Neck masses differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Differentiating neck masses from other Diseases

Differential diagnosis of neck masses include:

Category	Diseases		Benign/Malignant	Clinical manifestation								Paraclinical findings			Gold standard diagnosis	Associated findings
				Demography	History	Symptoms		Signs				Lab findings	Histopathology	Imaging
						Pain	Dysphagia	Mass exam	Skin changes	LAP	Others
Congenital	Branchial cleft cyst		Benign	Age: 1-15 yrs/ varies Familial occurence is noted	Lateral neck mass	-	+/-	Solitary Smooth Mobile Welldefined Non-pulsatile Fluctuant	A pit is found at the opening of the cyst	-	-	-	Squamous or ciliated epithelial lining Lymphoid tissue with germinal centers and subcapsular sinuses	CT: Well defined fluid attenuation with slight enhancement of the capsule Ultrasound: Typical features of a cyst are seen		Brachio-oto-renal syndrome Sinus Fistula
	Thyroglossal duct cyst		Benign	Age: 1-10 yrs/ varies	Midline neck mass	-	-	Mobile Moves upwards with tongue protrusion and swallowing	-	-	-	-	Squamous or ciliated pseudostratified columnar lining Foci of thyroid gland tissue Granulation tissue or giant cells if it gets infected	Ultrasound: Anechoic, thin walls, and heterogeneous with internal septae CT with contrast: Well circumscribed,homogeneous fluid attenuation, thin enhancing rim MRI: T1- dark, T2-bright images		-
	Haemangioma		Benign	Age: birth - 2 yrs Females>males	Presents with a flat red or purple patch	-	-	Firm Rubbery Well-demarcated	Blanching Telangiectasias Erythematous patch	-	Regress gradually with age	GLUT-1 VEGF	Lined by non atypical endothelial cells Vascular structures with RBC	Ultrasound: High flow with vascular channels MRI: With or without Gd is the modality of choice		POEMS and Castleman's disease
	Vascular malformations		Benign	Incidence: 1 in 2000 to 5000 births Sex: No predilection	Venous: Present with a bluish swelling AV malformations: Present with purple/red swelling	-/+	-	Soft Compressible Non-tender Venous: No thrill,↑ in size on valsalva AV malformations: Thrill, warm, pulsatile	-	-	Grow proportionally with age	↑ D-dimer level in venous malfomations	Lined by single endothelial layer	Doppler ultrasound: Venous malformations show slow flow, hypoechoic, AV malformations show high flow MRI with Gd: Diffuse enhancement	MRI	-
	Lymphatic malformations		Benign	Age: Birth - 5yrs Sex: No predilection	Presents with a large swelling mainly in the neck	-	+	Soft Non-compressible Non-pulsatile Fluctuant Transillumination+	-	-	Never regress, expand/contract based on inflammation	-	Dilated lymphatic channels lined by endothelial cells Positive D2-40 stain	Ultrasound: Hypo/anechoic with thick septa and fluid CT: Homogeneous and cystic mass MRI: Hyperintense on T2 & peripheral wall enhancement on T1		Down syndrome, turner syndrome
	Laryngocele		Benign	More common in adults Male: female = 5:1	Presents with a neck swelling, hoarseness, stridor and globus sensation Episodic in nature	-	+	Soft Reducible Increase in size on valsalva	-	-	Common in glass blowers, trumpet players	-	Lined by pseudostratified ciliated epithelium	X-ray, CT: Fluid and air containing cystic masses CT is the preferred one Direct laryngoscopy	CT scan is the gold standard imaging for diagnosis	-
	Ranula		Benign	Age: 1st and 2nd decade Female: male=1:1.4	Presents with a blue colored swelling in the floor of the mouth	-	-	Well circumscribed Fluctuant Soft	-	-	-	-	H&E: Shows mucin surrounded by inflammatory cells & fibrosis	CT: Shows cystic mass with tail sign	-
	Teratoma		Benign/malignant	Incidence: 1:4000 births Sex: No predilection	Presents as a firm lateral neck mass	-	-	Firm Non-tender	-	-	-	High ALP levels	Shows ecto, meso and endodermal tissues	CT & MRI: Shows calcifications
