What are the differential diagnoses for hairy-like patches on the palatine tonsils, particularly in immunocompromised individuals?

Differential Diagnoses for Hairy-Like Patches on Palatine Tonsils

Primary Differential: Oral Hairy Leukoplakia (OHL)

The most likely diagnosis for hairy-like patches on the palatine tonsils in an immunocompromised patient is oral hairy leukoplakia (OHL), an Epstein-Barr virus (EBV)-mediated condition that presents as white, corrugated patches typically on the lateral tongue but can occur on other oral mucosal surfaces. 1

Clinical Features of OHL

• Appearance: White, plaque-like lesions with a corrugated or "hairy" surface texture that cannot be scraped off (distinguishing feature from candidiasis) 2, 1
• Location: While classically bilateral on lateral tongue borders, OHL can present on other oral mucosal surfaces including the palatine tonsils 1, 3
• Histopathology: Acanthotic, hyperparakeratinized epithelium with a band of EBV-infected koilocyte-like cells in the upper prickle cell layers, characterized by swollen, pale-staining cells with prominent cell borders and perinuclear vacuoles 1

Risk Factors and Patient Populations

• HIV/AIDS patients with CD4+ counts <200 cells/µL are at highest risk 2
• Other immunocompromised states: Organ transplant recipients, patients on chronic corticosteroid therapy, systemic lupus erythematosus, acute leukemia (even before chemotherapy), and patients on other immunosuppressive medications 4, 5, 6
• Increasingly recognized in relatively immunocompetent patients, particularly elderly individuals (median age 64 years) and those using steroid inhalers, suggesting localized immunosuppression and immunosenescence as contributing factors 3

---

Key Differential: Oropharyngeal Candidiasis

Oropharyngeal candidiasis must be distinguished from OHL as it is the most common oral opportunistic infection in immunocompromised patients and presents similarly with white patches.

Distinguishing Features

• Appearance: Painless, creamy white, plaque-like lesions on buccal or oropharyngeal mucosa that can be easily scraped off with a tongue depressor, revealing erythematous base 2
• Alternative presentations: Erythematous patches without white plaques on the anterior or posterior upper palate or diffusely on the tongue 2
• Risk factors: CD4+ counts <200 cells/µL in HIV patients, diabetes, chronic corticosteroid use, broad-spectrum antibiotics 2
• Diagnosis: Clinical appearance plus KOH preparation showing yeast forms; culture identifies Candida species (increasingly non-albicans species like C. glabrata in advanced immunosuppression) 2

Critical Diagnostic Maneuver

Attempt to scrape the lesion: If it scrapes off easily → candidiasis; if it does not scrape off → consider OHL or other fixed lesions 2, 1

---

Additional Differential Diagnoses

Invasive Aspergillosis

• Presentation: Ulcerative or plaque-like lesions in the oropharynx, particularly in severely immunocompromised patients (neutropenia, hematologic malignancies, transplant recipients) 2
• Associated features: Fever, necrotic lesions, potential for tissue invasion and infarction 2
• Diagnosis: Biopsy showing mucosal invasion with fungal hyphae; culture to differentiate from Mucorales or other fungi 2

Sarcoidosis

• Presentation: Nodular mucosal thickening or granulomatous lesions that can affect the oropharynx 2
• Associated features: Multisystem involvement (lungs, skin, eyes), elevated serum ACE, hypercalcemia 2
• Diagnosis: Biopsy showing non-caseating granulomas; negative cultures for mycobacteria and fungi 2

Viral Infections

• Herpes zoster oticus (Ramsay Hunt syndrome): Vesicles on external ear canal and posterior auricle with severe otalgia, but can have oropharyngeal involvement 2
• Other herpesviruses: Varicella, measles, or herpes simplex can cause oral lesions in immunocompromised patients 2

Malignancy

• Squamous cell carcinoma or lymphoma: Can present as white patches, ulcers, or masses on the tonsils 2
• Risk factors: Tobacco/alcohol use, HPV infection, immunosuppression 2
• Red flags: Unilateral lesions, induration, persistent otalgia without obvious ear pathology (referred pain), neck masses 2

---

Diagnostic Approach

Initial Assessment

1. Attempt to scrape the lesion to differentiate candidiasis from fixed lesions 2, 1
2. Assess immune status: HIV status with CD4+ count, history of transplantation, immunosuppressive medications, diabetes, hematologic malignancies 2, 3, 4, 5, 6
3. Examine for systemic features: Fever, respiratory symptoms, skin lesions, lymphadenopathy 2

Confirmatory Testing

• For suspected OHL: Biopsy with histopathology showing characteristic koilocyte-like cells; confirm EBV by immunocytochemistry or DNA in situ hybridization 1
• For suspected candidiasis: KOH preparation of scrapings; culture if refractory or to identify species 2
• For suspected aspergillosis: Biopsy with culture (without homogenization to preserve fungal viability); histopathology to differentiate from Mucorales 2
• For suspected malignancy: Biopsy with histopathology; imaging (CT/MRI) for staging 2

Common Pitfalls

• Assuming all white oral patches are candidiasis without attempting to scrape them or considering OHL in immunocompromised patients 2, 1
• Missing OHL in non-HIV immunocompromised patients or even relatively immunocompetent elderly patients on steroid inhalers 3, 6
• Failing to biopsy persistent unilateral lesions that could represent malignancy, especially in patients with tobacco/alcohol use or HPV risk factors 2