Squamous-cell skin cancer, also known as cutaneous squamous-cell carcinoma (cSCC), is one of the main types of

skin cancer Skin cancers are cancers that arise from the skin. They are due to the development of abnormal cells that have the ability to invade or spread to other parts of the body. There are three main types of skin cancers: basal-cell skin cancer (BCC) ...

along with

basal cell cancer Basal-cell carcinoma (BCC), also known as basal-cell cancer, is the most common type of skin cancer. It often appears as a painless raised area of skin, which may be shiny with small blood vessels running over it. It may also present as a raise ...

and

melanoma Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...

. It usually presents as a hard lump with a scaly top but can also form an

ulcer An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing o ...

. Onset is often over months. Squamous-cell skin cancer is more likely to spread to distant areas than basal cell cancer. When confined to the outermost layer of the skin, a precancerous or ''in situ'' form of cSCC is known as Bowen's disease. The greatest risk factor is high total exposure to

ultraviolet radiation Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nm (with a corresponding frequency around 30 PHz) to 400 nm (750 THz), shorter than that of visible light, but longer than X-rays. UV radiation i ...

from the sun. Other risks include prior

scars A scar (or scar tissue) is an area of fibrous tissue that replaces normal skin after an injury. Scars result from the biological process of wound repair in the skin, as well as in other organs, and tissues of the body. Thus, scarring is a natu ...

, chronic wounds,

actinic keratosis Actinic keratosis (AK), sometimes called solar keratosis or senile keratosis, is a pre-cancerous area of thick, scaly, or crusty skin.Freedberg, et al. (2003). ''Fitzpatrick's Dermatology in General Medicine''. (6th ed.). McGraw-Hill. . Actinic k ...

, lighter skin, Bowen's disease,

arsenic Arsenic is a chemical element with the symbol As and atomic number 33. Arsenic occurs in many minerals, usually in combination with sulfur and metals, but also as a pure elemental crystal. Arsenic is a metalloid. It has various allotropes, but ...

exposure,

radiation therapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radia ...

tobacco smoking Tobacco smoking is the practice of burning tobacco and ingesting the resulting smoke. The smoke may be inhaled, as is done with cigarettes, or simply released from the mouth, as is generally done with pipes and cigars. The practice is believed ...

, poor immune system function, previous basal cell carcinoma, and

HPV infection Human papillomavirus infection (HPV infection) is caused by a DNA virus from the ''Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and res ...

. Risk from UV radiation is related to total exposure, rather than early exposure.

Tanning beds Indoor tanning involves using a device that emits ultraviolet radiation to produce a cosmetic tan. Typically found in tanning salons, gyms, spas, hotels, and sporting facilities, and less often in private residences, the most common device is a ho ...

are becoming another common source of ultraviolet radiation. Risk is also elevated in certain genetic skin disorders, such as

xeroderma pigmentosum Xeroderma pigmentosum (XP) is a genetic disorder in which there is a decreased ability to repair DNA damage such as that caused by ultraviolet (UV) light. Symptoms may include a severe sunburn after only a few minutes in the sun, freckling in sun- ...

and certain forms of

epidermolysis bullosa Epidermolysis bullosa (EB) is a group of rare medical conditions that result in easy blistering of the skin and mucous membranes. Blisters occur with minor trauma or friction and are painful. Its severity can range from mild to fatal. Inherited E ...

. It begins from

squamous cell Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...

s found within the

skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...

. Diagnosis is often based on skin examination and confirmed by

tissue biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a disea ...

