Differential Diagnosis for Chronic Unilateral Tonsillar Swelling and Irritation
Chronic unilateral tonsillar enlargement requires exclusion of malignancy through tonsillectomy or close surveillance, as lymphoma and squamous cell carcinoma are the most concerning diagnoses, though the majority of cases in isolation prove benign.
Malignant Causes (Primary Concern)
Lymphoma is the most common malignancy presenting as unilateral tonsillar enlargement, and all patients with tonsillar lymphoma demonstrate clinically apparent asymmetry at initial presentation 1. Key subtypes include:
- Non-Hodgkin lymphoma (lymphocytic and histiocytic types) represents the predominant malignant pathology 2
- Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) can present as isolated tonsillar asymmetry without lymphadenopathy or B-symptoms (fever, night sweats, weight loss), making it particularly insidious 3
- Hodgkin's disease, though rarer, must be considered 2
Squamous cell carcinoma is the second most common malignancy, particularly in adults over 40 years with tobacco or alcohol use history 4. The American Academy of Otolaryngology-Head and Neck Surgery mandates ENT referral for biopsy in any unilateral tonsillar abnormality persisting beyond 2-3 weeks in this population 4.
Other rare malignancies include extramedullary plasmacytomas, leukemia, and metastatic neoplasms 2.
Infectious and Inflammatory Causes
Group A Streptococcal (GAS) pharyngitis can present with unilateral tonsillar exudates and must be excluded even without systemic symptoms, as clinical diagnosis alone is unreliable 4. The CDC and AHA require either rapid antigen detection test (RADT) or throat culture for confirmation 4. Key distinguishing features include tonsillopharyngeal erythema, tender anterior cervical lymphadenopathy, and absence of cough/rhinorrhea/hoarseness 4.
Peritonsillar abscess presents with severe unilateral throat pain, trismus, uvular deviation, and "hot potato voice" 5. This is a polymicrobial infection occurring mainly in young adults and represents a life-threatening suppurative complication requiring urgent drainage 5.
Chronic tonsillitis with asymmetric inflammation can produce unilateral enlargement with irritation symptoms 5.
Infectious mononucleosis (Epstein-Barr virus) typically presents with pharyngitis, generalized lymphadenopathy (particularly posterior cervical), and splenomegaly, though asymmetric tonsillar involvement can occur 5.
Benign Non-Infectious Causes
Tonsilloliths (tonsillar stones) can cause unilateral enlargement with chronic irritation, though the American Academy of Family Physicians notes these typically present with visible white debris rather than true tonsillar hypertrophy 4.
Chronic inflammatory response without identifiable infection accounts for the majority (80%) of benign pathology in unilateral tonsillar enlargement 6.
Critical Risk Stratification
The presence of high-risk features dramatically increases malignancy probability from near-zero to 45% 7:
- Cervical lymphadenopathy (strongest predictor) 6
- Suspicious tonsillar appearance (ulceration, friability, necrosis) 6
- Chronic pain or dysphagia 7
- Tonsillar or peritonsillar mucosal abnormality 7
- History of malignancy or immunocompromise 6
- Age >40 years with tobacco/alcohol use 4
Isolated unilateral tonsillar enlargement without these features carries a malignancy rate of 0-5% in most series 7. However, the devastating consequences of missed malignancy warrant either close surveillance or tonsillectomy 1.
Recommended Diagnostic Algorithm
Immediate exclusion of acute infection: Perform RADT or throat culture to exclude GAS pharyngitis regardless of fever presence 4. Examine for peritonsillar abscess signs (uvular deviation, trismus, fluctuance) 5.
Risk stratification for malignancy: Assess for high-risk features listed above 6, 7. Any patient meeting criteria should proceed directly to tonsillectomy 4.
For isolated unilateral enlargement without high-risk features:
All excised tissue must undergo histopathologic examination to definitively exclude malignancy 2.
Common Pitfalls to Avoid
Do not rely on absence of B-symptoms to exclude lymphoma, as patients with tonsillar lymphoma frequently lack fever, night sweats, or weight loss at initial presentation 1, 3.
Do not assume absence of cervical lymphadenopathy excludes malignancy, as CLL/SLL can present with isolated tonsillar involvement 3.
Do not fail to perform microbiological testing when infection is suspected, as clinical diagnosis of pharyngitis is unreliable 4.
Do not delay tonsillectomy beyond 2-3 weeks in patients with persistent asymmetry and any high-risk feature, as prolonged time to diagnosis worsens outcomes in malignancy 1.