What are the differential diagnoses for a sore on the tongue?

Differential Diagnosis of Tongue Sores

A tongue sore requires systematic evaluation based on duration, morphology, and associated features, with any ulcer persisting beyond 2 weeks mandating biopsy to exclude malignancy. 1

Initial Clinical Assessment

Document the following characteristics immediately:

• Ulcer morphology: Size, number, depth, presence of white/yellow pseudomembrane, surrounding erythema, and border characteristics 1
• Duration: Acute (<2 weeks), recurrent (≥4 episodes/year), or chronic (>2 weeks) 2
• Location and shape: Whether the ulcer corresponds to a potential traumatic source (sharp tooth, dental appliance) 1
• Associated symptoms: Pain severity, difficulty eating, systemic symptoms (fever, weight loss, night sweats) 3

Primary Differential Diagnoses

Traumatic Ulceration

• Clinical features: Ulcer location and shape match the inciting object (sharp tooth, dental appliance, thermal/chemical injury) 1
• Management: Remove the source of trauma; healing should occur within 7-10 days 1

Recurrent Aphthous Stomatitis (Canker Sores)

• Clinical features: Well-demarcated, oval or round ulcers with white/yellow pseudomembrane and erythematous halo 1
• Triggers: Immune dysregulation, nutrient deficiency (iron, folate, B12), oral trauma, stress 1
• Most common ulcerative condition of the oral cavity 4

Infectious Causes

Herpes Simplex Virus

• Recurrent herpes labialis and stomatitis commonly cause oral ulcers 4
• May present with vesicles before ulceration 3

Oral Candidiasis

• Median rhomboid glossitis associated with candidal infection responds to topical antifungals 5
• Consider in patients with corticosteroid use, immunocompromise, antibiotics, or dentures 4

Tuberculosis

• Characteristic appearance: Stellate ulcers with undermined edges and well-defined borders 1
• Requires syphilis and tuberculosis serology testing 1

Syphilis

• Can present with oral ulceration at any stage 2
• Mandatory serology testing in persistent cases 1

Deep Fungal Infections

• Particularly in patients with hyperglycemia or immunosuppression 1

Autoimmune/Inflammatory Conditions

Oral Lichen Planus

• Can present as lacy reticulations or oral erosions and ulcerations 4
• Occurs in up to 2% of individuals 4

Pemphigus Vulgaris and Mucous Membrane Pemphigoid

• Bullous autoimmune diseases presenting with oral ulceration 2
• Require direct immunofluorescence for diagnosis 6

Burning Mouth Syndrome

• Burning of tongue and oral mucosa with normal-appearing mucosa 7
• Most common in peri- and post-menopausal women 7

Nutritional Deficiencies

Atrophic Glossitis

• Linked to deficiency of iron, folic acid, vitamin B12, riboflavin, or niacin 5
• Resolves with correction of underlying deficiency 5

Hematologic Malignancies

Acute Leukemia (especially Acute Myeloid Leukemia)

• Most urgent diagnosis: Presents with widespread necrotic ulcers when neutrophil counts <2% 2
• Requires immediate bone marrow biopsy and hematology consultation 6

NK/T-Cell Lymphoma

• Can present with severe oral erosion/necrosis 6
• Confirmed by hematoxylin-eosin staining and immunohistochemistry 6

Squamous Cell Carcinoma

• Any solitary chronic ulcer must be biopsied to rule out malignancy 1
• Tobacco and alcohol use increase risk 4

Mandatory Laboratory Evaluation

Before any biopsy, obtain:

• Complete blood count with differential (detect anemia, leukemia, neutropenia) 2
• Coagulation profile (identify contraindications to biopsy) 2
• Fasting blood glucose (exclude diabetes predisposing to fungal infection) 2
• HIV antibody test (screen for HIV in persistent cases) 2
• Syphilis serology 2
• Serum antibodies (Dsg1, Dsg3, BP180, BP230) if bullous disease suspected 2

Additional testing based on clinical suspicion:

• Bone marrow biopsy with immunophenotyping if hematologic malignancy suspected 6
• Serum 1,3-β-D-glucan and galactomannan for invasive fungal infection in neutropenic patients 6

Critical Biopsy Indications

Biopsy is mandatory for:

• Any ulcer persisting >2 weeks 1
• Ulcers not responding to 1-2 weeks of appropriate treatment 1
• Solitary chronic ulcers to exclude squamous cell carcinoma 1
• Atypical clinical features (unusual size, shape, induration) 2

Biopsy technique:

• Obtain adequate depth and size to avoid missing diagnostic features 2
• Multiple biopsies if ulcers vary in appearance across sites 1
• Delay biopsy until coagulation parameters are normal and platelet counts adequate 6

Specialist Referral Criteria

Refer to oral medicine specialist for:

• Ulcers lasting >2 weeks 1
• Ulcers not responding to 1-2 weeks of treatment 1
• Recurrent, severe, or atypical presentations requiring biopsy or advanced diagnostic testing 1
• Cases with systemic symptoms suggesting underlying disease 1

Critical Pitfalls to Avoid

• Never delay hematology consultation when neutropenia accompanies oral ulcers; prompt evaluation for acute leukemia is life-saving 6
• Do not perform oral biopsies before confirming normal coagulation and sufficient platelet count to prevent severe bleeding 6
• Avoid relying solely on topical treatments for persistent ulcers without establishing definitive diagnosis, as this delays identification of malignancy or systemic disease 1
• Do not overlook systemic causes: Multiple oral ulcers may indicate Crohn's disease, blood disorders, or autoimmune conditions 6
• Recognize that "inflammatory ulcer with lymphocytic infiltration" on pathology is nonspecific and may require repeat biopsy 2