Differentials
Squamous cell carcinoma (SCC) in situ (Bowen's disease)
SIGNS / SYMPTOMS
Lesions similar to AKs, with similar distribution, but usually solitary. Can become larger, indurated, inflamed, redder, ulcerated, and bleeding.
Can occur on covered areas including mucous membranes and genital areas.
Invasive SCC
SIGNS / SYMPTOMS
Lesions begin similarly to AKs or Bowen's disease.
Generally a larger red ulcer with a thick border and a granular base.
Has the potential to metastasise.
INVESTIGATIONS
Skin biopsy shows atypical (anaplastic) keratinocytes throughout entire epidermis, invading dermis.
Differentiated tumours have fewer atypical cells and more keratinisation (e.g., horn pearls) than undifferentiated.
Anti-cytokeratin 13 antibodies distinguish them from other tumours.[3][4][13][53][54]
Keratoacanthoma
SIGNS / SYMPTOMS
Very early and late lesions are most likely to resemble AKs.[3][54] Clinically similar to well-differentiated SCC.
Dome-shaped lesion, colour of normal skin or red, with a central keratinous crater.
Grows rapidly but tends to regress spontaneously.
INVESTIGATIONS
Early lesion skin biopsy shows ill-defined epidermal invaginations into dermis, containing keratinocytes with little nuclear atypia and mitotic figures, and some dyskeratotic cells.
Developed lesion biopsy shows a centred crater filled with keratin, surrounded by lip-shaped epidermal extensions. Many horn pearls are seen.[3][54]
Basal cell carcinoma
SIGNS / SYMPTOMS
A small, smooth nodule with a translucent pearly border, and telangiectasia seen through the surface.
Most are localised on the face; less likely to be found on the trunk.
Hyperpigmented lesions sometimes occur, resembling malignant melanoma and other melanocytic lesions.[54]
INVESTIGATIONS
Skin biopsy shows nodular masses of large basaloid cells with large nucleus and little cytoplasm, peripheral palisading that extends into dermis.
Cystic spaces present between tumour cells and stroma.[54]
Seborrhoeic keratosis
SIGNS / SYMPTOMS
Elevated, well-defined velvety plaques, localised on either sun-exposed or covered areas.
Most have a verrucous surface, and may have keratotic plugs and irregular crypts.
Lesions can grow and become thicker and more pigmented.
Localised discoid lupus erythematosus (DLE)
SIGNS / SYMPTOMS
Well-defined, erythematous, round papules and plaques, some infiltration, with thick scaling. As DLE plaques enlarge, a central area of atrophy and hypopigmentation develops with a hyperpigmented periphery.[57][58]
In general, lesions localised anywhere above the neck, in the same distribution as AKs.
Hypertrophic lupus erythematosus
SIGNS / SYMPTOMS
A variant of DLE with verrucous hyperkeratotic and crusting lesions.
Sub-acute cutaneous lupus erythematosus
SIGNS / SYMPTOMS
Non-scarring, non-atrophic papulosquamous or annular polycyclic lesions, morphologically intermediate between DLE and SLE.[58] About 20% of these patients have concomitant DLE lesions and 50% fulfil criteria for SLE.[54][63][64][65]
Localised on the trunk and extensor aspects of the upper extremities rather than face and neck.
Unlike AKs, more likely to occur in women.
Up to 70% of patients have extracutaneous manifestations including mild arthralgias.[54][63]
INVESTIGATIONS
Skin biopsy shows interface lichenoid dermatitis, basal keratinocytic vacuolisation, suprabasilar clefts and vesicles, lymphocytic exocytosis, colloid bodies in lower epidermis and papillary dermis, marked oedema, and focal erythrocyte extravasation.
Associated with HLA-DR2 and HLA-DR3. Seventy percent are anti-Ro (SS-A)-positive.[54][63][66]
Psoriasis
SIGNS / SYMPTOMS
Well-defined pink to erythematous confluent papules and plaques covered with silvery scales, revealing small bleeding points on scraping (Auspitz sign).
An eruptive form with small plaques (guttate psoriasis) may occur after acute group A beta-haemolytic streptococcal throat infections.
