What is the diagnosis and management for an adult with no significant medical history presenting with a unilateral sore on the inner cheek?

Unilateral Mouth Sore on Inner Cheek: Diagnosis and Management

Immediate Diagnostic Approach

For a unilateral sore on the inner cheek persisting beyond 2 weeks or not responding to 1-2 weeks of treatment, obtain blood work and strongly consider biopsy to rule out malignancy and systemic disease. 1

Critical History Elements

• Duration and progression: Ulcers present >3 weeks despite treatment require biopsy 1, 2
• Pain characteristics: Constant pain suggests malignancy or deep infection; intermittent pain with eating suggests salivary pathology 3
• Trauma history: Recent dental work, sharp tooth edges, or cheek biting can cause traumatic ulceration 1
• Associated symptoms: Fever, exposed bone, difficulty swallowing, or neck mass are red flags requiring urgent referral 3
• Medication history: Bisphosphonates or recent radiation therapy raise concern for osteonecrosis 3
• Risk factors: Age >40 with tobacco/alcohol use significantly increases malignancy risk 3

Physical Examination Priorities

• Ulcer morphology: Well-demarcated oval/round ulcers with yellow pseudomembrane and erythematous halo suggest aphthous ulceration; irregular borders with induration suggest malignancy 1, 3
• Palpation: Assess for induration, fixation to underlying tissue, and tenderness—firm, fixed lesions are concerning for cancer 3
• Bimanual palpation: Essential for floor of mouth and submandibular areas to detect masses 3
• Neck examination: Palpate for lymphadenopathy in levels I-III, which may indicate metastatic disease 3
• Cranial nerve testing: Check trigeminal nerve sensation to rule out neuropathic causes 4

Differential Diagnosis by Clinical Pattern

Benign Traumatic Ulcer

• Location corresponds to sharp tooth, denture, or cheek-biting pattern 1
• Management: Remove irritant; ulcer should heal within 7-14 days 1
• If no improvement after irritant removal, proceed to biopsy 1

Aphthous Ulcer (Canker Sore)

• Well-demarcated, painful, yellow-white pseudomembrane with red halo 1, 2
• Typically on non-keratinized mucosa (buccal, labial, tongue) 5
• First-line treatment: Betamethasone sodium phosphate 0.5 mg in 10 mL water as rinse-and-spit four times daily 2
• For localized lesions: Clobetasol 0.05% ointment mixed in 50% Orabase applied twice daily to dried mucosa 2
• Pain control: Benzydamine hydrochloride rinse every 3 hours, especially before eating 2
• Adjunct: Chlorhexidine 0.2% mouthwash twice daily to reduce bacterial colonization 2

Oral Squamous Cell Carcinoma

• Irregular, indurated ulcer with rolled borders in patient >40 years 3, 6
• Non-healing despite 2-3 weeks of appropriate treatment 1, 2
• Biopsy is mandatory—do not delay 3
• Refer to oral surgeon or ENT within 1-2 weeks maximum 3

Infectious Ulcers

• Herpes simplex: Typically on keratinized mucosa (hard palate, gingiva); preceded by vesicles 5
• Fungal (histoplasmosis, candida): Consider in immunocompromised or diabetic patients 1, 7
• Tuberculosis: Stellate ulcer with undermined edges 1

Initial Management Algorithm

Step 1: Pre-Treatment Blood Work

Obtain before biopsy to exclude contraindications and identify systemic causes: 1

• Complete blood count (rule out leukemia, anemia)
• Coagulation studies
• Fasting blood glucose (hyperglycemia predisposes to fungal infections)
• HIV antibody and syphilis serology if risk factors present

Step 2: Empiric Treatment for Presumed Aphthous Ulcer

Only if clinical appearance is classic and no red flags present: 2

• Betamethasone sodium phosphate 0.5 mg in 10 mL water rinse four times daily
• Benzydamine hydrochloride rinse every 3 hours for pain
• Avoid alcohol-based mouthwashes, spicy/acidic foods, hot beverages 2
• Warm saline rinses to maintain oral hygiene 2

Step 3: Reassess at 2 Weeks

If no improvement or worsening, this indicates incorrect diagnosis or need for biopsy 1, 2

Step 4: Biopsy Indications (Do Not Delay)

• Ulcer present >3 weeks 1, 2
• No response to 1-2 weeks of appropriate treatment 1
• Induration, fixation, or irregular borders 3
• Patient age >40 with tobacco/alcohol use 3
• Associated neck mass or systemic symptoms 3

When to Refer Urgently

Refer to oral surgeon or ENT within 1-2 weeks for: 3

• Any suspicion of malignancy based on clinical features
• Unilateral ulcer with palpable neck mass
• Exposed bone suggesting osteonecrosis
• Non-healing ulcer despite appropriate treatment
• Patient with bisphosphonate use or radiation history

Critical Pitfalls to Avoid

• Never prescribe antibiotics for undefined oral ulcers without obtaining cultures first—this creates culture-negative infections and delays diagnosis 1
• Do not assume traumatic etiology without removing the irritant and confirming healing within 2 weeks 1
• Hyperglycemia is a major predisposing factor for invasive fungal infections presenting as oral ulcers—always check fasting glucose 1
• Oral ulcers may be the first manifestation of systemic diseases including Crohn's disease, Behçet's disease, or hematologic malignancies—maintain high index of suspicion 2
• Neoplastic ulcers are notorious for mimicking benign lesions—when in doubt, biopsy 6

Second-Line Treatments for Refractory Aphthous Ulcers

If topical corticosteroids fail after 2 weeks: 2

• Tacrolimus 0.1% ointment twice daily for 4 weeks
• Intralesional triamcinolone 28 mg weekly with topical clobetasol
• Systemic prednisone 30-60 mg daily for 1 week, then taper (reserve for severe cases impacting quality of life)

Candidal Superinfection Management

If candidal infection suspected (white plaques, burning): 2

• Nystatin oral suspension 100,000 units four times daily for 1 week
• Or miconazole oral gel 5-10 mL held in mouth after food four times daily for 1 week
• Rule out with culture before treating 4