Cancer Dictionary · Head, neck and thyroid

Thyroid Cancer

Most thyroid cancer is differentiated papillary or follicular carcinoma with an excellent outlook, where the risk is overtreatment rather than undertreatment. Medullary thyroid carcinoma is a distinct disease with a strong inherited component. Anaplastic thyroid carcinoma is rare and aggressive, and is one of the situations in oncology where molecular testing is genuinely urgent.

Also called Papillary thyroid carcinoma, Medullary thyroid carcinoma, Anaplastic thyroid carcinoma.

Browse all entries Ask a question, free

Start here

The governing idea

Thyroid cancer spans one of the widest ranges of behaviour of any cancer, from disease that may never need treatment to among the most aggressive cancers known, and the histological type is what separates them.

01Before any molecular question

How it usually presents

Usually established first: histological type, extent of disease and nodal involvement. Many thyroid cancers are found incidentally on imaging performed for other reasons, which is part of why overdiagnosis is a live concern in this disease.

Usually already established

Histological type
Extent of disease and nodal status
Thyroglobulin or calcitonin level depending on type
Whether the disease takes up radioiodine

Major disease categories

The divisions below are not labels. Each one changes what the treatment discussion is actually about.

Papillary thyroid carcinoma

The most common type, usually with an excellent outlook. BRAF V600E and RET fusions are the characteristic alterations.

Follicular thyroid carcinoma

Less common, with RAS alterations and PAX8-PPARG fusions characteristic.

Medullary thyroid carcinoma

Arises from different cells entirely. RET alterations are central, and a substantial proportion are inherited.

Poorly differentiated and anaplastic carcinoma

Rare and aggressive. Anaplastic carcinoma is a situation where rapid molecular testing, particularly for BRAF V600E, is genuinely time-critical.

Radioiodine-refractory differentiated carcinoma

Where the usual treatment no longer works, and where profiling becomes relevant.

03What is discussed

Molecular considerations

BRAF V600E and RET fusions dominate papillary carcinoma; NTRK fusions occur less often. RAS alterations and PAX8-PPARG fusions characterise follicular carcinoma. In medullary thyroid carcinoma, RET alterations are central, and a germline RET alteration is the defining feature of multiple endocrine neoplasia type 2. TERT promoter alteration, particularly combined with BRAF, is associated with more aggressive behaviour. Anaplastic carcinoma frequently carries BRAF V600E, and identifying it quickly matters.

Biomarkers commonly discussed

BRAF V600E

Central in papillary and anaplastic carcinoma. In anaplastic disease, finding it quickly is time-critical.

RET

Fusions in papillary carcinoma; point mutations in medullary carcinoma. Two different findings in two different diseases.

NTRK

Fusions, uncommon but actionable.

RAS

Characteristic of follicular carcinoma.

TERT promoter

Associated with more aggressive behaviour, particularly alongside BRAF.

Calcitonin and CEA

Serum markers specific to medullary thyroid carcinoma.

This is not an exhaustive list, and which markers are relevant depends on the individual case. Not every marker listed is assessed in every patient.

04What is tested, and from what

Testing, inherited risk and blood-based monitoring

Genomic testing considerations

Molecular testing on thyroid nodule aspirates is used to help decide whether surgery is needed, which is a different application from profiling established cancer. In radioiodine-refractory differentiated carcinoma and in medullary carcinoma, profiling identifies targetable RET and NTRK alterations. In anaplastic carcinoma, rapid testing for BRAF V600E is a priority, because the disease moves quickly and the result can change the immediate plan.

Germline considerations

Medullary thyroid carcinoma has a strong inherited component, and germline RET testing is discussed for all patients with this diagnosis regardless of family history. A germline RET finding establishes multiple endocrine neoplasia type 2, which involves other endocrine glands and has direct implications for relatives, sometimes including preventive surgery. Differentiated thyroid carcinoma has weaker familial clustering and is also seen in syndromes such as familial adenomatous polyposis, Cowden syndrome and DICER1 syndrome.

Cancer genetics and hereditary risk

ctDNA and liquid biopsy considerations

ctDNA has a limited established role in thyroid cancer. Serum thyroglobulin in differentiated carcinoma and calcitonin in medullary carcinoma remain the practical circulating markers.

When molecular information matters

Testing that arrives after the decision it was meant to inform has already been made is a common and avoidable problem. This is the sequence in which molecular information tends to become relevant.

At nodule assessmentMolecular testing on an aspirate can help decide whether surgery is needed at all.
At diagnosis of medullary carcinomaGermline RET testing is discussed for all patients, not only those with a family history.
In anaplastic carcinomaRapid BRAF testing is time-critical, and delay has consequences in a disease that moves this quickly.
When differentiated disease becomes radioiodine-refractoryProfiling for RET and NTRK becomes relevant.
For relatives of a patient with germline RETTesting and preventive management can begin before any cancer develops.

06Take these to your team

Questions worth raising

When a decision is being made

Questions worth raising with a treating team.

Has the histological type been established, since the range of behaviour across thyroid cancer is extremely wide?
In medullary thyroid carcinoma, has germline RET testing been offered regardless of family history?
In anaplastic carcinoma, has rapid BRAF V600E testing been requested, given how quickly this disease moves?
In radioiodine-refractory disease, has profiling for RET and NTRK fusions been done?
Where the disease is low-risk, has the risk of overtreatment been discussed as openly as the risk of undertreatment?

At progression, recurrence or resistance

The molecular picture at diagnosis is not always the molecular picture later.

Has profiling been repeated where a targeted agent has stopped working, since RET resistance mutations are described?
Has the histology been reconsidered where a previously indolent cancer starts behaving aggressively?

07What shapes eligibility

Clinical trial considerations

Trial eligibility centres on specific alterations, particularly RET, BRAF and NTRK, and on histological type. Anaplastic thyroid carcinoma has its own trial landscape and referral routes given its rarity and pace.

Ask about trial matching

Plain-language glossary for this entry (5 terms)

Term	What it means
Differentiated thyroid cancer	Papillary and follicular carcinoma, which retain thyroid cell behaviour including radioiodine uptake.
Radioiodine-refractory	Disease that no longer takes up radioactive iodine, so that treatment stops working.
Medullary thyroid carcinoma	A cancer of the calcitonin-producing cells. Biologically unrelated to the more common thyroid cancers.
MEN2	Multiple endocrine neoplasia type 2. An inherited condition caused by germline RET alteration.
Overdiagnosis	Finding cancers that would never have caused harm. A recognised issue in thyroid cancer.

Where OnKommon fits

These are the services most often relevant to this cancer. Which of them applies is a clinical question, not an automatic one.

HeritageInherited-risk testing, and a tested pathway for relatives.See how it works Signature STt OProfiling from an existing FFPE tissue block.See how it works Signature STb O+The 523-gene comprehensive panel, with TMB and MSI.See how it works Blueprint CareThe decision report that reads the profile and ranks the options.See how it works

This entry is educational. It describes what is commonly discussed in this cancer, not what should happen for any individual. Which of it applies depends on the specific diagnosis, stage, prior treatment and the person themselves. Nothing here is a recommendation, and no list of biomarkers here is exhaustive. Decisions belong with a treating team who know the whole case.

Take the next step

Three ways forward. Pick the one that fits today.

Book a free consultation

A no-obligation conversation with our care team, arranged through KPCIRC.

Book a consultation

Begin Blueprint Care

Commission your decision report and a dedicated clinical team.

Explore Blueprint Care

Ask on WhatsApp, free

Signal replies to your first question within four hours, at no cost.

Start with Signal