Imaging In The Diagnosis Of Thyroid Cancer Biology Essay

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The purpose of this assignment is to clinically reason the most efficient way to medically image the thyroid and to determine diagnostically which nodules appear clinically as malignant and which may be benign.

As stipulated by the nature of this assignment the thyroid is going to be the main source of investigation. Nodular thyroid disease that has a benign outcome is common; thyroid cancer on the other hand is rare.

Diseases to the thyroid represent the most common form of endocrine disorders. The three most common neck masses which require medical imaging of some sort include enlarged cervical lymph nodes, parathyroid adenomas and thyroid nodules. (Bluth et al, 2004).

Thyroid cancer is relatively rare and accounts for 1% of all cancer cases. Each year in the UK there is an average of 1,200 new cases of thyroid cancer. Of these cases 75% will be women. Women are three times more likely to develop thyroid cancer than men. (NHS, 2010)

In recent years the reported number of new cases of thyroid cancer has been slowly rising. This may be indicative of the improvements in technology making it easier to detect the condition, rather than thyroid cancer becoming more widespread.

"The annual detection rate is 0.005%. Therefore the overwhelming majority of thyroid nodules are benign." (Bluth, 2004.p.614)

Thyroid cancer is classified in accordance to the cell type that is affected within the thyroid gland. The two most common types of thyroid cancer are papillary thyroid cancer which accounts for 80% of all thyroid cancer and follicular thyroid cancer which accounts for 11% of all thyroid cancer. These are also known as differentiated thyroid cancers. (DTCs). (Bluth et al, 2004.)

There are rarer types of thyroid cancer and are usually more aggressive, with a superior chance of metastasis these include medullary cancer, anaplastic cancer and thyroid lymphoma.

The prognosis for thyroid cancer is frequently positive. The common types of thyroid cancer are slow-growing and are usually confined to the thyroid gland once diagnosed. DTCs can be cured using a combination of surgery and radioactive iodine treatment. The prognosis for the rarer non-DTC types of thyroid cancer is less favourable. Two types of radiation have been established to have instigated thyroid cancer. Nuclear fall-out from a nuclear explosion and radiation that was often used from 1910 to1960 for medical treatments especially of the cervical area. (Reiners et al, 2006.)

Nuclear medicine, ultrasound, CT, and MRI are imaging methods that can be used to evaluate the thyroid gland. All these techniques provide a variety of structural information for the thyroid gland and demonstrate the location and size of thyroid nodules. Nuclear medicine is the only modality to add functional information and can be therapeutic.

Imaging studies are very useful in the setting of recurrent thyroid cancer. Ultrasound is extremely sensitive in the detection of malignancy in cervical lymph nodes and as a guide in performing a biopsy. CT is very useful in identifying distant metastases in the chest and abdomen but because of the use of radiation alongside any other tests it is not going to be the modality of choice for this assignment. Nuclear medicine scanning can detect functioning distant metastases when the metastases are from differentiated thyroid cancers. MRI can be used to evaluate the possibility of recurrent thyroid cancer, and soft tissue disruption in the mediastinum. However, because of its relatively high cost, it is used less frequently than other imaging methods. (Gorall et al, 2000.)

Fine-needle aspiration cytology is the next stage in diagnosing thyroid cancer. FNAC is carried out under local anaesthetic with the accuracy dependant on diagnostic views performed by ultrasound. They found that the sensitivity of FNA varies from 65% to 98% (mean, 83%), and the specificity varies from 72% to 100% (mean, 92%). (NHS, 2010)

If the FNAC is inconclusive further tests are scheduled for a more precise diagnosis.

In most cases however, when thyroid cancer has been diagnosed by FNAC, management will consist of a thyroidectomy, the more common DTCs that have not progressed into soft tissue have the best prognosis.

Nuclear Medicine

The thyroid scan used in nuclear medicine has been the most widely used method for investigating a thyroid nodule, on the basis that finding a solitary cold nodule increases the probability of malignancy.

The main basis of a thyroid nuclear scan is to diagnose an underlying cause of a thyroid nodule, aids in deciding prognosis, deciphering therapeutic options and determining functional implications of a thyroid nodule. (Emmett, L, 2010).

Various radioactive substances can be used and the particulars of varying substances are beyond this assignment. However, there are diagnostic and therapeutic treatments for example: technetium- 99m can be used for diagnostic imaging purposes. Whereas iodine is used as diagnostic and a therapeutic tool possibly after a thyroidectomy to fully eradicate any leftover cancerous tissue. (Emmett, L. 2010).

