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

• 19888858

classification	FNA cytology	Predicted risk of malignancy
Benign	Macrofollicular Adenomatoid/hyperplastic nodules Colloid adenomas (most common) Nodular goiter Lymphocytic thyroiditis Granulomatous thyroiditis	0–3 %
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
Malignant	PTC (most common) MTC Anaplastic carcinoma High-grade metastatic cancers	97–99 %

The risk of malignancy development based on the FNA result in case of indefinite diagnosis are as below:

• Nondiagnostic or Unsatisfactory: 1–4 % predicted risk of malignancy.
• Suspicious for malignancy: 60–75 % predicted risk of malignancy

Thyroid carcinomas are classified according to the cell type from which they develop

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
			follicular (11%)
			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

Follicular thyroid lesions	Benign follicular adenoma
	Minimally invasive follicular carcinoma
	Widely invasive follicular carcinoma
	Encapsulated follicular variant of papillary thyroid cancer
	Infiltrative variant of papillary thyroid cancer
	Classic varient
papillary thyroid cancer	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

These categories are based on five suspicious sonographic features of malignancy:

Subclassificaton

• TIRADS 4a: 
• TIRADS 4b: 
• TIRADS 4c: 
• TIRADS 5:

TIRADS 4a has , 4b and 4c may have TIRADS 5 category lesion have  3.