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

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Differential diagnosis of neck masses

Differential diagnosis of neck masses include:

Category Diseases Benign or 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[1]
  • Benign
  • Age: 1-15 yrs/ varies
  • Familial occurence is noted
  • Lateral neck mass
- +/-
  • Solitary
  • Smooth
  • Mobile
  • Welldefined
  • Nonpulsatile
  • 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[2][3]
  • 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[4]
  • Benign
  • Age: birth - 2 yrs
  • Females>males
  • Usually present with a flat red or purple patch
- -
  • Firm
  • Rubbery
  • Well-demarcated
  • Blanching
  • Telangiectasias
  • Erythematous patch
- -
  • GLUT-1
  • VEGF
  • Urinary BFGF
  • 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
Lymphatic malformations
Laryngocele[5][6][7]
  • Benign
  • More common in adults
  • Male: female = 5:1
  • Present 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
  • CT scan is the gold standard imaging for diagnosis
-
Ranula[8]
  • Benign
  • Age: 1st and 2nd decade
  • Female: male=1:1.4
  • Present with a blue colored swelling in the floor of the mouth
- -
  • Well circumscribed
  • Fluctuant
  • Soft
-
Teratoma Incidence: 1:4000 births High ALP levels
Dermoid cyst[9][10]
  • Benign
  • Incidence: 3 per 10000 population
  • Age: birth - 5 yrs
  • Presents as a slow growing mass or a sinus
- -
  • Freely mobile/Fixed
  • 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[11]
  • 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 or Malignant Demography History Pain Dysphagia Mass exam Skin changes LAP Others Lab findings Histopathology Imaging Gold standard diagnosis Associated findings
Inflammatory Acute sialadenitis [12]
  • Benign
  • No sex predilection
  • Occurs in all age groups
  • 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
  • Ultrasound: Hypoechoic with ductal dilatation
  • CT: Diffuse homogeneous enlargement
Chronic sialadenitis
  • Benign
  • No sex predilection
  • Occurs in all age groups
  • Presents with an unilateral swelling
  • Recurrent episodes common
+ -
  • Non-tender
  • Firm
  • Smooth
  • Mostly due to obstruction by a stone or stricture
  • ↑ ESR
  • Leukocytosis
Reactive viral lymphadenopathy CMV[13]
  • Age: 10-35 yrs mainly
  • No sex predilection
  • Flu-like illness
- -
  • Non-tender
  • Soft
  • Generalized/cervical
  • H&E stain: Typical owl-eye inclusions(nuclear)
  • Basophilic cytoplasmic inclusions
  • FNAC & serology
EBV[14][15]
  • Age: Mainly adolescents
  • Sex: No sex predilection
  • Sore throat
  • Fever
  • Malaise
  • Lymphadenopathy
- -
  • Non-tender
  • Firm
  • B/L posterior cervical, axillary, inguinal
  • Atypical lymphocytosis
  • + Monospot test
  • IgM & IgG antibodies
  • CD8+ lymphocytes
  • Tissue necrosis
  • B lymphocyte blasts
  • FNAC & serology
HIV
  • Flu-like illness
  • Rash
Viral URI
Bacterial lymphadenopathy Tularemia
Brucellosis
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 or Malignant 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

[16]

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 [17][18][19] 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

[20]

Malignant
  • Age:: Mean age of 59
  • Gender: Female predilection
  • Painlesss mass
  • Swelling in oral cavity
  • Lympadenopathy
+/- +/- Cystic and solid mass Normal +/- Association with CMV Gross findings:
  • Firm
  • Tan-white to yellow
  • Bosselated
  • Cystic

Microscopic:

  • Encapsulated squamous and glandular components
cystic and solid component with variable appearance Incisional biopsy and histopathological examination
Adenoid cystic carcinoma [21] 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: Tubular, cribriform and solid pattern of growrth

Microscopic: Components of large cells with pleomorphic nuclei

increased mitotic activity, and focial necrosis.

Imaging reveal dimensions of the tumor, local spread and distant metastasis Biopsy and histopathological examination
Adenocarcinoma

[22]

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 adenocarcimoma.

