What is the appropriate workup and management for a patient with a painful sore on the right side of their tongue that has been present for 6 weeks?

Workup for a Painful Tongue Sore Present for 6 Weeks

Any oral lesion persisting beyond 2 weeks mandates biopsy to exclude malignancy, particularly squamous cell carcinoma. 1

Immediate Diagnostic Workup

Blood Tests (Obtain Before Biopsy)

Perform the following blood work to exclude contraindications for biopsy and identify underlying systemic causes 2, 1:

• Complete blood count to rule out anemia, leukemia, or neutropenia 2, 1
• Coagulation studies to exclude surgical contraindications 2, 1
• Fasting blood glucose to identify diabetes, a major risk factor for invasive fungal infections and poor wound healing 2, 1
• HIV antibody testing to exclude immunodeficiency-related lesions 2, 1
• Syphilis serology to rule out infectious causes 2, 1

Clinical Documentation

Document the following features during oral examination 1:

• Lesion size, location, borders, color, and presence of induration 1
• Lymphadenopathy in the cervical and submandibular regions 1
• Complete oral cavity examination including all mucosal surfaces, floor of mouth, and oropharynx to identify synchronous lesions 1
• Morphological characteristics at multiple sites if present 2

Biopsy Protocol

Proceed with biopsy if the lesion has not responded to 1-2 weeks of symptomatic treatment or if blood work does not reveal contraindications. 2, 1

Biopsy Considerations

• Multiple biopsies should be performed if ulcers involve multiple sites with different morphological characteristics 2
• Incisional biopsy from the border of the lesion (not the necrotic center) provides the best diagnostic yield 1
• Send tissue for histopathology with hematoxylin and eosin staining as the initial step 2

Additional Testing Based on Biopsy Findings

If initial histopathology suggests specific diagnoses 2:

• Direct immunofluorescence (DIF) and serum antibodies (Dsg1, Dsg3, BP180, BP230) if bullous diseases are suspected 2
• Immunohistochemical assay and T-cell receptor immunophenotyping if hematopoietic or lymphoid neoplasm is suggested 2
• Fungal culture if candidal infection is suspected, particularly in patients with hyperglycemia 2, 1

Symptomatic Management During Workup

While awaiting biopsy results, provide pain control and prevent secondary infection 3, 1:

• Benzydamine hydrochloride oral rinse every 3 hours, particularly before eating 3, 1
• Viscous lidocaine 2% (15 mL per application) up to 3-4 times daily for severe pain 3, 1
• Gelclair mucoprotectant gel applied three times daily to form a protective barrier 3, 1
• 0.2% chlorhexidine digluconate mouthwash twice daily as antiseptic rinse 3, 1
• Warm saline mouthwashes to reduce bacterial colonization 3, 1

Imaging Studies

Obtain contrast-enhanced CT or MRI if biopsy confirms squamous cell carcinoma to assess tumor extent and lymph node involvement 1

Obtain chest imaging to assess for metastases or second primary lung cancer, particularly in smokers 1

Critical Red Flags

Do Not Delay Biopsy If:

• Constitutional symptoms are present (fever, weight loss, malaise) 3, 1
• Lesion appears indurated or has rolled borders suggesting malignancy 1
• Patient has risk factors including tobacco use, alcohol use, or immunosuppression 1
• Hyperglycemia is present, as this predisposes to invasive fungal infections that can mimic benign ulcers 2, 1

Common Pitfalls to Avoid

• Never assume a small or benign-appearing lesion is non-malignant, as squamous cell carcinoma can present deceptively 1
• Do not overlook systemic disease associations such as Crohn's disease, Behçet's disease, or hematologic malignancies 3, 1
• Always inquire about gastrointestinal symptoms and immunosuppression history as oral ulcers may be the first manifestation of systemic disease 3, 1

Referral Pathways

Immediate referral to head and neck surgery or oral maxillofacial surgery if biopsy confirms squamous cell carcinoma 1

Hematology-oncology referral if biopsy reveals lymphoma 1

Consider referral to oral medicine specialist if diagnosis remains unclear after initial workup 4