Continuing medical education
Cutaneous squamous cell carcinoma: Incidence, risk factors, diagnosis, and staging

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Cutaneous squamous cell carcinoma (cSCC), a malignant proliferation of cutaneous epithelium, represents 20% to 50% of skin cancers. Although the majority of cSCCs are successfully eradicated by surgical excision, a subset of cSCC possesses features associated with a higher likelihood of recurrence, metastasis, and death. The proper identification of these aggressive cSCCs can guide additional work-up and management. In the first article in this continuing medical education series, we discuss the incidence, recurrence rates, mortality rates, and risk factors associated with cSCC and review the staging systems used to stratify patients into high- and low-risk groups. The second article in this series reviews the treatment options for cSCC, with focused attention on the management of high-stage tumors.

Section snippets

Epidemiology and estimates of incidence

Key points

  1. Cutaneous squamous cell carcinoma is the second most common nonmelanoma skin cancer after basal cell carcinoma, and in some studies approaches the incidence of basal cell carcinoma

  2. The incidence of cutaneous squamous cell carcinoma is increasing yearly in the United States

  3. Estimates of mortality rates of cutaneous squamous cell carcinoma approximate that of renal and oropharyngeal carcinomas and melanoma in the southern and central United States

Cutaneous squamous cell carcinoma (cSCC) is the

Pathogenesis and etiologic risk factors

Key points

  1. Genes commonly mutated in patients with cutaneous squamous cell carcinoma include TP53, CDKN2A, Ras, and NOTCH1

  2. Risk factors that predispose to the development of cutaneous squamous cell carcinoma include light skin (Fitzpatrick skin types I-III), age, male sex, exposure to sunlight or other ultraviolet radiation, immunosuppression, human papillomavirus, chronic scarring conditions, familial cancer syndromes, and environmental exposures, such as arsenic

Clinical and histopathologic diagnosis

Key points

  1. Histopathologic subtypes of cutaneous squamous cell carcinoma that are well-differentiated with low metastatic potential include keratoacanthoma and verrucous carcinoma

  2. This includes Buschke–Lowenstein tumors found in the genitalia and groin and epithelioma cuniculatum, which is found on the plantar surface of the foot

  3. Histopathologic subtypes of cutaneous squamous cell carcinoma with poor prognosis include desmoplastic cutaneous squamous cell carcinoma, adenosquamous cutaneous squamous cell

Factors associated with local recurrence and metastases

Key points

  1. Tumor diameter >2.0 cm is the risk factor most highly associated with disease-specific death

  2. Perineural involvement of nerves >0.1 mm in caliber is associated with increased nodal metastases and increased mortality risk

Lymph node metastases from head and neck cSCC have a high cure rate when identified and treated early.48, 49 Risk factors that predispose an individual to a higher rate of local recurrence and metastasis are discussed below.

Various classification schemes and clinical application

Key points

  1. The American Joint Committee on Cancer's (AJCC) most recent staging system, AJCC-8, published in October 2016, uses tumor diameter ≥2 cm as the distinguishing factor between T1 and T2 tumors

  2. High-risk features in AJCC-8 staging, which result in upstaging to T3, include tumor diameter ≥4 cm, minor bone erosion, invasion of nerves 0.1 mm in caliber or in subcutis, or deep invasion (≥6 mm or beyond the subcutaneous fat)

  3. T4 is reserved for major bone involvement or skull base invasion

  4. An alternative

AJCC-8

In October 2016, the AJCC introduced the 8th edition of its cancer staging systems. AJCC-8 includes a revision of the cSCC staging system, which was developed within the head and neck committee and therefore only applies to cSCCs located on head and neck skin and vermillion lip. It is not specified how cSCCs located elsewhere on the body are to be staged. The AJCC-8 staging system classifies cases by local tumor burden (T), nodal status (N), and metastatic disease (M). The T category is based

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  • Cited by (0)

    Funding sources: None.

    Dr Schmults was involved in the development of the Brigham and Women's tumor staging system for cutaneous squamous cell carcinoma. Drs Que and Zwald have no conflicts of interest to declare.

    Reprints not available from the authors.

    Date of release: February 2018

    Expiration date: February 2021

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