Author: PathologyMCQ Editorial Team
Category: Head and Neck Pathology – Sinonasal Tract
Last Updated: October 2026 (WHO Head and Neck Tumours, 5th edition)
Read Time: 12 minutes
Difficulty: Moderate (MD/DNB, FRCPath, NEET-SS)
At a glance
- What: benign but locally aggressive epithelial neoplasms of the ectoderm-derived Schneiderian mucosa lining the nasal cavity and paranasal sinuses.
- Three types: inverted (commonest, lateral wall and sinuses), oncocytic (lateral wall and sinuses) and exophytic (nasal septum).
- Molecular drivers: EGFR exon 20 mutations in inverted, KRAS in oncocytic, and low-risk HPV 6/11 in exophytic papilloma.
- Why it matters: frequent recurrence and a risk of associated carcinoma, mainly with inverted and oncocytic types.
- In this post: a 3-tab virtual slide viewer (inverted papilloma, nasal polyp mimic, squamous papilloma comparison), updated tables and 10 interactive MCQs including 5 slide-based questions.
What is sinonasal papilloma?
Sinonasal (Schneiderian) papillomas are benign epithelial neoplasms of the mucosa lining the nasal cavity and paranasal sinuses. Unlike the rest of the respiratory tract, this mucosa is derived from ectoderm. The tumours are usually unilateral and present with nasal obstruction or epistaxis in adults, with a male predominance. Although benign, they recur frequently and can be associated with carcinoma, so correct typing and complete excision matter.
The three types at a glance
| Feature | Inverted | Oncocytic | Exophytic |
|---|---|---|---|
| Frequency | Commonest | Least common | Intermediate |
| Usual site | Lateral nasal wall, maxillary and ethmoid sinuses | Lateral nasal wall and sinuses | Nasal septum |
| Growth | Endophytic nests into stroma | Exophytic and endophytic | Exophytic papillary fronds |
| Epithelium | Thick squamous to transitional, non-keratinising, with mucous cells | 2–8 layers of columnar oncocytic cells | Squamous to transitional, minimal keratin, mucous cells |
| Key clue | Transmigrating neutrophils and microcysts | Intraepithelial microcysts with mucin and neutrophils | Septal location, fungiform appearance |
| Molecular | EGFR exon 20 mutations | KRAS mutations | Low-risk HPV 6/11 |
| Malignant risk | About 5–10% | Similar or higher | Very low |
Inverted papilloma
- Architecture: thickened epithelium grows down into the stroma as rounded nests and ribbons with smooth contours and an intact basement membrane.
- Epithelium: 5–30 cell layers of non-keratinising squamous to transitional cells, with scattered mucous cells and a surface layer of columnar cells.
- Hallmark: neutrophils migrating through the full thickness of the epithelium, often with microcysts.
- Stroma: oedematous, polyp-like; inflammatory polyps may coexist.
- Warning signs: marked keratinisation, dyskeratosis, atypia, atypical mitoses or irregular invasive nests should prompt careful sampling for squamous cell carcinoma.
Oncocytic papilloma
- Architecture: mixed exophytic and endophytic growth.
- Epithelium: 2–8 layers of tall columnar cells with abundant granular eosinophilic (mitochondria-rich) cytoplasm.
- Hallmark: intraepithelial microcysts filled with mucin and neutrophils.
- Molecular: KRAS mutations in nearly all cases; HPV negative.
- Clinical: can be associated with carcinoma, usually squamous cell carcinoma, at a rate similar to or higher than inverted papilloma.
Exophytic papilloma
- Site: almost always the nasal septum; also called fungiform or septal papilloma.
- Architecture: outward papillary fronds with fibrovascular cores; no endophytic nests.
- Epithelium: multilayered squamous to transitional cells with mucous cells and microcysts; keratinisation is usually minimal.
- Molecular: frequently low-risk HPV (6 and 11); no EGFR or KRAS mutations.
- Clinical: may recur, but malignant transformation is very rare.
See the patterns on real slides: the virtual slide viewer below has an inverted papilloma, an allergic nasal polyp and a squamous papilloma for comparison.
