Thyroid carcinoma is a malignant tumour of the thyroid gland. It is the most common malignancy of the endocrine (hormonal) system, but is very rare overall, accounting for around 1% of all malignant tumours.

Mortality due to thyroid carcinoma has fallen in recent decades as a result of earlier diagnosis, more effective treatment options and a decreasing proportion of prognostically unfavourable forms.

In thyroid carcinomas, a distinction is made between papillary (PTC) and follicular (FTC) carcinomas originating from the follicular cells of the thyroid gland - often grouped together as differentiated tumours - and anaplastic (ATC) and medullary thyroid carcinomas (MTC) originating from the parafollicular cells (so-called C-cells).

The percentage distribution of the different histological types of thyroid carcinoma is as follows: papillary 80-90%, follicular 5-10%, medullary up to 10% and anaplastic 3-5%. So-called sarcomas, lymphomas and metastases of the thyroid gland are extremely rare.

Papillary carcinomas have an age peak between the ages of 35 and 60, follicular carcinomas between the ages of 40 and 50. Anaplastic carcinomas are rare before the age of 40; the peak incidence is between the ages of 70 and 80. The age of patients with medullary thyroid carcinoma is highly variable; there is no recognisable peak in the age distribution. Geographical and ethnic differences in the incidence rate of thyroid carcinoma have been described. Incidence refers to the number of new cases under certain criteria.

While differentiated thyroid carcinomas (PCT and FTC) have a very good prognosis with 10-year survival rates of over 90%, anaplastic carcinoma is one of the most aggressive malignant tumours. Anaplastic thyroid carcinoma is characterised by a poor response to therapy and usually leads to death within a short period of time.

Thyroid carcinomas are caused by genetic changes in the cells of the thyroid tissue, which lead to uncontrolled tumour growth and spread to neighbouring structures (infiltration) and distant organs (metastases). The trigger for these genetic changes is unknown in the majority of cases.

The incidence of thyroid carcinoma increases with age. Age is also an important prognostic factor: thyroid carcinoma at a young age (< 20 years) or in older people (>45 years) is associated with a poorer prognosis. Thyroid carcinoma is twice as common in women as in men, but males are associated with a poorer prognosis.

Previous radiotherapy to the neck region (e.g. for the treatment of lymphoma) increases the risk of developing thyroid cancer. The time between exposure and diagnosis of thyroid carcinoma is between five and 30 years.

Following radiation accidents such as the Chernobyl reactor disaster in 1986, the incidence of thyroid cancer increased by a factor of around 30, particularly in children.

An iodine deficiency can favour the development of differentiated thyroid carcinomas, especially follicular carcinomas. Improved iodine intake, for example through increased iodine intake with food, taking iodine tablets or iodising table salt, has led to a reduction in anaplastic thyroid carcinomas.

A special feature of thyroid carcinomas is their frequent occurrence as hereditary (familial) carcinomas. Approximately 5% (papillary/follicular carcinoma) to 30% (medullary carcinoma) of all cases can be attributed to a familial form of thyroid carcinoma, which requires special treatment and aftercare.

Mutations of the RET tumour gene have been identified as the cause of familial medullary thyroid carcinoma. RET gene diagnostics plays an outstanding role in this tumour, on the one hand for the treatment and aftercare of affected patients, and on the other hand for the counselling, diagnosis and (if necessary) also for the preventive therapy of affected family members.

Thyroid carcinomas can be felt on the neck of many patients as rough, usually painless lumps, provided they have reached a certain size (usually >2 cm). A rapid increase in size is particularly suspicious for a carcinoma. A coarse, palpable cervical lymph node can also be a sign of an already metastasised (usually papillary) thyroid carcinoma. New onset of dysphagia and hoarseness may indicate an advanced carcinoma.

In many cases, however, affected patients show no typical signs of the disease, so that the diagnosis is often made after an ultrasound examination and thyroid surgery.

