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1Department of Internal Medicine, Center for Thyroid Cancer, National Cancer Center, Goyang, Korea
2Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
3Department of Hospital Pathology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
4Department of Radiology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea
Copyright © 2024 Korean Endocrine Society
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
CONFLICTS OF INTEREST
Young Joo Park is an editor-in-chief and Eun Kyung Lee is an associate editor of the journal. But they were not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported.
Category | US patterns | Suggested malignancy risk, % | Nodule size threshold for biopsy, cmb |
---|---|---|---|
High suspicion (K-TIRADS 5) | Solid hypoechoic nodule with any of the three suspicious US featuresc | >60 | >1d |
Intermediate suspicion (K-TIRADS 4)e | 1) Solid hypoechoic nodules without any of the three suspicious US features or | 10–40 | >1–1.5g |
2) Partially cystic or iso-/hyperechoic nodule with any of the three suspicious US features | |||
3) Entirely calcified nodulesf | |||
Low suspicion (K-TIRADS 3) | Partially cystic or iso-/hyperechoic nodule without any of the three suspicious US features | 3–10 | >2 |
Benign (K-TIRADS 2)h | 1) Iso-/hyperechoic spongiform | 3 | Not indicatedi |
2) Partially cystic nodule with intracystic echogenic foci and comet-tail artifact | |||
3) Pure cyst | |||
No nodule (K-TIRADS 1) | - | - |
Modified from Ha et al. [1].
US, ultrasonography; K-TIRADS, Korean Thyroid Imaging Reporting and Data System.
a Biopsy should be performed regardless of the size of the most suspicious nodule in cases with poor prognostic factors, including suspected cervical lymph node metastases, obvious extrathyroidal extension to adjacent structures (trachea, larynx, pharynx, recurrent laryngeal nerve, or perithyroidal vessels), confirmed distant metastases, or suspected medullary thyroid cancer;
b Fine-needle aspiration (FNA) is the primary pathology test and core needle biopsy can be performed as an adjunctive pathology test to FNA; it should be performed by a trained operator [11,47];
c Suspicious US features of thyroid nodule: punctate echogenic foci, nonparallel orientation, and irregular margins;
d Biopsy is recommended for small (>0.5 and ≤1 cm) high suspicion (K-TIRADS 5) nodules with high-risk features, including attachment of nodules to the trachea or posteromedial capsule along the course of the recurrent laryngeal nerve considering the potentials of high-risk microcarcinomas requiring immediate surgery. Biopsy may be considered for small (>0.5 and ≤1 cm) K-TIRADS 5 nodules without high-risk features to decide the management plan in adults. In children, biopsy should be considered for small K-TIRADS 5 nodules (>0.5 and ≤1 cm) to decide the management plan considering the clinical context;
e Extensive parenchymal punctate echogenic foci (microcalcifications) without discrete nodules (suspicious for diffuse sclerosing variant of papillary thyroid carcinoma) and diffusely infiltrative lesions (suspicious for infiltrative malignancy, such as metastasis or lymphoma) are considered to be intermediate suspicion suspicion (K-TIRADS 4) nodules;
f Entirely calcified nodules with complete posterior acoustic shadowing, with no soft tissue component identified due to dense shadowing on US (isolated macrocalcification);
g Cutoff size for biopsy should be determined within the range of 1 and 1.5 cm, based on the US features, nodule location, clinical risk factors, and patient factors (age, comorbidities, and preferences);
h Regardless of coexisting suspicious US features (punctate echogenic foci, nonparallel orientation, or irregular margin);
i Although biopsy is not routinely indicated, it may be performed for nodules that demonstrate continuous and significant growth or for nodules prior to ablation therapy or surgery.
Modified from Ali et al. [21], with permission from Mary Ann Liebert, Inc.
ROM, risk of malignancy; NIFTP, noninvasive follicular thyroid neoplasm with papillary-like nuclear features.
Modified from Jung [24].
ROM, risk of malignancy; CNB, core needle biopsy; NIFTP, noninvasive follicular thyroid neoplasm with papillary-like nuclear features.
