Thyroid cancer pathophysiology

Classification
Thyroid cancers can be classified according to their pathological characteristics. The following variants can be distinguished (distribution over various subtypes may show regional variation):
 * Papillary thyroid cancer (75%, incl. mixed papillary/follicular)
 * Follicular thyroid cancer (16%)
 * Medullary thyroid cancer (5-7%)
 * 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 previous radiation to the head and neck (in this group, the cancer tends to be multifocal with early lymphatic spread, and portends a relatively poor prognosis). Thyroglobulin can be used as a tumor marker for well-differentiated papillary thyroid cancer.

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 a lymph node metastasis from papillary thyroid carcinoma.

The genetics of medullary thyroid cancer
Mutations (DNA changes) in the RET proto-oncogene, located on chromosome 10, lead to the expression of a mutated receptor tyrosine kinase protein, termed RET. RET is involved in the regulation of cell growth and development and its mutation is responsible for nearly all cases of hereditary or familial medullary thyroid carcinoma. Its mutation may also be responsible for the development of hyperparathyroidism and pheochromocytoma. Hereditary medullary thyroid cancer is inherited as an autosomal dominant trait, meaning that each child of an affected parent has a 50/50 probability of inheriting the mutant RET proto-oncogene from the affected parent. DNA analysis makes it possible to identify children who carry the mutant gene; surgical removal of the thyroid in children who carry the mutant gene is curative if the entire thyroid gland is removed at an early age, before there is spread of the tumor. The parathyroid tumors and pheochromocytomas are removed when they cause clinical symptomatology. Hereditary medullary thyroid carcinoma or multiple endocrine neoplasia (MEN2) accounts for approximately 25% of all medullary thyroid carcinomas.

Seventy-five percent of medullary thyroid carcinoma occurs in individuals without an identifiable family history and is assigned the term "sporadic". Individuals who develop sporadic medullary thyroid carcinoma tend to be older and have more extensive disease at the time of initial presentation than those with a family history (screening is likely to be initiated at an early age in the hereditary form). Approximately 25% of sporadic medullary thyroid carcinomas have a somatic mutation (one that occurs within a single "parafollicular" cell) of the RET proto-oncogene. This mutation is presumed to be the initiating event, although there could be other as yet unidentified causes.