Thyroid Cancer: Epidemiology, Diagnosis, and Treatment

Background: Thyroid cancer, including carcinoma, metastases, sarcoma, and lymphoma of the thyroid gland, is much rarer (incidence of thyroid carcinoma, ca. 7 per 100 000 people per year in Germany) than benign nodular thyroid disease (prevalence: ca. 10% in young men to 80% in older women). The incidence of differentiated thyroid carcinoma has risen around the world in recent years.

Methods: This narrative review is based on publications retrieved by a search of PubMed.

Results: In Germany in 2022, approximately 4200 women and 1800 men received a diagnosis of thyroid carcinoma. The relative 10-year survival rate for this disease was 94% in women and 86% in men. Differentiated thyroid carcinoma (DTC), mainly of the papillary subtype (PTC), was the most common type of thyroid carcinoma in Germany (76% in women, 66% in men). Combined surgery and radioiodine therapy are still the most common treatment for DTC, although initially available prospective studies currently cast doubt on the benefit of radioiodine therapy in certain risk groups. The option of active surveillance has been introduced for selected patients with a small PTC. The treatment of radioiodine–refractory, poorly differentiated, and anaplastic thyroid carcinoma has improved with the introduction of targeted molecular therapies and immunotherapeutic drugs.

Conclusion: The treatment of thyroid carcinoma has become more individualized, with less aggressive approaches for small tumors and an expansion of systemic options for advanced cases.

Cite this as: Holzer K, Koehler VF, Bojunga J, Luster M, Bartsch DK, Eilsberger F: Thyroid cancer: epidemiology, diagnosis, and treatment.
Dtsch Arztebl Int 2026; 123: 423–30. DOI: 10.3238/arztebl.m2026.0050

Benign thyroid nodules are very common in routine clinical practice. Their prevalence, depending on multiple factors, ranges from 10% in young men to over 80% in elderly women (e1, e2). Thyroid cancer is much rarer: the incidence of thyroid carcinoma was only 7 per 100,000 people in Germany in 2022 (1). Newly identified, suspicious thyroid nodules and any thyroid findings that change noticeably in their clinical features or on ultrasonography must be evaluated for potential malignancy. The most important information can generally be obtained by history-taking and physical examination, cervical ultrasonography, and fine needle aspiration (FNA) biopsy. Diagnostic operations, such as a hemithyroidectomy to determine whether a thyroid nodule is malignant, are only rarely indicated today but are still too commonly performed (2, e3). Aggressive thyroid cancers require rapid diagnosis and are considered an endocrinological emergency, as any delay carries the risk of missing the window of opportunity for curative treatment, which is usually short. In such cases, a core needle biopsy (CNB) is often needed to obtain an adequately sized specimen for histological and timely molecular pathological examination.

Learning objectives

This article should enable readers to

• name the common types of cancer affecting the thyroid and describe their clinical features,
• be aware of the urgency of targeted diagnostic evaluation and appropriate treatment of rapidly growing thyroid nodules, and
• know the basic treatment options and their indications.

Methods

As the topic is complex, selective literature searches were performed on specific subjects, rather than a single, comprehensive search on thyroid cancer. Each PubMed search involved a term for the subject (e.g., “neoadjuvant therapy”) along with the terms “thyroid” and “cancer.” Current national and international guidelines were reviewed as well. Because of limited space, this article is restricted to the more common types of cancer, diagnostic methods, and treatments.

Epidemiology

In 2022, the incidence of thyroid cancer (TC) was 8.9 per 100,000 women and 3.6 per 100,000 men; the median age on diagnosis was 51 and 55 years, respectively. 80–90 % of thyroid carcinomas are differentiated thyroid carcinomas (DTC); more specifically, 66–76% are papillary thyroid carcinoma (PTC) and 10–13% are follicular thyroid carcinoma (FTC). Medullary (MTC) and anaplastic carcinomas (ATC) account for 5–7% and 2–4% of cases (1). The incidence of DTC is rising worldwide, while mortality remains stable. The prognosis depends, among other factors, on sex: the 5-year survival rate is 94% in women and 88% in men.

