What are the differential diagnoses for a 1 cm white plaque on the subglottic mucosa?

Differential Diagnosis of 1 cm White Plaque in Subglottic Area

A 1 cm white plaque in the subglottic region requires immediate laryngoscopy with biopsy to exclude malignancy, as this presentation demands histopathologic diagnosis rather than empirical treatment. 1

Primary Differential Considerations

Leukoplakia (Most Common White Lesion)

• Leukoplakia is a descriptive clinical term only – it designates a white patch or plaque that cannot be removed and cannot be explained by another disease, but must be complemented by histology for definitive diagnosis 2, 3
• The underlying pathology can range from benign keratosis to invasive squamous cell carcinoma, making biopsy mandatory 2, 3
• Laryngeal leukoplakia carries malignant potential, with transformation rates varying from 4% overall to 16% in lesions with dysplasia 4, 5
• Keratosis (orthokeratotic or parakeratotic) with acanthosis is the typical microscopic finding, though epithelial dysplasia of varying degrees may be present 4

Contact Granuloma/Ulcer (Post-Intubation or Trauma)

• Recent endotracheal intubation is strongly associated with laryngeal injury, with 94% of patients intubated >4 days experiencing injury and 44% developing vocal fold granulomas within 4 weeks of extubation 1
• These lesions can appear as white plaques when covered by fibrinous exudate or keratotic changes
• History of recent intubation, cardiac surgery (1.4% vocal cord injury rate), or voice trauma is critical 1
• Conservative management with antireflux therapy, voice rest, and voice therapy is first-line treatment unless malignancy cannot be excluded 6

Candidiasis (Fungal Infection)

• Presents as white plaques that may be removable with scraping (unlike true leukoplakia)
• Can be associated with epithelial dysplasia, requiring careful evaluation 7
• Consider in immunocompromised patients or those on inhaled corticosteroids

Lichen Planus (Atrophic-Erosive Forms)

• Atrophic-erosive forms of oral/laryngeal lichen planus can present as white lesions with erosions
• Carries lower malignant transformation risk than leukoplakia but still requires monitoring 5, 7
• Histology shows characteristic band-like lymphocytic infiltrate at the epithelial-stromal interface

Sarcoidosis (Granulomatous Disease)

• Can involve the supraglottis, hypopharynx, and any part of the upper airway with nodular hypertrophy 8
• Presents with non-caseating granulomas on biopsy (epithelioid cells, giant cells, CD4+ T cells) 8
• Special stains must be negative for mycobacteria and fungi to confirm diagnosis 8
• Consider when systemic features present (pulmonary involvement, elevated serum ACE, hypercalcemia) 8

Squamous Cell Carcinoma (Must Exclude)

• Age >60 years and tobacco use history are associated with 28% malignancy rate in patients with white lesions 1
• Suspicious features include ulceration, increased vascularity, exophytic growth, or fixation 6
• Immediate surgical biopsy is mandatory when malignancy is suspected 6

Diagnostic Approach

Immediate Evaluation Required

• Direct laryngoscopy is mandatory for any hoarseness or laryngeal lesion lasting >2 weeks – empirical treatment without visualization is not recommended 1
• Videostroboscopy should be performed to assess mucosal wave; absence or reduction of mucosal wave has 96.8% sensitivity and 92.8% specificity for invasive carcinoma 3
• Obtain detailed history focusing on:
  • Recent intubation or cardiac surgery 1
  • Tobacco use (critical risk factor) 1
  • Occupational voice use 1
  • Reflux symptoms 6

Biopsy Indications (Perform Immediately If Present)

• Any patient >60 years with tobacco history 1, 6
• Lesions with ulceration, increased vasculature, or exophytic features 6
• Reduced/absent mucosal wave on stroboscopy 3
• Symptoms persisting despite 4-8 weeks of conservative management 6

Management Algorithm

When Malignancy Cannot Be Excluded

• Proceed directly to surgical biopsy with histopathologic evaluation 6
• Delaying biopsy in high-risk patients results in higher cancer staging and reduced survival 1

When Benign Etiology Suspected (Post-Intubation, Reflux-Related)

• Initiate antireflux medications (high-dose PPI twice daily), voice rest, and referral to certified speech-language pathologist for 1-2 sessions weekly for 4-8 weeks 6
• Surgery is reserved only for cases refractory to conservative therapy or when satisfactory voice cannot be achieved 1, 6
• Avoid empirical antibiotics or corticosteroids without laryngoscopic diagnosis 1

Critical Pitfalls to Avoid

• Never treat empirically without laryngoscopy if symptoms persist >2 weeks 1
• Never delay biopsy in patients >60 years or with tobacco history – this is the highest-risk group 1, 6
• Do not assume all white plaques are benign keratosis; histology is mandatory to exclude dysplasia or carcinoma 2, 3
• Do not proceed directly to surgery for suspected benign lesions without adequate trial of conservative management 1