Cutaneous Squamous Cell Carcinoma – Causes, Symptoms, Diagnosis, Treatment and Ongoing care
- Squamous cell carcinoma (SCC) is a malignant epithelial tumor arising from keratinocytes of the epidermis. Cutaneous (nonmucous membrane) SCC is the second most common form of skin cancer. Lesions most frequently occur on sun-exposed sites of elderly, fair-skinned individuals. The majority of SCCs arise in solar keratoses (actinic keratoses). Such actinically derived SCCs that develop from solar keratoses are slow-growing, minimally invasive, unaggressive; and the prognosis is usually excellent because distant metastases that arise from these lesions are extremely rare. An SCC may appear de novo without a preceding solar keratosis. SCCs may also develop from causes other than sun exposure. For example, an SCC may arise in an old burn scar or from sites previously exposed to ionizing radiation. An SCC may also emerge from preexisting human papilloma virus infection (verrucous carcinoma). An SCC is capable of locally infiltrative growth, spread to regional lymph nodes, and distant metastasis, most often to the lungs. When metastases from SCC do occur, they are more likely to result from lesions that appear on the ears or on the vermilion border of the lips or from tumors >2 cm in diameter. Other risks for metastasis include lesions that arise on mucous membranes, from sites that received ionizing radiation, on the skin of organ transplant recipients, in chronic inflammatory lesions (e.g., discoid lupus erythematosus), or in long-standing scars or cutaneous ulcers (e.g., venous stasis ulcers) or other nonhealing wounds.
- System(s) affected: Skin/Exocrine
- Synonym(s): Squamous cell carcinoma of the skin; Epidermoid carcinoma; Prickle cell carcinoma
- Predominant age: Elderly population
- Predominant sex: Males > Females
- More common in geographic areas that have a high frequency of sun exposure
- The dramatic escalating incidence in the US due to an increase in sun exposure in the general population, aging of the population, earlier and more frequent diagnosis of SCC, and a rising number of immunosuppressed patients
- The incidence is highest in Australia and in the Sun Belt of the US.
Bowen disease and frank squamous cell carcinoma are 2 of the few skin cancers that should be considered in blacks. These non-sun–related skin cancers tend to arise on the extremities de novo or in an old scar or in a lesion of discoid lupus erythematosus.
- Older age
- Male sex: However, incidence is increasing in females due to lifestyle changes (e.g., suntan parlors, shorter dresses, etc.)
- Chronic sun exposure: SCC is noted more frequently in those with a greater degree of outdoor activity (e.g., farmers, sailors, gardeners).
- Patients with multiple solar keratoses are at increased risk.
- Personal or family history of skin cancer
- Northern European descent
- Fair complexion, fair hair, light eyes
- Poor tanning ability, with tendency to burn
- Organ transplant recipients, chronic immunosuppression
- Exposure to chemical carcinogens (e.g., arsenic, tar) or ionizing radiation
- Therapeutic UV and ionizing radiation exposure
- Defects in cell-mediated immunity related to lymphoproliferative disorders (CLL, lymphoma)
- Human papillomavirus (HPV) infection (certain subtypes)
- Chronic scarring and inflammatory conditions
- Specific genodermatoses (e.g., xeroderma pigmentosum)
- Persons of Irish or Scottish ancestry have the highest prevalence of SCC.
- SCC is relatively rare in people of African and Asian descent, although it is the most common form of skin cancer in these populations.
- Patients with oculocutaneous albinism are at greater risk.
Sun-avoidance measures: Sunscreens, hats, etc. Sunglasses with UV protection. Tinted windshields and side windows in cars. Sun-protective garments.
- Exact mechanisms are not established; however, it is well known that ultraviolet radiation damages skin cell nucleic acids (DNA) resulting in a mutant clone of the gene p53. This leads to uncontrolled growth of skin cells. Ultraviolet radiation also suppresses the immune response preventing recovery from this damage.