. New in vivo and in vitro studies have proven that the upregulation of FGFR2, a subset of the fibroblast growth factor receptor (FGFR) immunoglobin family, has a critical role to play in the progression of cSCC cells. Mutation in the

TPL2 Mitogen-activated protein kinase kinase kinase 8 is an enzyme that in humans is encoded by the ''MAP3K8'' gene. Function The gene was identified by its oncogenic transforming activity in cells. The encoded protein is a member of the serine/thr ...

gene causes overexpression of FGFR2, which activates mTORC1 and AKT pathways in both primary and metastatic cSCC cell lines. Only by using FGFR pan-inhibitor, AZD4547, could cell migration and cell proliferation on cSCC be attenuated Additionally, research has identified common driver mutations in cSCC, with alterations in the NOTCH and

p53 p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...

pathways occurring at high frequency and mutations in the Hippo and Ras/MAPK/PI3K occurring at lower frequency Decreasing exposure to ultraviolet radiation and the use of

sunscreen Sunscreen, also known as sunblock or sun cream, is a photoprotective topical product for the skin that mainly absorbs, or to a much lesser extent reflects, some of the sun's ultraviolet (UV) radiation and thus helps protect against sunburn and ...

appear to be effective methods of preventing squamous-cell skin cancer. Treatment is typically by surgical removal. This can be by simple excision if the cancer is small otherwise

Mohs surgery Mohs surgery, developed in 1938 by a general surgeon, Frederic E. Mohs, is microscopically controlled surgery used to treat both common and rare types of skin cancer. During the surgery, after each removal of tissue and while the patient waits, t ...

is generally recommended. Other options may include application of cold and

. In the cases in which distant spread has occurred

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...

biologic therapy A biopharmaceutical, also known as a biological medical product, or biologic, is any pharmaceutical drug product manufactured in, extracted from, or semisynthesized from biological sources. Different from totally synthesized pharmaceuticals, t ...

may be used. As of 2015, about 2.2 million people have cSCC at any given time. It makes up about 20% of all skin cancer cases. About 12% of males and 7% of females in the United States developed cSCC at some point in time. While prognosis is usually good, if distant spread occurs

five-year survival The five-year survival rate is a type of survival rate for estimating the prognosis of a particular disease, normally calculated from the point of diagnosis. Lead time bias from earlier diagnosis can affect interpretation of the five-year surviva ...

is ~34%. In 2015 it resulted in about 51,900 deaths globally. The usual age at diagnosis is around 66. Following the successful treatment of one case of cSCC people are at high risk of developing further cases.

Signs and symptoms

SCC of the skin begins as a small nodule and as it enlarges the center becomes necrotic and sloughs and the nodule turns into an ulcer, and generally are developed from an actinic keratosis. Once keratinocytes begin to grow uncontrollably, they have the potential to become cancerous and produce squamous cell carcinoma. * The lesion caused by SCC is often

asymptomatic In medicine, any disease is classified asymptomatic if a patient tests as carrier for a disease or infection but experiences no symptoms. Whenever a medical condition fails to show noticeable symptoms after a diagnosis it might be considered asy ...

* 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 A papule is a small, well-defined bump in the skin. It may have a rounded, pointed or flat top, and may have a dip. It can appear with a stalk, be thread-like or look warty. It can be soft or firm and its surface may be rough or smooth. Some h ...

, often with an opalescent quality, with tiny blood vessels * 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, as in multiple

actinic keratoses Actinic keratosis (AK), sometimes called solar keratosis or senile keratosis, is a pre-cancerous area of thick, scaly, or crusty skin.Freedberg, et al. (2003). ''Fitzpatrick's Dermatology in General Medicine''. (6th ed.). McGraw-Hill. . Actinic k ...

(solar keratoses) * The tumor grows relatively slowly

Spread

* Unlike

basal-cell carcinoma Basal-cell carcinoma (BCC), also known as basal-cell cancer, is the most common type of skin cancer. It often appears as a painless raised area of skin, which may be shiny with small blood vessels running over it. It may also present as a raise ...

( BCC), squamous cell carcinoma (SCC) has a higher risk of

metastasis Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...

