Case: 43-Year-Old Man With a 1 cm Oral Lesion – Pseudoepitheliomatous Hyperplasia vs Squamous Cell Carcinoma

Subtitle: Case: a 43-year-old man with a 1 cm painless oral lesion. How to separate pseudoepitheliomatous hyperplasia (PEH) from invasive squamous cell carcinoma: morphology, causes of PEH, IHC, biopsy pitfalls, video and 8 MCQs.

Author: PathologyMCQ Editorial Board

Category: Head and Neck Pathology

Last Updated: October 2026

Read Time: 5 minutes

At-a-Glance

PEH is a reactive downgrowth of squamous epithelium that can look invasive.
SCC: nuclear atypia, atypical mitoses, single-cell infiltration, desmoplasia, perineural invasion.
Keratin pearls and long, anastomosing rete ridges occur in both.
Always look underneath: granular cell tumour, fungi, necrotising sialometaplasia.
Shallow or tangential biopsies cause most errors: get deeper levels and history.

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The Case

A 43-year-old man has a 1 cm painless lesion in the oral cavity. The biopsy shows irregular tongues of squamous epithelium extending into the stroma. Is it squamous cell carcinoma or pseudoepitheliomatous hyperplasia? Watch the short case video first, then compare the two images.

First questions to ask: is the tissue properly oriented (if not, re-embed or cut deeper levels), and is there a clinical history (ulcer, infection, mass beneath the mucosa)?

PEH vs SCC

Pseudoepitheliomatous hyperplasia vs squamous cell carcinoma

Feature	PEH	SCC
Architecture	Elongated, anastomosing rete ridges; pseudoinvasive islands	Irregular nests, cords and single cells
Cytology	Bland, maturing cells	Nuclear pleomorphism, prominent nucleoli
Mitoses	Few, basal, typical	Frequent, suprabasal, atypical
Depth	Usually superficial	Deep infiltration, perineural or vascular invasion
Stroma	Inflammation, microabscesses; no desmoplasia	Desmoplastic reaction
Underlying lesion	Often present (granular cell tumour, fungi)	Absent
Keratin pearls	May be present	Common in well-differentiated SCC

Pseudoepitheliomatous hyperplasia over granular cell tumour with keratin pearls — Keratin pearls in the stroma without significant atypia: PEH over a granular cell tumour.

Causes of PEH

Tumours: granular cell tumour (classic), melanocytic naevi and melanoma, cutaneous lymphomas.
Infections: deep fungi (blastomycosis, chromoblastomycosis, paracoccidioidomycosis), chronic hyperplastic candidiasis and median rhomboid glossitis, mycobacteria.
Oral lesions: necrotising sialometaplasia, oral submucous fibrosis.
Inflammatory: granulomatosis with polyangiitis, chronic ulcers and wound edges.

Role of IHC

No marker is definitive. Diffuse aberrant p53, extended suprabasal Ki-67 and reduced E-cadherin favour carcinoma, while PEH usually shows a wild-type p53 pattern and basal Ki-67. Use special stains (PAS, GMS) and S100/SOX10 to find the cause of PEH, and rely on morphology, depth and clinical context for the final call.

Test Yourself: 8 MCQs

PEH vs SCC: 8 MCQs

Morphology, causes, pitfalls and IHC, with instant explanations.

Score: 0 / 8

More practice: the question banks →

Exam Pearls

Keratin pearls do not equal carcinoma.
Atypia, atypical mitoses and single cells mean SCC.
Granular cell tumour of the tongue + PEH is a classic trap.
Shallow biopsy? Ask for deeper levels and history.

For more diagnostic approaches, see the approach-based course in histopathology and cytology →

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