- Epidemiologic and experimental evidence suggests the following as causative agents: Sunlight (solar radiation), radiation exposure, tanning parlors, PUVA phototherapy exposure, inorganic arsenic exposure, coal tar and other oil derivatives
- Immunosuppression by medications or disease such as HIV
Commonly Associated Conditions
- Solar keratosis (some investigators consider a solar keratosis to be an early squamous cell carcinoma, although relatively few ultimately are found to develop into an SCC)
- Cutaneous horn
- Actinic cheilitis (solar keratoses of the mucous membranes of the lips) and leukoplakia of lip
- Xeroderma pigmentosum, albinism, and vitiligo
- Chronic skin ulcers and chronic thermal burns
Often a family or personal history of skin cancer
- Lesions occur chiefly on chronically sun-exposed areas:
- The face and the backs of the forearms and hands
- Bald areas of the scalp and top of ears in men
- The sun-exposed “V” of the neck, as well as the posterior neck below the occipital hairline
- In elderly females, lesions tend to occur on the legs and other sun-exposed locations.
- In blacks: Equal frequency in sun-exposed and unexposed areas
- Clinical appearance:
- Generally slow-growing, firm, hyperkeratotic papules, nodules, or plaques
- Most SCCs are asymptomatic, although bleeding, pain, and tenderness (all of which are unusual) may be noted.
- Lesions may have a smooth, verrucous, or papillomatous surface.
- Varying degrees of ulceration, erosion, crust, or scale
- Color is often red to brown, tan, or pearly, and may be indistinguishable from basal cell carcinoma
Diagnostic Tests & Interpretation
- Surgical biopsy to ensure diagnosis: Shave biopsy, punch biopsy, excisional biopsy, incisional biopsy
- Sentinel lymph node biopsy has been used to identify micrometastases in a small number of patients with high-risk SCC and clinically negative nodes. Complete lymphadenectomy of the draining nodal basin has also been suggested for high-risk tumors.
- Noninvasive SCC is characterized by an intraepidermal proliferation of atypical keratinocytes. Hyperkeratosis, acanthosis, and confluent parakeratosis are seen within the epidermis. Cellular atypia, including pleomorphism, hyperchromatic nuclei, and mitoses, are prominent. Atypical keratinocytes may be found in the basal layer and often extend deeply down hair follicles, but they do not invade the dermis.
- In the in situ type of SCC (Bowen disease), only the full thickness of the epidermis is involved. The basement membrane remains intact.
- An invasive squamous cell carcinoma penetrates through the basement membrane into the dermis. It has various levels of anaplasia and may manifest relatively few to multiple mitoses and display varying degrees of differentiation, such as keratinization.
- Poorly differentiated tumors are clinically more aggressive. SCCs proliferate 1st by local invasion. Metastases, when they do occur, spread via local lymph ducts to local lymph nodes.
- Solar keratosis (actinic keratosis). Early SCC lesions may be clinically difficult, if not impossible, to distinguish from a precursor solar keratosis.
- Basal cell carcinoma may be also indistinguishable from an SCC, particularly if the lesion is ulcerated.
- Verruca vulgaris
- The appearance of common warts is often similar to that of SCC lesions.
- A subungual SCC can easily be mistaken for a verruca.
- Seborrheic keratosis: “Stuck on” appearance
- Keratoacanthoma: This lesion also may be clinically impossible to differentiate from an SCC:
- Occurs in the elderly >60 years
- Fast growing
- A nodular lesion that usually has a characteristic central crater
- If ignored, lesions may involute spontaneously.
- Resembles an SCC histologically and is considered by some dermatologists and dermatopathologists to be a low-grade variant of an SCC. (Some investigators feel that it should be treated as an SCC.)
- Amelanotic melanoma and ulcerated melanoma may also be impossible to distinguish from an SCC.