The increased overall incidence of TC is largely accounted for by PTC and may be due in part to better detection with the increased use of cervical ultrasound (3). The incidence of all other types of thyroid cancer remains stable in Germany. Thyroid metastases from solid tumors, such as renal cell carcinoma, are very rare, as are primary lym-phoma and sarcoma of the thyroid (4, e4).

Etiology

Ionizing radiation in childhood and adolescence is a risk factor (e5). Obesity is also known to be associated with a higher incidence of TC (5). Elevated insulin resistance activates insulin-like growth factor (IGF), leading to changes in cellular proliferation and apoptosis. Given the higher prevalence of thyroid cancer in women, estrogen may also be a risk factor. Meta-analyses have not shown any correlation between the incidence of TC and smoking or alcohol use (6, 7). The risk of TC is higher in persons with hereditary tumor predisposition syndromes (including familial adenomatous polyposis) and familial non-medullary thyroid carcinoma (FNMTC).

One-quarter of MTC cases are hereditary, arising in association with activating, pathogenic germline variants in the Rearranged-during-transfection (RET) proto-oncogene (8). Familial medullary thyroid carcinoma without other manifestations and multiple endocrine neoplasia (MEN) type II A or type II B.

Chronic lymphocytic thyroiditis is considered a risk factor for thyroid lymphoma.

Classification and metastasis patterns of thyroid cancer

Malignant tumors of the thyroid gland can be of epithelial or non-epithelial origin. Epithelial tumors arise either from follicular cells (DTC, poorly differentiated thyroid carcinoma [PDTC], ATC) or from parafollicular C cells (MTC), Non-epithelial tumors (sarcoma, lymphoma) are much rarer.

PTC typically metastasizes to the cervical lymph nodes. FTC and oncocytic TC (OTC) are classified as minimally invasive (MIFTC), angioinvasive, or widely invasive. In FTC, distant metastases are more common than lymph node metastases. Poorly differentiated thyroid carcinoma (PDTC) is less differentiated than DTC, but more so than ATC, which is characterized by partial or complete dedifferentiation (9)

Diagnostic evaluation

A rapidly growing thyroid nodule that is hard on palpation, whether it causes hoarseness or not, is an urgent clinical warning sign. Hoarseness may be a sign of infiltration of the recurrent laryngeal nerve, whose course runs adjacent to the thyroid. Tenderness to palpation in the thyroid region should arouse suspicion of a tumor but may be due to benign thyroiditis. Cervical lymphadenopathy, Horner’s sign (due to tumor infiltration of the cervical sympathetic pathway), or stridor of new onset can also be presenting signs of thyroid cancer. A diagnostic algorithm is outlined in Figure 1. In Germany, half of all cases of DTC cases are detected incidentally, often during imaging studies for indications unrelated to cancer. MTC also often remains clinically asymptomatic for a long time. Some patients with markedly elevated serum calcitonin levels present with persistent diarrhea (e6).

Figure 1

Proposed diagnostic algorithm CT, computed tomography; MRI, magnetic resonance imaging; MTC, medullary thyroid carcinoma; PET, positron emission tomography; TIRADS, Thyroid Imaging Reporting Data System

Laboratory tests

Thyroid function is tested by measuring the serum concentration of thyroid-stimulating hormone (TSH). Free thyroxine (fT4) and free triiodothyronine (fT3) are additionally measured if the TSH level is abnormal. Parathyroid function (serum calcium and parathyroid hormone levels) should also be assessed before any planned thyroid surgery. There is no recommendation for the routine preoperative measurement of thyroglobulin (TG), as elevated levels can be detected in other thyroid disorders and in healthy individuals (10). Calcitonin testing is indicated in case of a suspicious nodule and before planned thyroid surgery (11, e7). For mildly elevated calcitonin levels (20–30 pg/mL in women and 30–60 pg/mL in men), follow-up measurements at intervals of 3–6 months are recommended. Baseline calcitonin levels above 30 pg/mL in women and above 60 pg/mL in men suggest the presence of MTC; levels above 100 pg/mL are highly suggestive in either sex (11, 12). High calcitonin levels are not 100% specific for C-cell carcinoma. Elevated calcitonin levels may also be caused by autoimmune thyroid disorders, alcohol consumption, smoking, the use of proton pump inhibitors, end-stage renal failure requiring dialysis, or atrophic gastritis (e7).

