Poorly differentiated and anaplastic thyroid carcinoma
- Lesion
A few thyroid cancers lose their resemblance to thyroid tissue and grow very fast. Anaplastic carcinoma is one of the deadliest cancers.
What it is
These carcinomas form a ladder of lost differentiation. High-grade differentiated carcinomas keep a papillary or follicular look but have necrosis or many mitoses; poorly differentiated carcinomas grow in solid, insular or trabecular sheets; anaplastic carcinoma no longer resembles thyroid at all. Most arise from a pre-existing well-differentiated tumour by adding TP53 and TERT promoter mutations, and they mainly affect older adults.
Structure
- Anaplastic: large, rapidly growing, hard mass invading neck structures; necrosis and haemorrhage.
- Micro: pleomorphic giant cells, spindle cells resembling sarcoma, or squamoid cells; many mitoses, atypical forms.
- A residual area of papillary or follicular carcinoma is often found.
- Poorly differentiated: nests (insulae) of uniform small cells separated by thin vessels, with necrosis.
Step by step
- A well-differentiated carcinoma carries a BRAF or RAS driver.
- TERT promoter mutation gives unlimited replication.
- TP53 loss removes apoptosis and cell-cycle arrest after DNA damage.
- Thyroid differentiation genes are silenced: no iodine uptake or thyroglobulin.
- The tumour behaves like an undifferentiated cancer with rapid local invasion.
Clinical notes
- Rapidly enlarging neck mass in an older person, with dyspnoea, dysphagia and hoarseness.
- Not responsive to radioiodine; BRAF V600E-positive anaplastic carcinoma may respond to targeted therapy.
Test yourself
Think of the answer, then tap the question to see it.
What two mutations typically mark progression to anaplastic thyroid carcinoma?
TP53 and TERT promoter mutations, usually on top of an earlier BRAF or RAS mutation.
Which growth patterns define poorly differentiated thyroid carcinoma?
Solid, insular (nested) or trabecular growth without papillary nuclear features, with necrosis, mitoses or convoluted nuclei.
Why does anaplastic carcinoma not respond to radioiodine?
Its cells have lost thyroid differentiation, including the sodium-iodide symporter, so they do not take up iodine.
Elsewhere in DurgiPedia
- Differentiation and anaplasia: how a tumour cell looks under the microscope
- Tumour suppressor genes: RB, TP53, APC, BRCA and the two-hit hypothesis
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Thyroid Cancer Treatment (PDQ®)–Health Professional Version (National Cancer Institute, 2025).
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Representative model, for educational purposes only.