. * Risk of metastasis is higher clinically in SCC arising in scars, on the lower lips or mucosa, and occurring in immunosuppressed and solid organ transplant patients. Risk of metastasis is also higher in SCC that are >2 cm in diameter, growth into the fat layer and along nerves, thickness >6mm.

Causes

Squamous cell carcinoma is the second-most common cancer of the skin (after

but more common than

). It usually occurs in areas exposed to the sun. Sunlight exposure and

immunosuppression Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse react ...

are

risk factors In epidemiology, a risk factor or determinant is a variable associated with an increased risk of disease or infection. Due to a lack of harmonization across disciplines, determinant, in its more widely accepted scientific meaning, is often use ...

for SCC of the skin, with chronic sun exposure being the strongest environmental risk factor. There is a risk of

starting more than 10 years after diagnosable appearance of squamous cell carcinoma, but the risk is low, though much higher than with basal-cell carcinoma. Squamous cell cancers of the lip and ears have high rates of local recurrence and distant metastasis. In a recent study, it has also been shown that the deletion or severe down-regulation of a gene titled Tpl2 (tumor progression locus 2) may be involved in the progression of normal keratinocytes into becoming squamous cell carcinoma. SCCs represent about 20% of the non-melanoma skin cancers, but 80-90% of those with metastatic potential are located on the head and neck. Tobacco smoking also increases the risk for cutaneous squamous cell carcinoma. The vast majority of SCCs are those of the skin, and are often the result of

ultraviolet Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nanometer, nm (with a corresponding frequency around 30 Hertz, PHz) to 400 nm (750 Hertz, THz), shorter than that of visible light, but longer than ...

exposure. SCCs usually occur on portions of the body commonly exposed to the

Sun The Sun is the star at the center of the Solar System. It is a nearly perfect ball of hot plasma, heated to incandescence by nuclear fusion reactions in its core. The Sun radiates this energy mainly as light, ultraviolet, and infrared radi ...

; the

face The face is the front of an animal's head that features the eyes, nose and mouth, and through which animals express many of their emotions. The face is crucial for human identity, and damage such as scarring or developmental deformities may aff ...

ears An ear is the organ that enables hearing and, in mammals, body balance using the vestibular system. In mammals, the ear is usually described as having three parts—the outer ear, the middle ear and the inner ear. The outer ear consists o ...

neck The neck is the part of the body on many vertebrates that connects the head with the torso. The neck supports the weight of the head and protects the nerves that carry sensory and motor information from the brain down to the rest of the body. In ...

hand A hand is a prehensile, multi-fingered appendage located at the end of the forearm or forelimb of primates such as humans, chimpanzees, monkeys, and lemurs. A few other vertebrates such as the koala (which has two opposable thumbs on each "h ...

s, or

arm In human anatomy, the arm refers to the upper limb in common usage, although academically the term specifically means the upper arm between the glenohumeral joint (shoulder joint) and the elbow joint. The distal part of the upper limb between th ...

. The main symptom is a growing bump that may have a rough, scaly surface and flat reddish patches. Unlike

s, SCCs carry a higher risk of

, and may spread to the regional

lymph node A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that inclu ...

s, ''Erythroplasia of Queyrat'' (SCC in situ of the

glans The glans (, plural "glandes" ; from the Latin word for "acorn") is a vascular structure located at the tip of the penis in male mammals or a homologous genital structure of the clitoris in female mammals. Structure The exterior structure ...

prepuce Prepuce , or as an adjective, preputial , refers to two homologous structures of male and female genitals: *Clitoral hood, skin surrounding and protecting the head of the clitoris *Foreskin, skin surrounding and protecting the head of the penis in ...

in males, M or the

vulva The vulva (plural: vulvas or vulvae; derived from Latin for wrapper or covering) consists of the external sex organ, female sex organs. The vulva includes the mons pubis (or mons veneris), labia majora, labia minora, clitoris, bulb of vestibu ...

e in females.) may be induced by

human papilloma virus Human papillomavirus infection (HPV infection) is caused by a DNA virus from the '' Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and r ...