	Dermoid cyst		Benign	Incidence: 3 per 10000 population Age: birth - 5 yrs	Presents as a slow growing mass or a sinus	-	-	Freely mobile Solitary Rubbery Nonpulsatile Noncompressible	Usually normal/sometimes a pit or sinus is seen A tuft of hair at the center of the pit for nasal dermoid cyst	-	-	-	Keratinizing squamous epithelium Occasional remnants of hair follicles, adipose tissue, and sweat glands	Ultrasound: Thin walled, unilocular CT: With contrast well circumscribed, unilocular, sac-of-marbles appearance due to fatty tissue
	Thymic cyst		Benign	Age: 1-10 yrs Males>Females	Presents as a soft mass, gradually enlarging, on left side of the neck(usual)	-	-	Soft Compressible	-	-	-	-	Squamous/cuboidal epithelium Lymphoid tissue in the cyst wall contains hassall corpuscles	Ultrasound: Unilocular cystic mass CT: Uni/multilocular, well circumscribed and nonenhancing
Category	Diseases		Benign	Demography	History	Pain	Dysphagia	Mass exam	Skin changes	LAP	Others	Lab findings	Histopathology	Imaging	Gold standard diagnosis	Associated findings
Inflammatory	Acute sialadenitis		Benign	Age:Occurs in all age groups Sex: No predilection	Presents with an unilateral erythematous swelling Bad breath Fever with chills	+	-	Tender Firm Purulent discharge expressed from the duct Smooth	Redness	-	More common in people with bad oral hygiene	↑ ESR Leukocytosis	Inflammatory infiltrate with microabscess formation	Ultrasound: Hypoechoic with ductal dilatation CT: Diffuse homogeneous enlargement	CT scan
	Chronic sialadenitis		Benign	Age:Occurs in all age groups Sex: No predilection	Presents with an unilateral swelling Recurrent episodes common	+	-	Non-tender Firm Smooth	-	-	Mostly due to obstruction by a stone or stricture	↑ ESR Leukocytosis	Hyperplastic lymphoid infiltrates with loss of salivary gland acini Fibrosis	X-ray: Shows radiopaque stones CT: Parenchymal volume is ↓	CT scan
	Reactive viral lymphadenopathy	CMV	Benign	Age: 10-35 yrs mainly Sex: No predilection	Flu-like illness	-	-	Non-tender Soft	-	Generalized/cervical	-	↑ESR ↑SGOT/SGPT	H&E stain: Typical owl-eye inclusions(nuclear) Basophilic cytoplasmic inclusions	Usually not necessary	FNAC & serology
		EBV	Benign	Age: Mainly adolescents Sex: No predilection	Sore throat Fever Malaise Lymphadenopathy	-	-	Non-tender Firm	-	B/L posterior cervical, axillary, inguinal	-	Atypical lymphocytosis + Monospot test IgM & IgG antibodies against VCA EBV ↑↑SGOT/SGPT	CD8+ lymphocytes Tissue necrosis B lymphocyte blasts	Usually not necessary	FNAC & serology
		HIV	Benign	Prevalence: 1.1 million in U.S Sex: Males>females	Flu-like illness Rash	-	-	Non-tender	-	Generalized	-	↓ CD4+ Tcells Thrombocytopenia Anemia ↑AST/ALT ↑CRP ↑ESR	Lymphoid hyperplasia	Usually not necessary	Western blot & P24 antigen assay
		Viral URI	Benign	Incidence: More in fall & winter Age: Common in elderly and infants	Sore throat Cough Runny nose Sneezing	-	-	Non-tender	-	Mild cervical	-	Lymphocytosis ↑ESR & C-reactive protein	Inflammatory infiltrate	No specific findings	-
	Bacterial lymphadenopathy	Tularemia	Benign	Age: Affects all age groups Sex: No predilection	Fever Chills Swelling Joint pains	+	-	Tender Edematous	Ulcer/rash Redness	Regional	-	↑ESR ↑C-reactive protein	Caseating granuloma +/- multinucleated giant cells	No specific findings	PCR & serology
		Brucellosis	Benign	Incidence: 100-200 cases anually in USA Sex: Males>females	Flu-like illness	+	-	Tender	-	Cervical	-	↑ESR	Non-caseating granuloma+ giant cells, epitheloid cells	No specific findings	Serology
		Cat-scratch disease
		Actinomycosis
		Mycobacterial infections
		Staphylococcal or streptococcal infection
	Parasitic lymphadenopathy	Toxoplasma gondii
	Sarcoidosis
	Amyloidosis
	Sjögren syndrome
	Castleman disease (angiofollicular lymphoproliferative disease)
	Kikuchi disease (histiocytic necrotizing lymphadenitis)
	Kimura disease
	Rosai-Dorfman disease
	Kawasaki disease
