Cutaneous Squamous Cell Carcinoma

Squamous cell carcinoma (SCC) is a malignant epithelial tumor arising from keratinocytes. Cutaneous (nonmucous membrane) SCC is the second most common form of skin cancer, occurring much less frequently than basal cell carcinoma (BCC) and in an older age group than does BCC.
Lesions most frequently occur on sun-exposed sites of elderly, fair-skinned individuals.
Most SCCs arise in actinic keratoses (solar keratoses) and these are slow-growing, minimally invasive, unaggressive, and have an excellent prognosis because distant metastases are extremely rare.
An SCC may also appear de novo without a preceding actinic keratosis or emerge from a pre-existing human papilloma virus infection (verrucous carcinoma).
SCCs may develop from causes other than sun exposure such as within an old burn scar or on sites previously exposed to ionizing radiation.
Metastases are more likely to occur in thicker tumors >6 mm deep. Other risk factors for metastases include lesions that arise on the ears, the vermilion border of the lips, or on mucous membranes.
Although SCC is very rare in people of African and Asian descent, an SCC tends to be more aggressive in these populations.
Also apt to be more aggressive are the non-sun-related SCCs such as an SCC in long-standing scars or in sites previously exposed to ionizing radiation or long-term psoralen and ultraviolet A (PUVA) light, on chronic inflammatory lesions (e.g., discoid lupus erythematosus), cutaneous ulcers (e.g., venous stasis ulcers), or other nonhealing wounds.
As with AKs and BCCs (see later discussion), SCC is related to sun exposure and is noted more frequently in those with a greater degree of outdoor activity.

Clinical Manifestations ⬆ ⬇

Most SCCs are asymptomatic, although bleeding, pain, and tenderness may be noted.
Slow-growing, firm papules with the ability to produce scale (keratinization) tend to be more clearly differentiated and are less likely to metastasize (Fig. 31.13).
Softer, nonkeratinizing lesions are less well differentiated and are more likely to metastasize (Fig. 31.14).
SCCs typically present as papules, plaques, or nodules that grow slowly.
Lesions may be scaly or ulcerated (Fig. 31.15) or have a smooth or thick hyperkeratotic surface.
As with actinic keratoses, an SCC may also produce a cutaneous horn on its surface.
An SCC may appear as a reddish brown nodule. It may, at times, be indistinguishable from a hypertrophic actinic keratosis or a BCC.
With the exception of mucous membrane SCCs, lesions of cutaneous SCC occur in exactly the same locations as do actinic keratoses: sun-exposed areas such as the face, the dorsa of the forearms and hands, and the “V” of the neck.
In men, SCCs tend to arise on the bald areas of the scalp and on the tops of the ears as well as the posterior neck below the occipital hairline.
In women, lesions tend to occur on the legs as well as other relatively sun-exposed locations.
In individuals of African origin there is an equal frequency of skin cancers in sun-exposed and unexposed areas.

Clinical Variant ⬆ ⬇

Intraepithelial Squamous Cell Carcinoma

Bowen disease (Fig. 31.16) is one of the few skin cancers that should be considered as a diagnosis in African-American, Afro-Caribbean, and African blacks. This non-sun-related skin cancer may arise on the extremities de novo (Fig. 31.17), in an old scar or in a lesion of discoid lupus erythematosus.
Bowen disease (SCC in situ) and erythroplasia of Queyrat are intraepithelial SCCs that often arise in sites that are not exposed to the sun. When an SCC in situ lesion occurs on the penis, it is referred to as erythroplasia of Queyrat (Fig. 31.18).

Squamous Cell Carcinoma of Mucous Membranes

This condition (Fig. 31.19) may initially present as leukoplakia, nonhealing fissures, or ulcerations. Such lesions have significant metastatic potential.
Treatment is beyond the scope of this publication.

Differential Diagnosis

Actinic Keratosis (see above)

Early SCC lesions may be clinically difficult, if not impossible, to distinguish from a precursor AK.

Basal Cell Carcinoma (see below)

Typically pearly and telangiectatic.
Appear at a younger age than do SCCs.
May be indistinguishable from SCC, particularly if the lesion is ulcerated.