Radioactive iodine treatment involves an intake of radioactive iodine orally, either in liquid or tablet form, or can be taken through the IV route. It is used in order to assess thyroid function, size, position and presence of nodules. "131 iodine is a b-emitting radionuclide with a physical half-life of 8.1 d, a principal g-ray of 364 KeV, and a principal b-particle with a maximum energy of 0.61 MeV, an average energy of 0.192 MeV, and a range in tissue of 0.8 mm." (Luster et al, 2008, p.2.)

Radioactive iodine is established as a cheap, simple and effective method of treating thyroid malfunctions and in most cases represents the treatment of choice. "Patients with toxic nodules respond well to radioiodine treatment, and the nodule usually decreases in size to 50-60% of the original volume." (Maisey et al, 2001, p,348)

 Nuclear imaging can be used to describe a nodule as hot, warm, or cold on the basis of its relative uptake of radioactive isotope. Hot nodules indicate autonomously functioning nodules, warm nodules suggest normal thyroid function, and cold nodules indicate hypo functional or non-functional thyroid tissue.

Hot nodules are rarely malignant and may signify a thyroid gland having a benign growth that is overactive. "Nodules that are functioning are rarely malignant. Significance of a hot nodule is important prognostically and the appearance helps determine the treatment required, single nodules may be removed surgically but multiple nodules are not surgical candidates." (Maisey et al 2001, p.245).

"Significance of a 'Cold' nodule signifies that the thyroid gland is underactive with 85-90% of solitary thyroid nodules are hypo functioning, 90% or cold nodules are degenerative nodules, 10% are malignant. The sensitivity is 97% and the specificity for detection of malignancy is 15%." (Maisey et al, 2001, p.246.)

The functional information gained from nuclear medicine exams is often unobtainable by any other imaging techniques, although other tests must be carried out before the complete diagnosis of thyroid cancer. Scan time about takes about five minutes and is relatively comfortable for the patient.

Image 1. Technetium-99m (99mTc) thyroid scan of a large, nontoxic multinodular goitre. Multiple cold and hot nodules are observed in the enlarged thyroid gland. The white arrow indicates the sternal notch marker. (Emmett.L, 2010, p.27).

Patient history and protocol are very important when undertaking nuclear medicine examination.

Nuclear medicine cannot be undertaken if the patient is either pregnant or breastfeeding, other issues that may affect using iodine treatment can include bone marrow depression, pulmonary function restriction, for example lung metastases.

Patient history involves previous radiation exposure, thyroid cancer in relatives, previous diagnostic treatments using radiopharmaceuticals.

If using iodine the exposure to iodine medication and following any low-iodine diet (or allergies to shellfish) this includes family planning, menstrual problems and pregnancy in women. (NHS, 2010).

Laboratory tests may include urinary stable iodine excretion, creatinine, calcium and calcitonin (post-surgery) Reactions to radioactive treatment may include tightness, or swelling, of their throat, and may feel flushed; side effects usually pass within 24 hours. (Guidelines for thyroid cancer, 2007.)

Patients under radioiodine treatment following a thyroidectomy are usually reviewed at 1, 3, 6, 9 and 12 months, a repeat thyroid scan is carried out at 6 months. Those with the possibility of a relapse will remain with some functional activity. Those who are not clear at 6 months are given an additional dose of iodine and followed as before. Once the patient has no diagnostic hot spots in the thyroid, annual examinations are required but post-radiation treatment recurrences are rare. Two tests can check for the return of cancerous cells thyroglobulin testing and a radioactive iodine scan. (Guidelines for thyroid cancer, 2007.)


Although ultrasonography cannot be relied upon solely to diagnose and differentiate between benign and malignant nodules. The etiology of the nodules found may be used to identify patients into those who require no further investigation and those who should undergo tissue sampling for further evaluation.

It is certain features discovered in ultrasound that can appear as benign or malignant. With current high definition ultrasound equipment the wall irregularity, internal solid elements and debris are sometimes clearly visible. Hyper echoic nodules which have an egg-shell type calcification are inclined to be typical of benign thyroid modules. (Bluth et al, 2004)

"Malignant modules are different in appearance and the presence of at least one malignant feature has an overall sensitivity of 83% and specificity of 74%." (Bluth et al, 2004, p. 620).