Ultrasonography

B-scan ultrasonography, supplemented by elastography where available, is the most precise and least costly technique for the diagnostic assessment of thyroid nodules (13, 14). Elastography yields a measure of nodule harness.

An ultrasound-based Thyroid Imaging Reporting and Data System (TIRADS), such as ACR-TIRADS, EU-TIRADS, or KWAK-TIRADS, is recommended for the risk stratification of thyroid nodules. Focal lesions detected by ultrasonography are classified by defined criteria including their composition (cystic, solid, spongiform—see eFigure 1), echogenicity (anechoic, hypoechoic), shape (wider than tall, taller than wide), margins (smooth, lobulated, infiltrative), and echogenic foci (macrocalcifications, punctate echogenic foci) to assess the likelihood of malignancy (eFigure 2) (15). Spongiform (eFigure 1) or cystic thyroid nodules are almost always benign, as are elastographically soft nodules in 97–99 % of cases (16, 17). The cervical lymph nodes can also be evaluated with ultrasonography.

eFigure 1

Ultrasonography of the left thyroid lobe in transverse section, showing a ventrally lying spongiform thyroid nodule

eFigure 2

TIRADS of the American College of Radiology (ACR) (15) FNA, fine needle aspiration biopsy; TIRADS, Thyroid Imaging Reporting Data System

[99mTc]Tc-pertechnetate thyroid scintigraphy

Thyroid scintigraphy with ¹²³iodine [¹²³I] or ^99mtechnetium [99mTc]Tc-pertechnetate is the simplest method for visualizing sodium-iodide symporter (NIS) expression in vivo. Compared to normal thyroid tissue, thyroid carcinoma displays reduced NIS expression and appears as a hypofunctional lesion. For focal lesions that are not purely cystic and are 1 cm or larger in size, scintigraphy should be performed regardless of the TSH level to rule out functional autonomy and to identify hypofunctional lesions for risk stratification (e8, 11).

CT and MRI

In cases with a high level of suspicion, especially those in which ultrasonography shows disease extension beyond the thyroid capsule or infiltrating into the surrounding tissues, preoperative imaging can be supplemented with computed tomography (CT) scan. Iodinated contrast medium should be avoided, as the large amount of stable iodine with it can delay adjuvant radioiodine therapy (RAIT). Magnetic resonance imaging (MRI) is less sensitive than ultrasonography, particularly for the assessment of growth beyond the thyroid capsule (e9). In cases of MTC with calcitonin levels above 500 pg/mL and/or suspected metastases, a CT or MRI should be performed (11).

Functional imaging

An [¹⁸F]fluorodeoxyglucose (FDG) positron emission tomography (PET) scan combined with CT (PET/CT) should be obtained for all patients with aggressive histological types of thyroid cancer (ATC, advanced PDTC), as it can reveal distant metastases with high sensitivity and specificity.

An [¹⁸F]FDOPA-PET/CT study is indicated for patients with MTC and persistently high calcitonin levels (> 150 pg/mL) after surgery, of if distant metastases are suspected in their further course.

Fine needle aspiration biopsy

An FNA biopsy of suspicious thyroid nodules of diameter 1 cm or more should be performed after scintigraphic exclusion of autonomy and risk stratification with TIRADS. The Bethesda System is the best-established cytological classification (18). As 10–20% of FNAs yield inconclusive results, molecular pathological tests have been introduced to improve diagnosis; these tests detect typical molecular genetic alterations in thyroid carcinomas, such as the B-Raf proto-oncogene (BRAF) (e10).

If MTC is suspected (ultrasonographically suspicious thyroid nodule and high baseline calcitonin), FNA should not be performed. Puncturing an MTC leads to an iatrogenic desmoplastic stromal reaction (fibrous connective tissue proliferation) within the thyroid nodule. According to recent studies, MTCs are much more likely to spread to the lymph nodes if they are desmoplastic, while desmoplasia-free MTCs are thought not to do so at all (11, e11).

