What is the differential diagnosis for a left-sided neck mass?

Differential Diagnosis for a Left-Sided Neck Mass in Adults

In adults, a persistent neck mass must be considered malignant until proven otherwise, as malignant neoplasms far exceed any other etiology of adult neck masses. 1

Primary Malignant Etiologies (Most Critical to Exclude)

The following malignancies represent the most important diagnoses to rule out, as delayed diagnosis directly affects tumor stage and worsens prognosis 1:

• Metastatic squamous cell carcinoma (HNSCC) from primary sites including oral cavity, oropharynx, hypopharynx, nasopharynx, or larynx 1
• HPV-positive oropharyngeal cancer (tonsil and base of tongue), which often presents as cystic cervical metastases that may be mistaken for branchial cleft cysts 1
• Lymphoma (Hodgkin's and non-Hodgkin's) 1
• Thyroid cancer (particularly in women under age 40) 1
• Salivary gland malignancies 1
• Metastatic cutaneous malignancies (melanoma, squamous cell carcinoma, basal cell carcinoma from scalp, face, or neck) 1

Benign Neoplastic Etiologies

• Thyroid nodules or goiter 1
• Benign salivary gland tumors (pleomorphic adenoma, Warthin's tumor) 1
• Paragangliomas (carotid body tumors) 2
• Lipomas 2
• Schwannomas or neurofibromas 2

Congenital Lesions

• Branchial cleft cysts (second branchial cleft most common, typically anterior to sternocleidomastoid muscle) 1, 3
• Thyroglossal duct cysts (midline, moves with swallowing and tongue protrusion) 4, 3
• Dermoid or epidermoid cysts 3
• Cystic hygroma/lymphangioma 3

Infectious/Inflammatory Etiologies

• Reactive lymphadenopathy from viral or bacterial infections (more common in children, but can occur in adults) 3, 5
• Mycobacterial infection (tuberculosis or atypical mycobacteria) 1
• Cat-scratch disease (Bartonella henselae) 1
• HIV-related lymphadenopathy 1
• Epstein-Barr virus (EBV) or cytomegalovirus (CMV) infection 1
• Toxoplasmosis 2

Autoimmune/Systemic Conditions

• Sarcoidosis 1
• Sjögren's syndrome (bilateral parotid enlargement) 1
• Systemic lupus erythematosus 1

Critical Red Flags for Malignancy

The following characteristics dramatically increase suspicion for malignancy and mandate urgent workup 1:

Mass Characteristics:

• Mass present ≥2 weeks or of uncertain duration 1
• Absence of infectious etiology 1
• Firm texture (malignant nodes lack tissue edema) 1
• Reduced mobility/fixation to adjacent tissues (suggests capsular invasion) 1
• Size >1.5 cm 1
• Nontender (infectious masses are typically tender) 1
• Ulceration of overlying skin 1

Patient History Red Flags:

• Age >40 years 1
• Tobacco and alcohol use (synergistic risk factors for HNSCC) 1
• History of prior head and neck malignancy (including skin cancer of scalp, face, or neck) 1

Associated Symptoms:

• Pharyngitis or throat pain (may indicate mucosal ulceration) 1
• Dysphagia 1
• Ipsilateral otalgia with normal ear exam (referred pain from pharynx) 1
• Recent voice change 1
• Ipsilateral hearing loss (suggests nasopharyngeal malignancy with middle ear effusion) 1
• Ipsilateral nasal obstruction and epistaxis 1
• Unexplained weight loss 1
• Oral cavity or oropharyngeal ulcer 1
• Tonsil asymmetry 1

Location-Specific Considerations

Left-sided masses follow the same differential as right-sided masses, but specific anatomic locations provide diagnostic clues 2, 5:

• Anterior triangle masses: thyroid pathology, submandibular gland pathology, lymph nodes, carotid body tumors
• Posterior triangle masses: lymph nodes (higher suspicion for malignancy, especially supraclavicular), lipomas, cystic hygroma
• Supraclavicular masses: extremely high suspicion for malignancy (thoracic or abdominal primary, lymphoma) 6, 3
• Midline masses: thyroglossal duct cyst, thyroid pathology, dermoid cyst

Common Pitfalls to Avoid

Never perform open biopsy before complete evaluation, as this violates oncologic principles and may compromise subsequent treatment if malignancy is present 1, 6. Cystic masses on imaging or FNA should not be assumed benign—HPV-positive oropharyngeal metastases are frequently cystic and mistaken for branchial cleft cysts 1. Do not routinely prescribe antibiotics unless clear signs of bacterial infection exist, as this delays cancer diagnosis 1. Normal anatomic structures frequently mistaken for pathologic masses include submandibular glands, hyoid bone, C2 transverse process, and carotid bulb 1.