Conditions: Thyroid Cancer

Thyroid nodule versus thyroid cancer

A thyroid nodule is a general term for a growth or lump that forms within the thyroid gland. As about 5% of all nodules are cancerous, almost all thyroid nodules prove not to be cancerous after evaluation.

Thyroid cancers

The word cancer means a growth that has potential to spread to other parts of the body, and is therefore more dangerous than a benign tumor that does not spread like that. Thyroid cancers come in four general categories:

I. Follicular Cell–Derived Thyroid Cancers (~95–98% of all thyroid cancers)

These arise from thyroid follicular epithelial cells (thyrocytes) and are subdivided by differentiation status: [2-4]

A. Well-Differentiated Thyroid Carcinoma (DTC) (~90% of all thyroid cancers)

• Papillary thyroid carcinoma (PTC) — the most common subtype (~84%), typically indolent with excellent long-term survival (5-year survival ~96%). Driven predominantly by BRAF V600E mutations (~60%) and RAS mutations (~13%), with RET and NTRK gene fusions in a subset. Metastasizes primarily to cervical lymph nodes. Recognized variants include classical, follicular variant, tall-cell variant, columnar cell variant, and papillary microcarcinoma. [1-3]

• Follicular thyroid carcinoma (FTC) (~4%) — encapsulated follicular-patterned tumors classified as minimally invasive, encapsulated angioinvasive, or widely invasive. Driven by RAS mutations (30–50%), PAX8::PPARγ fusions, and DICER1 mutations. Tends to metastasize hematogenously to lungs and bones. Generally responsive to radioactive iodine. [1-3]

• Invasive encapsulated follicular variant of PTC (IEFVPTC) — behaves similarly to FTC with a tendency for vascular invasion and distant metastasis; driven by RAS mutations. [1-2]

• Oncocytic thyroid carcinoma (OTC) (~2–3%, formerly Hürthle cell carcinoma) — now recognized as a distinct entity rather than an FTC subtype. Characterized by near-haploid genome, mitochondrial DNA mutations, and widespread chromosomal losses. Often not radioiodine-avid despite retaining other differentiated features. Metastasizes to both lymph nodes and distant sites. [1][3]

B. High-Grade Follicular Cell–Derived, Non-Anaplastic Carcinoma

This is a newer WHO category with behavior intermediate between DTC and anaplastic thyroid carcinoma: [1][4]

• High-grade differentiated thyroid carcinoma (DHGTC) — retains DTC morphology but shows high-grade features (mitotic count ≥5 per 2 mm² or tumor necrosis). Harbors BRAF V600E (30–80%), TERT promoter (40%), and NRAS (30%) mutations. [1-2]

• Poorly differentiated thyroid carcinoma (PDTC) — shows solid/insular growth pattern with necrosis or elevated mitotic activity. Driven by RAS (45%), TERT (44%), and TP53 (15%) mutations. [1-2]

C. Undifferentiated (Anaplastic) Thyroid Carcinoma (ATC)

One of the most aggressive human cancers, arising from dedifferentiation of pre-existing DTC through accumulation of additional mutations (TP53 in 40–80%, TERT in 30–75%, BRAF V600E in 10–50%). Not responsive to radioactive iodine. All cases are staged as at least stage IVA at diagnosis. [2-3][5]

II. Parafollicular C Cell–Derived Cancer

• Medullary thyroid carcinoma (MTC) (~4%) — arises from neural crest–derived parafollicular C cells that produce calcitonin. Approximately 25% are hereditary, most commonly associated with multiple endocrine neoplasia type 2 (MEN2) due to germline RET mutations. Sporadic cases also frequently harbor somatic RET mutations or RAS mutations. [2-3][6]

III. Other Rare Thyroid Neoplasms

• Primary thyroid lymphoma — typically diffuse large B-cell or MALT lymphoma, often arising in the setting of Hashimoto thyroiditis. [7-8]

