Types of thyroid cancer
There are several different types of thyroid cancers and they are broadly broken into categories based on the cells that they originate from and their behaviour. Most thyroid cancers are low grade, differentiated thyroid cancers that originate from thyroid follicle cells, generally behave in an indolent fashion and have very high rates of survival. At the other end of the spectrum are anaplastic thyroid cancers that are among the most aggressive human cancers, have a rapidly progressive disease course and have rates of disease specific death approaching 100%. In between these are a group of poorly differentiated cancers that also originate from thyroid follicular cells, occur in older patients and do worse than differentiated thyroid cancers. Finally, there is medullary thyroid cancer, a neuroendocrine tumour of parafollicular c cell origin that just happens to occur in the thyroid gland but is not of thyroid cell origin. We now understand quite a lot about the molecular pathways involved in the development of thyroid cancers and this has helped to classify variants of these tumours and also helped to identify therapeutic strategies in cancers that are beyond surgical treatment. The mainstay of treatment of thyroid cancer however, remains surgery and the vast majority of thyroid cancers are cured with this and sometimes the use of I131.
Differentiated Thyroid Cancer
Papillary Thyroid Cancer
Papillary thyroid cancer (PTC) is the most common thyroid malignancy making up 75-80% of all thyroid cancers. It occurs in woman 4 x more frequently than men and is predominantly a tumour of adulthood in the child bearing age group but it does occur in children. 67% present with a thyroid nodule, 13 % present with a nodule and lymph nodes and 20% present with lymph nodes alone. Lymph nodes can be small and can undergo cystic change and be mistaken for branchial cleft cysts. Occult micropapillary cancers occur in 6% of the population and are present at autopsy. There are a number of variants of PTC some of which have behaviour similar to or better than classic variant PTC like Follicular Variant , Encapsulated Variant, Cribriform-morular variant and Diffuse Sclerosing variant. Some have worse behaviour and generally occur in older patients such as Tall Cell Variant, Columnar Cell Variant, Hobnail Cell Variant and Solid and Trabecular Variant PTC.
Follicular Thyroid Cancer
Follicular thyroid cancer (FTC) is the next most common making up 6-10% of all thyroid cancers. 75% occur in women and age incidence peaks at 40-60 years. Iodine deficiency and radiation exposure are risk factors. Most present with a thyroid nodule and lymph node involvement is uncommon but up to 69% develop distant metastases to lung and bone . There are 3 main types of FTC: Minimally Invasive FTC with a very good long term prognosis, Encaspulated Angioinvasive FTC which does worse and Widely Invasive FTC with a high distant metastatic rate and 50% longterm mortality.
Hurthle Cell Cancer
A follicular tumour with >75% oncocytic cells. The oncocytic (Hurthle) cells are due to being packed with abnormal mitochondria. These tumours are most common in older men ( mean age 57yrs). Hurthle cell cancers are more aggressive than follicular cancers with more extrathyroid extension, more metastases to lymph nodes and higher rates of mortality ( up to 80%)
Poorly Differentiated Thyroid Cancer
This is a malignancy of Follicular cell origin that makes up 0.3-7% of all thyroid cancers. It occurs in older patients and presents as a large solid thyroid mass. There is a high rate of nodal and haematogenous metastases and a 3 yr survival rate of around 35%. It has behaviour that sits between differentiated thyroid cancer and anaplastic cancer and can originate de novo or from a differentiated thyroid cancer or goitre and can under go a series of mutations to de-differentiate. There are insular, solid and trabecular variants and these cell pattern types can be mixed. Tumours must also demonstrate tumour necrosis, a high mitotic rate and or convoluted nuclei.
Medullary Cancer
A neuroendocrine tumor derived from C cells of the ultimobranchial body of the neural crest, which secrete calcitonin. Makes up 1 – 2% of thyroid carcinomas. 70% are sporadic (nonhereditary) and 30% familial (hereditary). The sporadic tumours are solitary and peak in ages 40 – 60. The hereditary type occurs in younger patients (mean age 35) and are usually bilateral and multicentric with C cell hyperplasia. Familial MTC is due to MEN 2A or 2B syndromes, familial medullary thyroid carcinoma (FMTC) syndrome, von Hippel-Lindau disease or neurofibromatosis. This is caused by gain of function germline mutations in the RET gene. Presents as a hard thyroid mass and up to 75% have nodal metastases. Serum calcitonin correlates with tumour burden and those with systemic metastases may have diarrhoea and flushing. 5 year survival is 65-90% and prognosis is worse with higher stage, nodal metastases, male, MEN2B, 918RET mutation, high mitotic activity and vascular invasion.
Anaplastic Cancer
Anaplastic thyroid cancer (ATC) is among the most aggressive and deadly human cancers. It makes up 2-5% of thyroid cancers but is responsible for 40% of thyroid cancer deaths. This tumour presents as a rapidly progressive large neck mass with invasion of central compartment structures associated symptoms of hoarseness, dyspnoea and dysphagia. There are usually involved lymph nodes and 30-40% present with distant metastases. 50% have a prior multi nodular goitre and 20% have a prior differentiated thyroid cancer. 20% have a concurrent differentiated thyroid cancer and dedifferentiation occurs in this tumour with a high rate of TP53 mutation. 1 year survival is in the 10-20% range.