Subtitle: Actinic keratosis, Bowen disease (SCC in situ) and invasive cutaneous squamous cell carcinoma: the histological spectrum, useful IHC (p53, Ki-67, p16), mimics, high-risk features, two virtual slides, an image question and 8 MCQs.
Author: PathologyMCQ Editorial Board
Category: Skin Pathology
Last Updated: October 2026
Read Time: 6 minutes
At-a-Glance
- Actinic keratosis: partial-thickness atypia, parakeratosis alternating with orthokeratosis, solar elastosis.
- Bowen disease: full-thickness atypia with an intact basement membrane (SCC in situ).
- SCC: atypical keratinocytes invade the dermis; keratin pearls show differentiation.
- IHC is supportive only: p53 is positive at all stages; p16 helps in Bowen disease; CK7, SOX10 exclude mimics.
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Keratinocyte neoplasia on sun-damaged skin is a continuum. Actinic keratosis sits at one end, Bowen disease (squamous cell carcinoma in situ) in the middle, and invasive squamous cell carcinoma at the other. The diagnosis depends on how much of the epidermis is atypical and whether the basement membrane has been breached.
Actinic Keratosis
- Atypical keratinocytes with enlarged, hyperchromatic nuclei in the basal and lower epidermis; maturation is preserved above.
- Parakeratosis alternating with orthokeratosis over adnexal ostia (the “flag sign”); buds of atypical cells into the papillary dermis.
- Solar elastosis in the dermis.
- Variants: hypertrophic, atrophic, acantholytic, lichenoid, pigmented, bowenoid.
Bowen Disease (SCC In Situ)
- Full-thickness disorderly atypia with loss of maturation, atypical mitoses and dyskeratotic cells at all levels.
- Hyperkeratosis and parakeratosis; adnexal epithelium is often involved.
- The basement membrane is intact; no dermal invasion.
- Pagetoid and clear-cell variants mimic extramammary Paget disease and melanoma in situ.
Invasive Squamous Cell Carcinoma
- Irregular nests and tongues of atypical keratinocytes breach the basement membrane into the dermis, with desmoplastic stroma.
- Keratin pearls and intercellular bridges mark squamous differentiation; poorly differentiated tumours may need IHC (p40, CK5/6).
- High-risk features: thickness >6 mm or invasion beyond subcutaneous fat, perineural and lymphovascular invasion, poor differentiation, desmoplastic or acantholytic subtype, ear or lip site.
- Keratoacanthoma is classified with well-differentiated SCC.
Comparison Table
| Feature | Actinic keratosis | Bowen disease | Squamous cell carcinoma |
|---|---|---|---|
| Extent of atypia | Lower epidermis; maturation preserved | Full thickness; maturation lost | Full thickness plus dermal invasion |
| Keratin layer | Parakeratosis alternating with orthokeratosis | Hyperkeratosis, parakeratosis | Variable; keratin pearls in tumour |
| Basement membrane | Intact | Intact | Breached |
| Dermis | Solar elastosis | Solar elastosis, lymphocytes | Invasive nests, desmoplasia |
| p53 | Often positive | Positive | Positive |
| Ki-67 | Basal/parabasal | Full thickness | Diffuse |
| p16 | Patchy or negative | Often block-like | Variable |
Virtual Slides
Compare the partial-thickness atypia of actinic keratosis with an invasive keratinising squamous cell carcinoma.
What to look for
Drag to pan · pinch or double-tap to zoom · use the + / − buttons
Immunohistochemistry and Mimics
Immunohistochemistry is supportive, not diagnostic. p53 is frequently positive even in actinic keratosis because UV-induced TP53 mutation is an early event, so it does not separate the three lesions. Ki-67 highlights the proliferating compartment: basal in AK, full thickness in Bowen disease. p16 block positivity supports Bowen disease, especially HPV-related genital or digital lesions. For pagetoid Bowen disease, CK7, CEA (Paget disease) and SOX10, Melan-A (melanoma) exclude the mimics; Bowen disease is CK5/6 and p63 positive.
Image Question
What is the diagnosis?
Show answer
A. Bowen disease. Full-thickness dysplasia with an intact basement membrane. In doubtful cases, cytokeratins, p16 and Ki-67 help; p53 expression is variable.
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AK, Bowen disease and SCC: 8 MCQs
Histology, IHC, mimics and prognosis, with instant explanations.
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Exam Pearls
- Partial thickness + flag sign + solar elastosis = AK.
- Full thickness + intact basement membrane = Bowen disease.
- Breach of the basement membrane = SCC; report depth, differentiation, PNI and LVI.
- p53 is positive at every stage; use p16, Ki-67 and the mimic panel instead.
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References
- WHO Classification of Tumours Editorial Board. Skin Tumours. 5th ed. IARC; 2023.
- Patterson JW. Weedon’s Skin Pathology. 5th ed. Elsevier; 2021.
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