What are the guidelines on the diagnosis of follicular thyroid carcinoma (FTC)?

Updated: Jun 18, 2020
  • Author: Luigi Santacroce, MD; Chief Editor: Neetu Radhakrishnan, MD  more...
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Answer

All the guidelines advocate ultrasound 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. [1, 5, 40, 38]

Although all 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 [37, 1, 39] :

  • >0.5 cm in diameter (ATA) [37]
  • >1 cm in diameter (ESMO) [38]
  • ≥1 cm for high ultrasound risk thyroid lesions; >2 cm for intermediate ultrasound risk lesions or low ultrasound risk only when increasing in size or associated with a risk history (AACE/AME/ETA) [39]
  • >1 cm if suspicious sonographic features are present;  ≥1.5 cm for moderately suspicious nodules and ≥2.5 cm for mildly suspicious nodules. (NCCN) [1]

NCCN and AACE/AME/ETA recommend radionuclide imaging in patients with a low TSH level. [37, 1, 39]

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 economical 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 ultrasound (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. [37]  

Papillary thyroid cancer is characterized by the following US features:

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

Follicular thyroid cancer is characterized by the following US features:

  • Iso- to hyper-echoic
  • Thick irregular halo

Benign US features are as follows:

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

In 2017, an ATA task force recommended that encapsulated follicular variant papillary thyroid carcinoma (eFVPTC) without capsular or vascular invasion be reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), given its excellent prognosis. This was a weak recommendation based on moderate-quality evidence. [41]

The 2019 ESMO guidelines recommend pathological diagnosis of all thyroid tumors be made according to the 2017 WHO classification. [38]

Malignancy risk

Cytological analysis of FNAB specimens is used to estimate malignancy risk. The most appropriate cytological classification of malignancy risk is the Bethesda system for thyroid cytopathology, which comprises the following categories [42] :

  • 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)
  • Non-diagnostic or unsatisfactory (risk 1-4%)
  • Benign (risk 0-3%)

For cytology “diagnostic of” or “suspicious for” papillary thyroid cancer, surgery is recommended. [37]

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. [37]

An iodine-123 (123I) thyroid scan may be considered if the cytology report documents a follicular neoplasm, especially if serum thyroid-stimulating hormone (TSH) is in the low-normal range. [37] 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. [37]

The NCCN recommends FNAB as 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) [1] :

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

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