- Clinical variants of SCC:
- Bowen disease (squamous cell carcinoma in situ): This is a solitary lesion that resembles a scaly psoriatic or eczematous plaque. By definition, the atypia of SCC in situ involves the full thickness of the epidermis without invasion into the dermis.
- Cutaneous horn: SCC with an overlying cutaneous horn. A cutaneous horn represents a fingernail platelike keratinization produced by the SCC. Bowen disease may also produce a cutaneous horn on its surface.
- HPV-associated SCC: Virally induced SCC most commonly manifests as a new or enlarging warty growth on the penis, vulva, perianal area, or periungual region.
- Erythroplasia of Queyrat refers to Bowen disease of the glans penis, which manifests as 1 or more velvety red plaques.
- Subungual SCC: Such lesions typically mimic a wart and are misdiagnosed prior to biopsy.
- Anogenital SCC: SCC in the anogenital region may manifest as a moist, red plaque on the glans penis or perianal area; indurated or ulcerated lesions may be seen on the vulva, external anus, or scrotum.
- Verrucous carcinoma, a subtype of SCC, can be locally destructive but rarely metastasizes. Lesions are “cauliflowerlike” verrucous nodules or plaques.
- Imiquimod (Aldara) (1,2) 5% cream is approved for the treatment of solar keratoses, genital warts, and for superficial basal cell carcinomas. It is now being used “off-label” for SCC in situ (Bowen disease), and may have some utility in treating selected patients who have highly differentiated SCCs.
- In patients with multiple or recurrent SCCs, chemoprevention with systemic retinoids (3,4) such as acetrecin may be effective for reducing the number of new SCCs; shown to be beneficial in treating existing SCCs or at reducing the risk of recurrence after treatment.
- Photodynamic therapy (PDT): Treatment with PDT involves the application of a photosensitizer (given topically or systemically) followed by exposure to a light source. PDT is used primarily to treat large numbers of solar keratoses and is not recommended for treatment of invasive SCC.
- Radiotherapy is a primary treatment option that is generally restricted to older patients who are physically debilitated or are unable to undergo, or refuse to undergo, excisional surgery.
- Topical chemotherapy: Topical formulations of 5-fluorouracil (5-FU) are available for the treatment of Bowen disease and solar keratoses.
- Intralesional 5-FU has also been used to successfully treat keratoacanthomas.
- Electrocautery (electrodesiccation) and curettage (ED&C):
- For small lesions (generally <1 cm) on flat surfaces (e.g., forehead, cheek) and SCC in situ (Bowen disease). ED&C may be used to treat superficially invasive SCCs without high-risk characteristics, but it is not appropriate for certain high-risk anatomic locations (see below).
- Cryosurgery with LN2 in selected lesions, such as Bowen disease
- Total excision, which is the preferred method of therapy for SCC, permitting histologic diagnosis of the tumor margins
- Micrographic (Mohs) surgery is a microscopically controlled method of removing skin cancers that allows for controlled excision and maximum preservation of normal tissue. It has the highest cure rate of all surgical treatments. Mohs surgery may be indicated for:
- Large or invasive carcinomas
- Recurrent SCCs
- Lesions with a poorly delineated clinical border
- An SCC within an orifice (e.g., ear canals or nostrils)
- Locations where preservation of normal tissue is extremely important (e.g., tip of the nose, eyelids, ala nasi, ears, lips, and glans penis)
- Bone or cartilage invasion
- A lesion in an area of late radiation change
- Micrographic (Mohs) surgery provides the best available cure rates (94–99%) for SCC.
- Metastatic disease requires aggressive management by a multidisciplinary team involving plastic, ENT/maxillofacial, a general surgeon, or a surgical oncologist.
After therapy, periodic skin exam every month for 3 months, 6 months after treatment, and then yearly
- SCCs that arise in areas of non-sun–exposed skin or those that originate de novo on areas of sun-exposed skin have a greater tendency to metastasize.
- An SCC arising on a mucous membrane, one arising from a chronic ulcer, or one arising in an immunocompromised patient should be regarded as potentially metastatic.