• Primary mesenchymal tumors — extremely rare, including sarcomas. [7]

• Thyroid metastases — secondary deposits from renal cell carcinoma, lung, breast, or melanoma. [8]

IV. Borderline/Pre-Malignant Lesion

• Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) — reclassified from the former noninvasive encapsulated follicular variant of PTC. Considered a neoplasm of very low malignant potential rather than a carcinoma, sparing patients from the treatment intensity of a cancer diagnosis. [1][3]

The molecular characterization of thyroid cancers has become integral to classification, prognosis, and treatment selection, particularly for advanced disease where targeted therapies (e.g., BRAF/MEK inhibitors, selective RET inhibitors, NTRK inhibitors, and multikinase inhibitors) are guided by the tumor's mutational profile. [3]

Papillary thyroid carcinoma

Papillary thyroid carcinoma is the most common type of thyroid cancer, accounting for about 80% of all cases. It typically affects women more than men and occurs most frequently in individuals between the ages of 30 and 50. This cancer is characteristically slow-growing and is often identified as a painless lump in the neck or noticed incidentally on medical imaging performed for some other reason. While papillary thyroid carcinoma has the tendency to spread to nearby lymph nodes, it is generally associated with a favorable prognosis. Initial treatment consists of surgery in almost all cases, excluding individuals who are too ill to undergo surgery. The extent of surgery (removal of part or all of the thyroid gland, and possibly removing lymph nodes as well) depends on a given individual’s risk status. After surgery radioactive iodine therapy, and hormone replacement therapy may be undertaken. Regular monitoring and follow-up care are important for managing the condition effectively and achieving the good outcome most can expect..

Follicular thyroid carcinoma

Follicular thyroid carcinoma is a less common type of cancer that originates in the follicular cells of the thyroid gland. This type of thyroid cancer also typically presents as a painless lump or nodule in the neck or is noted incidentally upon medical imaging performed for some other reason. While follicular thyroid carcinoma is often slow-growing, it does have the potential to spread to other parts of the body, including lymph nodes and distant organs such as the lungs. For most, the prognosis is favorable, as it typically responds well to treatment. Surgical removal of the affected thyroid gland, often accompanied by radioactive iodine therapy, is the primary treatment approach. Treatment with radioactive iodine may be used after the entire thyroid gland has been removed when additional treatment is needed. Regular monitoring and follow-up care are crucial to allow early detection of potential recurrence.

Medullary thyroid carcinoma

Medullary thyroid carcinoma (MTC) is a fairly rare form of thyroid cancer that originates in the parafollicular, or C cells, of the thyroid gland. MTC tends to be more aggressive than other forms of thyroid cancer and has a higher risk of spreading to nearby lymph nodes and distant organs. It usually presents with symptoms such as an enlarged thyroid, neck pain, hoarseness, and/or difficulty swallowing. Unlike papillary and follicular types of thyroid cancer, MTC does not respond to radioactive iodine and for this reason surgical removal of the thyroid gland is the primary treatment approach, often combined with lymph node dissection. Immunotherapy has shown effectiveness when used after surgery. Additionally, targeted therapies may be utilized, especially for advanced or metastatic cases.

Inheriting a mutation of a specific gene (RET) is the cause for this cancer in 25% of cases, but non-inherited (spontaneous) mutations of the gene account for some cases of MTC as well. Testing for inheritance of this gene is important to identify family members who may also be at risk. Also, the specific type of mutation within this gene indicates the expected aggressiveness of a given MTC and this can be used to inform treatment decisions.

MTC is also sometimes only one part of specific syndromes of tumors of the glands. Called Multiple Endocrine Neoplasia type 2a and type 2b, these genetic syndromes predispose affected individuals to other glandular tumors such as pheochromocytoma, a tumor of the adrenal gland that can cause dangerously high blood pressure or parathyroid gland tumors that would cause the surgeon to include parathyroid surgery with thyroid surgery. Multiple Endocrine Neoplasia is usually inherited, but can occasionally occur as a spontaneous genetic mutation.

