What are the possible etiologies for a cobblestone‑appearing posterior tongue?

Cobblestone Appearance of the Posterior Tongue

The most common cause of a cobblestone-appearing posterior tongue is multifocal epithelial hyperplasia (Heck disease), caused by HPV types 13 and 32, which presents as multiple small, slightly elevated papules clustered tightly together on the tongue, giving the characteristic cobblestone appearance. 1

Primary Differential Diagnoses

Multifocal Epithelial Hyperplasia (Heck Disease)

• Most commonly presents in children as multiple small, slightly elevated, and minimally keratinized papules located mainly on the tongue, as well as labial and buccal mucosae 1
• Caused specifically by HPV 13 and HPV 32, with lesions occurring in a tight cluster that creates the cobblestone appearance 1
• Risk factors include crowded unhygienic living conditions and the HLA-DR4 allele 1
• Also reported in immunosuppressed patients 1
• Spontaneous regression is common after months to years, similar to verrucae 1
• Treatment: Surgical excision is recommended despite the benign nature, as these lesions are infectious 1

Lingual Tonsil Hypertrophy

• The posterior tongue contains lingual tonsillar tissue that can become hypertrophic and appear cobblestoned 1, 2
• Swollen lingual tonsils can create a bumpy, irregular appearance on the tongue base 1
• May be associated with obstructive symptoms if significantly enlarged 1
• Surgical management options include lingual tonsillectomy when the mass is specifically lingual tonsillar tissue 2

Chronic Lingual Papulosis

• Represents focal or diffuse enlargement of numerous lingual papillae, primarily the filiform papillae 3
• Presents as multiple, moderately firm, slightly pedunculated, normally colored masses that can be clustered at the tip of the tongue, covering the dorsal surface, or on the lateral border 3
• Usually has adult onset (average age 49 years) and most likely represents papillary reaction to very low-grade chronic irritation or desiccation 3
• All lesions are typically asymptomatic and have been present for many years 3
• Associated with mouth breathing, tongue-thrust habit, geographic tongue, or fissured tongue 3
• No treatment or biopsy is required once systemic disorders and syndromes are ruled out 3

Pigmented Fungiform Papillae (in Dark-Skinned Individuals)

• Dark brown to black colored pinhead papules or bumps observed primarily in dark-skinned children 4
• Dermoscopic examination shows a cobblestone-like distribution and rose petal pattern 4
• This is an ethnic, acquired, and benign condition 4
• May be associated with hyperpigmentation of other sites such as proximal nail folds and gums 4

Important Pitfalls to Avoid

Do Not Confuse with Other HPV-Related Lesions

• Verruca vulgaris (HPV 2 and 4) presents as well-circumscribed growth with prominent hyperkeratosis and white pebbly surface, but is uncommon in the mouth 1
• Oral squamous papilloma (HPV 6 and 11) appears as exophytic, sessile, or pedunculated growth but typically presents as individual lesions rather than clustered cobblestone pattern 1
• Condyloma acuminatum (HPV 6 and 11) presents as sessile or pedunculated lesions with papillary projections, more common in adolescents and young adults 1

Rule Out Systemic Conditions

• Before diagnosing chronic lingual papulosis, systemic disorders and syndromes must be ruled out 3
• Consider immune status assessment, particularly in adults with new-onset lesions 1
• Geographic tongue (erythema migrans) may coexist with fissured tongue and present with altered papillary patterns 5, 6, 7

Clinical Examination Pearls

• Assess the distribution pattern: Heck disease shows tight clustering creating true cobblestone appearance 1
• Evaluate patient age: Heck disease most common in children; chronic lingual papulosis typically in adults 1, 3
• Check for associated findings: Geographic tongue, fissured tongue, mouth breathing habits 3, 5
• Assess immune status: Immunosuppressed patients may develop Heck disease or other HPV-related lesions 1

When to Biopsy

• Surgical excision is recommended for Heck disease because lesions are infectious, even though only a few can be dysplastic 1
• Biopsy is not required for chronic lingual papulosis once systemic conditions are excluded 3
• Consider biopsy if lesions are symptomatic, rapidly growing, or associated with systemic symptoms 3