. It is reported to occur in the corneoscleral limbus. Erythroplasia of Queyrat may also occur on the anal mucosa or the oral mucosa. Some sources state that this condition is synonymous with

Bowen's disease Squamous-cell skin cancer, also known as cutaneous squamous-cell carcinoma (cSCC), is one of the main types of skin cancer along with basal cell cancer and melanoma. It usually presents as a hard lump with a scaly top but can also form an ulcer. ...

, however generally speaking Bowen's disease refers to carcinoma in situ of any location on the skin such as the lower leg. Genetically, SCC tumors harbor high frequencies of NOTCH and

mutations as well as less frequent alterations in histone acetyltransferase

EP300 Histone acetyltransferase p300 also known as p300 HAT or E1A-associated protein p300 (where E1A = adenovirus early region 1A) also known as EP300 or p300 is an enzyme that, in humans, is encoded by the ''EP300'' gene. It functions as histone ace ...

, subunit of the

SWI/SNF In molecular biology, SWI/SNF (SWItch/Sucrose Non-Fermentable), is a subfamily of ATP-dependent chromatin remodeling complexes, which is found in eukaryotes. In other words, it is a group of proteins that associate to remodel the way DNA is pack ...

chromatin remodeling complex

PBRM1 Protein polybromo-1 (PB1) also known as BRG1-associated factor 180 (BAF180) is a protein that in humans is encoded by the ''PBRM1'' gene. Structure and function Component of the SWI/SNF-B (PBAF) chromatin-remodeling complex, which contains at ...

, DNA-repair deubiquitinase USP28, and

NF-κB Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular ...

signaling regulator CHUK.

Immunosuppression

People who have received solid organ transplants are at a significantly increased risk of developing squamous cell carcinoma due to the use of chronic immunosuppressive medication. While the risk of developing all skin cancers increases with these medications, this effect is particularly severe for SCC, with hazard ratios as high as 250 being reported, versus 40 for basal cell carcinoma. The incidence of SCC development increases with time posttransplant. Heart and lung transplant recipients are at the highest risk of developing SCC due to more intensive immunosuppressive medications used. Squamous cell cancers of the skin in individuals on immunotherapy or who have lymphoproliferative disorders (e.g.

leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...

) tend to be much more aggressive, regardless of their location. The risk of SCC, and non-melanoma skin cancers generally, varies with the immunosuppressive drug regimen chosen. The risk is greatest with calcineurin inhibitors like cyclosporine and tacrolimus, and least with mTOR inhibitors, such as sirolimus and everolimus. The antimetabolites azathioprine and mycophenolic acid have an intermediate risk profile.

Diagnosis

Diagnosis is confirmed via

biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a diseas ...

of the tissue or tissues suspected to be affected by SCC. For the skin, look under

skin biopsy Skin biopsy is a biopsy technique in which a skin lesion is removed to be sent to a pathologist to render a microscopic diagnosis. It is usually done under local anesthetic in a physician's office, and results are often available in 4 to 10 days. ...

. The pathological appearance of a squamous cell cancer varies with the depth of the biopsy. For that reason, a biopsy including the subcutaneous tissue and basilar epithelium, to the surface is necessary for correct diagnosis. The performance of a shave biopsy (see

) might not acquire enough information for a diagnosis. An inadequate biopsy might be read as

with follicular involvement. A deeper biopsy down to the dermis or subcutaneous tissue might reveal the true cancer. 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.