Category	Diseases		Benign	Demography	History	Pain	Dysphagia	Mass exam	Skin changes	LAP	Others	Lab findings	Histopathology	Imaging	Gold standard diagnosis	Associated findings
Neoplasm	Primary thyroid tumor
	Salivary gland neoplasm	Pleomorphic adenoma	+
		Warthin's tumor	+
		Lymphoepithelioma	+
		Oncocytoma	Benign	Race: Caucasian patients predilection Gender: No gender preference Age: 50–70 years	Growing palpable painless mass Facial swelling Lymphadenopathy (if transformed to malignant)	+/-	+/-	Firm, multilobulated and mobile mass	Normal Redness Swelling Skin ulceration	-		Normal Anemia	Epithelial cells with eosinophilic granular cytoplasm rich in mitochondria	CT: Isodense expansive mass Enhancement after intravenous contrast Hypodense areas MRI: Isodensties on T1 Mass is hyperintense on T2 Enhancement on contrast	Incisional biopsy and histopathological examination
		Monomorphic adenoma	Benign or malignant	Age: From 26 to 76 years Rare in children Sex: No sex predilection	Growing palpable painless mass on jaw or in oral cavity Facial swelling Lymphadenopathy (if transformed to malignant) Pain and ulceration (in later stage)	+/-	+/-	Nodular and fluctuant swelling	Normal Redness Skin ulceration	+/-		Normal	Straw colored fluid on aspiration	Ultrasound: Used to biopsy the lesion May show cystic an solid components CT: useful for lesions with calcification and venous pleboliths MRI: Test of choice Differentiate benign from malignant Defines tumor extent Shows perineural spread	Incisional biopsy and histopathological examination
		Mucoepidermoid carcinoma	Malignant	Age:: Mean age of 59 Gender: Female predilection	Painlesss mass Swelling in oral cavity Lymphadenopathy	+/-	+/-	Cystic and solid mass	Normal	+/-	Association with CMV		Gross findings: Firm Tan-white to yellow Bosselated Cystic Microscopic findings: Encapsulated squamous and glandular components	cystic and solid component with variable appearance	Incisional biopsy and histopathological examination
		Adenoid cystic carcinoma	Malignant	Age: 40s to 60s Gender: Female predominance	Slow growing painless mass	+/-	+/-	Solid mass	Normal to ulcerated lesions	+/-	Slow growing rare tumor with low recurrence		Gross findings: Tubular, cribriform and solid pattern of growth Microscopic findings: Components of large cells with pleomorphic nuclei increased mitotic activity, and focal necrosis.	Imaging reveal dimensions of the tumor, local spread and distant metastasis	Biopsy and histopathological examination
		Adenocarcinoma	Malignant	Age: young age predilection	Its a tumor of minor salivary glands so may present as small ulceration or nodules in oral cavity	-	-	Small nodules and oral cavity with or without lymphadenopathy	Skin stays intact or may show some ulceration	+/-	There are several subtypes of adenocarcinoma. Some are more infiltrating in nature	Can be normal or may show anemia and blood cell disorders with distant bone invasion	On histology it is confused with Adeocyctic carcinoma with components of gland and cyst formations. It has more perineural invasion.	CT and MRI both can be used to visualize the tumor. MRI being more accurate for adjacent tissue involvement and lymphadenopathy.	Biopsy and histopathological examination
		Salivary duct cancer	Malignant (Highly aggressive)	Incidence: 1% to 3% Gender: Men Mean age: 55 to 61 years	Presents as rapidly growing mass	+/-	+/-	Painless, hard and non-compressible mass In case of facial nerve involvement may present with facial paralysis	Jaw involvement results in ulceration of mucosa and may cause ulceration of skin as well	+/-	Rapidly growing mass with jaw involvement and facial paralysis in case of facial nerve involvement	Pathomorphologically tumor of salivary ducts resembles tumor of breast ducts, and that where it name is derived from	Gross findings: Firm mass Cystic component of variable size and dimension Microscopic finding: Microscopically it resembles ductal carcinoma of breast Intraductal components invading surrounding tissues Intra-ductal component of tumor arrange in several forms: cribriform, papillary, solid with comedo-like central necrosis	Non-specific features on CT and MRI but it can show neural and jaw involvement.	Biopsy and histopathological examination
