What is the differential diagnosis for a soft, non-mobile neck swelling?

Differential Diagnosis of a Soft, Non-Mobile Neck Swelling

A soft, non-mobile swelling on the right side of the neck requires urgent evaluation for malignancy, particularly cystic metastatic lymphadenopathy from head and neck squamous cell carcinoma (HNSCC), lymphoma, or thyroid cancer, as the "soft" texture does not exclude malignancy and "non-mobile" (fixed) character is a high-risk feature. 1

Critical Context: Soft Texture Does NOT Mean Benign

The most dangerous assumption is that a soft neck mass is benign—cystic metastases from HPV-positive oropharyngeal cancer, papillary thyroid carcinoma, and lymphoma frequently present as soft masses, and up to 80% of cystic neck masses in patients >40 years are malignant. 1

• A soft texture indicates fluid content, which can represent either benign cystic lesions OR malignant cystic metastases with central necrosis 1
• The "non-mobile" (fixed) characteristic is a stand-alone red flag for malignancy, as it suggests invasion of adjacent structures through lymph node capsule violation 1

Primary Differential Diagnoses

Malignant Etiologies (MUST Rule Out First)

Cystic Metastatic Lymphadenopathy:

• HPV-positive oropharyngeal squamous cell carcinoma is the leading cause, with up to 62% of metastases from Waldeyer ring sites (tonsils, base of tongue, nasopharynx) presenting as cystic masses 1
• Papillary thyroid carcinoma with cystic lymph node metastases 1
• Lymphoma (can present with soft, rubbery consistency) 2
• Cutaneous malignancies (melanoma, squamous cell carcinoma) metastatic to cervical nodes 2

Primary Malignant Neck Tumors:

• Salivary gland malignancies (can be cystic) 1
• Soft tissue sarcomas 3

Benign Etiologies (Consider After Malignancy Excluded)

Congenital/Developmental:

• Branchial cleft cyst (traditionally considered most common lateral cystic neck mass, but malignancy mimics this clinically and radiologically) 1
• Ectopic thyroid tissue (rare lateral presentation) 4
• Thyroglossal duct cyst (typically midline)

Inflammatory/Infectious:

• Lymphadenitis with abscess formation (would typically have warmth, erythema, tenderness, fever) 1
• Tuberculous lymphadenitis (cold abscess—soft but typically mobile unless advanced)

Vascular:

• Vascular malformations (low-flow lesions can be soft and compressible) 1

Other Benign Neoplasms:

• Lipoma (soft, mobile—inconsistent with "non-mobile" description)
• Aggressive fibromatosis/desmoid tumor (typically firm, but can vary) 5

Risk Stratification Algorithm

High-Risk Features Present (Immediate Workup Required):

Your patient has a non-mobile (fixed) mass, which is a stand-alone indication for malignancy workup regardless of other features. 1

Additional high-risk features to assess:

• Age >40 years 1
• Mass present ≥2 weeks or uncertain duration 1
• Size >1.5 cm 1
• Tobacco and alcohol use 1
• Associated symptoms: ipsilateral otalgia, dysphagia, voice change, unilateral hearing loss, nasal obstruction/epistaxis, unexplained weight loss 1, 2
• History of prior head and neck malignancy 1

Mandatory Workup for High-Risk Patients:

1. Imaging: CT neck with IV contrast (or MRI with contrast) to assess mass characteristics, identify solid components within cystic lesions, evaluate for multiple nodes, and assess for primary tumor sites 1

2. Fine-needle aspiration (FNA) as first-line tissue diagnosis (NOT open biopsy initially) 1, 2

   • For cystic masses, image-guided FNA directed at solid components or cyst wall is critical, as sensitivity is lower (73%) compared to solid masses (90%) 1
   • If initial FNA is non-diagnostic, repeat with image guidance before proceeding to open biopsy 1

3. Examination of upper aerodigestive tract (oral cavity, oropharynx, nasopharynx, hypopharynx, larynx, base of tongue) to identify primary tumor site 1, 2

4. Referral to otolaryngology for comprehensive evaluation and potential examination under anesthesia if primary site not identified 1, 2

Critical Pitfalls to Avoid

Never prescribe antibiotics for a fixed neck mass without clear signs of infection (warmth, erythema, tenderness, fever)—this is the most common error leading to delayed cancer diagnosis and worse outcomes. 1, 2

• Even if infection is suspected, reassessment within 2 weeks is mandatory to confirm resolution 2
• Multiple courses of empiric antibiotics without definitive diagnosis is dangerous practice 2

Do not assume a cystic/soft mass is a benign branchial cleft cyst without tissue diagnosis, especially in patients >40 years. 1

Do not perform open excisional biopsy before imaging and FNA, as this can worsen outcomes if malignancy is present and risks tumor spillage. 1, 6