Characteristics

Histopathologically, the epidermis in SCC ''in situ'' (Bowen's disease) will show hyperkeratosis and parakeratosis. There will also be marked acanthosis with elongation and thickening of the rete ridges. These changes will overly keratinocytic cells which are often highly atypical and may in fact have a more unusual appearance than invasive SCC. The atypia spans the full thickness of the epidermis, with the keratinocytes demonstrating intense mitotic activity, pleomorphism, and greatly enlarged nuclei. They will also show a loss of maturity and polarity, giving the epidermis a disordered or "windblown" appearance. Two types of multinucleated cells may be seen: the first will present as a multinucleated giant cell, and the second will appear as a dyskeratotic cell engulfed in the cytoplasm of a keratinocyte. Occasionally, cells of the upper epidermis will undergo vacuolization, demonstrating an abundant and strongly eosinophilic cytoplasm. There may be a mild to moderate lymphohistiocytic infiltrate detected in the upper dermis. File:Histopathology of squamous cell carcinoma in situ.jpg, Histopathology of squamous cell carcinoma in situ (black arrow), compared to normal skin, showing marked atypia. File:Micrograph of squamous cell carcinoma in situ - 100x.jpg, Squamous cell carcinoma ''in situ'', showing prominent dyskeratosis and aberrant mitoses at all levels of the epidermis, along with marked parakeratosis.

In situ disease

Bowen's disease is essentially equivalent to and used interchangeably with SCC ''in situ'', when not having invaded through the

basement membrane The basement membrane is a thin, pliable sheet-like type of extracellular matrix that provides cell and tissue support and acts as a platform for complex signalling. The basement membrane sits between Epithelium, epithelial tissues including mesot ...

. Depending on source, it is classified as precancerous or SCC ''in situ'' (technically cancerous but non-invasive). In SCC ''in situ'' (Bowen's disease), atypical squamous cells proliferate through the whole thickness of the epidermis. The entire tumor is confined to the epidermis and does not invade into the dermis. The cells are often highly atypical under the

microscope A microscope () is a laboratory instrument used to examine objects that are too small to be seen by the naked eye. Microscopy is the science of investigating small objects and structures using a microscope. Microscopic means being invisibl ...

, and may in fact look more unusual than the cells of some invasive squamous cell carcinomas. File:Micrograph of squamous cell carcinoma in situ - 400x.jpg, SCC ''in situ'', high magnification, demonstrating an intact basement membrane. Image:Bowen disease (1).jpg, SCC ''in situ'' Image:Bowen disease (2).jpg, SCC ''in situ'' Image:Bowen disease (3).jpg, SCC ''in situ'' Image:Bowen disease (4).jpg, SCC ''in situ'' Erythroplasia of Queyrat is a particular type of Bowen's disease that can arise on the

in males, and the

e in females. It mainly occurs in uncircumcised males, over the age of 40. It is named for French dermatologist

Louis Queyrat Vincent Jules Louis Queyrat (2 December 1856 in Chavanat, Creuse, France – 18 October 1933 in Paris, France)venereal Human sexual activity, human sexual practice or human sexual behaviour is the manner in which humans experience and express their sexuality. People engage in a variety of sexual acts, ranging from activities done alone (e.g., masturbation) ...

hospital in Paris, now

Hôpital Cochin The Hôpital Cochin is a hospital of public assistance in the rue du Faubourg-Saint-Jacques Paris 14e. It houses the central burn treatment centre of the city. The Hôpital Cochin is a section of the Faculté de Médecine Paris-Descartes. It comm ...

Invasive disease

In invasive SCC, tumor cells infiltrate through the basement membrane. The infiltrate can be somewhat difficult to detect in the early stages of invasion: however, additional indicators such as full thickness epidermal atypia and the involvement of hair follicles can be used to facilitate the diagnosis. Later stages of invasion are characterized by the formation of nests of atypical tumor cells in the dermis, often with a corresponding inflammatory infiltrate. File:Gross pathology of squamous cell carcinoma.jpg, Gross slice of a squamous cell carcinoma of the skin. File:Micrograph of invasive squamous cell carcinoma - 150x.jpg, Superficially invasive squamous cell carcinoma (SCCSI). These lesions often do not show the marked pleomorphism and atypical nuclei of SCC ''in situ'', but demonstrate early keratinocyte invasion of the dermis. File:Micrograph of invasive squamous cell carcinoma - 200x.jpg, High magnification demonstrates the pleomorphism of the invading keratinocytes. File:Ulcer border of a squamous cell skin cancer.jpg, Invasive nests with characteristic large celled centers. Ulceration (at left) is common in invasive SCC.