Recommendation level | Definition | Meaning |
---|---|---|
1 | Strong recommendation | There is sufficient objective evidence and/or general agreement of significant health benefit or harm from the recommended behavior. |
2 | Conditional recommendation | There is objective evidence of significant health benefits or harms from the recommended behavior, but the evidence is not clear or sufficient to make a strong recommendation. |
3 | Expert consensus | There is insufficient objective evidence but beneficial based on the patient's situation and expert consensus. |
4 | Inconclusive | There is no evidence of significant health benefits or harms from taking the recommended action, or there is much disagreement, so there is neither support for nor opposition to taking the action. |
Section 1: Thyroid cancer screening in high-risk groups | |
---|---|
1.A. Screening family members with three or more cases of differentiated thyroid cancer in the family may lead to an earlier diagnosis, but there is no evidence supporting that doing so reduces morbidity and mortality; therefore, ultrasonography (US) screening for this purpose is not recommended. Recommendation level 4 | |
1.B. Family members of patients with familial thyroid cancer or hereditary tumor syndromes should receive genetic counseling and be offered screening and treatment based on their genetic mutation status. Recommendation level 2 | |
1.C. US screening for thyroid cancer is not usually recommended for patients with Graves̕ disease, Hashimoto̕s thyroiditis, or hyperparathyroidism. Recommendation level 4 | |
1.D. US screening should be considered for those in 1A–C with the following features: suspected thyroid nodules, asymmetric thyroid goiter, or lymph node enlargement on physical examination. Recommendation level 2 | |
Section 2: Diagnostic evaluation of incidental or clinically detected thyroid nodules | |
2.A. Thyroid function tests, including thyroid stimulating hormone (TSH), should be performed as part of the initial work-up for thyroid nodules, and a thyroid scan should be performed if the TSH level is below the normal range. Recommendation level 1 | |
2.B. Routine serum thyroglobulin measurements for all thyroid nodules are not recommended. Recommendation level 1 | |
2.C. Measurement of serum calcitonin may be considered before the surgical or non-surgical treatment of thyroid nodules. Recommendation level 2 | |
2.D. Incidental focal uptake lesions in the thyroid on 18F-FDG PET/CT are highly suggestive of thyroid cancer and should undergo pathological evaluation in conjunction with the US findings. In patients with diffuse uptake on 18F-FDG PET/CT with US and clinical findings consistent with chronic lymphocytic thyroiditis, no further imaging or pathological testing is recommended. Recommendation level 1 | |
2.E. Thyroid US, including a cervical lymph node evaluation, is recommended in all patients with known or suspected thyroid nodules. Recommendation level 1 | |
Section 3: The pathological diagnosis of thyroid nodules | |
3.1. Role of pathological tests and molecular markers | |
3.1.A. Fine needle aspiration (FNA) is the gold standard for the pathological diagnosis of thyroid nodules. Recommendation level 1 | |
3.1.B. FNA results of thyroid nodules should be reported according to the diagnostic categories of the Bethesda system. Recommendation level 1 | |
3.1.C. Core needle biopsy (CNB) results of thyroid nodules should be reported according to the diagnostic categories of the Korean Thyroid Association pathological diagnosis recommendations. Recommendation level 2 | |
3.1.D. Molecular marker testing can be performed based on the pathological category to help assess malignancy risk and decide whether to perform surgical resection, considering clinical risk factors, US findings, and patient preferences. Recommendation level 3 | |
3.2. Management strategies according to pathological diagnosis | |
3.2.1. Nondiagnostic | |
3.2.1.A. Nondiagnostic nodules on initial FNA should be reevaluated with a US-guided pathological examination. Recommendation level 1 | |
3.2.1.B. Cystic nodules that remain nondiagnostic on a repeated pathological examination (without US features highly suggestive of malignancy) may require careful surveillance or surgical excision. Recommendation level 3 | |
