History and exam
Key diagnostic factors
common
presence of risk factors
Key risk factors include UV exposure; older age; immunosuppression; fair skin; human papillomavirus; hereditary skin conditions; exposure to ionising radiation, arsenic, soot, or tar; actinic keratosis; and male sex.
growing tumours
Squamous cell carcinomas (SCCs) tend to appear and grow over 3-6 months (as opposed to basal cell carcinomas which usually grow at a slower rate). Keratoacanthomas, in particular, grow rapidly and may spontaneously involute. Keratoacanthoma-like SCCs may not involute and may progress with malignant potential.
Other diagnostic factors
common
previous skin cancer
Evidence demonstrates that a history of previous skin cancer significantly increases the risk of experiencing second primary squamous cell carcinoma (SCC). For melanoma survivors there is a 2.6-fold increase in incidence of SCC.[55]
bleeding
SCC tumours may be friable and bleed easily.
crusting
The extent of hyperkeratosis varies, and retention of compact keratin layers may result in the formation of a cutaneous horn. SCCs appear as erythematous papules or plaques that often have a scale or haemorrhagic crust.
evidence of sun damage to skin
Solar elastosis, cutaneous furrowing, and wrinkles are also more likely to be present in sun-exposed areas.
tender or itchy non-healing wound originally caused by trauma
Marjolin ulcer presents in an area of previously traumatised, chronically inflamed or scarred skin.
erythematous papules or plaques
May present as lesions that often have scale or haemorrhagic crust.
thin, flesh-coloured or erythematous plaques
In situ tumours (Bowen's disease) may present as thin, flesh-coloured or erythematous plaques.
dome-shaped nodule
Keratoacanthoma presents as a rapidly growing, dome-shaped nodule with a central keratin-filled crater.
exophytic, fungating, verrucous nodules or plaques
Verrucous carcinoma presents as exophytic, fungating, verrucous nodules or plaques on skin or mucosa.
uncommon
ulcerated tumours
Invasive SCC may present as ulcerated tumours.
lymphadenopathy
Lymphadenopathy may be present with metastatic disease.
bone pain
Bone pain may be present with metastatic disease.
hepatomegaly
Hepatomegaly may be present with metastatic disease.
neurological signs
Patients with perineural involvement may present with neurological signs.
Risk factors
strong
ultraviolet radiation exposure
Ultraviolet (UV) radiation increases risk for squamous cell carcinoma; incidence is higher on sun-exposed skin such as head, neck, extensor arms, and upper torso.[40]
Incidence varies dramatically depending on skin phototype, cumulative sun exposure, and geographic latitude.
UV-B radiation (290-320 nm) is principally responsible, with UV-A radiation (320-400 nm) adding to the risk.[41]
Previous psoralen and UVA light therapy for psoriasis may also increase risk.
solid organ transplant recipient
immunosuppression
Patients with immunocompromise (other than solid organ transplantation) are at risk for squamous cell carcinoma (SCC).
There is a direct correlation between duration of immunosuppression and skin cancer development. For example, the cutaneous effects of rapidly accelerated fibrosarcoma kinase B (BRAF) inhibitors include the development of SCCs (especially invasive phenotypes), keratoacanthoma, and photosensitivity.[46] In one study, keratoacanthoma and SCCs comprised 22% of lesions in patients with BRAF inhibitor-induced skin lesions.[47]
Fitzpatrick skin phototype
People with Fitzpatrick skin type I and II (white) are at increased risk for the development of skin cancer.[7][8]
Despite people with Fitzpatrick skin type V and VI (brown and black) having more melanin within their melanosomes, which protects the keratinocyte nucleus from UV damage, squamous cell carcinoma is the most common skin cancer for black people, and the second most common for Hispanic and Asian people.[7][13][14]
hereditary skin conditions
In people with certain genodermatoses, such as oculocutaneous albinism, squamous cell carcinomas may develop on sun-exposed areas because there is insufficient protective pigment.[48]
In those with xeroderma pigmentosum, UV radiation-induced mutations in DNA cannot be repaired, and as a result multiple skin cancers may develop at an early age.[49]
older age
This imparts a longer history of sun exposure. In addition to increased cumulative UV exposure, older patients have decreased immune surveillance and tumour detection.[50]
male sex
exposure to carcinogens
Exposure to carcinogens such as arsenic, soot, or tar predisposes people to squamous cell carcinoma development.[23][51][52]
Arsenical keratoses occur in people chronically exposed to arsenic, and are less common now than historically.
Exposure is usually through drinking water that is obtained from contaminated wells, but may occur in occupational or therapeutic settings.[51]
Affected patients typically have palmoplantar keratotic papules and pits.
actinic keratosis
The rate of transformation of actinic keratoses to invasive squamous cell carcinoma (SCC) is not completely clear, although estimates range from 0.025% to 16% per lesion per year.[53] The vast majority of SCCs arise within or close to actinic keratoses. There is evidence to suggest that patients with Olsen grade 3 actinic keratosis are at the highest risk of developing invasive SCC.[54]
previous skin cancer
Increases the likelihood of developing an squamous cell carcinoma.[55]
weak
exposure to ionising radiation
Studies on the relative risk of squamous cell carcinoma (SCC) in patients receiving ionising radiation have been conflicting; however, they may have an increased incidence of SCC, particularly those with sun-sensitive skin.[56]
human papillomavirus
Human papillomavirus is involved in the development of skin cancers, particularly in immunosuppressed individuals.[24][57][58][59][60]
However, clinical and experimental data suggest that viral infection alone is not often sufficient to induce malignant progression of infected cells, and that additional alterations in host cells may be required for skin cancer formation.
tobacco smoking
thiazide diuretics and cardiac drugs
tattoos
Tattooing introduces exogenous pigments to the dermis, such that metallic salts and organic dyes remain in the skin permanently. Squamous cell carcinoma (SSC) and keratoacanthoma have been reported on tattoos.[66] SCC arising only in the red inked areas within a multi-coloured tattoo has been described, suggesting that red tattoo ink in the skin may be an infrequent risk factor for developing SCC.[25] Nonetheless, the number of skin cancers arising in tattoos appears to be low, and coincidental occurrence cannot be excluded.
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