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Cutaneous squamous cell carcinoma
See also in: Anogenital,Hair and Scalp,Nail and Distal Digit
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Cutaneous squamous cell carcinoma

See also in: Anogenital,Hair and Scalp,Nail and Distal Digit
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Contributors: Gaurav Singh MD, MPH, Belinda Tan MD, PhD, Sarah Hocker DO, Susan Burgin MD
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Synopsis

Squamous cell carcinoma (SCC), a keratinocyte carcinoma, is the second most common skin cancer worldwide, and its incidence is increasing. The lifetime risk of developing SCC is 9%-14% for men and 4%-9% for women. It generally presents in later decades of life. TP53 gene mutations have been implicated in the development of SCC. Actinic keratoses mark a patient's increased risk for developing SCC, but the rates of transformation of actinic keratoses into SCCs are low.

Skin phototype is the most important factor related to developing this cancer, as individuals with lighter skin types are at about 80 times higher risk than darkly pigmented individuals. In individuals with darker skin phototypes, 30%-40% of SCCs develop within scars and chronic nonhealing ulcers (compared to 2% developing within such areas in people with lighter skin phototypes).

A variety of other risk factors increase the likelihood of developing SCC. These include ultraviolet (UV) exposure, solid organ transplantation, ionizing radiation exposure, cigarette smoking, human papillomavirus (HPV), chemical exposure (ie, arsenic, mineral oil, coal tar, soot, mechlorethamine, polychlorinated biphenyls, and psoralen plus UVA treatment), freckling, red hair, immunosuppression such as human immunodeficiency virus (HIV) disease / AIDS, and chronic nonhealing wounds. Dermatoses associated with a risk of SCC include discoid lupus erythematosus, lichen planus (ie, erosive, hypertrophic), and lichen sclerosus. A variety of genetic syndromes have also been associated with SCC. These include xeroderma pigmentosum, oculocutaneous albinism, epidermodysplasia verruciformis, dystrophic epidermolysis bullosa (recessive), Ferguson-Smith syndrome, and possibly Muir-Torre syndrome. Medications can also lead to the development of SCCs. Immunosuppressives, such as systemic immunomodulators or biologics, increase the risk of SCC, and the risk is proportional to length of therapy. Other implicated medications include voriconazole, thiopurine in patients with irritable bowel disease, BRAFV600 inhibitors such as vemurafenib and dabrafenib, and photosensitizing antihypertensive drugs such as alpha‐2 receptor agonists and diuretics.

Although SCC can arise on any skin surface including mucosa, the most common areas of involvement are sun-exposed areas such as the head, neck, arms, and hands. It most commonly presents as an erythematous to flesh-colored papulonodule on chronically sun-damaged skin. However, the clinical presentation is highly variable among different demographic groups and tumor subtypes. Lesions may grow slowly or evolve rapidly.

The rate of metastasis is approximately 4%. The most common site of metastasis is the regional lymph node, but distal metastasis has been reported. Risk of metastasis is higher in immunosuppressed individuals, particularly solid organ transplant recipients, in primary lip lesions, and in non-UV-related SCCs.

Some features classify SCC as having a high risk of recurrence. These include aggressive histopathologic types (acantholytic, adenosquamous, carcinosarcomatous), depth more than 2 mm, size more than 2 cm, poorly defined borders, location at a site of prior radiation / burn or chronic inflammatory process, specific anatomic location (ie, tongue, vulva, penis), history of immunosuppression, moderate or poor differentiation on pathology, desmoplasia, and perineural or angiolymphatic invasion. These features may lead to selection of a treatment option with lower recurrence rates. Mohs micrographic surgery (MMS) has been shown to have less recurrence than standard surgical excision.

Various staging systems exist, although none is universally accepted. See Work Group. Guidelines of care for the management of cutaneous squamous cell carcinoma. J Am Acad Dermatol. 2018 Mar;78(3):560-578.

Related topics: Oral squamous cell carcinoma, Squamous cell carcinoma in situ

Codes

ICD10CM:
C44.92 – Squamous cell carcinoma of skin, unspecified

SNOMEDCT:
402815007 – Squamous cell carcinoma

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Diagnostic Pearls

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Differential Diagnosis & Pitfalls

Best Tests

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Management Pearls

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Therapy

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Drug Reaction Data

Below is a list of drugs with literature evidence indicating an adverse association with this diagnosis. The list is continually updated through ongoing research and new medication approvals. Click on Citations to sort by number of citations or click on Medication to sort the medications alphabetically.

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References

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Last Reviewed: 09/27/2018
Last Updated: 09/11/2019
Copyright © 2019 VisualDx®. All rights reserved.
Cutaneous squamous cell carcinoma
See also in: Anogenital,Hair and Scalp,Nail and Distal Digit
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Cutaneous squamous cell carcinoma : Friable papule, Verrucous scaly papule, Verrucous scaly plaque, Sun-exposed distribution
Clinical image of Cutaneous squamous cell carcinoma
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