What are the causes of bilateral submandibular swelling?

Bilateral Submandibular Swelling: Causes and Diagnostic Approach

Bilateral submandibular swelling requires systematic evaluation for inflammatory, autoimmune, infectious, and neoplastic etiologies, with sarcoidosis, Sjögren's syndrome, and bilateral sialadenitis being the most common causes in adults. 1

Primary Inflammatory and Autoimmune Causes

Sarcoidosis

• Sarcoidosis is the leading differential diagnosis for bilateral salivary gland involvement, with symmetrical parotid and submandibular enlargement being a characteristic "probable" clinical feature 1
• Parotid uptake on imaging is considered "highly probable" for sarcoidosis diagnosis 1
• Look for hypercalcemia/hypercalciuria with abnormal vitamin D metabolism and elevated ACE level (>50% upper limit of normal) 1
• Biopsy demonstrates non-caseating granulomas with special stains negative for mycobacteria and fungi 1

Sjögren's Syndrome

• Presents with bilateral submandibular and parotid gland enlargement associated with dry eyes and dry mouth 2
• Lacrimal glands may also be bilaterally enlarged 1
• Requires serologic testing for anti-SSA/SSB antibodies and consideration of minor salivary gland biopsy 3

IgG4-Related Disease

• Can cause bilateral salivary gland swelling with characteristic IgG4+ plasma cell infiltration on histology 1
• Often associated with elevated serum IgG4 levels and involvement of other organs 1

Infectious Etiologies

Viral Sialadenitis

• Mumps is a classic cause of bilateral submandibular and parotid swelling, particularly in unvaccinated individuals 2
• HIV-associated salivary gland disease can present with bilateral enlargement 3
• Epstein-Barr virus (infectious mononucleosis) may cause bilateral submandibular lymphadenopathy and glandular swelling 2

Bacterial Sialadenitis

• Bilateral bacterial sialadenitis is less common but can occur with ductal obstruction or systemic predisposing factors 4, 5
• Look for purulent discharge from Wharton's ducts on intraoral examination 4
• Associated with dehydration, poor oral hygiene, or medications causing xerostomia 4

Granulomatous Infections

• Tuberculosis can cause bilateral granulomatous inflammation requiring special stains for acid-fast bacilli 1
• Syphilis, fungal diseases, and atypical mycobacterial infections should be considered in appropriate clinical contexts 1

Obstructive Causes

Bilateral Sialolithiasis

• Submandibular stones are the most common cause of salivary obstruction, with 80-90% occurring in the submandibular system 6
• Bilateral stones are uncommon but can occur, causing recurrent meal-related swelling 7
• Intraoral inspection and bimanual palpation are essential to identify stones in Wharton's duct 4, 8
• Chronic obstruction can lead to chronic sialadenitis and even malignant transformation in rare cases 7

Vasculitic and Eosinophilic Disorders

Eosinophilic Granulomatosis with Polyangiitis (EGPA)

• Consider with pharyngeal involvement and peripheral eosinophilia (>1500 cells/μL or >10%) 1
• p-ANCA positivity occurs in 26-48% of cases 1
• Associated with asthma and systemic vasculitis 1

Kimura's Disease and Angiolymphoid Hyperplasia

• Rare causes of bilateral submandibular swelling with eosinophilic infiltration 9
• Histology shows periductal sclerosis with lymphoplasmacytic infiltrate rich in eosinophils 9

Neoplastic Causes

Lymphoma

• Bilateral involvement with lymphadenopathy should raise suspicion for lymphoma 1
• Look for B symptoms: fever, weight loss, night sweats 1
• Intraglandular lymphatic tissue predisposes parotid and submandibular glands to lymphoma 1

Metastatic Disease

• In patients over 40 years old, metastatic disease is the greatest cause of asymmetric submandibular enlargement 2
• Always seek to eliminate a primary site in the head, neck, and oral cavity 2
• Consider distant primaries from lung, breast, kidney, or gastrointestinal tract 2

Diagnostic Algorithm

Initial Clinical Assessment

• Perform intraoral inspection and bimanual palpation to identify ductal stones or masses 4, 8
• Assess for meal-related swelling (suggests obstruction) versus constant swelling (suggests inflammatory or neoplastic process) 6
• Examine for systemic features: dry eyes/mouth (Sjögren's), asthma/eosinophilia (EGPA), B symptoms (lymphoma) 1

First-Line Imaging

• Ultrasound is the preferred initial imaging modality for evaluating submandibular gland pathology due to effectiveness, safety, and accessibility 4, 8
• Can identify stones, masses, and assess glandular architecture 8

Advanced Imaging

• CT with contrast is useful for evaluating extent of disease, bone invasion, or metastatic disease 8
• MRI with contrast provides superior soft tissue resolution for suspected tumors or complex cases 8
• Chest CT should be obtained if pulmonary sarcoidosis or EGPA is suspected 1

Laboratory Workup

• Complete blood count with differential (assess for eosinophilia) 1
• Serum ACE level and calcium/vitamin D metabolism studies (sarcoidosis) 1
• ANCA panel (c-ANCA for GPA, p-ANCA for EGPA) 1
• Anti-SSA/SSB antibodies (Sjögren's syndrome) 3
• Serum IgG4 level (IgG4-related disease) 1

Tissue Diagnosis

• Fine needle aspiration or core biopsy of affected glands is essential for definitive diagnosis 1
• Histology identifies non-caseating granulomas (sarcoidosis), IgG4+ plasma cells, vasculitis, or malignancy 1
• Special stains for mycobacteria and fungi are mandatory to exclude infectious granulomatous disease 1

Critical Pitfalls to Avoid

• Do not assume bilateral swelling is benign; lymphoma and metastatic disease can present bilaterally 1, 2
• Do not rely solely on imaging; tissue diagnosis is often required for definitive management 1
• In patients over 40, always exclude malignancy before attributing swelling to inflammatory causes 2
• Chronic sialadenitis from obstruction can rarely lead to malignant transformation; maintain surveillance 7
• Bilateral presentation does not exclude unilateral pathology on each side (e.g., bilateral stones) 7