(See also Overview of Skin Cancer Overview of Skin Cancer Skin cancer is the most common type of cancer and commonly develops in sun-exposed areas of skin. The incidence is highest among outdoor workers, sportsmen, and sunbathers and is inversely related... read more .)
Squamous cell carcinoma is the 2nd most common type of skin cancer after basal cell carcinoma Basal Cell Carcinoma Basal cell carcinoma is a superficial, slowly growing papule or nodule that derives from certain epidermal cells. Basal cell carcinomas arise from keratinocytes near the basal layer, which are... read more 
, with 1.8 million cases annually in the United States, and 15,000 deaths (1 Reference Squamous cell carcinoma is a malignant tumor of epidermal keratinocytes that invades the dermis; this cancer usually occurs in sun-exposed areas. Local destruction may be extensive, and metastases... read more 
). It may develop in normal tissue, in a preexisting actinic keratosis Actinic keratoses Chronic affects of sunlight include photoaging, actinic keratoses, and skin cancer. (See also Overview of Effects of Sunlight.) Chronic exposure to sunlight ages the skin (photoaging, dermatoheliosis... read more 
, in a patch of oral leukoplakia Premalignant (dysplastic) changes Growths can originate in any type of tissue in and around the mouth, including connective tissues, bone, muscle, and nerve. Most commonly, growths form on the lips, the sides of the tongue,... read more 
, or in a burn scar. Lighter-skinned people are much more susceptible to squamous cell carcinoma than darker-skinned people.
Reference
1. The Skin Cancer Foundation: Skin Cancer Facts & Statistics: Nonmelanoma skin cancer. Accessed 08/30/2022.
Symptoms and Signs of Squamous Cell Carcinoma
The clinical appearance is highly variable, but any nonhealing lesion on a sun-exposed surface should be suspect. The tumor may begin as a red papule or plaque with a scaly or crusted surface and may become nodular or hyperkeratotic, sometimes with a warty surface. In some cases, the bulk of the lesion may lie below the level of the surrounding skin. Eventually the tumor ulcerates and invades the underlying tissue.
Squamous cell carcinoma has a highly variable appearance; any nonhealing lesion on a sun-exposed area should be suspect. It may cause extensive local destruction and may metastasize in advanced stages.
Image provided by Thomas Habif, MD.
This erythematous, irregular plaque on an extremity was diagnosed as squamous cell carcinoma on biopsy.
© Springer Science+Business Media
The appearance of squamous cell carcinoma is variable. These hyperpigmented, scaly lesions on the earlobe were diagnosed as squamous cell carcinoma on biopsy.
DR P. MARAZZI/SCIENCE PHOTO LIBRARY
This squamous cell carcinoma on the lip is highly keratinized; not all squamous cell carcinomas of the lip are as highly keratinized.
Photo courtesy of Gregory L. Wells, MD.
Diagnosis of Squamous Cell Carcinoma
Biopsy
Biopsy is essential.
Differential diagnosis
Differential diagnosis varies based on the lesion's appearance.
Nonhealing ulcers should be differentiated from pyoderma gangrenosum Pyoderma Gangrenosum Pyoderma gangrenosum is a chronic, neutrophilic, progressive skin necrosis of unknown etiology often associated with systemic illness and sometimes skin injury. Diagnosis is clinical. Treatment... read more 
and venous stasis ulcers Diagnosis Stasis dermatitis is inflammation, typically of the skin of the lower legs, caused by chronic edema. Symptoms are itching, scaling, and hyperpigmentation. Ulceration can be a complication. Diagnosis... read more 
.
Nodular and hyperkeratotic lesions should be differentiated from keratoacanthomas Keratoacanthoma Keratoacanthomas are round, firm, usually flesh-colored nodules with sharply sloping borders and a characteristic central crater containing keratinous material; they usually resolve spontaneously... read more 
(probably squamous cell carcinomas themselves) and verruca vulgaris Warts Warts are common, benign, epidermal lesions caused by human papillomavirus infection. They can appear anywhere on the body in a variety of morphologies. Diagnosis is by examination. Warts are... read more 
.