Molecular pathological testing

The introduction of molecularly targeted treatments and immunotherapeutic approaches has ushered in a new era in the treatment of aggressive forms of thyroid cancer (radioiodine-refractory DTC, PDTC, ATC). Molecular pathological testing (including BRAF, RET, and NTRK) is strongly recommended.

Treatment

A treatment algorithm for PTC, the most common type of thyroid carcinoma in Germany, is found in Figure 2. In view of the complexity of the treatment scenarios, the reader is referred to the S3 guideline (11) for all other entities. Only a small number of prospective clinical trials of treatment for thyroid carcinoma have been conducted to date (Table).

Figure 2

Threatment algorithm for papillary thyroid carcinoma *1 Risk factors: aggressive cytology, multifocality, familial predisposition, or prior radiation exposure *2 Risk factors: vascular invasion, lymph node metastases, capsular infiltration, familial predisposition, or prior radiation exposure *3 If the postoperative outcome is excellent, no RAIT; *4 With prophylactic compartment resection PTC, papillary thyroid carcinoma; RAIT, adjuvant radioiodine therapy

Active surveillance for papillary thyroid carcinoma

For selected patients with small PTCs (≤ 1 cm), an active surveillance strategy can be used if the patient wishes and has no other risk factors (e.g., proximity to the trachea, esophagus, or recurrent laryngeal nerve). Miyauchi et al. showed that the likelihood of disease progression is inversely related to age, from 60 % for patients aged 20–29 to only 3.5% for those over 70 (19). The 10– and 20-year rates of new lymph node metastasis were at most 1.6 %. None of the patients managed with active surveillance developed distant metastases or died of the disease.

Surgical treatment

The central role of surgery in the treatment of thyroid cancer is undisputed. Often, only an R0 resection—involving the removal of the primary tumor and all lymph node metastases—provides a chance of cure. The extent of resection depends on the type of thyroid cancer and the extent of local spread. Thyroid cancers should be operated on by surgeons with experience in thyroid surgery. Transient (1.8%–5 %) and permanent (0.3%–1 %) paralysis of the recurrent laryngeal nerve, as well as transient (10%–22 %) or permanent (1%–5 %) hypoparathyroidism, are potential complications of thyroid surgery (e12, e13, e14, e15). Many studies have shown that both surgical success and the rate of complications depend to a large degree on hospital and surgeon caseload.

Papillary thyroid carcinoma

PTCs measuring up to 1 cm in diameter are found in up to 30 % of autopsies. If detected during the patient’s lifetime, these small carcinomas are usually of low clinical significance, and a unilateral hemithyroidectomy generally suffices (see active surveillance strategy). Aggressive (e.g., “tall-cell”) histological variants call for the completion of surgical treatment with a thyroidectomy. Until recently, the standard surgical treatment for PTC larger than 1 cm was thyroidectomy, with or without central lymphadenectomy. Current data show, however, that hemithyroidectomy can also be curative for these larger PTCs (Table). Patients with risk factors—aggressive tumor variants, lymph node metastases, familial predisposition, capsular infiltration, multifocality, angioinvasion, or prior radiation exposure—are not suitable candidates for less than total thyroidectomy. The patient must be informed that hemithyroidectomy precludes RAIT.

Table

Treatments for thyroid cancer

Follicular and oncocytic thyroid carcinoma

Hemithyroidectomy without central cervical lymphadenectomy suffices for MIFTC less than 4 cm in size, more aggressive subtypes (angioinvasive and broadly invasive) and OTC should be treated with total thyroidectomy; RAIT is indicated for these cases as well. It is not uncommon for bone metastases from a previously undiagnosed FTC to come to medical attention with a pathological fracture. In such cases as well, thyroidectomy should be performed. The bone metastases, which are usually multiple, can then be treated with RAIT (11).

