What is the next step in managing a patient with a persistently swollen right tonsil for 3 months, who has tested negative for streptococcus (strep)?

Urgent ENT Referral for Biopsy to Rule Out Malignancy

A unilateral tonsillar enlargement persisting for 3 months with negative strep testing requires urgent otolaryngology referral for tissue biopsy to exclude malignancy, as asymmetric tonsillar hypertrophy is a red flag for squamous cell carcinoma or lymphoma. 1, 2

Why This is Not Recurrent Tonsillitis

The clinical scenario described does not fit the pattern of recurrent bacterial or viral tonsillitis:

• Recurrent tonsillitis involves multiple discrete episodes (≥7 in past year, ≥5/year for 2 years, or ≥3/year for 3 years), not persistent unilateral swelling 1, 3
• Bacterial tonsillitis presents with sudden onset of sore throat, fever >38°C, tonsillar exudates, and tender cervical lymphadenopathy—not chronic unilateral enlargement 1
• Viral pharyngitis is self-limited, typically resolving within 1 week, not persisting for months 4

Critical Red Flags Present

Unilateral tonsillar enlargement lasting >2-3 weeks is a concerning finding that warrants tissue diagnosis:

• Asymmetric tonsil size is a classic presentation of tonsillar malignancy, particularly HPV-related squamous cell carcinoma or lymphoma 5
• Duration of 3 months far exceeds the natural history of infectious causes 4, 2
• The negative strep test appropriately rules out group A streptococcal infection, but this does not explain the persistent unilateral swelling 4

Differential Diagnosis to Consider

While awaiting ENT evaluation, consider these alternative diagnoses:

Malignancy (Most Important)

• Squamous cell carcinoma (HPV-related or non-HPV) presents as unilateral tonsillar mass with or without associated lymphadenopathy 5
• Lymphoma can present as asymmetric tonsillar enlargement 5

Infectious Causes (Less Likely Given Duration)

• Primary syphilis can present as painless unilateral tonsillar ulceration or mass, especially in sexually active adults with oral exposure 6, 5
• Intracellular S. aureus is associated with recurrent tonsillitis but typically presents with multiple acute episodes, not persistent unilateral swelling 7

Other Considerations

• Peritonsillar abscess would present acutely with severe pain, trismus, and uvular deviation—not chronic swelling 2, 7

Immediate Management Steps

Before ENT referral:

1. Obtain sexual history to assess risk for sexually transmitted infections, particularly syphilis 6, 5
2. Order syphilis serology (RPR and treponemal antibody) given the unilateral presentation and negative strep test 6
3. Document exact duration, associated symptoms (dysphagia, odynophagia, weight loss, night sweats, otalgia), tobacco/alcohol use, and HPV risk factors 5
4. Examine for cervical lymphadenopathy and document size/laterality of the enlarged tonsil 5

Do NOT:

• Prescribe empiric antibiotics without tissue diagnosis—this delays appropriate workup and can mask malignancy 4
• Assume this is simply "chronic tonsillitis" requiring tonsillectomy without biopsy 1, 3
• Wait for additional symptoms to develop before referring 5

Common Pitfalls to Avoid

• Treating with multiple courses of antibiotics for presumed bacterial infection without confirming diagnosis delays cancer detection 4
• Assuming negative strep test means "just viral" ignores the red flag of unilateral, persistent enlargement 4
• Referring for tonsillectomy without biopsy risks inadequate surgical margins if malignancy is present 1, 3