squamous cell carcinoma

Squamous cell carcinoma, NOS
Classification and external resources
SCC of the skin tends to arise from pre-malignant lesions, actinic keratoses; surface is usually scaly and often ulcerates (as shown here).
ICD-10	C44.
ICD-9	173
ICD-O:	M8070/3
MedlinePlus	000829
eMedicine	derm/401
MeSH	D002294

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).

Classification

Squamous cell carcinoma may be classified into the following types:^[1]:473

• Adenoid squamous cell carcinoma (Pseudoglandular squamous cell carcinoma)
• Clear cell squamous cell carcinoma (Clear cell carcinoma of the skin)
• Spindle cell squamous cell carcinoma
• Signet-ring cell squamous cell carcinoma
• Basaloid squamous cell carcinoma
• Verrucous carcinoma
• Keratoacanthoma

Terminology

A large squamous cell carcinoma of the tongue.

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 and symptoms

It begins as a small nodule and as it enlarges the center becomes necrotic and slaughs and the nodule turns into an ulcer.

• 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)
• On the lip, the tumor forms a small ulcer, which fails to heal and bleeds intermittently
• 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. ^[2]

Sites for SCC and their respective causes

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.^[2] 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%)^[3]. Squamous cell cancers of the skin in individuals on immunotherapy or having lymphoproliferative disorders (leukemias) are much more aggressive, regardless of their location.^[4]

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.^{[citation needed]}

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.^[5]

Head and neck cancer

Biopsy of a highly differentiated squamous cell carcinoma of the mouth. Haematoxylin & eosin stain.

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

Causation: 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.

Esophagus

Esophageal cancer may be due to either squamous cell carcinoma (ESCC) or adenocarcinoma (EAC). SCCs tend to occur closer to the mouth, while adenocarcinomas occur closer to the stomach. Dysphagia (difficulty swallowing, solids worse than liquids) and odynophagia are common initial symptoms. If the disease is localized, esophagectomy may offer the possibility of a cure. If the disease has spread, chemotherapy and radiotherapy are commonly used.

Lung

Photograph of a squamous cell carcinoma. Tumour is on the left, obstructing the bronchus (lung). Beyond the tumour, the bronchus is inflammed and contains mucus.

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

Penis

When squamous cell carcinoma in situ (Bowen's disease) is found on the penis, it is called erythroplasia of Queyrat^[6]. This type of cancer responds very well to imiquimod.

Prostate

When associated with the prostate, squamous cell carcinoma is very aggressive in nature. It is difficult to detect as there is no increase in prostate specific antigen levels seen; meaning that the cancer is often diagnosed at an advanced stage.

Vagina and cervix

Vaginal squamous cell carcinoma spreads slowly and usually stays near the vagina, but may spread to the lungs and liver. This is the most common type of vaginal cancer.

Diagnosis of squamous cell carcinoma

Diagnosis is via a biopsy. For the skin, look under skin 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.

Mohs surgery is frequently utilized; considered the treatment of choice for squamous cell carcinoma of the skin, physicians have also utilized the method for the treatment of squamous cell carcinoma of the mouth, throat, and neck.^[7]

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)^[8] to provide photoprotection for organ transplant patients against squamous cell carcinoma of the skin and actinic keratosis.^[9][10]

Related conditions

• Erythroplasia of Queyrat
• Keratoacanthoma is a low-grade malignancy of the skin. It originates in the pilo-sebaceous glands, and is similar in clinical presentation and microscopic analysis to squamous cell carcinoma, except that it contains a central keratin plug. Statistically, it is less likely to become invasive than squamous cell carcinoma.
• Bowen's disease is a sunlight-induced skin disease, and is considered to be an early form of squamous cell carcinoma.
• Marjolin's ulcer is a type of squamous cell carcinoma that arises from a non-healing ulcer or burn wound.
• Melanoma
• Basal Cell Carcinoma

External links

• Information on Squamous Cell Carcinoma from The Skin Cancer Foundation
• Article by Stephen D Hess, MD, PhD
• DermNet NZ: Squamous cell carcinoma
• Squamous cell carcinoma in transplant recipients
• Including TCC, CIS and papillary tumour SCC
• Cancer Management Handbook: Head and Neck Tumors

References