Medullary thyroid carcinoma

MTC is an often multifocal neuroendocrine tumor that metastasizes early via lymphatic spread and lacks physiological expression of NIS (originating in C-cells), making postoperative RAIT impossible. The treatment of choice is thyroidectomy, usually with central lymph node dissection. If lateral cervical lymph node involvement is evident on physical examination and ultrasonography, ipsi- or bilateral lateral lymph node dissection should be performed. Central lymph node dissection may be omitted if no desmoplasia is seen on frozen section analysis (20).

Poorly differentiated thyroid carcinoma

If a PDTC is resectable, without invasion of adjacent organs (the esophagus, trachea, or larynx) a thyroidectomy should be performed, including the removal of all of the involved lymph nodes (11).

Anaplastic thyroid carcinoma

If an ATC is resectable, the extent of resection depends on the local spread of the tumor. If the tumor is confined to a single thyroid lobe, hemithyroidectomy may suffice as oncological treatment. Clinically or radiologically suspicious cervical lymph nodes should be resected as well. Now that targeted molecular therapies (e.g., dabrafenib/trametinib, lenvatinib, pembrolizumab) have been successfully developed, these can be used as neoadjuvant therapy before the surgical resection of locally advanced disease (21, 22).

Thyroid metastases, thyroid lymphoma, and thyroid sarcoma

The surgical management of thyroid metastases should be determined by the tumor board in light of the underlying disease. Lesions confined to one side of the thyroid are treated with a hemithyroidectomy; lesions that have spread beyond the thyroid may require an extended resection. Primary lymphoma is usually treated with radiotherapy and chemotherapy; surgery can be used to relieve symptomatic local compression. For resectable thyroid sarcomas, the principles of sarcoma surgery apply.

Radioiodine therapy for differentiated and poorly differentiated thyroid carcinoma

RAIT uses ¹³¹iodine [¹³¹I] for the selective internal irradiation of thyroid (tumor) tissue that takes up iodine. It is used as an adjuvant therapy for DTC and PDTC. Some patients with PDTC, however, do not take up radioiodine because of low or absent NIS expression. The goals of RAIT may include adjuvant treatment of any remaining tumor residue and unknown (lymph node) metastases, ablative destruction of residual thyroid tissue, or treatment of known metastases. The use of RAIT is tailored to the risk of recurrence. Systematic reviews show that patients with a DTC of size greater than 1 cm are more likely to benefit from RAIT in terms of recurrence-free survival (23). Recent prospective, randomized, multicenter trials have shown the non-inferiority of postoperative follow-up alone compared to ablative RAIT in low-risk patients (ESTIMABL2, IoN) (24, 25). These trials have been criticized for, among other things, the short follow-up period (< 10 years), the low dose of radioiodine used, and the patient population in the ESTIMABL2 study that underwent extensive surgery.

Redifferentiating treatments

Selective inhibitors that specifically target BRAF (e.g., dabrafenib, vemurafenib) or mitogen-activated protein kinase (MEK, e.g., trametinib) not only have an antiproliferative effect, but also influence NIS expression. In some cases, this can induce renewed radioiodine uptake in previously iodine-negative DTC/PDTC, thereby enabling the use of repeat RAIT with the goal of stabilizing the disease (26, 27).

Systemic therapies

Systemic therapy of DTC with approved kinase inhibitors or those available in clinical trials is indicated for patients with rapidly progressive, metastatic, symptomatic, and/or locally threatening TC, provided that RAIT is no longer an option (5–10% of DTC cases become radioiodine-refractory), local treatments have been exhausted, and a watch-and-wait strategy is no longer justifiable. An overview of the relevant evidence is provided in the Table.

Differentiated thyroid carcinoma

For more than ten years now, the multi-tyrosine kinase inhibitors (TKIs) sorafenib and lenvatinib have been available for the treatment of radioiodine-refractory DTC, and their effectiveness has also been confirmed by real-world clinical data (28, 29, 30). Cabozantinib has been approved since 2022 for cases with disease progression during first-line therapy (31). Selective inhibitors, such as selpercatinib, are now in use as well (32, 33).

