[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Endocrine system](https://durgical.com/en/general-pathology/areas/endocrine/) › Poorly differentiated and anaplastic thyroid carcinoma # 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. Updated Nov 12, 2026 ## Key points - High-grade differentiated: papillary or follicular architecture plus tumour necrosis or high mitotic count. - Poorly differentiated: solid, insular (nested) or trabecular growth without papillary nuclei, with necrosis, mitoses or convoluted nuclei. - Anaplastic: giant cells, spindle cells, squamoid cells; often only keratin and PAX8 remain; thyroglobulin is lost. - TP53 and TERT promoter mutations drive progression; many retain an earlier BRAF or RAS mutation. - Anaplastic carcinoma grows within weeks, invades the trachea and oesophagus, and most patients die within a year. ## 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. ## Memory aid Climb down the thyroid ladder: differentiated, high-grade, poorly differentiated, anaplastic; at the bottom there is no thyroid left in the cells. ## 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. [Add to my cards (3)](https://durgical.app/estudiar/?add=/en/general-pathology/poorly-differentiated-and-anaplastic-thyroid-carcinoma/) [More Pathology questions →](https://durgical.com/en/practice/?f=pathology) ## Elsewhere in DurgiPedia - [Differentiation and anaplasia: how a tumour cell looks under the microscope](https://durgical.com/en/general-pathology/differentiation-and-anaplasia-how-a-tumour-cell-looks-under-the-microscope/) - [Tumour suppressor genes: RB, TP53, APC, BRCA and the two-hit hypothesis](https://durgical.com/en/general-pathology/tumour-suppressor-genes-rb-tp53-apc-brca-and-the-two-hit-hypothesis/) ## Connections ## Related 4 - [Thyroid cancer: genetics and radiation](https://durgical.com/en/general-pathology/thyroid-cancer-genetics-and-radiation/) - [Papillary thyroid carcinoma](https://durgical.com/en/general-pathology/papillary-thyroid-carcinoma/) - [Follicular thyroid carcinoma and NIFTP](https://durgical.com/en/general-pathology/follicular-thyroid-carcinoma-and-niftp/) - [Differentiation and anaplasia: how a tumour cell looks under the microscope](https://durgical.com/en/general-pathology/differentiation-and-anaplasia-how-a-tumour-cell-looks-under-the-microscope/) ## Related conditions 2 - [Follicular, oncocytic (Hürthle cell) and anaplastic thyroid carcinoma](https://durgical.com/en/conditions/follicular-oncocytic-and-anaplastic-thyroid-carcinoma/) - [Thyroid cancer (papillary)](https://durgical.com/en/conditions/thyroid-cancer/) [← All of general pathology](https://durgical.com/en/general-pathology/) 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](https://www.cancer.gov/types/thyroid/hp/thyroid-treatment-pdq) (National Cancer Institute, 2025). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/general-pathology/poorly-differentiated-and-anaplastic-thyroid-carcinoma/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/poorly-differentiated-and-anaplastic-thyroid-carcinoma/