Thyroid nodule classification

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mahshid Mir, M.D. [2]

Overview

There are various methods for classifying a thyroid nodule. A method has been developed by the National Cancer Institute (NCI) to address terminology and other issues related to thyroid fine-needle aspiration (FNA), called "The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC)". The other classification method is the TNM classification (tumor-node-metastasis) method developed by the American Joint Committee on Cancer and the International Union against Cancer focused on prognosis has been established to avoid heterogeneity of prognostic classification schemes used for differentiated thyroid cancers. Thyroid nodules may also be classified based on their ultrasound properties according to the TIRAD classification method, which has been proposed by Horvath et al, with a modified recommendation from Jin Kwak et al, and finally, thyroid nodules may also be classified on the basis of origin.

The Bethesda System For Reporting Thyroid Cytopathology

To address terminology and other issues related to thyroid fine-needle aspiration (FNA), the National Cancer Institute (NCI) developed a new classification method called "The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC)".

Classification	FNA cytology	Predicted risk of malignancy
Benign	Macrofollicular Adenomatoid/hyperplastic nodules Colloid adenomas (most common) Nodular goiter Lymphocytic thyroiditis Granulomatous thyroiditis	0–3 %
Nondiagnostic or unsatisfactory	---	1–4 %
Follicular lesion of undetermined significance	Mixed macro- and microfollicular nodules	5–15 %
Atypia of undetermined significance	Atypical cells
Follicular neoplasm	Microfollicular nodules Hurthle cell lesions	15–30 %
Suspicious for a follicular neoplasm	Suspicious for Hurthle cell neoplasm	60–75 %
Malignant	PTC (most common) MTC Anaplastic carcinoma High-grade metastatic cancers	97–99 %

Abbreviations: PTC- Papillary thyroid carcinoma, MTC- Medullary thyroid carcinoma

Classification Based On TNM Staging

The TNM classification (tumor-node-metastasis) was adopted by the American Joint Committee on Cancer and the International Union against Cancer more than 10 years ago. This classification system mainly focuses on prognosis and is developed to avoid heterogeneity of prognostic classification schemes used for differentiated thyroid cancers.

Differentiated and anaplastic thyroid carcinoma TNM staging AJCC UICC 2017

Papillary, follicular, poorly differentiated, Hurthle cell and anaplastic thyroid carcinoma
Primary tumor (T)					Regional lymph nodes (N)		Distant metastasis (M)
T category	T criteria				N category	N criteria	M category	M criteria
TX	Primary tumor cannot be assessed				NX	Regional lymph nodes cannot be assessed	M0	No distant metastasis
T0	No evidence of primary tumor				N0	No evidence of locoregional lymph node metastasis	M1	Distant metastasis
T1	Tumor ≤2 cm in greatest dimension limited to the thyroid				N0a	One or more cytologically or histologically confirmed benign lymph nodes
T1a	Tumor ≤1 cm in greatest dimension limited to the thyroid				N0b	No radiological or clinical evidence of local regional lymph node metastases
T1b	Tumor >1 cm but ≤2 cm in greatest dimension limited to the thyroid				N1	Metastasis to regional nodes
T2	Tumor >2 cm but ≤4 cm in greatest dimension limited to the thyroid				N1a	Metastases to level VI or VII (pretracheal, paratracheal, or prelaryngeal/Delphian, or upper mediastinal) lymph nodes. This can be unilateral or bilateral disease
T3	Tumor >4 cm limited to the thyroid, or gross extrathyroidal extension invading only strap muscles				N1b	Metastasis to unilateral, bilateral, or contralateral neck lymph nodes (levels I, II, III, IV, or V) or retropharyngeal lymph nodes
T3a	Tumor >4 cm limited to the thyroid
T3b	Gross extrathyroidal extension invading only strap muscles (sternohyoid, sternothyroid, thyrohyoid, or omohyoid muscles) from a tumor of any size
T4	Includes gross extrathyroidal extension
T4a	Gross extrathyroidal extension invading subcutaneous soft tissues, larynx, trachea, esophagus, or recurrent laryngeal nerve from a tumor of any size
T4b	Gross extrathyroidal extension invading prevertebral fascia or encasing the carotid artery or mediastinal vessels from a tumor of any size

Thyroid Nodule Classification Based On Ultrasound Features

A classification system has been proposed by Horvath et al, with a modified recommendation from Jin Kwak et al.

Ultrasound classification		Features		Risk of Malignancy
TIRADS 1		Normal thyroid gland
TIRADS 2		Benign lesions	Avascular anechoic lesion with echogenic specks (colloid type I) Vascular heteroechoic non-expansile, non-encapsulated nodules with peripheral halo (colloid type II) Isoechoic or heteroechoic, non-encapsulated, expansile vascular nodules (colloid type III)	0% risk of malignancy
TIRADS 3		Probably benign lesions	Nodule property: Hyperechoic, iso-echoic or hypoechoic nodules, with partially formed capsule and peripheral vascularity, usually in the setting of Hashimoto's thyroiditis	<5% risk of malignancy
TIRADS 4	4a	One suspicious feature	Suspicious lesions: Solid component High stiffness of nodule on elastography if available Markedly hypoechoic nodule Microlobulations or irregular margins Microcalcifications Taller-than-wider shape	5-10% risk of malignancy
	4b	Two suspicious features		10-80% risk of malignancy
	4c	Three/four suspicious features
TIRADS 5		All five suspicious features	Probably malignant lesions (more than 80% risk of malignancy)	>80% risk of malignancy
TIRADS 6		Biopsy proven malignancy

Classification Of Neoplastic Thyroid Nodules Based On Their Origin:

Origin	Prevalence	Origin	Histologic Classification	Subclass
Nonmedullary thyroid cancers (NMTCs)	95% of tumors	Thyroid epithelial cells	Papillary (85%)	Classic variant Tall cell variant Insular variant Columnar variant Hürthle or oxyphilic variant Solid or trabecular variant Clear cell variant Diffuse sclerosing variant Cribriform-morular variant Hobnail variant
			Follicular (11%)	Benign follicular adenoma Minimally invasive follicular carcinoma Widely invasive follicular carcinoma Encapsulated follicular variant of papillary thyroid cancer Infiltrative variant of papillary thyroid cancer
			Hürthle cell (3%)
			Anaplastic (1%)
Medullary thyroid cancers (MTCs)	5% of all thyroid malignancies	Calcitonin-producing parafollicular cells		20% they are familial and occur as part of the multiple endocrine neoplasia (MEN) syndromes