Squamous cell carcinoma (SCC), the second most common form of skin cancer, is a malignant neoplasm of the keratinizing epidermal cells with histological evidence of full epidermal involvement (superficial SCC) or dermal invasion (invasive SCC). There is evidence of DNA mutations that prevent normal squamous cell apoptosis, resulting in uncontrolled over-growth of the cells.

Risk factors for SCC include the following: exposure to ultraviolet A and B light (especially chronic sun exposure with little or no tanning), fair skin and blue eyes, history of xeroderma pigmentosum (extreme sensitivity to the sun rays), radiation therapy, and antirejection medications after organ transplant.[i] A recent study by Lipper confirmed that the antihypertensive drug hydrochlorothiazide (HCTZ) is a potent photosensitizer and increases the risk of SCC, especially on the lip, and recommends that patients with other risk factors for SCC be placed on alternative antihypertensive agents.[ii] Most SCCs occur on the face, hands, arms, and feet (areas that are exposed most extensively to the sun); however, they can also occur on the genitals. The best preventative strategy is continuous and frequent use of sunscreen with an SPF of at least 30.

If the SCC occurs in the area of a previous wound (e.g. a burn, venous ulcer, osteomyelitis, or traumatic wound), often with a latency period years after the initial wounding, it is termed a Marjolin ulcer. It occurs most frequently in wounded areas that have repeated irritation, friction, or other mechanical stress on the tissue.[iii] This type of SCC is usually very aggressive and requires excision beyond its margins in addition to radiation therapy.[iv]^,[v]

Superficial SCC presents as a non-healing or expanding scaly chronic rash, whereas invasive SCC usually presents first as a firm smooth red papule, nodule, or plaque. The edges are poorly defined and the surrounding skin is scaly. It is commonly hyperkeratotic or ulcerated and may metastasize and grow rapidly. Dermal lesions may also occur as a result of squamous cell carcinoma in other areas, such as the mouth, throat, or lungs, in which case they begin as a nodule that subsequently ulcerates and becomes an open lesion. These lesions are to differentiated from cutaneous SCC and usually indicate a poor prognosis for the underlying malignancy.

Diagnosis of SCC is made with a sufficiently deep-shave biopsy. Smaller, low-risk SCCs are treated with surgical excision, electrodessication and curettage, or cryotherapy; larger, high-risk lesions are best treated with Mohs micrographic surgery which has the highest overall cure rate. If the SCC metastasizes, chemotherapy and radiation therapy are indicated, as well as excision of nodules and any regional lymph nodes that are involved.[vi]

Because of the chemotherapy and radiation of affected tissue, wounds are not uncommon after excision of SCC. Supportive wound care is required, including infection control, pain management, lymphedema management, and frequent inspection for new lesions. Absorbent antimicrobial dressings are useful in preventing secondary infections, in managing drainage, and in preventing further skin maceration at the wound site.

In summary, SCC can be either cutaneous or from a deeper malignancy. Early diagnosis and treatment is critical in order to prevent metastasis to the lymphatic system and deeper tissues.

[i] Green AC, McBride P. Squamous cell carcinoma of the skin (non-metastatic). BMJ Clin Evid. 2014. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4144167/. Accessed June 7, 2020.

[ii] Lipper GM. Hydrochlorothiazide and skin cancer: raised red flag. Available at https://medscape.com/viewarticle/895942?nlid=122267_1521&src. Accessed June 7, 2020.

[iii] Tobin C, Sanger JR. Marjolin’s ulcers: a case series and literature review. Wounds. 2014;26(9):248-254.

[iv] Franco R. Basal and squamous cell carcinoma associated with chronic venous leg ulcer.   Intern J Dermatol. 2001;40:539-544.

[v] Kirsner RS, Spencer J, Falanga V, Garland LE, Kerdel FA. Squamous cell carcinoma arising in osteomyelitis and chronic wounds. Dermatol Surg. 1996;22(12):1015-1028.

[vi] Firnhaber JM. Diagnosis and treatment of basal cell and squamous cell carcinoma. Am Fam Physician. 2012;86(2):161-168.