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 carcinoma

[23][24][25]

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

[26][27]

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: Shows skin tissue and thinning of skin

Microscopically:

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 tumors

[28][29][30]

Malignant Incidence: Rare

Mean age : 44 to 54 years

Gender: Female predilection

  • Presents with the hyperparathyroidi
  • 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 cone density
Biopsy and histopathological examination
Carotid body tumors
- - -
Paraganglioma

[31][32][33]

Benign (Majority)

Malignnat (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

Catecholamine-secreting 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

[34][35][36]

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 Noirmal - 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 diagnose
Lymphoma [37][38]

[39][40][41][42]

Benign/ malignnat 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)
  • Skin rash
  • Waxing and waning lymphadenopathy
  • Abdominal fullness ( hepatomegaly and spleenomegaly)
  • Infections (cytopenias)
- +/-
  • Multiple chain lympadeopathy
  • Hepatomegaly
  • Splenomegaly
  • Mesenteric lymph adenopathy
  • Ascities
  • Chest auscultation may show crackles and fibrosis
Skin 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 [43][44]

[45][46]

Malignnat 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:

Adipoce 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 [47][48][49] 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.

Lipoma's 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 biopy

Glomus vagale, glomus jugulare tumors

[50][51][52][53]

[54][55]

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
  • 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.
  • Glomus tumors arise from nonchromaffin cells thir histopathology reveals "salt and pepper" chromatin which is typical of tumor.
  • On immunohistochemistry tumor cells show chromogranin and S-100 positivisty.
Metastatic head and neck carcinoma

[56][57]

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

[58][59]

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 anasthesia.
- -
  • Smoking is the most common risk factor
  • Smoking with alcohol iincreases 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

[60]

Benign/Malignnat
  • 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
Goiter
Category Diseases Benign Demography History Pain Dysphagia Mass exam Skin changes LAP Others Lab findings Histopathology Imaging Gold standard diagnosis Associated findings

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Diseases Clinical manifestations Para-clinical findings Pap Smear Histopathology Gold standard Additional findings
Symptoms Physical examination
Lab Findings Imaging
Menorrhagia Post Menstrual

Bleeding

Pelvic Pain Other

symptoms

Pelvic examination Abdominal examination Hb B-HCG CEA-19 Ultrasound MRI
Endometrial cancer + + +
Uterine

sarcoma

+/- + +
Uterine

lymphoma

+/- +/-

or

N

Uterine leiomyoma +/- +/-

or

N

Malignant mixed

Mullerian

tumour

(MMMT)

of the uterus

+/- +/-
Cervical cancer

with

uterine

invasion

+ +
Metastasis to the uterus from a

non-gynaecologcial

malignancy

+ +
Endometrial

polyp

+ + +

or

N

Endometrial

hyperpalsia

+ + +
Uterine

adenomyoma

- - +
Hematometra - - +
Gestational

trophoblastic

disease

Incomplete

abortion

Fetus No

Menstrual cycle

+/- -
Diseases Clinical manifestations Para-clinical findings Gold standard Additional findings
Symptoms Physical examination
Lab Findings Imaging Histopathology
Symptom 1 Symptom 2 Symptom 3 Physical exam 1 Physical exam 2 Physical exam 3 Lab 1 Lab 2 Lab 3 Imaging 1 Imaging 2 Imaging 3
Uterine cancer
Uterine sarcoma
Infection
Diseases Symptom 1 Symptom 2 Symptom 3 Physical exam 1 Physical exam 2 Physical exam 3 Lab 1 Lab 2 Lab 3 Imaging 1 Imaging 2 Imaging 3 Histopathology Gold standard Additional findings
Abscess
Septic emboli
Fungi
Differential Diagnosis 1
Differential Diagnosis 2
Differential Diagnosis 3
Diseases Symptom 1 Symptom 2 Symptom 3 Physical exam 1 Physical exam 2 Physical exam 3 Lab 1 Lab 2 Lab 3 Imaging 1 Imaging 2 Imaging 3 Histopathology Gold standard Additional findings
Differential Diagnosis 4
Differential Diagnosis 5
Differential Diagnosis 6

Table for Differential Diagnosis of Small Intestine Cancer

ABBREVIATIONS:

N/A: Not available, NL: Normal,

References