Medical history

The starting point for the diagnosis of thyroid carcinoma is a precise medical history (anamnesis). Particular attention is paid to possible radiotherapy of the neck region and the exact family history. Enquiry of the so-called B-symptoms is also part of the completion of the anamnesis interview.

Physical examination findings

Only larger tumours in the thyroid gland and neck region can usually be easily palpated. Coarse, painless lumps are typical of thyroid carcinoma.

Laboratory tests

Serum markers allow the detection of residual or recurrent disease, whereby the determination of thyroglobulin is used for PTC and FTC and that of calcitonin for MTC. To assess thyroid function, the hormones TSH and fT3 and fT4 (as free hormone) are determined in the blood.

If an autoimmune thyroid disease is suspected, it is necessary to determine the thyroid antibodies (TAK, TRAK and TPO).

Calcitonin in the blood is a very sensitive and specific marker for medullary thyroid carcinoma. Calcitonin should be determined at least once for every detected thyroid nodule in order to rule out this form of tumour. Calcitonin is also the most important parameter in the aftercare of medullary carcinoma.

After a complete thyroidectomy and radioiodine therapy, thyroglobulin is regularly determined in order to recognise the recurrence of malignant thyroid cells.

Further blood tests (blood count, mineral balance, kidney and liver values) are a regular part of tumour aftercare.

Sonography

Sonography (ultrasound) of the thyroid gland is the basic examination and is now the leading method in thyroid diagnostics. It is indicated for all suspected or proven nodules, enlargements or functional disorders of the thyroid gland. As a simple, quick and less stressful procedure (important: no radiation exposure), sonography is particularly suitable for screening, follow-up and aftercare.

Elastography (measurement of the elasticity of the tissue) is a newer imaging procedure and a further development of ultrasound diagnostics. Similar to manual palpation (examination by touch), elastography makes use of the fact that tumour tissue can often be compressed differently (firmer, coarser) than healthy tissue.

Scintigraphy

Thyroid scintigraphy is recommended for sonographically detected thyroid nodules that are 1 cm or larger. As a primarily function-oriented procedure, scintigraphy supplements the morphological (structural) information of thyroid nodules.

Due to the storage behaviour of the radioactive marker used here (technetium or iodine), non-storing ("cold") nodules can be identified that have a higher probability of carcinoma and therefore require further clarification.

Fine needle aspiration biopsy

In fine needle aspiration biopsy, thyroid nodules can be punctured using a thin needle under ultrasound guidance. The microscopic examination of the cells obtained can provide information as to whether a malignant tumour is present. If malignant cells are detected, either definitely or questionably, thyroid surgery is immediately necessary.

In the case of malignant thyroid tumours, four main forms of carcinoma can be distinguished on the basis of histological characteristics, which also differ in terms of their natural course, treatment and prognosis.

Depending on size and spread, thyroid carcinomas are classified according to the TNM system (UICC 2010). The criteria here are the tumour size in cm and the spread to neighbouring structures (T), the presence of lymph node metastases (N) or distant metastases (M).

In clinical practice, a staging of thyroid carcinomas based on the TNM classification, the patient's age and the histological (histological) type is also widely used. Fortunately, the majority of all patients are in the prognostically favourable stages I and II at the time of diagnosis. In the prognostically less favourable stages III and IV, either a very large tumour (>4cm), lymph node metastases or distant metastases are present. Anaplastic carcinomas are generally categorised as stage IV due to their very poor prognosis.

Papillary microcarcinoma (size ≤ 10 mm), which is often diagnosed as an incidental finding after thyroid surgery for other reasons, occupies a special position. The prognosis of papillary microcarcinoma is very favourable, so that patients almost always have a normal life expectancy for their age after complete surgical removal of the tumour. According to the current guidelines of the German Society for Surgery, single-focus microcarcinomas limited to the thyroid gland that are discovered by chance during the histological processing of thyroid surgery specimens do not require any further treatment.