		Squamous cell carcinoma	Malignant	Incidence: rare tumor Age: Old age , 61 to 68 years Gender: Male predilection	Present as painful growing mass on jaw	+	-	Teneder Firm Solitary swelling on jaw	Thinning and discoloration of skin	-	Submandibular gland predilection	Past radiation exposure is a strong risk factor	Gross findings: Shows skin tissue and thinning of skin Microscopically findings: Nest and solid sheets of tumor cells arranged in glandular pattern. It is derived from epidermoid cells of salivary gland. May show vascular invasion and inflammatory infiltrate. Immunohistochemical staining can be used to mark the squamous and keratin component.	Tumor dimension can be delineated using both CT and MRI	Biopsy and histopathological examination
	Parathyroid cancer		Malignant	Incidence: Rare Mean age : 44 to 54 years Gender: Female predilection	Presents with the hyperparathyroidism Tachycardia Weight loss Sweating Neck swelling Bone pains Stomach pain Nausea and vomiting Fatigue Confusion	+	+	Lower neck mass with	Skin stays intact most of the time	-	Labs may show hypercalcemia and its consequences such as pancreatitis and decrease bone density on DEXA scan.	Low TSH Increased T4 and T3 Hypercalcemia	Microscopic findings:Tumor shows trabecular growth pattern with high mitosis and surrounding thick fibrous bands. Capsular involvement and vascular invasion is common	CT and MRI shows more frequent lower lobe involvement, vascular involvement , lymph node metastasis and perineural involvement. Bone scan may show decreasing bone density	Biopsy and histopathological examination
	Carotid body tumors		Benign	Age: 26-55 years Gender: Male predominance	A slow growing pulsating and expanding neck mass pain Change in voice Dizziness Tinnitus Headache	-	-	Mobile non-tender neck mass (horizontally more than vertically) Pulsatile nodule in neck Bruit may be present	Normal	-	Urine analysis for metanephrine levels	May show Increased catecholamine levels	Microscopically they are extra- adrenal paragangliomas	Doppler ultrasound, CT, MRI and angiography is used to visualize the tumor. Metaiodobenzylguanidine (MIBG) testing	Histopathology analysis and catecholamine levels
	Paraganglioma		Benign (Majority) Malignant (rare)	Mean age:age from 50 to 70 years Gender: More in females	May be an accidental finding depending on their secretory nature or present with following symptoms: Palpitations Tremor Pulse-like vibratory sense Headache Change in voice Vertigo Catecholaminesecreting paragangliomas present with : Hypertension Headache Sweating Tachycardia	-	-	No visible mass as they are located deep in the the neck along the glossopharyngeal and vagal nerves.	skin stays intact and usually is normal	-	Associated with some hereditary syndromes and MEN2B syndrome, Neurofibromatosis type 1 and VHL disease	Biochemical testing may show catecholamine metabolites in serum or urine samples	These are highly vascular tumors that involves nerves around vessels Gross findings: Fleshy tumors Pink to red brown to gray in color Associated with hemorrhage or fibrosis Microscopic findings: Round or polygonal cells arranged inside capsule in the form of nests or forming trabecular structures. Differentiation between benign or malignancy form is done depending microscopic features of invasion and high mitotic index	Following imaging techniques can be used to diagnose the tumor: Ultrasound Computed tomography Magnetic resonance imaging As these are secretory tumors further testing with following techniques can confirm diagnoses: Angiography metaiodobenzylguanidine (MIBG) 18F-fluoro-2-deoxyglucose Positron emission tomography (FDG-PET)	Imaging and serum catecholamine analysis
