Thyroid, Papillary Carcinoma, Early Guidelines

Updated: May 07, 2021
  • Author: Eric J Lentsch, MD; Chief Editor: Arlen D Meyers, MD, MBA  more...
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Guidelines Summary

Guidelines Contributor:  Kemp M Anderson Medical University of South Carolina College of Medicine


The following organizations have released guidelines for the diagnosis and/or management of thyroid cancer:

  • American Thyroid Association (ATA) [50]
  • National Comprehensive Cancer Network (NCCN) [51]
  • American Association of Clinical Endocrinologists/American College of Endocrinology/Associazione Medici Endocrinologi (AACE/ACE/AME) [52]  

All of the guidelines advocate ultrasonographic (US) evaluation of thyroid nodules along with measurement of serum thyroid-stimulating hormone (TSH) levels to determine whether a fine needle aspiration biopsy (FNAB) is indicated. A routine measurement of serum thyroglobulin (Tg) for the initial evaluation of thyroid nodules is not recommended, because Tg levels are elevated in most benign thyroid conditions. [50, 51, 52]

Although all of the guidelines recommend FNAB as the procedure of choice in the evaluation of solid thyroid nodules, there is variance in the size of the nodule as an indication for FNAB, as follows [50, 51, 52] :

  • ATA - Nodules ≥1cm with high- or intermediate-risk US features; nodules ≥1.5 cm with low-risk US features; for nodules ≥2 cm with very–low-risk US features, consider FNAB (observation is a reasonable alternative in such cases) [50]
  • AACE/ACE/AME - US high-risk nodules ≥1 cm; US intermediate-risk nodules >2 cm; US low-risk nodules only when >2 cm and increasing in size or associated with a risk history and before thyroid surgery or minimally invasive ablation therapy [52]
  • NCCN - Nodules >1 cm if suspicious US features are present; nodules >1.5 cm if no suspicious US features are present [51]

AACE/ACE/AME and NCCN suggest a serum calcitonin assay as an optional test,  [51, 52]  but the ATA guidelines make no recommendation on the routine measurement of serum calcitonin, because of insufficient evidence.  [50]  All three guidelines recommend radionuclide imaging in patients with a low TSH level. [50, 51, 52]

Differentiated Thyroid Cancers

Differentiated thyroid cancers arise from thyroid follicular epithelial cells and constitute 90% of all thyroid cancers. The subtypes and approximate frequencies of differentiated thyroid cancers are as follows:

  • Papillary - 85%
  • Follicular - 10%
  • Hürthle or oxyphil - 5%

ATA guidelines state that FNAB provides the most economic and accurate methodology for diagnosing differentiated thyroid cancers. Due to potential false negatives or sampling error, it is recommended that FNAB procedures be performed under US guidance. US guidance is particularly important for nodules located posteriorly and for those that are difficult to palpate. Additionally, certain features found on US examination are predictive for malignancy and may guide FNAB decision-making. [50]  

Papillary thyroid cancer is characterized by the following US features:

  • Solid or predominantly solid
  • Hypoechoic
  • Microcalcifications (highly specific)
  • Infiltrative irregular margins (common)
  • Increased nodular vascularity

Follicular thyroid cancer is characterized by the following US features:

  • Isoechoic to hyperechoic
  • Thick irregular halo

Benign US features are as follows:

  • Purely cystic nodule
  • Spongiform appearance (aggregation of multiple microcystic components >50% volume)

Malignancy risk

Cytologic analysis of FNAB specimens is used to estimate malignancy risk. The most appropriate cytologic classification of malignancy risk is the Bethesda system for thyroid cytopathology, which includes the following categories [53] :

  • Malignant (risk 97-99%)
  • Suspicious for malignancy (risk 60-75%)
  • Follicular neoplasm or suspicious for follicular neoplasm (risk 15-30%)
  • Atypia of undetermined significance or follicular lesion of undetermined significance (risk 5-15% based on repeated atypicals)
  • Nondiagnostic or unsatisfactory (risk 1-4%)
  • Benign (risk 0-3%)

For cytology “diagnostic of” or “suspicious for” papillary thyroid cancer, surgery is recommended. [50]

If FNAB cytology is indeterminate, the use of molecular markers such as BRAF, RAS, RET/PTC, Pax8-PPARɣ, or galectin-3 may be considered to guide management. [50]

An iodine-123 (123I) thyroid scan may be considered if the cytology report documents a follicular neoplasm, especially if serum TSH is in the low-normal range. [50] No radionuclide scan is needed for a reading of “suspicious for papillary carcinoma” or “Hürthle cell neoplasm,” as either lobectomy or total thyroidectomy is recommended, depending on the nodule size and risk factors.

The NCCN recommends that FNAB should be the primary test for differentiated thyroid cancer. If FNAB reveals papillary carcinoma, follicular neoplasm, follicular lesion of undetermined significance, or Hürthle cell neoplasm, the following diagnostic recommendations should be undertaken (these are uniform for all differentiated thyroid carcinomas) [51] :

  • Thyroid and neck ultrasonography (including central and lateral compartments) if not previously done
  • CT scanning/MRI for fixed, bulky, or substernal lesions (iodinated contrast optimal for cervical imaging)
  • Consider evaluation of vocal cord mobility


The treatment of choice for papillary thyroid cancer is surgery, whenever possible, followed by radioiodine (131I) in selected patients and thyrotropin suppression in most patients, according to the National Comprehensive Cancer Network (NCCN) guidelines. [51]

NCCN guidelines recommend total thyroidectomy for patients who meet any of the following criteria [51] :

  • Radiation history
  • Known distant metastases
  • Bilateral nodularity
  • Extrathyroidal extension
  • Tumor >4 cm in diameter
  • Cervical lymph node metastases
  • Poorly differentiated tumor

The NCCN considers either total thyroidectomy or lobectomy to be acceptable for patients who meet all of the following criteria [51] :

  • No prior radiation
  • No distant metastases
  • No cervical lymph node metastases
  • No extrathyroidal extension
  • Tumor < 4 cm in diameter

If a lobectomy is performed, completion of the thyroidectomy is recommended for any of the following [51] :

  • Tumor >4 cm in diameter
  • Positive margins
  • Extrathyroidal extension
  • Macroscopic multifocal disease
  • Macroscopic nodal metastases
  • Confirmed contralateral disease
  • Vascular invasion

American Thyroid Association (ATA) guidelines recommend near-total or total thyroidectomy for all patients with thyroid cancer >1 cm, unless there are contraindications to this surgery. Lobectomy may be considered for small (< 1 cm), low-risk, thyroidal papillary carcinomas in the absence of prior radiation or clinically involved cervical nodal metastases. [50]

Both the NCCN and ATA recommend that therapeutic neck dissection for patients with clinically involved central or lateral neck lymph nodes should accompany total thyroidectomy to provide clearance of disease from the central neck. Prophylactic central-compartment neck dissection (level VI) may be considered in patients with clinically uninvolved central neck lymph nodes, especially for advanced primary tumors (T3 or T4). [50, 51]