Degree of differentiation

File:Micrograph of well-differentiated and invasive squamous-cell carcinoma.jpg, Well-differentiated (and yet invasive) SCC, showing prominent keratinization and may form "pearllike" structures where dermal nests of keratinocytes attempt to mature in a layered fashion. Well-differentiated SCC has slightly enlarged, hyperchromatic nuclei with abundant amounts of cytoplasm. Intercellular bridges will frequently be visible. File:Micrograph of moderately differentiated and invasive squamous-cell carcinoma.jpg, Moderately differentiated lesions of invasive SCC show much less organization and maturation with significantly less keratin formation. File:Micrograph of clear-cell squamous-cell carcinoma.jpg, Poorly differentiated, where attempts at keratinization are often no longer evident. This is a clear-cell squamous cell carcinoma. The dysplastic cells here infiltrate in cords through the dermis. Poorly differentiated SCC has greatly enlarged, pleomorphic nuclei demonstrating a high degree of atypia and frequent mitoses. File:Micrograph of clear-cell squamous-cell carcinoma with focus of obvious squamous-cell features, annotated.jpg, Poorly differentiated clear-cell squamous cell carcinoma. For this type of SCC, immunostains will likely be required to classify it unless other areas of the tumor show obvious squamous cell features such as seen here (arrow).

Prevention

Appropriate sun-protective clothing, use of broad-spectrum (UVA/UVB)

with at least SPF 50, and avoidance of intense sun exposure may prevent

. A 2016 review of sunscreen for preventing squamous cell skin cancer found insufficient evidence to demonstrate whether it was effective.

Management

Most squamous cell carcinomas are removed with surgery. A few selected cases are treated with

topical A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes ...

medication. Surgical excision with a free margin of healthy tissue is a frequent treatment modality. Radiotherapy, given as

external beam radiotherapy External beam radiotherapy (EBRT) is the most common form of radiotherapy (radiation therapy). The patient sits or lies on a couch and an external source of ionizing radiation is pointed at a particular part of the body. In contrast to brachyt ...

or as

brachytherapy Brachytherapy is a form of radiation therapy where a sealed radiation source is placed inside or next to the area requiring treatment. ''Brachy'' is Greek for short. Brachytherapy is commonly used as an effective treatment for cervical, prosta ...

(internal radiotherapy), can also be used to treat squamous cell carcinomas. There is little evidence comparing the effectiveness of different treatments for non-metastatic SCC of the skin.

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. An equivalent method of the

CCPDMA Complete circumferential peripheral and deep margin assessment (CCPDMA) is the preferred method for the removal of certain cancers, especially skin cancers. There are two forms of CCPDMA surgery: Mohs surgery and surgical excision coupled with mar ...

standards can be utilized by a pathologist in the absence of a Mohs-trained physician.

Radiation In physics, radiation is the emission or transmission of energy in the form of waves or particles through space or through a material medium. This includes: * ''electromagnetic radiation'', such as radio waves, microwaves, infrared, visi ...

therapy is often used afterward in high risk cancer or patient types. Radiation or

radiotherapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radia ...

can also be a standalone option in treating SCCs. As a non invasive option

serves a painless possibility to treat in particular but not only difficult to operate areas like the earlobes or genitals. An example of this kind of therapy is the High dose brachytherapy Rhenium-SCT which makes use of the beta rays emitting property of Rhenium-188. The radiation source is enclosed in a compound which is applied to a thin protection foile directly over the

lesion A lesion is any damage or abnormal change in the tissue of an organism, usually caused by disease or trauma. ''Lesion'' is derived from the Latin "injury". Lesions may occur in plants as well as animals. Types There is no designated classifi ...

