Thyroid nodule differential diagnosis

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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]

Thyroid nodule differential diagnosis

In rare cases, a thyroid nodule may reflect one of the hereditary nonmedullary thyroid cancer syndromes such as familial adenomatous polyposis, Werner’s syndrome, Carney complex type 1, or Gardner’s syndrome

		Nodule property	Spread			Nodular growth	Laboratory		Thyroid scintigraphy				Biopsy result if indicated
			LN	Vessle	Metastasis		TSH	FT4/T3	Hot	Cold	US finding	FNA finding		Associated mutation	special consideration
Benign	Colloid adenoma		-	-	-	Intermediate Slow	NL	NL
	Hashimoto's thyroiditis	Rarely painful	-	-	-	Rapid Intermediate	↓↓	↓	+					HLA-A HLA-B
	Cysts nodules	Most common cause of painful neck lesion	-	-	-	Rapid Intermediate	NL	NL	-	+	cystic non-calcified nodules	Follicular cells Macrophages RBC Colloid	-	-	Mostly due to degenerating thyroid adenomas
	Follicular adenomas		-	-	-	Intermediate Slow	↑↑↑	↑						PAX8-PPAR gamma 1
	Hyperplastic nodules		-	-	-	Rapid Intermediate	↑↑↑	↑
	Macrofollicular adenomas		-	-	-	Intermediate Slow	↑↑	↑
	Microfollicular or cellular adenomas		-	-	-	Intermediate Slow	↑↑	↑
	Hürthle cell adenomas		-	-	-	Intermediate Slow	↑↓	↑↓
Malignant	Papillary carcinoma	Fixed Painless	↑↑↑	↑↑↑	Pulmonary Skeletal metastases	Intermediate Slow	NL	NL		+	multifocal	unencapsulated and may be partially cystic	papillae consisting of one or two layers of tumor cells surrounding a well-defined fibrovascular core; follicles and colloid are typically absent The nuclei are large, oval, and appear crowded and overlapping on microscopic sections. They may contain hypodense powdery chromatin, cytoplasmic pseudoinclusions due to a redundant nuclear membrane, or nuclear grooves.	RET/PTC NTRK1 RAS BRAF
	Follicular carcinoma	Fix Painless		↑↑↑	Bone Lung	Intermediate Slow	↑↓	↑↓			Unifocal	FLUS	Tumor capsule Vascular invasion	RAS mutations PAX8-PPAR gamma 1	Most common thyroid cancer in iodine deficient areas
	Oxyphilic (Hürthle cell) type carcinoma					Intermediate Slow
	Medullary carcinoma		↑↑↑		Locally to neck all body organ systems	Intermediate Slow					Unifocal May present as multifocal	hypoechoic, microcalcifications			May be associated with other co-existing diseases Associated with high levels of calcitonin
	Anaplastic carcinoma					Slow	↑
	Primary thyroid lymphoma					Intermediate Slow
	Metastatic carcinoma					Intermediate Slow
	Thyroglossal duct cysts	Mostly midline Can be painful if get infected				Intermediate Slow
	Parathyroid cysts					Rapid Intermediate