Skin self-exam, encourage sun avoidance techniques, sunscreens, etc. Artificial tanning devices should be avoided.
- 90–95% cure rate with appropriate treatment
- Head and neck lesions have better prognosis (5).
- The ability to produce scale (keratinization) indicates a tendency for a lesion to be more differentiated and less likely to metastasize.
- Softer, nonkeratinizing lesions are not as well differentiated and thus are more likely to spread.
- Lesions ≥2 cm more prone to recur
- SCCs that are deeply invasive in subcutaneous fat or deeper, or those that have perineural involvement, are more likely to metastasize.
- When SCC does metastasize, it usually occurs within several years from the time of diagnosis and involves draining lymph nodes.
- Once nodal metastasis of cutaneous SCC has occurred, the overall 5-year survival rate has historically been in the range of 25–35%.
An SCC that is histopathologically described as being “poorly differentiated” should be treated more aggressively.
Untreated, SCC becomes indurated, with a tendency to ooze, ulcerate, or bleed. Local recurrence. Metastatic disease.
1. Patel GK, Goodwin R. Imiquimod 5% cream monotherapy for cutaneous squamous cell carcinoma in situ (Bowen’s disease): A randomized, double-blind, placebo-controlled trial. J Am Acad Dermatol. 2006;54(1):25–32.
2. Hengge UR, Schaller J. Successful treatment of invasive squamous cell carcinoma using topical imiquimod. Arch Dermatol.2004;140:404–6.
3. Harwood CA, Leedham-Green M, Leigh IM, et al. Low-dose retinoids in the prevention of cutaneous squamous cell carcinomas in organ transplant recipients: a 16-year retrospective study. Arch Dermatol. 2005;141:456–64.
4. Chen K, Craig JC, Shumack S. Oral retinoids for the prevention of skin cancers in solid organ transplant recipients: a systematic review of randomized controlled trials. Br J Dermatol. 2005;152:518–23.
5. Clayman GL, Lee JJ, Holsinger FC, et al. Mortality risk from squamous cell skin cancer. J Clin Oncol. 2005;23:759–65.
Schmults CD. High-risk cutaneous squamous cell carcinoma: identification and management. Adv Dermatol. 2005;21:133–52.
- 173.0 Other malignant neoplasm of skin of lip
- 173.1 Other malignant neoplasm of skin of eyelid, including canthus
- 173.2 Other malignant neoplasm of skin of ear and external auditory canal
- 173.3 Other malignant neoplasm of skin of other and unspecified parts of face
- 173.4 Other malignant neoplasm of scalp and skin of neck
- 173.5 Other malignant neoplasm of skin of trunk, except scrotum
- 173.6 Other malignant neoplasm of skin of upper limb, including shoulder
- 173.7 Other malignant neoplasm of skin of lower limb, including hip
- 173.8 Other malignant neoplasm of other specified sites of skin
- 173.9 Other malignant neoplasm of skin, site unspecified
- 254651007 Squamous cell carcinoma of skin (disorder)
- 403892001 squamous cell carcinoma of skin of face (disorder)
- 231831002 squamous cell carcinoma of eyelid (disorder)
- 403894000 squamous cell carcinoma of skin of ear (disorder)
- 403891008 squamous cell carcinoma of scalp (disorder)
- 403899005 squamous cell carcinoma of skin of trunk (disorder)
- 403897007 squamous cell carcinoma of upper extremity (disorder)
- 403898002 squamous cell carcinoma of skin of lower extremity (disorder)
- 423284006 squamous cell carcinoma of skin of neck (disorder)
- An early lesion of SCC is difficult to distinguish from a solar keratosis.
- SCCs that develop from solar keratoses are generally unaggressive.
- An SCC arising on a mucous membrane such as the glans penis, lip, or from a chronic ulcer, or one arising in an immunocompromised patient, is potentially metastatic.