Virtual slides · real cases
Inverted papilloma and its look-alikes
Compare the endophytic Schneiderian epithelium with an inflammatory polyp and a keratinising squamous papilloma.
What to look for
Drag to pan · pinch or double-tap to zoom · use the + / − buttons
HPV and molecular pathology
| Type | Main driver | HPV | Practical note |
|---|---|---|---|
| Inverted | EGFR exon 20 insertions (most cases) | Minority; mostly low-risk | Carcinomas arising in inverted papilloma are often EGFR-mutant; transcriptionally active high-risk HPV occurs in a subset of EGFR-wild-type cases |
| Oncocytic | KRAS mutations (nearly all) | Negative | KRAS mutation is also found in carcinomas arising from oncocytic papilloma |
| Exophytic | No recurrent driver mutation | Low-risk HPV 6/11 common | Lowest malignant potential of the three |
Typing remains morphological; molecular testing is not needed for routine diagnosis. p16 immunostaining is not a reliable surrogate for HPV in these lesions.
Recurrence and malignant transformation
- Recurrence mostly reflects incomplete excision; endoscopic resection with removal of the underlying mucoperiosteum lowers it.
- Carcinoma, usually squamous cell carcinoma, occurs in about 5–10% of inverted papillomas and a similar or higher proportion of oncocytic papillomas; it can be synchronous or metachronous.
- Sampling: submit the specimen generously and look for keratinisation, dysplasia and stromal invasion.
- Follow-up: long-term endoscopic surveillance is advised because recurrences can appear years later.
Differential diagnosis
| Mimic | Clues |
|---|---|
| Inflammatory or allergic polyp | Thin ciliated surface epithelium, thick basement membrane, oedematous eosinophil-rich stroma; no thickened epithelial proliferation |
| Respiratory epithelial adenomatoid hamartoma (REAH) | Posterior septum; glands lined by ciliated epithelium with thick hyalinised basement membrane |
| Squamous cell carcinoma ex papilloma | Atypia, keratinisation, irregular infiltrative nests and desmoplasia |
| Non-keratinising squamous cell carcinoma | Ribbons of atypical cells with pushing borders; marked atypia and mitoses; check HPV status and DEK::AFF2 when appropriate |
| HPV-related multiphenotypic sinonasal carcinoma | Basaloid cells with myoepithelial and ductal differentiation, often with surface dysplasia; high-risk HPV |
| Sinonasal adenocarcinoma (oncocytic mimic) | Back-to-back glands with invasion; lacks the multilayered oncocytic epithelium and microcysts |
| Squamous papilloma of the vestibule | Keratinising skin-type squamous epithelium at the nasal vestibule, not Schneiderian mucosa |
Featured course · Approach-Based Histopathology and Cytology
Papilloma, polyp or carcinoma? Learn the approach.
The Approach-Based course teaches you to work through head and neck biopsies the way you report them: pattern first, then the key features and the stains or tests that settle the diagnosis.
- Pattern-based approach to sinonasal, oral and salivary lesions
- Virtual slides with annotated features and mimics
- Image-based MCQs for FRCPath, NEET-SS and MD/DNB
Test yourself: 10 MCQs
5 slide-based questions (inverted papilloma, nasal polyp, squamous papilloma) plus 5 on types, molecular drivers and mimics. Tap an answer for the explanation.
More practice: the full quiz is below, and the head and neck pathology MCQ bank (WHO 5th edition) →
More practice: sinonasal papilloma quiz
Exam pearls and key takeaway
- Inverted: lateral wall, endophytic, transmigrating neutrophils, EGFR, highest recurrence, about 5–10% carcinoma.
- Oncocytic: columnar oncocytic cells with microcysts of mucin and neutrophils, KRAS, HPV negative.
- Exophytic: nasal septum, fungiform fronds, low-risk HPV 6/11, lowest malignant risk.
- Keratinisation, dyskeratosis or atypia in a papilloma means sample more and exclude carcinoma.
- Key takeaway: type the papilloma on site, growth pattern and epithelium; molecular drivers explain the biology but morphology makes the diagnosis.
Go further
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The Pathology MCQ app
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Related reads: Head and neck pathology MCQs (WHO 5th edition) → · NEET-SS Oncopathology: top rankers’ approach →
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