Skip to content
How It Works
Explore
Resources Ask a Question
Who It's For
Patients
Decode results, prep for appointments, weigh options.
Caregivers & advocates
Carry the research load for someone you love.
Providers & clinicians
Resources for patients in your practice.
Log In Ask a Question
PubMed This is a summary of 25 peer-reviewed journal articles Updated
Oncology

The Biology and Types of Rare Thyroid Carcinomas

At a Glance

Rare thyroid carcinomas include four main types: Medullary (MTC), Oncocytic (Hürthle Cell), Poorly Differentiated (PDTC), and Anaplastic (ATC). Because these cancers are unique, obtaining a molecular profile through genetic testing is critical to identify the right targeted treatment options.

To understand your diagnosis, it helps to know that the thyroid gland contains two main types of cells. The cancer’s behavior depends entirely on which cell it started from [1]:

  • Follicular Cells: These cells make thyroid hormone and use iodine to do their job [1]. Most thyroid cancers, including the rare ones like Anaplastic, Poorly Differentiated, and Oncocytic (Hürthle Cell), start here [1][2].
  • C-cells (Parafollicular Cells): These are neuroendocrine cells that make a hormone called calcitonin [1]. Medullary Thyroid Carcinoma (MTC) is the only type that arises from these cells [1][2]. Because C-cells do not use iodine, MTC cannot be treated with radioactive iodine [2].

Understanding the Four Rare Types

The 2022 WHO classification refined how we identify these aggressive or unusual cancers based on their biology and “grade” (how fast they grow) [3][4].

1. Medullary Thyroid Carcinoma (MTC)

This cancer behaves more like a neuroendocrine tumor than a typical thyroid cancer [2]. It is almost always driven by a mutation in a gene called RET [5]. In about 25% of cases, this mutation is hereditary, meaning it can be passed down through families (a condition called MEN2) [5][6]. Doctors use blood tests for calcitonin and CEA to monitor this cancer [7].

2. Oncocytic Carcinoma (formerly Hürthle Cell Carcinoma)

In 2022, the WHO officially renamed Hürthle Cell Carcinoma to Oncocytic Carcinoma [8][3]. These tumors are made of “oncocytes”—cells packed with abnormal mitochondria (the powerhouses of the cell) [8][9]. These cancers are often less likely to take up radioactive iodine, making them more challenging to treat with traditional methods [10][11].

3. Poorly Differentiated (PDTC) and the New “High-Grade” Category (DHGTC)

These cancers are more aggressive than common thyroid cancers but less aggressive than Anaplastic cancer [12][13].

  • PDTC: Defined by a specific growth pattern (solid or “insular”) and signs of rapid cell division [14][1].
  • Differentiated High-Grade Thyroid Carcinoma (DHGTC): This is a new category introduced in 2022 [15]. It describes a cancer that looks like a “normal” thyroid cancer under the microscope but has acquired “high-grade” features, such as a high mitotic count (many cells actively dividing) or necrosis (areas of cell death) [16][17].

4. Anaplastic Thyroid Carcinoma (ATC)

ATC is the rarest and most aggressive form of thyroid cancer [2][18]. It occurs when follicular cells “dedifferentiate,” meaning they lose all the characteristics of a normal thyroid cell and begin to grow uncontrollably [19][20]. This change is often driven by mutations in genes like BRAF, RAS, and TERT [7][6].

Note on symptoms: For aggressive tumors like ATC or PDTC, sudden hoarseness or a change in your voice can be a sign that the tumor is affecting the vocal cord nerves. This is an important symptom to report to your doctor immediately [21][22].

Why Genetics Matter

In rare thyroid cancers, the “name” of the cancer is only half the story. The genetic mutations (the “drivers”) are just as important [23]. Modern medicine uses Next-Generation Sequencing (NGS) to map these mutations, which helps doctors choose targeted therapies that act like a key in a lock for your specific tumor [24][7]. Obtaining a “molecular profile” of your tumor is a critical step in managing a rare diagnosis [25].