Keratoacanthoma (see below)

This lesion also may be clinically and, at times, histopathologically, indistinguishable from a SCC; considered by some to be a low-grade variant of an SCC.
It is fast growing and less aggressive.
Has a central hyperkeratotic crater.

Melanoma (see below)

An amelanotic melanoma (lacking typical pigmentation) or an ulcerated melanoma may also be impossible to distinguish from an SCC.

Psoriasis/Eczema

Bowen disease resembles a scaly solitary psoriatic or eczematous plaque (seeChapters 13and14).

Seborrheic Keratosis (see Chapter 30: Benign Cutaneous Neoplasms)

“Stuck on” appearing.

Verruca Vulgaris

The appearance of common warts is often similar to that of SCC lesions.

Management

Treatment

Electrocautery and curettage for small lesions (generally less than 1 cm in diameter). This is done in a fashion similar to that performed for BCC treatment (see subsequent discussion). It is particularly useful on flat surfaces (e.g., forehead, cheek) and SCC in situ (Bowen disease).
As with superficial BCCs, selected SCCs may be treated using cryosurgery with LN₂.
Total excision, the preferred method of therapy for SCC, permits histologic diagnosis of the tumor margins.

Immunotherapy

Imiquimod (Aldara) 5% cream is approved for the treatment of actinic keratoses (see previous discussion), for superficial BCCs (see later discussion), and is used “off-label” for SCC in situ (Bowen disease).
Aldara may also have some utility in treating selected patients who have highly differentiated SCCs and in some renal transplant patients who tend to develop numerous SCCs.
Micrographic (Mohs) surgery (see Fig. 35.25A-D) is useful for excessively large or invasive carcinomas, for recurrent lesions, for lesions with poorly delineated clinical borders, for SCCs within an orifice (e.g., ear canals or nostrils), and for carcinomas in locations where preservation of normal tissue is extremely important (e.g., tip of the nose, eyelids, nasal alae, ears, lips, and glans penis). It is also a treatment of choice for a lesion in an area of late radiation change.
Radiation therapy is used for those patients who are physically debilitated or who are unable to, or refuse to undergo, excisional surgery. It is also suitable for larger, advanced lesions.
For metastatic squamous cell carcinoma, oral 5-FU has been used alone or in combination with SC interferon. More recently, epidermal growth factor receptor (EGFR) inhibitors, such as cetuximab, are used in combination with systemic chemotherapy for metastatic disease.

Surgery/Other Procedures

Complete lymphadenectomy of the draining nodal basin for high-risk tumors.
Metastatic disease requires aggressive management by a multidisciplinary team, involving plastic, ENT/maxillofacial, and general surgeons, or a surgical oncologist.

Prevention

Sun avoidance measures
Sunscreens, sun-protective garments, and hats
Sunglasses with ultraviolet protection
Tinted windshields and side windows in cars
Avoidance of contact with known carcinogenic compounds

Helpful Hints

A subungual SCC can easily be mistaken for a verruca.
High-risk SCCs may require imaging studies.
Lymph node biopsy is indicated for suspected nodal involvement.

SEE PATIENT HANDOUT “Sun Protection Advice” IN THE COMPANION eBOOK EDITION.

SEE PATIENT HANDOUT “Squamous Cell Carcinoma” IN THE COMPANION eBOOK EDITION.

Points to Remember

Bowen disease (SCC in situ) and frank SCC are two of the few skin cancers that should be considered in African-Americans. Such non-sun-related SCCs tend to arise on the extremities de novo, in an old scar, or in a lesion of discoid lupus erythematosus.
An early lesion of SCC is difficult to distinguish from a precursor actinic keratosis.
SCCs that develop from AKs are generally unaggressive.
An SCC that is histopathologically “poorly differentiated” should be treated more aggressively.
SCCs arising on a mucous membrane, in a chronic ulcer, or in an immunocompromised are at higher risk of metastasis.

Outline
Intraepithelial Squamous Cell Carcinoma
Squamous Cell Carcinoma of Mucous Membranes

section name header

Basics ⬇

Clinical Manifestations ⬆ ⬇

Clinical Variant ⬆ ⬇

Other Information ⬆