the fact.
In terms of diagnostic accuracy, shows that US's sensitivity and specificity is comparable with more invasive and costly imaging modalities.
Ultrasound accuracy continues to improve as the technology and understanding of pathology improves. Standard ultrasound may be augmented with doppler ultrasound to map lesions with increased vascularity and new techniques such as elastography (Sipos, 2009 and Rago et al. 2007)
For the majority of lesions, US and FNA are adequate to make a diagnosis of thyroid cancer.
Table . Summary of studies into efficacy of imaging modalities in the diagnosis of thyroid cancer (Kharchenko et al, 2010).
CT (no contrast)
CT (with contrast)
As stated in , MRI has greater accuracy but is not used as first investigation due to significant disadvantages. It's an expensive, time-consuming and not widely available with significant waiting lists depending on location. Compared to US, it is poorly tolerated by patients, because it can be claustrophobic and contraindicated for patients with metal foreign bodies i.e. aneurysm clips.
CT provides better spatial resolution than MRI, has shorter scan times, can be used on patients with metal and overall is cheaper and more widely available. However, it is seldom used for diagnosis since the use of iodine-based contrast inhibits uptake of subsequent radiopharmaceuticals used in the treatment (stunning effect) and the fact that CT delivers a significant radiation dose to the neck of a patient. CT dose of the head and neck is 1.4-3.1 mSv equivalent to 100 chest x-ray (Hart and Wall (2002) citied in The Royal College of Radiologists, 2007, p.17). CT guided biopsy is only indicated when incidentally diagnosed masses of the thyroid gland are not reachable by US.
RNI can be used for diagnosis if results from other modalities are inadequate, but as US has become more sophisticated; RNI's role has become more important in post-treatment follow-up and for the surveillance of recurrent malignancies.
Formal staging is essential in establishing the optimal multidisciplinary approach to the next steps in management of the patient.
Like many cancers, thyroid cancer is now staged using the TNM system where each letter of relates to tumour infiltration, nodal involvement and distant metastases respectively (King, 2008). By classifying patients and investigations, treatment can be selected best on efficacy reported in published studies (evidence-based practice) for patients at similar stages. Imaging plays a key role in all components of the TNM staging for thyroid cancer.
US is used initially because of previously mentioned advantages and is enough to determine whether it has spread however not to determine the extent. Its limitations mean complete staging is unachievable for more aggressive thyroid cancer. If the chance of lymphatic spread is low then US may be adequate for detecting lymphatic involvement in superficial cervical nodes otherwise MRI or CT would be indicated.
Pre-operative nodal staging utilising imaging reduces 'berry-picking' in surgery, so that the lymph node dissection can be targeted and planned (Kim et el, 2008).
Compared to CT MRI has better soft tissue differentiation and this is further enhanced with the use of gadolinium contrast producing a high-signal on T1-weighted images for nodal changes and invasion into neighbouring structures with more accuracy (King, 2007).
Scanning of secondary bone lesions may by directed by patients symptoms and comprehensive bone surveys can be carried out using whole body CT or MRI scans. CTs superiority in demonstrating fine bone detail (Hermans et al., 2010) may make it a first choice, it describes foci before bone destruction occurs but its low soft tissue contrast can make it difficult to spot features such as spinal cord compression to which MRI are more sensitive as determined by Muresan et al., (2008). Due to the lack of fluid MRI is generally not good for viewing cortical bone or calcifications.
With CT metastatic deposits as small as 3mm can be detected but this is improving with introduction of dual-source multi-detectors machines capable of thinner slices. Newer MRI machines are increasing producing slices of 1-3mm thickness which makes detection of very small nodes good comparable to CT.
CT does have a slight advantage in detection as it is able to highlight small calcifications (a sign of a suspicious nodule) and in the case of solid tumours of the abdomen and chest, CT is often preferred due to its speed and convenience to extend an examination.
It is worth noting that very really small tumours are easily overlooked with these modalities which is why US is better first choice if it can reach. Kim et el (2008) determined using US and CT for staging of cervical metastatic lymph nodes is better than using individual modalities alone.
Other advantages CT has over MRI include less image degradation from motion artefact due to its speed of acquisition and reconstruction in any plane. However, CT also has a number of disadvantages, image quality can be severely degraded by dental filling or other radio-opaque object. Its biggest disadvantage is radiation exposure.