	Schwannoma		Benign	Rare tumor Incidence: 1% to 10%	Slow growing mass presents with the localized neural deficit depending on the site of peripheral nerve involved. Vagal involvement: Hoarseness Dysphagia Sympathetic nerve involvement may present as Horner's syndrome: Dilated pupil Decrease sweating Dropping eye lid Vestibular Schwannoma (most common): Hearing impairment	+	+/-	Multiple slow growing nodules on the skin	Normal	-	Associated with neurofibromatosis type II. Most common nerve involved in vestibular nerve	May be normal	It is a peripheral nerve tumor vagus nerve or superior cervical sympathetic chain being most common locations. Histology shows encapsulated neural tissue growth.	Imaging can diagnose the tumor. Its hard to discriminate Carotid body tumor from Schwannoma on CT. MRI and MRI angiography can confirm the diagnoses.	Imaging is used for diagnoses
	Lymphoma		Benign/ malignant	Age: Predilection for older age Mean age: 55	Insidious onset slow growing lymph nodes with non-specific systemic B symptoms (fever, night sweats, weight loss) Rash Waxing and waning lymphadenopathy Abdominal fullness hepatomegaly and splenomegaly Infections due tocytopenias	-	+/-	Multiple chain lymphadenopathy Hepatomegaly Splenomegaly Mesenteric lymphadenopathy Ascites Chest auscultation may show crackles and fibrosis	Rash and pruritus	-	With acquired form of C1 inhibitor deficiency patients may develop angioedema	Anemia Thrombocytopenia Leukopenia Hypercalcemia Hyperuricemia (increased cell turnover) Monoclonal immunoglobulin (M-spike) Raised LDH levels	Fine needle aspiration (FNA) with cytometry is used for screening. Tissue biopsy is used for diagnose. On complete node analysis four patterns are described: Nodular/follicular Diffuse pattern Transition from a nodular to a diffuse pattern in adjacent nodes Transition from a lower to a higher grade of involvement within a single node	Imaging is used to stage the disease. Positron emission tomography with computed tomography (PET/CT) is preferred over MRI.	Lymph node biopsy coupled with cytometry
	Liposarcoma		Malignant	Rare tumors Age: Relatively in older age Gender: No gender predilection	Mobile masses with very few symptoms until they grow enough to compress the surrounding structures, which produces symptoms of neural deficit, pain, tingling or skin changes.	+/-	-	Mobile soft mass with intact overlying skin and in some cases with blue discoloration due to intra-lesion hemorrhage	Intact and normal color	-	-	Normal	Gross findings: Bulk of yellow colored fat tissue. Microscopic features: Adipose tissue containing that containing lipoblasts atypical nucleus pushed to side by intracytoplasmic vacuoles. Tissue biopsy may show histological sub-groups: Well-differentiated Myxoid/round cell Pleomorphic liposarcomas	Imaging is not usually used for diagnoses except to look for deeper invasion. Ultrasound shows homogeneous hyperechoic mass.	Biopsy and histopathology analysis
	Lipoma		Benign	Genetic predisposition Unspecific gender or age association	One or multiple soft, painless skin nodules. May causes pain or compressive symptoms	+/-	-	Mobile soft nodule with intact overlying skin	Intact and normal in color	-	Multiple lipomas are associated with familial multiple lipomatosis	Normal	Diagnoses is usually clinical but tissue biopsy may show Bundle of well-demarcated lipocytes with single nuclei aligned to the side and intra-cytoplasimic fat granules.	Diagnoses is usually clinical but ultrasound is used to differentiate lipoma from other benign lesions such as epidermoid cyst or a ganglion.	Clinical evaluation and tissue biopsy