Common questions in this guide

What are the four types of rare thyroid carcinoma?
The four main types of rare thyroid cancer are Medullary Thyroid Carcinoma (MTC), Oncocytic Carcinoma (formerly Hürthle Cell), Poorly Differentiated (PDTC), and Anaplastic Thyroid Carcinoma (ATC). Each type behaves differently based on its cell of origin and genetic mutations.
What is the difference between Medullary Thyroid Carcinoma and other thyroid cancers?
Medullary Thyroid Carcinoma starts in the thyroid's C-cells, which produce calcitonin, rather than the follicular cells where most thyroid cancers begin. Because C-cells do not use iodine, MTC cannot be treated with radioactive iodine therapy.
Why is genetic testing important for rare thyroid cancers?
Genetic testing, such as Next-Generation Sequencing, maps out the specific mutations driving your tumor's growth, like BRAF or RET. Identifying these genetic drivers helps your doctor match you with targeted therapies that are designed specifically for your cancer's molecular profile.
What does a high-grade thyroid carcinoma diagnosis mean?
A high-grade diagnosis means the tumor cells show signs of rapid division or areas of cell death under the microscope. This indicates the cancer may be more aggressive and require specialized treatment approaches.
Why did my doctor ask about a history of thyroid cancer in my family?
About 25 percent of Medullary Thyroid Carcinoma cases are hereditary, meaning they are passed down through families due to an inherited genetic mutation. If you have this type of thyroid cancer, your doctor may recommend genetic testing for you and your blood relatives.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Which of the four rare types of thyroid cancer do I have, and does it come from follicular cells or C-cells?
  2. 2.Has my pathology report been reviewed using the updated 2022 WHO criteria (specifically looking for things like 'DHGTC' or 'high-grade' features)?
  3. 3.What specific genetic mutations (like BRAF, RET, or TERT) were found in my tumor, and how do they change my treatment plan?
  4. 4.For my specific type of cancer, what is the likelihood that it will respond to radioactive iodine therapy?
  5. 5.If I have Medullary Thyroid Carcinoma, should I (and my family) undergo genetic testing for a germline RET mutation?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (25)
  1. 1

    SEAP-GETNE consensus on prognostic and predictive molecular biomarkers in thyroid cancer.

    Ruz-Caracuel I, Alonso-Gordoa T, Hernández S, et al.

    Revista espanola de patologia : publicacion oficial de la Sociedad Espanola de Anatomia Patologica y de la Sociedad Espanola de Citologia 2026; (59(2)):100859 doi:10.1016/j.patol.2026.100859.

    PMID: 41747300
  2. 2

    Updates on the Management of Thyroid Cancer.

    Araque KA, Gubbi S, Klubo-Gwiezdzinska J

    Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 2020; (52(8)):562-577 doi:10.1055/a-1089-7870.

    PMID: 32040962
  3. 3

    Overview of the 2022 WHO Classification of Thyroid Neoplasms.

    Baloch ZW, Asa SL, Barletta JA, et al.

    Endocrine pathology 2022; (33(1)):27-63 doi:10.1007/s12022-022-09707-3.

    PMID: 35288841
  4. 4

    WHO 2022 updates on follicular cell and c-cell derived thyroid neoplasm.

    Goswami P, Patel T, Dave R, et al.

    Journal of medicine and life 2024; (17(1)):15-23 doi:10.25122/jml-2023-0270.

    PMID: 38737660
  5. 5

    RET Gene Alterations in Clinical Practice: A Comprehensive Review and Database Update.

    Ricciardi Tenore C, Tulli E, Perrucci A, et al.

    Genes 2025; (16(12)) doi:10.3390/genes16121472.

    PMID: 41465145
  6. 6

    Current status of the prognostic molecular markers in medullary thyroid carcinoma.

    Oczko-Wojciechowska M, Czarniecka A, Gawlik T, et al.

    Endocrine connections 2020; (9(12)):R251-R263.

    PMID: 33112827
  7. 7

    Role of TERT gene mutation in the pathogenesis of anaplastic thyroid carcinoma (Review).

    Alhejaily AG, Alhuzaim O, Aljohani N, et al.

    Molecular and clinical oncology 2025; (23(2)):74 doi:10.3892/mco.2025.2869.

    PMID: 40630941
  8. 8

    The Initial Risk Stratification System for Differentiated Thyroid Cancer: Key Updates in the 2024 Korean Thyroid Association Guideline.

    Moon S, Song YS, Jung KY, et al.

    Endocrinology and metabolism (Seoul, Korea) 2025; (40(3)):357-384 doi:10.3803/EnM.2025.2465.

    PMID: 40598904
  9. 9

    Unraveling Hürthle cell lesions of the thyroid using molecular findings.

    Wong KS

    Cancer cytopathology 2022; (130(6)):405-406 doi:10.1002/cncy.22567.

    PMID: 35285577
  10. 10

    Molecular Alterations and Comprehensive Clinical Management of Oncocytic Thyroid Carcinoma: A Review and Multidisciplinary 2023 Update.

    Bischoff LA, Ganly I, Fugazzola L, et al.

    JAMA otolaryngology-- head & neck surgery 2024; (150(3)):265-272 doi:10.1001/jamaoto.2023.4323.

    PMID: 38206595
  11. 11

    Effect of adjuvant radioactive iodine therapy on survival in rare oxyphilic subtype of thyroid cancer (Hürthle cell carcinoma).

    Yang Q, Zhao Z, Zhong G, et al.

    PeerJ 2019; (7()):e7458 doi:10.7717/peerj.7458.

    PMID: 31523497
  12. 12

    Mutational profiling of poorly differentiated and anaplastic thyroid carcinoma by the use of targeted next-generation sequencing.

    Duan H, Li Y, Hu P, et al.

