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]

Bethesda System for Reporting Thyroid Cytopathology

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 %

Classification of neoplastic thyroid nodules based on their origin:

		Origin	histologic subtypes
Nonmedullary thyroid cancers (NMTCs)	95% of tumors	thyroid epithelial cells	papillary (85%)	95% are sporadic tumors 5% may be related to inherited genetics due to familial origin Classic varient tall cell variant insular varient 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

Of the differentiated cancers, papillary cancer comprises about 85% of cases compared to about 10% that have follicular histology, and 3% that are Hu¨rthle cell or oxyphil tumors

Neoplastic thyroid nodules subclassification:

Neoplasm	Subclass	Features
Follicular thyroid lesions	Benign follicular adenoma
	Minimally invasive follicular carcinoma	only invasion of the capsule of the tumor without vascular invasion
	Widely invasive follicular carcinoma	Extensive invasion of the tumor capsule A multinodular tumor without a well-defined capsule invading the normal thyroid surrounding the tumor Extensive vascular invasion (>4 foci of angioinvasion)
	Encapsulated follicular variant of papillary thyroid cancer	minor vascular invasion (≤4 foci of angioinvasion within the tumor or capsule of the tumor) with or without capsular invasion
	Infiltrative variant of papillary thyroid cancer
papillary thyroid cancer	Classic varient
	tall cell variant	more aggressive tumor than classical papillary cancer tumor cells with eosinophilic cytoplasm that are twice as tall as they are wide. The primary tumors tend to be large, they are often invasive, and many patients have both local and distant metastases at the time of diagnosis
	insular varient	solid nests of tumor, often separated by fibrous bands, but the tumor cell nuclei have the same characteristics as do the nuclei of classical papillary cancers.
	columnar variant	elongated cells with palisading nuclei.
	Hürthle or oxyphilic variant	Cellular features of Hürthle cell carcinomas but cells that are arranged in papillary formations.
	solid or trabecular variant
	clear cell variant	must be distinguished from clear cell carcinomas of other organs such as the kidney or colon that have metastasized to the thyroid.
	diffuse sclerosing variant	diffuse involvement of the thyroid, stromal fibrosis, and prominent lymphocytic infiltration
	cribriform morular variant	Prominent cribriform pattern with solid and spindle cell areas as well as squamous morules. This variant is often associated with familial adenomatous polyposis.
	hobnail variant	harbors BRAF V600E mutations and appears to be associated with a high risk of distant metastases and an increased disease-specific mortality

Thyroid nodule classification based on the sonographhic features:

Classification system has been proposed by Horvath et al 3, with a modified recommendation from Jin Kwak et al 4.

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 setting of Hashimoto's thyroiditis (Hashimoto's pseudonodule)	<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