What is the recommended approach for an oral lesion workup?

Oral Lesion Workup

For oral lesions that persist beyond 2 weeks or fail to respond to 1-2 weeks of treatment, proceed directly to pre-biopsy blood work followed by tissue biopsy, as clinical examination alone is insufficient for definitive diagnosis of difficult and complicated oral ulcerations. 1

Initial Clinical Assessment

History and Physical Examination

• Document lesion duration, pain characteristics, and treatment response to identify lesions requiring aggressive workup (those >2 weeks duration or non-responsive to initial therapy) 1
• Assess malignancy risk factors including age >40 years, tobacco use, alcohol abuse, immunocompromised status, multiple sexual partners, and history of prior head/neck malignancy 1
• Evaluate for systemic symptoms including fever, night sweats, weight loss, dysphagia, odynophagia, hemoptysis, or distant lymphadenopathy that suggest lymphoma or disseminated disease 1

Oral Cavity Examination Technique

• Remove dentures completely before examining all mucosal surfaces 1
• Use gauze to grasp and extend the tongue laterally to visualize lateral tongue borders and floor of mouth 1
• Palpate the oral tongue, floor of mouth, base of tongue, and tonsils to detect masses not visible on inspection 1
• Examine the oropharynx with mouth open but tongue NOT protruded (tongue protrusion obscures the oropharynx and limits visualization) 1
• Document lesion characteristics including size, location, texture, color, morphology (ulcerated vs mass vs pigmented), and presence of undermined edges or induration 1, 2, 3
• Photograph oral, conjunctival, and cutaneous lesions for documentation of disease extent 1

Multiple Lesion Considerations

• For recurrent or multiple ulcerations, inquire about ulcers on skin, genitals, or eyes, and accompanying systemic symptoms suggesting Behçet's disease or other systemic conditions 2
• If multiple sites with different morphologies exist, plan for multiple biopsies 1

Pre-Biopsy Blood Work (Part 1)

Before proceeding to biopsy, obtain comprehensive blood work to exclude contraindications and provide diagnostic clues: 1

Essential Laboratory Tests

• Complete blood count (CBC) to detect anemia, leukemia, or neutropenia that may indicate hematologic malignancy 1
• Coagulation studies to rule out bleeding contraindications to biopsy 1
• Fasting blood glucose to exclude diabetes (hyperglycemia predisposes to invasive fungal infections) 1
• HIV antibody testing to rule out HIV-associated oral ulceration 1
• Syphilis serology to exclude syphilitic ulceration 1

Additional Testing for Suspected Conditions

• Serum autoantibodies (Dsg1, Dsg3, BP180, BP230) if bullous diseases are suspected clinically 1
• If CBC suggests anemia or leukemia, proceed to serum iron, folate, vitamin B12, bone marrow biopsy, and immunotyping before tissue biopsy 1

Tissue Biopsy (Part 2)

If blood work does not establish diagnosis and no contraindications exist, proceed to biopsy: 1

Biopsy Technique Considerations

• For suspected bullous diseases, biopsy perilesional tissue (not the ulcer itself) for direct immunofluorescence (DIF) studies 1
• Multiple biopsies are required when ulcers involve multiple sites with different morphological characteristics 1
• Include adequate tissue from both ulcer edge and adjacent normal tissue for optimal histopathologic evaluation 2

Post-Biopsy Specialized Testing

• If HE staining suggests bullous disease, perform DIF, indirect immunofluorescence, and ELISA with recombinant autoantigens 1
• If hematopoietic/lymphoid neoplasm is suspected, add immunohistochemistry and T-cell receptor immunophenotyping 1
• For non-specific inflammatory findings ("inflammatory ulcer with lymphocytic infiltration"), send paraffin-embedded specimens for expert pathology consultation 1
• Consider Ziehl-Nielsen staining if granulomatous inflammation is identified to detect acid-fast bacilli (tuberculosis) 1

Imaging Studies

Indications for Advanced Imaging

• Chest X-ray to assess for pulmonary involvement in Kaposi sarcoma or tuberculosis 1
• Upper and lower endoscopy if gastrointestinal involvement is suspected (fecal occult blood positive) 1
• Contrast CT chest/abdomen/pelvis, MRI, or PET/CT for suspected visceral involvement, lymphadenopathy, or bone lesions 1
• Intraoral dental radiographs if dental trauma or infection is the suspected etiology 4

Screening for Systemic Disease (Part 3)

If biopsy is contraindicated or diagnosis remains unestablished after pathology consultation, perform comprehensive systemic disease screening: 1

• C-reactive protein, HHV-8 serum viral load, serum protein electrophoresis, interleukin-6, and interleukin-10 for unexplained fevers with Kaposi sarcoma to evaluate for multicentric Castleman disease or KSHV-associated inflammatory cytokine syndrome 1
• Excisional lymph node biopsy if lymphadenopathy is present to exclude multicentric Castleman disease 1

Referral Patterns

Most general dental practitioners (65.4%) refer patients with suspicious oral lesions for consultation/biopsy rather than performing biopsy themselves: 5

• 87.2% of referrals go to oral and maxillofacial surgeons 5
• Refer to oral medicine or oral surgery specialist when complete examination is impossible due to anatomic constraints or when diagnosis remains uncertain 1, 3
• Coordinate care with HIV specialist for all HIV-positive patients with oral lesions 1
• Involve infectious disease specialist when opportunistic infections (bacillary angiomatosis, blastomycosis, cryptococcosis) may mimic malignancy 1

Critical Pitfalls to Avoid

• Never assume benign appearance excludes malignancy—neoplastic oral lesions frequently mimic benign ulcerative lesions, making biopsy essential for non-healing lesions 2
• Do not delay biopsy beyond 2 weeks for persistent lesions or those failing initial treatment 1
• Avoid biopsying suspected bullous lesions without obtaining serum autoantibodies first, as this guides appropriate tissue handling for immunofluorescence studies 1
• Recognize that physical examination has significant limitations for identifying malignancy in cervical nodes, even among experienced surgeons 1