Table . Summary of studies into efficacy of imaging modalities in the detection of nodal and bone metastases
US (E. Kim et al., 2008)
MRI (Klerkx, 2010)
CT (E. Kim et al., 2008)
Whole-body MRI (Muresan et al., 2008)
Whole-body CT (Muresan et al., 2008)
Protocols as to which modality is used depend greatly on the doctor/hospital but MRI is preferred in staging over CT because it does not require the use of iodinated contrast, which may introduce delays to the treatment plan. Gadolinium contrast used in MRI does not compromise subsequent uptake by the thyroid and has reduced incidences of an allergic reaction compared to iodinated contrasts (Thomsen and Webb, 2009). CT without contrast decreases spatial resolution.
Treatment of thyroid cancer will usually involve surgery and/or radioactive iodine ablation. Follow-ups for patient should be life-long with US surveillance performed annually (BTA and RCP, 2007).
Whole-body scintigraphy may be used to stage a patient, but is more useful post-operatively as a functional imaging modality to search for uptake of an iodine radioisotope or increased glucose uptake from residual thyroid tissue and to detect uptake from ectopic thyroid tissue (metastasis).
As well as post-operatively, a patient may be sent for a nuclear imaging whenever a surveillance blood test shows raised thyroglobulin levels after a total thyroidectomy. Thyroid tissue may show up as hotspots which can be resolved in 3D to identify the approximate anatomical location of metastasis.
In plain radioiodine scans, I-123 is technically and clinically superior as it can be given in a low dose avoiding the 'stunning' effect of the thyroid but I-131 is more commonly used despite side effects because it's cheaper, and easier to store: it doesn't need a cyclotron, has longer half-life, and widely available.
I-124 is even better as it emits a positron can be detected with a PET scanner but it's also expensive and hard to store.
Compared to gamma cameras, PET scanners offer images with significantly reduced background noise, and improved spatial and contrast resolution. PET images are like tomographic images can be reviewed slice by slice, allows removal of radioactivity in front or behind areas (Van Nostrand et al., 2010)
The main drawback of radioiodine scans is that undifferentiated cancers have low iodine uptake and negative result in which case 18F-FDG PET is becoming more popular in detecting recurrent or metastatic thyroid cancer based on identifying metabolic hotspots. The administration of exogenous TSH stimulates metabolic activity in thyroid tissue and is useful for enhancing the sensitivity of the scan.
18F-FDG PET has a sensitivity and specificity of 75% and 90% respectively (IAEA, 2009, p.176).
They key disadvantage with PET is that whole radiopharmaceutical supply must be built to support the timely delivery of isotopes with short half-life from a regional cyclotron. In practice, there is a compromise between ideal isotope for clinical imaging and cost and delivery of ligands.
All types of nuclear imaging carry significant radiation dose which itself increases the risk of cancer, especially if the investigation has to be repeated periodically and is relatively time consuming with the patient having to wait for several hours after injection before the scan can proceed.
Use of dual imaging of PET combined with other modality is, growing especially single gantry PET/CT where functional activity can be superimposed on a high resolution anatomical scan allowing accurate localisation of lesions - something that standard PET and scintigraphy performs poorly at.
The use of CT and MRI in follow-up is only indicated if there is evidence of recurrent disease; therefore it is used in re-staging.
We have shown that imaging and radiographic techniques are fundamental to the diagnosis and management of thyroid cancer. And although modalities have been presented as the best choice for each stage, there is considerable overlap in their use due to their individual advantages and limitations. Skill and judgement are required to match the appropriate modality to the patient, being influenced by diverse factors such as tumour type patient anatomy, claustrophobia all the way to organisational/cost issues: often this means that the best modality suggested by the literature is not readily available. However by default US is primarily used for diagnosis, MRI/CT for staging and RNI for follow-up.
Imaging helps surgeons understand the extent of cancer and plan operations more effectively before knife hits the skin thus minimizing the extent of resection. Follow up imaging measures the effectiveness of the surgery and provides the MDT with a clear picture of cancer spread - something that would be impossible without imaging.
Although none of the modalities are 100% accurate alone, when used together alongside medical test, they offer a patient an informed prognosis, which allows them to plan for the future.
Imaging technology is far from static, the literature showed a hive of activity related to improvements in both diagnostic yield and reduction of patient side effects. Elastography may further bolster ultrasound's accuracy in discriminating thyroid cancers and increased availability of PET-CT may offer better resolution of exact anatomical location of metastasis.
Imaging is fundamental to realise the vision that early detection and prevention is better than late cure.
Provides a bridge between scientific advances