3.2.1.C. Diagnostic surgical resection should be considered if a repeated pathological examination is nondiagnostic, if US findings strongly suggest malignancy, if there is a 20% or greater increase in size during follow-up, or if there is a clinically suspected risk of malignancy. Recommendation level 3 | |
3.2.2. Benign | |
3.2.2.A. A benign nodule on pathological examination does not require immediate further investigation or treatment. Recommendation level 1 | |
3.2.3. Atypia of unknown significance (AUS) | |
3.2.3.A. For pathological category 3 (AUS) nodules, US surveillance, repeated FNA, CNB, or molecular marker testing may be performed to assess malignancy risk and guide decision-making regarding diagnostic surgery, considering clinical risk factors, US findings, patient preferences, and feasibility. Recommendation level 3 | |
3.2.3.B. If repeated FNA, CNB, or molecular marker testing is not performed or is inconclusive, US surveillance or diagnostic surgery may be performed considering clinical risk factors, US findings, and patient preferences. Recommendation level 2 | |
3.2.4. Follicular neoplasm | |
3.2.4.A. Tumors larger than 2 cm diagnosed as follicular neoplasms should be considered for surgery, as the risk of malignancy increases with size. For tumors of 2 cm or smaller, malignancy risk still exists, and diagnostic surgery may be considered based on clinical judgment. Recommendation level 2 | |
3.2.4.B. Based on clinical and US findings, US surveillance can be pursued or molecular marker testing can be performed to assess malignancy risk and surgical suitability. Clinical decisions should be based on patient preferences and feasibility. Recommendation level 3 | |
3.2.5. Suspicious for malignancy | |
3.2.5.A. If the pathological diagnosis is suspicious for papillary thyroid carcinoma (PTC) suspicious for malignancy, surgical resection should be performed as if it is malignant, with consideration of clinical risk factors, US features, and patient preferences. Recommendation level 2 | |
3.2.5.B. Molecular marker testing may be considered if the results could influence the decision-making process regarding whether to proceed with surgery, with consideration of clinical risk factors, US features, and patient preference. Recommendation level 3 | |
3.2.6. Malignancy | |
3.2.6.A. If the pathological diagnosis is malignant, surgery is generally recommended. Recommendation level 1 | |
3.2.6.B. Active surveillance (AS) may be considered in low-risk adult patients with papillary thyroid microcarcinoma (PTMC) confirmed on pathology and imaging such as US, if there are no high-risk features including high-risk histology (aggressive cellular subtype), adjacent tissue invasions (e.g., airways or nerves), and cervical lymph node or distant metastases. Recommendation level 2 | |
Section 4: Long-term follow-up of thyroid nodules | |
4.1. Follow-up of pathologically confirmed benign thyroid nodules | |
4.1.A. High suspicion (K-TIRADS 5): Perform US within 12 months and a repeated pathological examination if there is no reduction in size. Recommendation level 1 | |
4.1.B. Low or intermediate suspicion (K-TIRADS 3 or 4): Perform US within 12–24 months. If the US examination shows an increase in nodule size (greater than 2 mm in at least two dimensions with a diameter increase of 20% or greater, or a volume increase of 50% or greater) or new suspicious features, consider a pathological evaluation or continue surveillance until a further increase in size before a pathological evaluation. Recommendation level 3 | |
4.1.C. Benign (K-TIRADS 2): If a pathological evaluation is performed due to an increase in nodule size or for treatment planning, and the nodule is subsequently confirmed as benign, no further surveillance US is necessary to assess the risk of malignancy. Recommendation level 2 | |
4.1.D. Benign on repeated pathological examination: If a nodule is confirmed to be benign on a repeated pathological examination during follow-up and shows no malignant changes in US, further pathological examination is not necessary. Recommendation level 1 | |