	Glomus vagale, glomus jugulare tumors		Benign	Rare tumor	Painless slowly enlarging mass in the neck May have compressive symptoms such as: Dysphagia Hoarseness Cranial nerves deficits Horner's syndrome	-	+/-	Firm, non-compressible and non-tender swelling. Absent thrill or bruit differentiate it from carotid aneurysm. Normal overlying skin.	Normal and mobile overlying skin	-	Secretory tumors are diagnosed by biochemical testing using Metaiodobenzylguanidine (MIBG) , followed by imaging to locate the tumor	Normal	Glomus tumors arise from Non Chromaffin cells their histopathology reveals "salt and pepper" chromatin which is typical of tumor. On immunohistochemistry tumor cells show chromogranin and S-100 positivisty	Imaging is important for the diagnosis. Imaging of choice is MRI. MRI may show typical appearance of the tumor along Vagus nerve. USG may used to see the tumor but it is for early stage of diagnoses. US shows isoechoic to hypoechoic well defined tumor. CT can show vascularity of tumor. Biochemical testing to see secretary nature of tumor	Imaging and MIBG testing
	Metastatic head and neck cancer		Malignant	Depends on the nature of metastatic tumor	Asymptomatic Painless lymphadenopathy. Supra clavicular fullness in case of stomach cancer metastasis	-	+/-	Non-tender mass in the neck or non-tender lymphadenopathy	Normal skin	-	Majority of metastatic head and neck cancer metastatise from GIT and lungs and are squamous cell caners	Vary depending on the underlying cancer	Histology of primary cancer	CT and MRI shows extend of the tumor and other regions of metastasis	Biopsy and histopathology of the primary site of tumor
Other	Laryngeal cancer		Benign/Malignant	Older males Younger patients with HPV infection or smoking history	Neck mass Hoarseness Throat pain Snoring Obstructive sleep apnea	+/-	+/-	Examination of neck and oral cavity may show mass and lymphadenopathy. Examination of laryngeal cancer is done using flexible laryngoscopy under anesthesia.	-	-	Smoking is the most common risk factor Smoking with alcohol increases the risk Oropharyngeal cancers presenting with neck masses are associated with human papillomavirus (HPV) infection	HPV testing may show HPV infection	FNA of neck mass followed by biopsy is done to diagnose laryngeal cancer. It show type cancerous cells.	CT, MRI and PET are used to see local infiltration by cancer and also distant metastases. Panendoscopy is done to see extent of the tumor.	Laryngoscopy and biopsy
	Arteriovenous fistula		Benign/Malignant	Depends on the risk factors	Expanding neck mass Headaches Dizziness Neurological sequels	-	-	Pulsating neck mass Bruit	Intact overlying skin with normal color and texture	-	May be associated with vasculopathies and metastatic invasion of vessels and neck surgery		Varies depending on the etiology	MR angiography may be used to visualize the tract	MR angiography
	Thyroid nodule/ Goiter		Benign/ Malignant	Female predominance Young age (benign causes) Old age (malignant etiology)	Growing painless neck mass in front of neck Weight loss Palpitation Hoarseness Irritability	+/-	+/-	Painless non-tender and asymmetrical neck mass in front of neck with smooth overlying skin and nodular surface Depending on the type may be mobile or adherent to the underlying structure Lymphadenopathy in case of malignant features	Intact	-	Goiter is most commonly associated with iodine deficiency	Normal to low TSH levels in case of malignancy High TSH levels in case of goiter	FNA is done in case of goiter and core biopsy is performed if malignancy is suspected	USG: Shows nodular or non- nodular lesions in Thyroid. US is better than CT. Thyroid radionuclide imaging: Shows radioiodine uptake and is usually cold in case of malignancy and may be cold or hot in case of goiter.	Biopsy and histopathology of nodules
Category	Diseases		Benign	Demography	History	Pain	Dysphagia	Mass exam	Skin changes	LAP	Others	Lab findings	Histopathology	Imaging	Gold standard diagnosis	Associated findings