Monitoring for recurrence of medullary thyroid carcinoma is assisted by physical exam, monitoring the blood levels of calcitonin and carcinoembryonic antigen as well as imaging studies.

Anaplastic thyroid carcinoma

Anaplastic thyroid carcinoma (ATC) is an extremely rare and aggressive form of thyroid cancer. It arises from the follicular cells of the thyroid gland and is characterized by rapid growth and poor prognosis. ATC accounts for less than 2% of all thyroid cancers, but it is responsible for the majority of thyroid cancer-related deaths. This formidable disease often presents with symptoms such as a rapidly enlarging neck mass, hoarseness, difficulty breathing, and swallowing. Due to its rapid progression and tendency to spread to nearby structures and distant organs, surgical intervention, radiation therapy, and systemic treatment are often required. Unfortunately, ATC is known to be resistant to standard thyroid cancer therapies, making it challenging to treat. The current research on ATC primarily focuses on identifying novel targeted therapies and immunotherapies that can potentially improve the prognosis and overall survival of patients facing this aggressive cancer.

Cancers that spread to the thyroid gland

Rarely, a cancer that originated in a different organ can spread to the thyroid gland. Determination of this scenario usually depends on obtaining a biopsy of the tumor in the thyroid and microscopic identification of the type of tumor. Kidney (renal) cancer, colorectal cancer, lung cancer and breast cancer are the more common types of cancer that spread to the thyroid gland from their site of origin.

Monitoring for recurrence after thyroidectomy

Monitoring for recurrence of thyroid cancer after thyroidectomy is a crucial aspect of postoperative care. After the surgery, regular follow-up appointments are scheduled to evaluate the patient's condition and monitor for any signs of recurrent disease. These appointments typically involve blood tests, though the specific tests performed depend on the type of cancer. Additionally, imaging tests, such as ultrasound, may be performed to assess the thyroid bed and neck lymph nodes. Radioactive iodine uptake scanning may be used for papillary and follicular thyroid carcinomas. In cases where radioactive iodine uptake scanning has become unhelpful because a thyroid cancer stops incorporating iodine into its cells, PET-CT scanning becomes more useful. By closely monitoring for recurrence, healthcare professionals can promptly intervene and provide appropriate treatment if needed, offering patients the best chance for long-term remission and improved quality of life.

References:

1. 2025 American Thyroid Association Management Guidelines for Adult Patients With Differentiated Thyroid Cancer.

Thyroid : Official Journal of the American Thyroid Association. 2025. Ringel MD, Sosa JA, Baloch Z, et al.RecentGuideline

2. Management of Differentiated Thyroid Cancer.

The New England Journal of Medicine. 2026. Hegedüs L, Wirth LJ, Tuttle RM.RecentReview

3. Thyroid Cancer: A Review.

The Journal of the American Medical Association. 2024. Boucai L, Zafereo M, Cabanillas ME.Review

4. Diagnosis and Management of Tropomyosin Receptor Kinase Fusion-Positive Thyroid Carcinomas: A Review.

JAMA Oncology. 2023. Haddad R, Elisei R, Hoff AO, et al.Review

5. Thyroid Carcinoma.

National Comprehensive Cancer Network. Updated 2026-06-02.Guideline

6. Biologic and Clinical Perspectives on Thyroid Cancer.

The New England Journal of Medicine. 2016. Fagin JA, Wells SA.Review

7. Comprehensive Guidance on the Diagnosis and Management of Primary Mesenchymal Tumours of the Thyroid Gland.

The Lancet. Oncology. 2020. Gubbi S, Thakur S, Avadhanula S, et al.Review

8. Thyroid Cancer: Epidemiology, Diagnosis, and Treatment.

Deutsches Arzteblatt International. 2026. Holzer K, Koehler VF, Bojunga J, et al.RecentReview