Thyroid cancer

What is thyroid cancer? .
Thyroid cancer is a disease in which cancer (cancerous) cells are found in the tissues of the thyroid gland. The thyroid gland is at the base of the throat. It has two lobes, one on the right side and one on the left. The thyroid gland makes important hormones that help the body function normally.

Certain factors may increase the risk of developing thyroid cancer

• Thyroid cancer occurs more often in people between the ages of 25 and 65 years.
• People who have been exposed to radiation or received radiation therapys to the head and neck during infancy or childhood have a greater chance of developing thyroid cancer. The cancer may occur as early as 5 years after exposure or may occur 20 or more years later.
• People who have had goiter (enlarged thyroid) or a family history of thyroid disease have an increased risk of developing thyroid cancer.
• Thyroid cancer is more common in women than in men.
• Asian people have an increased risk of developing thyroid cancer.

There are four forms: papillary, follicular, medullary and anaplastic. The most common forms (papillary and follicular) are fairly benign, and the medullary form also has a good prognosis; the anaplastic form is fast-growing and poorly responsive to treatment.

Masses of the thyroid are diagnosed by fine needle aspiration (FNA) or frequently by thyroidectomy (surgical removal and subsequent pathological examination). As the thyroid concentrates iodine, radioactive iodine is a usually used modality in thyroid carcinomas.

Symptoms

Most often the first symptom of thyroid cancer is a nodule in the thyroid region of the neck, but only 4% of these nodules are cancerous. Sometimes the first sign is an enlarged lymph node. Other symptoms that can be present are pain, changes in voice and symptoms of hypo- or hyperthyroidism.

Diagnosis

After a nodule is found during a physical examination, thyroid function is investigated by measuring, among other markers, Thyroid Stimulating hormone (TSH), the thyroid hormones thyroxine (T4) and triiodothyronine (T3), and Thyroid Binding Globulin (TBG). Tests for serum thyroid autoantibodies are also sometimes done. The blood assays are commonly accompanied by ultrasound imaging of the nodule to determine the position, size and texture. Most clinicians will also request technetium and/or radioactive iodine imaging of the thyroid. The most cost-effective, sensitive and accurate test to determine whether the nodule is cancerous is the fine needle biopsy, which is almost always done. Often, the suspected nodule is removed surgically for pathological examination, or a biopsy is done using a coarse needle, so that the arrangement of the cells can be examined (where the fine needle biopsy can only give individual cells).

Classification

Thyroid cancers can be classified according to their pathological characteristics. The following variants can be distinguished:

• Papillary thyroid cancer (75%, incl. mixed papillary/follicular)
• Follicular thyroid cancer (16%)
• Medullary thyroid cancer (5%)
• Anaplastic thyroid cancer (3%)
• Lymphoma (1%)
• Squamous cell carcinoma, sarcoma (0.5 - 2%)

Papillary thyroid cancer

This is the most common type of thyroid cancer. It occurs more frequently in women and presents in the 30-40 year age group. It is also the predominant cancer type in children with thyroid cancer, and in patients with thyroid cancer who have had prior radiation to the head and neck (in this group, the cancer tends to be multifocal with early lymphatic spread, and portends a poor prognosis).

Pathology

• Characteristic Orphan Annie eye nuclear inclusions and psammoma bodies on light microscopy
• Lymphatic spread is more common than hematogenous spread
• Multifocality is common
• The so-called Lateral Aberrant Thyroid is actually lymph node metastasis from papillary thyroid carcinoma.

Prognostic indicators

• AGES - Age, Grade, Extent of disease, Size
• AMES - Age, Metastasis, Extent of disease, Size
• MACIS - Metastasis, Age at presentation, Completeness of surgical resection, Invasion (extrathyroidal), Size (this is a modification of the AGES system)
• TNM - Tumor, node, metastasis

Surgical therapy

• Minimal disease - hemithyroidectomy (or unilateral lobectomy) and isthmectomy is sufficient
• Gross disease - total thyroidectomy

Arguments for total thyroidectomy are:

• Reduced risk of recurrence
• Papillary carcinoma is a multifocal disease (hemithyroidectomy may leave disease in the other lobe)
• Ease of monitoring with thyroglobulin (sensitivity for picking up recurrence is increased in presence of total thyroidectomy)
• Ease of detection of metastatic disease with thyroid scans

Follicular thyroid cancer

This occurs more usually in women of older age group (more than 50 years)

Surgical Treatment

• Unilateral hemithyroidectomy is uncommon due to the aggressive nature of this form of thyroid cancer.
• Total thyroidectomy is almost automatic with this diagnosis. This is invariably followed by radioiodine therapy at levels from 100 to 200 millicuries. Occasionally therapy must be repeated if annual scans indicate remaining tissue.
• Annual thyroid scans consist of withdrawal from thyroxine medicine and/or injection of recombinant human Thyroid Stimulating Hormone (TSH). Low dose radioiodine of a few millicuries is administered. Full body nuclear medicine scan follows using a gamma camera.
• Recombinant human TSH, commercial name Thyrogen, is produced in cell culture from genetically engineered hamster cells.

Hurthle cell variant

This type of thyroid cancer is a variant of follicular cell carcinoma with some exceptions

• They are more often bilateral and multifocal
• They are more likely to metastasize to lymph nodes than follicular carcinoma
• Management - like follicular carcinoma, unilateral hemithyroidectomy is performed for non-invasive disease, and total thyroidectomy for invasive disease

Medullary thyroid cancer

This form of thyroid carcinoma originates from the parafollicular cells (C cells), which produce the hormone calcitonin. While the increased calcitonin itself is probably not harmful, it is useful as a marker which can be tested in blood.

Its prognosis is poorer than that of follicular and papillary thyroid cancer. In a proportion, the cancer runs in families, both in isolated form or as part of the syndrome of multiple endocrine neoplasia (MEN).

Anaplastic thyroid cancer

This form of thyroid cancer has a very poor prognosis due to its aggressive behavior and resistance to cancer therapys. It rapidly invades surrounding tissues (such as the trachea).

Treatment

Unlike its counterparts, anaplastic thyroid cancer is not curable by surgery, and is in fact commonly unresectable due to its high propensity for invading surrounding tissues. Treatment consists of radiation treatment commonly combined with chemotherapy.

References

• Bennedbæk F.N.; Perrild H.; Hegedüs L. (1999). Diagnosis and therapy of the solitary thyroid nodule. Results of a European survey, Clinical Endocrinology, 50(3): 357-363.
• Carlo Ravetto, Luigia Colombo, Massimo E. Dottorini (2000). Usefulness of fine-needle aspiration in the diagnosis of thyroid carcinoma, Cancer Cytopathology, 90(6): 357-363.