Differentials
Squamous cell carcinoma (SCC) in situ (Bowen 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 disease.
Generally a larger red ulcer with a thick border and a granular base.
Has the potential to metastasize.
INVESTIGATIONS
Skin biopsy shows atypical (anaplastic) keratinocytes throughout entire epidermis, invading dermis.
Differentiated tumors have less atypical cells and more keratinization (e.g., horn pearls) than undifferentiated.
Anti-cytokeratin 13 antibodies distinguish them from other tumors.[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, color 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 centered 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 localized 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 tumor cells and stroma.[54]
Seborrheic keratosis
SIGNS / SYMPTOMS
Elevated, well-defined velvety plaques, localized 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.
Localized 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 localized 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.
Subacute cutaneous lupus erythematosus
SIGNS / SYMPTOMS
Nonscarring, nonatrophic papulosquamous or annular polycyclic lesions, morphologically intermediate between DLE and SLE.[58] About 20% of these patients have concomitant DLE lesions and 50% fulfill criteria for SLE.[54][63][64][65]
Localized 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 vacuolization, suprabasilar clefts and vesicles, lymphocytic exocytosis, colloid bodies in lower epidermis and papillary dermis, marked edema, 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-hemolytic streptococcal throat infections.
May be nail involvement including pitting, erythrodermia, arthritis, and pustular lesions.[54][67][68]
INVESTIGATIONS
Skin biopsy shows acanthosis, focal vacuolization, and disappearance of granular cells with overlying parakeratosis, edema, and capillary dilation in elongated papillary dermis.
Lymphocytes infiltrate perivascular area. Neutrophils in parakeratotic areas form Munro microabscesses, and neutrophils in spinous layer form pustules of Kogoj.[54][68]
Disseminated superficial actinic porokeratosis
SIGNS / SYMPTOMS
Lesions are localized mostly in the extensor surfaces of the extremities and can occur in the face.
Small, superficial, skin-colored, 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 disease.[69][70][71][72][73]
INVESTIGATIONS
Skin biopsy shows large keratinocytes with large nuclei arranged in a disorganized 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 localized over sun-exposed areas.
INVESTIGATIONS
Skin biopsy shows elongated, fused rete ridges, with small budlike 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 vacuolization (koilocytotic cells), and parakeratotic cells.
PCR HPV-DNA amplification may detect viral antigens including HPV common antigen.
In-situ hybridization 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 localized 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 bandlike 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-gray 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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