Scaling plaques should be differentiated from basal cell carcinoma Basal Cell Carcinoma Basal cell carcinoma is a superficial, slowly growing papule or nodule that derives from certain epidermal cells. Basal cell carcinomas arise from keratinocytes near the basal layer, which are... read more , actinic keratosis Actinic keratoses Chronic affects of sunlight include photoaging, actinic keratoses, and skin cancer. (See also Overview of Effects of Sunlight.) Chronic exposure to sunlight ages the skin (photoaging, dermatoheliosis... read more , verruca vulgaris Warts Warts are common, benign, epidermal lesions caused by human papillomavirus infection. They can appear anywhere on the body in a variety of morphologies. Diagnosis is by examination. Warts are... read more , seborrheic keratosis Seborrheic Keratoses Seborrheic keratoses are superficial, often pigmented, epithelial lesions that are usually verrucous but may occur as smooth papules. The cause of seborrheic keratosis is unknown, but genetic... read more 
, psoriasis Psoriasis Psoriasis is an inflammatory disease that manifests most commonly as well-circumscribed, erythematous papules and plaques covered with silvery scales. Multiple factors contribute, including... read more 
, and nummular dermatitis Nummular Dermatitis Nummular dermatitis is inflammation of the skin characterized by coin-shaped or discoid eczematous lesions. Diagnosis is clinical. Treatment may include topical corticosteroids and phototherapy... read more 
(nummular eczema).
Prognosis for Squamous Cell Carcinoma
In general, the prognosis for small lesions removed early and adequately is excellent. Regional and distant metastases of squamous cell carcinomas on sun-exposed skin are uncommon but do occur, particularly with poorly differentiated tumors. Characteristics of more aggressive tumors include
Size > 2 cm in diameter
Invasion depth of > 2 mm
Perineural invasion
Location near the ear or vermilion border
About one third of lingual or mucosal cancers have metastasized before diagnosis (see Oral Squamous Cell Carcinoma Oral Squamous Cell Carcinoma Oral cancer refers to cancer occurring between the vermilion border of the lips and the junction of the hard and soft palates or the posterior one third of the tongue. Over 95% of people with... read more 
).
Late-stage disease, which may require extensive surgery, is far more likely to metastasize. It spreads initially regionally to surrounding skin and lymph nodes and eventually to nearby organs. Cancers that occur near the ears or the vermilion border, in scars, or that have perineural invasion are more likely to metastasize. The overall 5-year survival rate for metastatic disease is 34% despite therapy.
Treatment of Squamous Cell Carcinoma
Usually locally destructive techniques
Treatment of squamous cell carcinoma is similar to that for basal cell carcinoma Treatment Basal cell carcinoma is a superficial, slowly growing papule or nodule that derives from certain epidermal cells. Basal cell carcinomas arise from keratinocytes near the basal layer, which are... read more and includes curettage and electrodesiccation, surgical excision, cryosurgery, topical chemotherapy (imiquimod or 5-fluorouracil) and photodynamic therapy, or, occasionally, radiation therapy. Treatment and follow-up must be monitored closely because of the greater risk of metastasis compared with a basal cell carcinoma.
Squamous cell carcinoma on the lip or other mucocutaneous junction should be excised; at times, cure is difficult.
Recurrences and large tumors should be treated aggressively with Mohs microscopically controlled surgery, in which tissue borders are progressively excised until specimens are tumor-free (as determined by microscopic examination during surgery), or by a team approach with surgery and radiation therapy. Because tumors with perineural invasion are aggressive, radiation therapy should be considered after surgery.
Metastatic disease is responsive to radiation therapy if metastases can be identified and are isolated. Widespread metastases do not respond well to chemotherapeutic regimens. For inoperable advanced disease or metastatic disease, programmed death receptor 1 (PD-1) inhibitors (eg, cemiplimab, pembrolizumab) are now an option.
Prevention of Squamous Cell Carcinoma
Because squamous cell carcinoma seems to be related to ultraviolet (UV) exposure, a number of measures are recommended to limit exposure.
Sun avoidance: Seeking shade, minimizing outdoor activities between 10 AM and 4 PM (when sun's rays are strongest), and avoiding sunbathing and the use of tanning beds
Use of protective clothing: Long-sleeved shirts, pants, and broad-brimmed hats
Use of sunscreen: At least sun protection factor (SPF) 30 with broad-spectrum UVA/UVB protection, used as directed (ie, reapplied every 2 hours and after swimming or sweating); should not be used to prolong sun exposure
Key Points
Squamous cell carcinoma, because of its high frequency of occurrence and highly variable appearance, should be considered in any nonhealing lesion in a sun-exposed area.
Metastases are uncommon but are more likely in cancers involving the lingual or mucosal surfaces; that occur near the ears, the vermilion border, or in scars; or that have perineural invasion.
Treatment is usually with locally destructive methods, sometimes also with radiation therapy (eg, for tumors that are large, recurrent, or have perineural invasion).
PD-1 inhibitors such as cemiplimab and pembrolizumab may be useful in patients with advanced or metastatic disease.
Drugs Mentioned In This Article
| Drug Name | Select Trade |
|---|---|
imiquimod |
Aldara, Zyclara |
fluorouracil |
Adrucil, Carac, Efudex, Fluoroplex, Tolak |
cemiplimab |
LIBTAYO |
pembrolizumab |
Keytruda |