    Histopathology 2019; (75(6)):890-899 doi:10.1111/his.13942.

    PMID: 31230400
  13. 13

    Aggressive Thyroid Carcinomas Clinical and Molecular Features: A Systematic Review.

    Schipor S, Publik MA, Manda D, Ceausu M

    International journal of molecular sciences 2025; (26(12)) doi:10.3390/ijms26125535.

    PMID: 40564998
  14. 14

    No Longer Well-Differentiated: Diagnostic Criteria and Clinical Importance of Poorly Differentiated/High-Grade Thyroid Carcinoma.

    Cracolici V

    Surgical pathology clinics 2023; (16(1)):45-56 doi:10.1016/j.path.2022.09.006.

    PMID: 36739166
  15. 15

    Comparative analysis of follicular cell- derived thyroid carcinoma: assessing the impact of high-grade features in an advanced disease cohort.

    Caldeira M, Canberk S, Macedo S, et al.

    Virchows Archiv : an international journal of pathology 2025; (486(6)):1305-1315 doi:10.1007/s00428-025-04109-2.

    PMID: 40312532
  16. 16

    Papillary thyroid carcinoma tall cell subtype (PTC-TC) and high-grade differentiated thyroid carcinoma tall cell phenotype (HGDTC-TC) have different clinical behaviour: a retrospective study of 1456 patients.

    Ghossein R, Katabi N, Dogan S, et al.

    Histopathology 2024; (84(7)):1130-1138 doi:10.1111/his.15157.

    PMID: 38528726
  17. 17

    A Comprehensive Review and Insights into the New Entity of Differentiated High-Grade Thyroid Carcinoma.

    Harahap AS, Roren RS, Imtiyaz S

    Current oncology (Toronto, Ont.) 2024; (31(6)):3311-3328 doi:10.3390/curroncol31060252.

    PMID: 38920735
  18. 18

    Promising Therapeutic Targets for Recurrent/Metastatic Anaplastic Thyroid Cancer.

    Abdalla AS, Rahman M, Khan SA

    Current treatment options in oncology 2024; (25(7)):869-884 doi:10.1007/s11864-024-01219-y.

    PMID: 38862695
  19. 19

    Aberrant DNA repair as a potential contributor for the clonal evolution in subsets of anaplastic thyroid carcinomas arising through dedifferentiation: implications for future therapeutic algorithms?

    Juhlin CC

    Cancer drug resistance (Alhambra, Calif.) 2020; (3(4)):992-1000 doi:10.20517/cdr.2020.66.

    PMID: 35582231
  20. 20

    Mouse Model of Thyroid Cancer Progression and Dedifferentiation Driven by STRN-ALK Expression and Loss of p53: Evidence for the Existence of Two Types of Poorly Differentiated Carcinoma.

    Nikitski AV, Rominski SL, Condello V, et al.

    Thyroid : official journal of the American Thyroid Association 2019; (29(10)):1425-1437 doi:10.1089/thy.2019.0284.

    PMID: 31298630
  21. 21

    The Role of Tracheostomy in Anaplastic Thyroid Carcinoma.

    Xu J, Liao Z, Li JJ, et al.

    World journal of oncology 2015; (6(1)):262-264 doi:10.14740/wjon899w.

    PMID: 29147413
  22. 22

    Initial Management of BRAF V600E-Variant Anaplastic Thyroid Cancer: The FAST Multidisciplinary Group Consensus Statement.

    Hamidi S, Dadu R, Zafereo ME, et al.

    JAMA oncology 2024; (10(9)):1264-1271 doi:10.1001/jamaoncol.2024.2133.

    PMID: 38990526
  23. 23

    Characterizing thyroid carcinomas in the elderly: Histological subtypes and TERT promoter mutation analysis based on the latest WHO classification.

    Koh MJ, Noh S, Kim JK, Kim GJ

    Annals of diagnostic pathology 2026; (80()):152578 doi:10.1016/j.anndiagpath.2025.152578.

    PMID: 41135466
  24. 24

    Consensus Statement: Recommendations on Actionable Biomarker Testing for Thyroid Cancer Management.

    Mete O, Boucher A, Schrader KA, et al.

    Endocrine pathology 2024; (35(4)):293-308 doi:10.1007/s12022-024-09836-x.

    PMID: 39579327
  25. 25

    Anaplastic Thyroid Carcinoma: An Update.

    Jannin A, Escande A, Al Ghuzlan A, et al.

    Cancers 2022; (14(4)) doi:10.3390/cancers14041061.

    PMID: 35205809

This page provides educational information about rare thyroid carcinomas and their biology. It is not medical advice; always consult your oncologist and endocrinologist for a diagnosis and treatment plan tailored to your specific tumor.

Get notified when new evidence is published on Rare thyroid carcinoma.

We monitor PubMed for new peer-reviewed studies on this topic and email a short summary when something meaningful changes.