Thyroid cancer is solid and hypo echoic although further tests must be carried out because benign tumours are much more common, a misdiagnosis could be possible. "Internal calcification with or without acoustic shadowing is a facet found in the more common thyroid papillary cancer, and are considered to be deposits of calcium from psammona bodies within the tumour." (Bluth, 2004.p 618).

The rarer type of medullary thyroid carcinoma has a similar appearance inclined to be hypo echoic and solid. This diagnostically presents by having a coarser appearance than papillary and are thought to be collections of amyloid and calcium.

Follicular thyroid carcinomas are usually indistinguishable from benign due to the histological similarities of the tumours, but features that suggest malignancy are irregular margins and a thick irregular halo.

Anaplastic thyroid carcinoma is rare but when seen is large, solid, hypo echoic and invades adjacent muscles and vessels. (Bluth, 2004)

Doppler ultrasound can be applied to the evaluation of thyroid nodules. Rim vascularity is the initial detection of a thyroid mass with benign nodules showing as having minimal blood flow. Malignant thyroid masses demonstrate more blood flow located around the lesion; in addition it can be used to measure thyroid volumes.

However there is no solid evidence that it can determine between the two types but is more relevant to the size of the tumour in relation to blood flow rather than the histology. Ultrasound will not identify any invasion of the major vessels; also ultrasound may miss any pathology for example; air in the trachea.

Image 2. Ultrasound of the left lobe of the thyroid demonstrating

an hypo echoic papillary carcinoma with calcification (arrows). (King et al, 2006, p.223)

Ultrasound is readily available, has no contra-indications, it is cheap, relatively painless to the patient and it is quick scan time. The possible side effect may be heating of the neck.

Magnetic Resonance Imaging

Cross sectional imaging MRI is not particular sensitive for detecting intrathyroidal lesions and cannot reliably distinguish between benign and malignant nodules. Although cross sectional imaging is not part of routine staging for thyroid cancer, it is useful for assessing substernal thyroid masses, for evaluating local extension and staging of patients with proved thyroid malignancy and distant metastatic disease. (Cline et al, 2009)

It is difficult to establish the difference between a benign and a malignant mass with MRI because of the similar appearances such as calcifications and haemorrhage.

IV contrast must be used in order to identify highlights patterns of peripheral enhancement and any invasion of the mediastininum or chest wall will suggest an aggressive malignancy. (Juhl, 1998)

MRI is not as sensitive as ultrasound for the detection of intrathyroidal lesions but is beneficial for evaluation of mediastinal or extension of thyroid masses. Enlarged cervical lymph nodes and other surrounding structures are well assessed with this modality. (King et al, 2006).

"The sensitivity of MRI is greatest in the mediastinum, with up to 88% sensitivity, compared with 72% sensitivity in the neck." (Hopkins, 2006, p.56)

All details must be checked with the patient for pregnancy, allergies and metal work in which case the patient will have CT. Contrast may have contra-indications to the patient and an allergy check must be carried out.

Side effects may be dizziness and nausea and if claustrophobic or in pain MRI may be difficult as scan times are longer.

Image 3. Primary thyroid tumour demonstrating the invasion of the posterior wall of the trachea. Axial T1-weighted contrast-enhanced MR image. (King et al, 2006, p.224)

Recurrence of this site can lead to haemorrhaging into the trachea which can cause mortality and has implications for the extent of surgery. (King et al, 2006)

In Conclusion

Nuclear medicine should be the first imaging modality purely because it is the only modality that can determine functional implications of nodules.

It also has the advantage that iodine nuclear scans can be therapeutic as well as diagnostic due to the thyroid uptake of iodine. It is relatively quick, available and cost effective with a high sensitivity of 97% but low specificity of about 5%.

Due to the low specificity of nuclear medicine ultrasound should then be performed for identifying nodular thyroid carcinomas and differentiate between benign and malignant nodules. It is quick, inexpensive, requires no contrast and has the advantage over MRI of being able to identify a small primary tumour in the neck with a higher sensitivity than MRI, but is not efficient for deeper tissues.

MRI is the next modality in the patient pathway and should be reserved for those cases in which the tumour extends to the thyroid margin, so that spread of an aggressive malignant tumour, especially into the trachea, can be assessed. It may also be used to assess the thyroid and nodes in the upper mediastinum where MRI has a higher specificity than US. However as with most cases in MRI it is expensive, there are patient implications and there are machine availability issues. In this case CT can be used in place of MRI. (Cline et al, 2009)