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Squamous-cell carcinoma

Squamous cell carcinoma, NOS

In medicine, squamous cell carcinoma (SCC) is a form of cancer of the carcinoma type that may occur in many different organs, including the skin, lips, mouth, esophagus, urinary bladder, prostate, lungs, vagina, and cervix. It is a malignant tumor of squamous epithelium (epithelium that shows squamous cell differentiation).

Terminology

A carcinoma can be characterized as either in situ (confined to the original site) or invasive, depending on whether the cancer invades underlying tissues; only invasive cancers are able to spread to other organs and cause metastasis. Squamous cell carcinoma in situ are also called Bowen's disease.

HPV and Squamous Cell Cancers

Human papilloma virus has been associated with SCC of the oropharynx, lung, fingers, anogenital region.

Signs & Symptoms

• The lesion caused by SCC is often asymptomatic
• Ulcer or reddish skin plaque that is slow growing
• Intermittent bleeding from the tumor, especially on the lip
• The clinical appearance is highly variable
• Usually the tumor presents as an ulcerated lesion with hard, raised edges
• The tumor may be in the form of a hard plaque or a papule, often with an opalescent quality, with telangiectasia
• The tumor can lie below the level of the surrounding skin, and eventually ulcerates and invades the underlying tissue
• The tumor commonly presents on sun-exposed areas (e.g. back of the hand, scalp, lip, and superior surface of pinna)
• Evidence of chronic skin photodamage, such as multiple actinic keratoses (solar keratoses)
• The tumor grows relatively slowly
• Unlike basal cell carcinoma (BCC), squamous cell carcinoma (SCC) has a substantial risk of metastasis
• Risk of metastasis is higher in SCC arising in scars, on the lower lips or mucosa, and occurring in immunosuppressed patients. About one-third of lingual and mucosal tumors metastasize before diagnosis (these are often related to tobacco and alcohol use)

Demographics

Incidence of squamous cell carcinoma varies with age, gender, race, geography, and genetics. The incidence of SCC increases with age and the peak incidence is usually around 66 years old. Males are affected with SCC at a ratio of 2:1 in comparison to females. Caucasians are more likely to be affected, especially those with fair Celtic skin, if chronically exposed to UV radiation. There are also a few rare congenital diseases predispose to cutaneous malignancy.In certain geographic locations, exposure to arsenic in well water or from industrial sources may significantly increase the risk of SCC.

Skin

Squamous cell carcinoma is the second most common cancer of the skin (after basal cell carcinoma but more common than melanoma). It usually occurs in areas exposed to the sun. Sunlight exposure and immunosuppression are risk factors for SCC of the skin with chronic sun exposure being the strongest environmental risk factor. The risk of metastasis is low, but is much higher than basal cell carcinoma. Squamous cell cancers of the lip and ears have high metastatic and recurrence rate (20 to 50%). Squamous cell cancers of the skin in individuals on immunotherapy or having lymphoproliferative disorders (leukemias) are much more aggressive, regardless of their location.

Squamous cell carcinoma can generally be treated by excision or mohs surgery. Nonsurgical options for the treatment of cutaneous SCC include topical chemotherapy, topical immune response modifiers, photodynamic therapy (PDT), radiotherapy, and systemic chemotherapy. The use of topical therapy and PDT is generally limited to premalignant (ie, AKs) and in situ lesions. Radiation therapy is a primary treatment option for patients in whom surgery is not feasible and is an adjuvant therapy for those with metastatic or high-risk cutaneous SCC. At this time, systemic chemotherapy is used exclusively for patients with metastatic disease.

Australian scientist Ian Frazer who developed the cervical cancer vaccine, says that animal tests have been effective in preventing squamous cell carcinoma in animals, and there may be a human vaccine against this kind of skin cancer within the decade.

Head and neck cancer

Molluscum lesions on an arm

Most cases of head and neck cancer (cancer of the mouth, nasal cavity, throat and associated structures) are due to squamous cell carcinoma. Symptoms may include a poorly healing mouth ulcer, a hoarse voice or other persistent problems in the area. Treatment is usually with surgery (which may be extensive) and radiotherapy. Risk factors include smoking and alcohol consumption Cancers of the head and neck are usually caused by tobacco and alcohol, but according to the CDC, recent studies show that about 25% of mouth and 35% of throat cancers are caused by HPV. The 5 year disease free survival rate for HPV positive cancer is significantly higher when appropriately treated with surgery, radiation and chemotherapy as compared to non-HPV positive cancer, substantiated by multiple studies including research conducted by Dr. Maureen Gillison et. al. of Johns Hopkins Sidney Kimmel Cancer Center.

When associated with the lung, it often causes ectopic production of parathyroid hormone-related protein (PTHrP), resulting in hypercalcemia.

Diagnosis of Squamous Cell Carcinoma

Diagnosis is via a biopsy

The pathological appearance of a squamous cell cancer varies with the depth of the biopsy. For that reason, a biopsy including the subcutanous tissue and basalar epithelium, to the surface is necessary for correct diagnosis. The performance of a shave biopsy (see skin biopsy) might not acquire enough information for a diagnosis. An excision biopsy is ideal, but not practical in most cases. An incisional or punch biopsy is preferred. A shave biopsy is least ideal, especially if only the superficial portion is acquired.

Treatment

Most squamous cell carcinomas are removed with surgery or topical medication.

Imiquimod (Aldara) has been used with success for squamous cell carcinoma in situ of the skin and the penis, but the morbidity and discomfort of the treatment is severe. An advantage is the cosmetic result: after treatment, the skin resembles normal skin without the usual scarring and morbidity associated with standard excision. Imiquimod is not FDA-approved for any squamous cell carcinoma.

In 2007, Australian biopharmaceutical company Clinuvel Pharmaceuticals Limited began clinical trials with an experimental treatment, a melanocyte-stimulating hormone called afamelanotide (formerly CUV1647) to provide photoprotection for organ transplant patients against squamous cell carcinoma of the skin and actinic keratosis.