cSCC (Cutaneous Squamous Cell Carcinoma)

What is Cutaneous Squamous Cell Carcinoma (cSCC)? Cutaneous squamous cell carcinoma (cSCC) is a non-melanoma type of skin cancer that arises from keratinocytes. It is the second most common type of skin cancer in the US, with an incidence of about one million cases diagnosed per year.

Who gets cSCC?

cSCC is seen most commonly in light-skinned men over the age of 50, but may be present in anyone with high exposure to UV rays.

Common risk factors for cSCC include:

  • UV exposure (through sun or tanning beds)
  • Male gender, thought to be due to increased exposure to UV with less use of protective factors such as sun block or clothing.
  • Fair skin (Fitzpatrick skin types I-III) that is more prone to burning with UV exposure.
  • Immunosuppression, especially in those who are recipients of solid organ transplants. 
  • Older age, with an annual increase of 50-200% in the last three decades of life. This is likely because of an increased risk of immunosuppression coupled with an increase in cumulative UV exposure.
  • Cigarette smoking.

Rare risk factors include:

  • HPV infection.
  • Chronic inflammation of the region.
  • Environmental exposure to arsenic, radon, polycyclic aromatic hydrocarbons, nitrosamines, and alkylating agents.
  • Familial syndromes, including xeroderma pigmentosa, albinism, epidermolysis bullosa,  and bloom syndrome.
  • Other genetic vulnerabilities, such as mutations in TP53, Ras mutations, CDKN2A mutations, and mutations of Notch homolog 1.

What does cutaneous squamous cell carcinoma look like?

The gross morphology of cSCC varies, but may present as scaling, flat or nodular, erythematous, or bleeding lesions found in areas that are least protected from the sun, including the face, bald scalp, ears, and dorsal arms. cSCC can often present with a precursor lesion called actinic keratosis, a rough scaly patch on skin exposed areas, that should be removed as a precaution

The severity of the disease is often tied to the histopathology of the lesion. Low-to-moderate risk lesions are usually well differentiated, while high-risk variants often have characteristics such as:

  • Acanthylosis.
  • Poorly differentiated lesions with pleomorphic spindle cells and high levels of mitotic activity.
  • Mixed squamous and glandular differentiation.

Source: Waldman, A., & Schmults, C. (2019). Cutaneous Squamous Cell Carcinoma. Hematology/Oncology Clinics of North America33(1), 1–12.