4.2. Follow-up of thyroid nodules that do not meet the indications for a pathological examination. | |
4.2.A. Highly suspicion (K-TIRADS 5): Repeat US every 6–12 months for the first 1–2 years, then every year thereafter if there is no increase in size. Recommendation level 2 | |
4.2.B. Low-risk or intermediate suspicion (K-TIRADS 3 or 4): Consider repeating surveillance US at 1–2-years intervals or longer. For nodules measuring 1 cm or smaller with low-risk US features, surveillance US may be repeated every 2–5 years. Recommendation level 3 | |
4.2.C. Benign (K-TIRADS 2): Surveillance US is not required, but may be considered after 2–5 years based on the size of the nodule and clinical assessment. Recommendation level 3 | |
Section 5: Treatment of thyroid nodules | |
5.A. Routine thyroid hormone suppression for benign thyroid nodules is not recommended. There may be a treatment response, but the potential harm outweighs the benefit of suppressive therapy. Recommendation level 1 | |
5.B. Periodic surveillance is recommended for nodules with increasing size that are nonetheless confirmed benign on cytology. Surveillance without treatment is recommended for most asymptomatic nodules with a slight increase in size. Recommendation level 2 | |
5.C. There is no evidence supporting thyroid hormone suppression for benign nodules that increase in size. Recommendation level 4 | |
5.D. If a thyroid nodule is diagnosed as benign on repeated pathological examinations, treatment may be considered for pressure symptoms, cosmetic concerns, or an autonomous nodule. Treatment options including surgery, radioiodine therapy, and non-surgical ablation (ethanol, radiofrequency and laser), should be chosen based on clinical characteristics, comorbidities, treatment advantages and disadvantages, patient preferences, and feasibility. Recommendation level 3 | |
5.E. Nodules larger than 4 cm that continue to increase in size may be considered for surgery if there are significant compressive symptoms or clinical concerns of malignancy. Recommendation level 3 | |
5.F. Benign solid thyroid nodules with normal thyroid function may be considered for surgery or non-surgical intervention if there are pressure symptoms or cosmetic concerns. Recommendation level 2 | |
5.G. Radiofrequency or laser ablation is recommended as a non-surgical treatment for benign solid nodules. Recommendation level 2 | |
5.H. For recurrent benign cystic nodules, ethanol ablation is recommended as the first-line treatment if there are pressure symptoms or cosmetic concerns. Recommendation level 1 | |
5.I. For overt hyperfunctioning thyroid nodules, radioactive iodine or surgery should be considered as the first-line treatment. Recommendation level 1 | |
Section 6: Thyroid nodules in pregnant women | |
6.1. If a thyroid nodule is found in a pregnant woman, consider FNA based on the US features as in nonpregnant women. If serum TSH is persistently low after the first trimester, defer the pathological evaluation until after delivery, when a thyroid scan can be performed to assess the function of the nodule. Recommendation level 1 | |
6.2. Thyroid cancer diagnosed in the first trimester requires US surveillance, and surgery should be considered if there is significant growth (greater than 2 mm in at least two dimensions with a diameter increase of 20% or greater, or a volume increase of 50% or greater) by 24 weeks of gestation or if cervical lymph node metastases are detected. However, surgery may be performed after delivery if there is no change in size by the second trimester or if the cancer is first diagnosed in the second trimester. For advanced thyroid cancer, surgery is preferably performed during the second trimester. Recommendation level 3 |
Category | US patterns | Suggested malignancy risk, % | Nodule size threshold for biopsy, cm |
---|---|---|---|
High suspicion (K-TIRADS 5) | Solid hypoechoic nodule with any of the three suspicious US features |
>60 | >1 |
Intermediate suspicion (K-TIRADS 4) |
1) Solid hypoechoic nodules without any of the three suspicious US features or | 10–40 | >1–1.5 |
2) Partially cystic or iso-/hyperechoic nodule with any of the three suspicious US features | |||
3) Entirely calcified nodules |
|||
