Thyroid Malignancy

Thyroid Cancer

Thyroid cancers include a spectrum of carcinomas which have unique features. These range from the relatively good prognosis malignancies such as papillary carcinoma to those with a terrible prognosis such as undifferentiated carcinoma. Each of the types has a specific set of common genetic abnormalities.


Thyroid cancer occurs preferentially in females at a ratio of 2:1 – 4:1. The cause of this is unknown but a sex hormone receptor is suspected. It occurs more commonly in younger people than many other malignancies. Papillary carcinoma occurs at a younger mean age (40s) than follicular carcinoma (50s); undifferentiated carcinomas usually occur later in life.
In general, although the incidence rates of thyroid cancers are climbing the mortality from the disease is falling due to improved treatment techniques. Iceland and Hawaii have the highest rates of thyroid cancer in the world. The incidence in Australia is 5.8/100,000 for women and 2.2/100,000 for men.


Papillary carcinoma is the most common, accounting for about 85% of all thyroid carcinomas. It is characterised by the presence of specific nuclear appearances with 'empty' appearing nuclei. It is typically arranged with papillary architecture but many variants exist; follicular variant is similar to follicular (below) but with the characteristic papillary nuclei. RET mutations are common in this group (as with medullary thyroid cancer). BRAF mutations occur in about 50% of cases.
Follicular carcinoma is less common (5-10%) and is often encapsulated. A rare variant (oncocytic or Hurthle cell carcinoma) appears mahogany brown. On microscopic examination, follicular carcinoma often forms follicular structures with central colloid. Genetic abnormalities in the PI-3K/AKT pathway is common.
Anaplastic carcinoma is thought to be a highly aggressive, dedifferentiated form of papillary/follicular carcinoma. It is usually metastatic at diagnosis. TP53 mutation is common.
Medullary carcinoma is a rare neuroendocrine tumour of the thyroid gland. It grows in trabeculae, nests or rarely follicles. The cells are polygonal, spindle or small cells. About 30% are related to germline mutations in RET (MEN2A or 2B); these tend to be multifocal and occur at a young age (for MEN2B, in early childhood).


Staging for thyroid cancers is interesting as age and histology play a role in determining the final stage.

T Stage (Differentiated)

The T Stage is different for undifferentiated thyroid carcinoma (see below).

T Stage Description
T1a < 1 cm
T1b 1 – 2 cm
T2 2 – 4 cm
T3 > 4 cm or minimal extracapsular extension
T4a Involvement of trachea, oesophagus, larynx or recurrent laryngeal nerve
T4b Encasement of carotid artery or mediastinal vessles, or prevertebral fascia involvement

T Stage (Undifferentiated)

T Stage Description
T4a Tumour located within the thyroid gland
T4b Tumour extends beyond the thyroid gland

N Stage

N stage is identical for all carcinomas.

N Stage Description
N1a Involvement of level VI nodes
N1b Involvement of cervical or superior mediastinal nodes

M Stage

M Stage Description
M1 Distant metastases

Final Stage

The final stage is influenced by:

  • The age of the patient (if they have follicular or papillary carcinoma)
  • Undifferentiated thyroid carcinoma (always stage IV)

Staging of Differentiated Carcinoma (under 45 years old)

Stage T N M
I Tany Nany M0
II Tany Nany M1

Staging of Differentiated Carcinoma (over 45 years old)

Stage T N M
I T1 N0 M0
II T2 N0 M0
IVB T4b Nany M0
IVC Tany Nany M1

Staging of Undifferentiated Thyroid Carcinoma

Stage T N M
IVA T4a Nany M0
IVB T4b Nany M0
IVC Tany Nany M1