What is the differential diagnosis for a submandibular mass in an adult patient with no significant medical history?

Differential Diagnosis for Submandibular Mass

The differential diagnosis for a submandibular mass in an adult includes salivary gland pathology (inflammatory and neoplastic), lymphadenopathy (infectious, malignant, or reactive), congenital lesions, and metastatic disease—with malignancy being the primary concern until proven otherwise. 1, 2

Salivary Gland Pathology (Most Common Origin)

Submandibular gland disease accounts for approximately 71% of all submandibular masses. 3

Inflammatory/Obstructive Disease

• Chronic sialadenitis due to sialolithiasis (salivary stones) is a frequent cause, presenting as recurrent swelling, particularly with meals 4, 3
• Chronic sialadenitis without stones accounts for 27% of submandibular masses in surgical series 3
• Sialoadenosis (non-inflammatory gland enlargement) can occur with eating disorders, diabetes, or alcoholism 4

Benign Neoplasms

• Pleomorphic adenoma is the most common benign tumor of the submandibular gland, comprising 22.7% of all submandibular masses 3
• Other rare benign tumors include Warthin's tumor, oncocytic lipoadenoma, and granular cell tumors 2, 5, 6

Malignant Neoplasms

• Salivary gland malignancies (adenoid cystic carcinoma, mucoepidermoid carcinoma, adenocarcinoma) comprise 3% of submandibular masses but carry significant morbidity 2, 3
• Malignant tumors represent 23% of all submandibular gland tumors when present 3

Lymphadenopathy

Metastatic Malignancy (Critical to Exclude)

• Metastatic squamous cell carcinoma from oral cavity, oropharynx, or occult primary sites is the most concerning diagnosis in adults with persistent neck masses 1, 2
• HPV-positive oropharyngeal cancer frequently presents as cystic cervical metastases that mimic benign lesions 2
• Metastatic cutaneous malignancies (melanoma, squamous cell carcinoma from scalp/face) must be considered 2
• Lymphoma (Hodgkin's and non-Hodgkin's) can present as isolated submandibular lymphadenopathy 2, 7

Infectious/Reactive Lymphadenopathy

• Reactive lymphadenitis accounts for 15% of submandibular masses 3
• Mycobacterial infection (tuberculosis or atypical mycobacteria) presents as chronic, firm lymphadenopathy 1, 2
• Cat-scratch disease (Bartonella henselae) causes regional lymphadenopathy 1, 2
• HIV-related lymphadenopathy or EBV/CMV infection should be considered in appropriate clinical contexts 1, 2

Congenital Lesions

• Branchial cleft cysts (second branchial cleft most common) typically present anterior to the sternocleidomastoid muscle and may become infected 2
• These are less common in the submandibular triangle compared to other neck locations 2

Autoimmune/Systemic Conditions

• Sjögren's syndrome can cause bilateral submandibular gland enlargement 1, 2
• Sarcoidosis may present with salivary gland or lymph node involvement 1, 2

Critical Red Flags Mandating Urgent Malignancy Workup

The American Academy of Otolaryngology-Head and Neck Surgery identifies these high-risk features: 1, 2

Mass Characteristics

• Firm consistency (malignant nodes lack tissue edema) 2
• Fixation to adjacent tissues suggesting capsular invasion 1, 2
• Size >1.5 cm 1, 2
• Nontender (infectious masses are typically tender) 1, 2
• Present ≥2 weeks without fluctuation or uncertain duration 1, 2
• Ulceration of overlying skin 1, 2

Patient Risk Factors

• Age >40 years 2
• Tobacco and alcohol use (synergistic risk for head and neck cancer) 2
• History of prior head/neck malignancy including skin cancer 2

Associated Symptoms

• Ipsilateral otalgia with normal ear exam (referred pain from pharyngeal malignancy) 1, 2
• Dysphagia, odynophagia, or throat pain 2
• Voice change 2
• Unexplained weight loss 2
• Oral cavity ulcers or tonsil asymmetry 1, 2

Diagnostic Approach Algorithm

Initial Evaluation

1. Intra-oral inspection and bimanual palpation of the floor of mouth to differentiate submandibular gland from lymph node and identify masses or stones 4
2. Complete head and neck examination including visualization of oral cavity, oropharynx, and scalp for primary malignancy sites 1

Imaging

• Ultrasound is the first-line radiologic evaluation for submandibular masses 3
• CT with contrast or MRI with contrast should be ordered for all patients at increased risk for malignancy 1, 2

Tissue Diagnosis

• Fine-needle aspiration (FNA) is preferred over open biopsy for diagnostic uncertainty, with 88% diagnostic accuracy 3
• Excisional biopsy should only be performed when FNA is non-diagnostic and after complete evaluation including upper aerodigestive tract examination 1, 3

Ancillary Testing (When Indicated)

Based on clinical suspicion, consider: 1

• CBC with differential for infection or lymphoma
• HIV testing in appropriate risk populations
• PPD/tuberculin testing for mycobacterial infection
• EBV/CMV titers for viral lymphadenopathy
• Thyroid ultrasound if thyroid pathology suspected

Critical Pitfalls to Avoid

• Never perform open biopsy before complete evaluation—this violates oncologic principles and may compromise treatment if malignancy is present 2
• Do not assume cystic masses are benign—HPV-positive oropharyngeal metastases are frequently cystic and mistaken for branchial cleft cysts 1, 2
• Avoid empiric antibiotics without clear bacterial infection—this delays cancer diagnosis and worsens outcomes 2, 7
• Do not mistake normal submandibular glands for pathologic masses—these are frequently palpable in thin individuals 1
• When FNA is non-diagnostic (12% failure rate), proceed to excisional biopsy rather than repeat FNA indefinitely 3