Medullary thyroid carcinoma

Systemic therapy should be considered for patients with advanced MTC who have progressive disease with a high tumor burden and/or pronounced symptoms, such as severe diarrhea. Currently, cabozantinib is the only drug approved for MTC with or without a RET mutation (34). Vandetanib is approved only for the treatment of tumors with a confirmed RET mutation (35). Since 2021, selpercatinib has been available for first-line therapy in RET-mutated MTC; it has been shown to be superior to vandetanib and cabozantinib and is well tolerated (36).

Anaplastic thyroid carcinoma

In the past, despite limited evidence, chemoradiotherapy (carboplatin, paclitaxel) was the standard of care both as adjuvant therapy and for the nonsurgical treatment of locally advanced or metastatic disease (37). Given the poor prognosis of these patients, there is an urgent need for new therapies. In view of the high mutation burden and activation of various signaling pathways in ATC, molecularly targeted neoadjuvant and adjuvant treatments for ATC are under evaluation. In the United States, the combination of dabrafenib and trametinib was approved in 2018 for BRAF-mutated ATC (38). A recent analysis of 36 patients, mostly in stage IVC, showed a 56% response rate and a median overall survival (OS) of 14.5 months (39). Most recently, neoadjuvant treatment with dabrafenib/trametinib has also been pursued in BRAFV600-mutated ATC. In initial case series, this enabled complete surgical resection of the tumor in many cases, with an overall one-year survival rate of up to 83% (21, 22).

Immunotherapy for anaplastic thyroid carcinoma

The high mutation burden and Programmed Cell Death-1 (PD-1)/PD-L1 expression seen in ATC opens the door to promising immunotherapeutic approaches. Of particular note are various combination therapies, such as those involving tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors, which are currently in use in clinical trials and in individual treatment trials (22, e16, e20, e21). In six patients with ATC, combination therapy with lenvatinib and pembrolizumab led to complete remission (CR) in three cases, as well as disease stabilization, with a median progression-free survival (PFS) of 16.5 months and an overall survival (OS) of 18.5 months (40).

Follow-up treatment

In addition to monitoring tumor markers—thyroglobulin (TG) for DTC/PDTC, calcitonin and carcinoembryonic antigen (CEA) for MTC—systematic ultrasonographic imaging of the thyroid bed and cervical lymph nodes should be performed during follow-up. If TG antibodies are present, TG measurement may not be diagnostically useful; moreover, some tumors stop producing TG as they become increasingly undifferentiated. Follow-up is personalized, based on the dynamic risk profile (initial risk and response to therapy) and the biological behavior of the tumor (well-differentiated thyroid carcinoma typically grows slowly). Follow-up appointments should be every six months for the first five years and annually thereafter, if the course is uneventful. The recurrence rate for DTC depends on the initial response to treatment after surgery and RAIT (if any), and ranges from 1% to 20%, depending on whether the response to treatment is excellent, indeterminate, or biochemically incomplete (14). Undetectable calcitonin three months after a thyroidectomy indicates a good prognosis for MTC; rising CEA levels may indicate dedifferentiation. All patients receive thyroid hormone replacement therapy after thyroidectomy, typically with levothyroxine. TSH levels in patients with DTC/PDTC are managed on the basis of the pathophysiological relationship (a high TSH level stimulates tumor cells). For patients with a low risk of recurrence and an excellent treatment response, the target TSH level is up to 2 mU/L; for those at high risk, the target is 0.1 mU/L or less. For patients with MTC, the treatment is adjusted to preserve euthyroid function.

Conflict of interest statement
FE has served as a paid consultant for Bayer, IBSA, Ipsen, Lilly and Sanofi-Aventis. She has received lecture honoraria from IBSA, Ipsen, Lilly, Sanofi-Aventis, Curium, and reimbursement of travel expenses from Ipsen and Sanofi-Aventis.

KH received lecture honoraria and reimbursement of travel expenses from Sanofi-Aventis.

The remaining authors state that they have no conflict of interest.

Manuscript received on 4 August 2025; revised version accepted on 19 March 2026.

Translated from the original German by Ethan Taub, M.D.

Corresponding author
Prof. Dr. med. Katharina Holzer

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