May be nail involvement including pitting, erythrodermia, arthritis, and pustular lesions.[54][67][68]
INVESTIGATIONS
Skin biopsy shows acanthosis, focal vacuolisation, and disappearance of granular cells with overlying parakeratosis, oedema, and capillary dilation in elongated papillary dermis.
Lymphocytes infiltrate perivascular area. Neutrophils in parakeratotic areas form Munro micro-abscesses, and neutrophils in spinous layer form pustules of Kogoj.[54][68]
Disseminated superficial actinic porokeratosis
SIGNS / SYMPTOMS
Lesions are localised mostly in the extensor surfaces of the extremities and can occur in the face.
Small, superficial, skin-coloured, erythematous or pigmented plaques surrounded by a narrow, elevated hyperkeratotic ridge.[54]
INVESTIGATIONS
Clinical findings should suffice to distinguish from AKs. Skin biopsy shows characteristic deep invaginations of keratin into the epidermis with central parakeratosis (cornoid lamella).[54]
Large cell acanthoma
SIGNS / SYMPTOMS
A small hyperkeratotic, well-defined plaque that develops in sun-exposed areas.
Resembles AKs, in the type of lesion, the pattern of distribution (e.g., head and extremities), and size of the lesions (<1 cm).
It has been related to lentigo senilis (solar lentigo), stucco keratosis, lichen planus-like AK, and Bowen's disease.[69][70][71][72][73]
INVESTIGATIONS
Skin biopsy shows large keratinocytes with large nuclei arranged in a disorganised pattern.[54]
Nuclear dysplasia may be present and mitoses are infrequent. Acanthosis, hypergranulosis, and orthohyperkeratosis may also be present.
Solar lentigo
SIGNS / SYMPTOMS
Well-defined, irregular, very small hyperpigmented macules localised over sun-exposed areas.
INVESTIGATIONS
Skin biopsy shows elongated, fused rete ridges, with small bud-like extensions. Thin epidermis over the rete ridges. Low epidermis with hyperpigmented basaloid cells and strong DOPA-positive dendritic melanocytes.
Dermoscopy: discrete regular network, uniform pigmented background, absent brown globules.[56]
Warts
SIGNS / SYMPTOMS
Well-defined, usually round, firm, papillomatous papules associated with human papilloma virus (HPV) infection.
Located on dorsal aspects of the fingers and hands, where they can resemble hyperkeratotic AKs.
The filiform variant is mostly seen on the face and scalp of older children rather than in older people.[54]
INVESTIGATIONS
Skin biopsy shows a thick epidermis with papillomatosis, and hyperkeratosis. Elongated rete ridges, focal cell vacuolisation (koilocytotic cells), and parakeratotic cells.
PCR HPV-DNA amplification may detect viral antigens including HPV common antigen.
In-situ hybridisation may identify viral genomic material.[54]
Lichen planus
SIGNS / SYMPTOMS
Few or multiple violaceous well-defined papules with fine white lines on the surface.
Lichen planus-like (lichenoid) AK lesions morphologically resemble lichen planus, and tend to be localised on sun-exposed areas.
In addition, lichen planus can be frequently found in mucous membranes, genitals, and nails.
INVESTIGATIONS
Skin biopsy reveals characteristic hyperkeratotic epidermis, irregular acanthosis, focal thickening of the granular layer, liquefaction of basement membrane, and band-like lymphocytic infiltrate in the upper dermis.[54]
Lentigo maligna and melanoma in situ
SIGNS / SYMPTOMS
Clinically resemble pigmented and spreading pigmented AK (SPAK).[74]
INVESTIGATIONS
Dermoscopy: asymmetrically pigmented follicular ostia, irregular size and slate-grey dots and globules that are more irregularly and asymmetrically distributed. Hypopigmented follicular openings surrounded by a hyperpigmented rim.[74]
Skin biopsy shows atypical melanocytes at the basal layer of atrophic sun-damaged skin; melanocyte nesting, vertical stacking, and pagetoid spread.[74]
Immunostaining shows positivity to melanocyte antigen related to T cells (MART)-1, Melan-A, S-100, and HMB-45.[74]
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