Diagnostics

Disease

Malignant Disease of the Thyroid 

General

Although benign disease of the thyroid is relatively common, malignancy occurs relatively infrequently.  Carcinoma of the thyroid represents approximately 1% of newly diagnosed cancers each year and is the most common endocrine malignancy.  Although a great number of people will have a thyroid nodule at some point in their lives, only about 20,000 people in the United States will be diagnosed with thyroid cancer each year.  Fortunately, for most individuals, the prognosis is excellent, and the most common types of thyroid cancer can be completely removed by surgical resection.  This is particularly true for well-differentiated tumors, such as papillary and follicular carcinomas.  In fact, the 5-year survival rates are among the highest of all cancers (over 90%).  Poorly differentiated tumors (medullary and anaplastic carcinomas), although much less common, tend to be aggressive, metastasize early, and have a poorer prognosis.

There are four main varieties of thyroid cancer (papillary, follicular, medullary, and anaplastic), however, for clinical management purposes, they are generally divided into two categories (the first two types being well-differentiated and the latter two types being poorly differentiated).  While a complete and comprehensive overview of all the histologic details of each cancer is beyond the scope of this tutorial, certain clinical features, the clinical course, and treatment options will be discussed.

Papillary Carcinoma

Representing approximately 75-85% of cases, papillary carcinoma is the most common thyroid malignancy.  It is one of two (follicular carcinoma being the other) that make up the well-differentiated thyroid cancers and is commonly associated with previous exposure to ionizing radiation.  Although this form of cancer can occur at any age, papillary carcinoma is commonly encountered in the 20's to 40's and develops three times as frequently in women than in men.

Papillary carcinomas are solitary or multifocal, slow growing tumors that arise from the thyroxin and thyroglobulin producing follicular cells of the thyroid.  They typically present as asymptomatic thyroid nodules, however, the first manifestation may be enlargement of a cervical lymph node, where metastases travel primarily.  Distant spread of papillary carcinoma typically occurs to the lungs and bone. Approximately 5-10% of patients will develop distant metastases.

Because the tumor associated with papillary carcinoma cannot be distinguished from a benign nodule by physical exam alone, fine needle aspiration and biopsy of the tissue is ultimately necessary for definitive diagnosis. 

Treatment is usually either by thyroid lobectomy and isthmusectomy or total thyroidectomy.  The prognosis is typically very good

Follicular Carcinoma

Follicular carcinoma is the second most common thyroid malignancy, constituting 10-20% of cases (except in iodine deficient areas of the world where they account for even more).  Similar to papillary carcinoma, follicular carcinoma occurs in women with three times the frequency than in men, however, this form of cancer tends to present at a more advanced age (typically in the 40's and 50's).  They similarly arise from the follicular cells of the thyroid and present as slowly enlarging, painless masses.

Because of their low propensity for invading lymphatics, regional lymph node invasion is rare, however, vascular invasion is common, with metastasis to bone, lungs, and liver being the most common distant sites.  In contrast to papillary carcinoma, the rate of metastasis is somewhat higher (about 20%).  Fortunately, well-differentiated metastases usually take up radioactive iodine, which can aid in identifying and ablating such lesions.

Treatment is similar to that of papillary carcinoma.  Thyroid lobectomy and isthmusectomy or total thyroidectomy are both surgical options with very good prognoses. 

Medullary Carcinoma

Medullary carcinomas constitute approximately 5-7% of thyroid cancers, and are considered poorly-differentiated.  They are neuroendocrine neoplasms which arise from the parafollicular C cells of the thyroid gland, and like their normal counterparts, secrete calcitonin (a hormone which plays an important role in the diagnosis and postoperative follow-up of patients with this disease).  Unlike the well-differentiated carcinomas, medullary carcinoma is not thought to arise from radiation exposure.  Of the cases of medullary carcinoma that present themselves, approximately 75% are sporadic and 25% are familial.  The familial cases arise from an autosomal dominant mutation in the ret proto-oncogene which manifests as familial medullary carcinoma (FMC) or multiple endocrine neoplasia (MEN 2A or 2B).

Like other thyroid malignancies, medullary carcinomas present as painless, solitary thyroid nodules (although multiple nodules involving both lobes of the thyroid are not uncommon).  Plasma screening typically shows elevated levels of calcitonin, which can later be used as a marker for disease following therapy.

Medullary carcinoma has a much lower cure rate than does the well-differentiated thyroid cancers (papillary and follicular), but cure rates are higher than they are for anaplastic thyroid cancer (see below). Overall 10 year survival rates are 90% when all the disease is confined to the thyroid gland, 70% when there is spread to cervical lymph nodes, and 20% when there is metastases to distant sites.  Sporadic medullary carcinoma and those arising in patients with MEN 2B are typically more aggressive than other types, with a propensity to spread via the bloodstream, giving them an even worse prognosis (5 year survival rate of about 50%).  All forms have the ability to spread via the lymphatics and occur in over 50% of cases.

Treatment of both sporadic and familial cases of medullary carcinoma obviate total surgical resection (thyroidectomy) with lymphatic dissection of the anterior compartment of the neck.  In addition, prophylactic thyroidectomy and central lymph node compartment dissection is now being performed in children diagnosed with the familial syndromes, as those who inherit the disease typically develop this cancer in the first decade of life.

Anaplastic Carcinoma

Anaplastic carcinomas of the thyroid represent about 1-3% of all thyroid cancers.  They are undifferentiated tumors which arise from follicular cells of the thyroid gland, and in contrast to the other types of malignancies, are extremely aggressive with the worst survival rates.  Mortality rates approach 100%.

Like the other neoplasms, women are more commonly affected than men (2:1 to 3:1), and this cancer tends to present later in life (60's and 70's).  In contrast to the other cancers, anaplastic tumors grow rapidly, and patients often present with associated symptoms from local invasion, such as hoarseness, dysphagia, or dyspnea.  Involvement of the recurrent laryngeal nerve and airway occur in up to 50% of individuals.

Physical exam often reveals a firm thyroid mass (or masses).  Vocal cord paralysis presents in 30% of patients and 40% have palpable cervical metastases.  At least 50% or more will have distant metastases at diagnosis (the most common sites being the lungs, bones, and brain).

In terms of treatment, surgical resection is mainly palliative (giving airway relief).  Resection of the tumor does not appear to affect prognosis and survival is typically less than 1 year (even in the best of circumstances).