Thyroid surgery

If the diagnosis of thyroid carcinoma is confirmed or probable, surgical treatment in the form of total organ removal (thyroidectomy) with lymph node removal is the treatment of choice. All differentiated thyroid carcinomas should be surgically removed. In addition to the removal of the primary tumour, the operation allows a precise histological diagnosis and staging. Lymph node involvement can also be assessed during the operation and the affected lymph nodes removed. The surgical strategy depends largely on the tumour type and the stage of the disease and should always be discussed individually with the patient.

Radioiodine therapy

In the case of follicular and papillary thyroid carcinomas, ^131Iradioiodine therapy is carried out 4-6 weeks after the operation. The aim of this treatment is to selectively destroy any remaining thyroid (tumour) cells and any metastases. An exception is papillary microcarcinoma, for which radioiodine therapy is not necessary due to the very favourable prognosis, provided the tumour has been completely surgically removed.

Radioiodine therapy is also the treatment of choice if metastases are detected during tumour follow-up.

Medullary and anaplastic thyroid carcinomas do not store iodine and are therefore not suitable for radioiodine therapy.

External radiotherapy (percutaneous radiotherapy)

The primary treatment of differentiated thyroid carcinomas by means of surgery and radioiodine therapy leads to long-lasting remissions (permanent or temporary reduction of disease symptoms). With regular follow-up care, local recurrences (relapses) and distant metastases (metastases) can also be treated well with appropriate measures, so that the overall prognosis can be described as good, even without additional radiotherapy following surgery and radioiodine therapy. Under certain circumstances, however, patients with unfavourable prognosis parameters and a very high risk of recurrence may benefit from percutaneous (external) radiotherapy. A decision is always made on a case-by-case basis together with the patient. If there is a large residual tumour or a lack of response to treatment, percutaneous radiotherapy may also be useful to alleviate local symptoms or complications.

Systemic drug therapy

In the majority of cases, differentiated thyroid carcinomas respond very well to radioiodine treatment. Progression after radioiodine therapy is associated with a loss of the ability to absorb iodine. In this situation, the question of another systemic therapy arises. The expected therapeutic benefit must be weighed against the drug-related side effect profile. The following treatment options are currently available: Multi-tyrosine kinase inhibitors (e.g. sorafenib), cytotoxic chemotherapy (doxorubicin, cisplatin) and radio-immuno- and receptor therapy (Y-90-DOTATOC).

Supplementary drug therapy (TSH suppression therapy)

After surgical removal or radioiodine therapy of the thyroid gland, a lifelong intake of the thyroid hormone preparation levothyroxine is generally required. As most tumours are still TSH-sensitive, TSH-suppressive therapy with levothyroxine is one of the main pillars in the treatment of thyroid carcinoma. Although TSH suppression provides a clear therapeutic benefit, there are no prospective studies to determine the optimal range of TSH suppression. A reasonable treatment goal is to suppress TSH as much as possible without causing symptoms of hyperthyroidism. In follicular and papillary thyroid carcinomas, the levothyroxine dose is set high enough to achieve complete suppression of TSH, i.e. a reduction below the reference range. In medullary thyroid carcinoma, levothyroxine is administered exclusively for hormone replacement, for which a lower dosage is usually sufficient.

Preventive thyroidectomy (prophylactic thyroidectomy)

In the rare case of hereditary medullary thyroid carcinoma with evidence of an RET gene mutation, a genetic family examination should be carried out. In family members who also have a mutation, the risk of carcinoma is over 90%, so prophylactic thyroidectomy is recommended for these individuals. Ideally, the operation should be performed in childhood and, according to previous experience, is associated with a high clinical success rate.

Prophylactic thyroidectomy is generally not recommended for non-medullary thyroid carcinomas.

In most cases, malignant neoplasms of the thyroid gland have a good prognosis, depending on the histology, the age of the patient and the stage of the tumour. The more differentiated the carcinoma is, i.e. the more similar the degenerated gland cells are to healthy cells, the greater the chances of recovery. Anaplastic thyroid carcinoma, on the other hand, has a very poor prognosis. Consistent follow-up care for thyroid carcinoma is fundamentally important.