Low suspicion (K-TIRADS 3) | Partially cystic or iso-/hyperechoic nodule without any of the three suspicious US features | 3–10 | >2 |
Benign (K-TIRADS 2) |
1) Iso-/hyperechoic spongiform | 3 | Not indicated |
2) Partially cystic nodule with intracystic echogenic foci and comet-tail artifact | |||
3) Pure cyst | |||
No nodule (K-TIRADS 1) | - | - |
Diagnostic category | ROM in adults, % (range) | ROM in children, % (range) | Estimated final ROM if excluding NIFTP |
---|---|---|---|
I. Nondiagnostic | 13 (5–20) | 14 (0–33) | 12 |
II. Benign | 4 (2–7) | 6 (0–27) | 2 |
III. Atypia of undetermined significance | 22 (13–30) | 28 (11–54) | 16 |
IV. Follicular neoplasm | 30 (23–34) | 50 (28–100) | 23 |
V. Suspicious for malignancy | 74 (67–83) | 81 (40–100) | 65 |
VI. Malignant | 97 (97–100) | 98 (86–100) | 94 |
CNB diagnostic category | Diagnostic frequency, % | ROM based on final diagnosis from clinical and/or surgical follow-up, % | Change in ROM due to NIFTP |
---|---|---|---|
I. Nondiagnostic or unsatisfactory | 2 (2–3) | 33 (18–50) | No significant change |
II. Benign | 46 (40–52) | 4 (2–6) | No significant change |
III. Indeterminate | 10 (7–14) | 39 (32–45) | 24% decrease (24–34) |
IV. Follicular neoplasm | 7 (5–9) | 52 (46–57) | 20% decrease (37–45) |
V. Suspicious for malignancy | 2 (2–3) | 98 (96–100) | No significant change |
VI. Malignant | 28 (23–34) | 100 | No significant change |
FDG, fluorodeoxyglucose; PET, positron emission tomography; CT, computed tomography; K-TIRADS, Korean Thyroid Imaging Reporting and Data System.
Modified from Ha et al. [ US, ultrasonography; K-TIRADS, Korean Thyroid Imaging Reporting and Data System. Biopsy should be performed regardless of the size of the most suspicious nodule in cases with poor prognostic factors, including suspected cervical lymph
node metastases, obvious extrathyroidal extension to adjacent structures (trachea, larynx, pharynx, recurrent laryngeal nerve, or perithyroidal vessels), confirmed distant metastases, or suspected medullary thyroid cancer; Fine-needle aspiration (FNA) is the primary pathology test and core needle biopsy can be performed as an adjunctive pathology test to FNA; it should be performed by a trained operator [ Suspicious US features of thyroid nodule: punctate echogenic foci, nonparallel orientation, and irregular margins; Biopsy is recommended for small (>0.5 and ≤1 cm) high suspicion (K-TIRADS 5) nodules with high-risk features, including attachment of nodules to the trachea or posteromedial capsule along the course of the recurrent laryngeal nerve considering the potentials of high-risk microcarcinomas requiring immediate surgery. Biopsy may be considered for small (>0.5 and ≤1 cm) K-TIRADS 5 nodules without high-risk features to decide the management plan in adults. In children, biopsy should be considered for small K-TIRADS 5 nodules (>0.5 and ≤1 cm) to decide the management plan considering the clinical context; Extensive parenchymal punctate echogenic foci (microcalcifications) without discrete nodules (suspicious for diffuse sclerosing variant of papillary thyroid carcinoma) and diffusely infiltrative lesions (suspicious for infiltrative malignancy, such as metastasis or lymphoma) are considered to be intermediate suspicion suspicion (K-TIRADS 4) nodules; Entirely calcified nodules with complete posterior acoustic shadowing, with no soft tissue component identified due to dense shadowing on US (isolated macrocalcification); Cutoff size for biopsy should be determined within the range of 1 and 1.5 cm, based on the US features, nodule location, clinical risk factors, and patient factors (age, comorbidities, and preferences); Regardless of coexisting suspicious US features (punctate echogenic foci, nonparallel orientation, or irregular margin); Although biopsy is not routinely indicated, it may be performed for nodules that demonstrate continuous and significant growth or for nodules prior to ablation therapy or surgery.
Modified from Ali et al. [ ROM, risk of malignancy; NIFTP, noninvasive follicular thyroid neoplasm with papillary-like nuclear features.
Modified from Jung [ ROM, risk of malignancy; CNB, core needle biopsy; NIFTP, noninvasive follicular thyroid neoplasm with papillary-like nuclear features.