What are the differential diagnoses for a patient with a CT scan of the neck showing diffuse inflammation of the bilateral parotid (parotid gland) and submandibular (submandibular gland) glands with extension to the pharyngo-laryngeal wall?

Differential Diagnoses for Bilateral Parotid and Submandibular Gland Inflammation with Pharyngo-Laryngeal Extension

The most critical differentials to consider are sarcoidosis, IgG4-related disease, and systemic granulomatous/vasculitic conditions (EGPA, GPA), followed by infectious causes including viral sialadenitis, bacterial suppurative parotitis, and COVID-19-associated sialadenitis. 1, 2, 3

Primary Differential Considerations

Systemic Inflammatory/Autoimmune Diseases

Sarcoidosis is a leading consideration given the bilateral salivary gland involvement. 1

• Parotid uptake on imaging is considered "highly probable" for sarcoidosis diagnosis 1
• Symmetrical parotid enlargement is a "probable" clinical feature 1
• Lacrimal glands may be bilaterally enlarged 1
• Hypercalcemia/hypercalciuria with abnormal vitamin D metabolism supports diagnosis 1
• Elevated ACE level (>50% upper limit of normal) is a probable feature 1
• Biopsy shows non-caseating granulomas; special stains negative for mycobacteria and fungi 1

IgG4-Related Disease presents with subacute bilateral submandibular and/or parotid swelling and sialadenitis. 2

• This is a rare, immune-mediated systemic disease characterized by lymphocyte infiltration and fibrosis 2
• Frequently misdiagnosed as it mimics infectious, inflammatory, and neoplastic diseases 2
• Diagnosis requires clinical, serologic, radiologic, and pathologic correlation 2
• Most cases respond quickly to systemic glucocorticoids 2

Eosinophilic Granulomatosis with Polyangiitis (EGPA) should be considered, particularly with pharyngeal involvement. 1

• Peripheral eosinophilia (>1500 cells/μL or >10%) is characteristic 1
• p-ANCA positivity in 26-48% of cases, higher (75%) with renal involvement 1
• Associated with adult-onset asthma, recurrent CRS with nasal polyps 1
• Hypopharynx and supraglottis can be involved 1

Granulomatosis with Polyangiitis (GPA) is part of the differential for granulomatous diseases. 1

• Distinguished from EGPA by absence of marked eosinophilia and asthma 1
• c-ANCA positivity more common than in EGPA 1

Infectious Etiologies

Viral Parotitis remains a common cause of bilateral parotid inflammation. 4

• Paramyxovirus (mumps), Epstein-Barr virus, coxsackievirus, influenza A, and parainfluenza viruses 4
• COVID-19-associated sialadenitis can present with bilateral parotid and sublingual gland enlargement with surrounding fat stranding 3

Acute Suppurative Parotitis typically presents with more acute symptoms. 4

• Caused by Staphylococcus aureus, Streptococcus species, rarely gram-negative bacteria 4
• Anaerobic bacteria (Peptostreptococcus, Bacteroides, Porphyromonas, Prevotella species) increasingly recognized 4
• Beta-lactamase-producing organisms isolated in three-fourths of patients 4
• Predisposing factors: dehydration, malnutrition, immunosuppression, sialolithiasis, medications reducing salivation 4

Other Granulomatous Diseases

The differential includes other granulomatous conditions: 1

• Tuberculosis (requires special stains for mycobacteria) 1
• Syphilis 1
• Rhinoscleroma 1
• Fungal diseases 1
• Berylliosis 1
• Leprosy 1

Drug-Induced Sialadenosis

Valproic acid-associated sialadenosis causes bilateral, non-inflammatory salivary gland swelling. 5

• Can affect both parotid and submandibular glands 5
• Granular sialadenosis on histology 5

Malignancy-Related

Lymphoma should be considered with bilateral involvement and lymphadenopathy. 1, 6

• Intraglandular lymphatic tissue predisposes parotid glands to lymphoma 1
• Fever, weight loss, night sweats suggest lymphoma 6

Diagnostic Workup Algorithm

Initial imaging: CT neck with contrast already obtained shows diffuse inflammation 1, 7, 8

Next steps based on clinical context:

1. Laboratory evaluation:

   • Complete blood count with differential (eosinophilia for EGPA) 1
   • ANCA testing (p-ANCA for EGPA, c-ANCA for GPA) 1
   • Serum ACE level (elevated in sarcoidosis) 1
   • Serum calcium, urinary calcium, vitamin D metabolites (sarcoidosis) 1
   • IgG4 levels (IgG4-related disease) 2
   • Viral serologies including COVID-19, EBV, mumps 4, 3

2. Tissue diagnosis is essential:

   • Fine needle aspiration or core biopsy of affected glands 6, 2
   • If pus present, culture for aerobic/anaerobic bacteria, mycobacteria, fungi 4
   • Histology to identify non-caseating granulomas (sarcoidosis), IgG4+ plasma cells, or vasculitis 1, 2

3. Additional imaging if indicated:

   • MRI neck with and without contrast for better soft tissue characterization 1, 6
   • Chest CT to evaluate for pulmonary sarcoidosis or EGPA 1
   • FDG-PET for systemic disease assessment in sarcoidosis 1

Critical Pitfalls to Avoid

• Do not assume infectious etiology without tissue diagnosis when bilateral involvement and pharyngeal extension are present, as systemic inflammatory diseases are more likely 1, 2
• Beta-lactamase-producing organisms are common in suppurative parotitis; empiric antibiotics must cover these 4
• Negative ANCA does not exclude EGPA, particularly in head and neck phenotype 1
• IgG4-related disease is frequently misdiagnosed due to its mimicry of other conditions 2
• Monitor for airway compromise with pharyngeal involvement, maintaining low threshold for intervention 7, 8