. This way the radiation source can be applied to complex locations and minimize radiation to healthy tissue. After removal of the cancer, closure of the skin for patients with a decreased amount of skin laxity involves a split-thickness skin graft. A donor site is chosen and enough skin is removed so that the donor site can heal on its own. Only the epidermis and a partial amount of dermis is taken from the donor site which allows the donor site to heal. Skin can be harvested using either a mechanical dermatome or Humby knife. Electrodessication and curettage (EDC) can be done on selected squamous cell carcinoma of the skin. In areas where SCC's are known to be non-aggressive, and where the patient is not immunosuppressed, EDC can be performed with good to adequate cure rate. Treatment options for SCC ''in situ'' (Bowen's disease) include

photodynamic therapy Photodynamic therapy (PDT) is a form of phototherapy involving light and a photosensitizing chemical substance, used in conjunction with molecular oxygen to elicit cell death (phototoxicity). PDT is popularly used in treating acne. It is used cl ...

with 5-aminolevulinic acid,

cryotherapy Cryotherapy, sometimes known as cold therapy, is the local or general use of low temperatures in medical therapy. Cryotherapy may be used to treat a variety of tissue lesions. The most prominent use of the term refers to the surgical treatment, s ...

, topical

5-fluorouracil Fluorouracil (5-FU), sold under the brand name Adrucil among others, is a cytotoxic chemotherapy medication used to treat cancer. By intravenous injection it is used for treatment of colorectal cancer, oesophageal cancer, stomach cancer, pancrea ...

or imiquimod, and excision. A meta-analysis showed evidence that PDT is more effective than cryotherapy and has better cosmetic outcomes. There is generally a lack of evidence comparing the effectiveness of all treatment options. High-risk squamous cell carcinoma, as defined by those occurring around the eye, ear, or nose, is of large size, is poorly differentiated, and grows rapidly, requires more aggressive, multidisciplinary management. Nodal spread: # Surgical block dissection if palpable nodes or in cases of Marjolin's ulcers but the benefit of prophylactic block lymph node dissection with Marjolin's ulcers is not proven. # Radiotherapy #

Adjuvant therapy Adjuvant therapy, also known as adjunct therapy, adjuvant care, or augmentation therapy, is a therapy that is given in addition to the primary or initial therapy to maximize its effectiveness. The surgeries and complex treatment regimens used in ...

may be considered in those with high-risk SCC even in the absence of evidence for local metastasis.

Imiquimod Imiquimod, sold under the brand name Aldara among others, is a medication that acts as an immune response modifier that is used to treat genital warts, superficial basal cell carcinoma, and actinic keratosis. Scientists at 3M's pharmaceuticals ...

(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 general, squamous cell carcinomas have a high risk of local recurrence, and up to 50% do recur. Frequent skin exams with a dermatologist is recommended after treatment.

Prognosis

The long-term outcome of squamous cell carcinomas is dependent upon several factors: the sub-type of the carcinoma, available treatments, location and severity, and various patient health-related variables (accompanying diseases, age, etc.). Generally, the long-term outcome is positive, as less than 4% of Squamous cell carcinoma cases are at risk of metastasis. When it does metastasize, the most common involved organs are the lungs, brain, bone and other skin locations. One study found squamous cell carcinoma of the penis had a much greater rate of mortality than some other forms of squamous cell carcinoma, that is, about 23%, although this relatively high mortality rate may be associated with possibly latent diagnosis of the disease due to patients avoiding genital exams until the symptoms are debilitating, or refusal to submit to a possibly scarring operation upon the genitalia. Squamous cell carcinoma occurring in the organ transplant population is also associated with a higher risk of mortality.

Epidemiology

Melanoma and other skin cancers world map - Death - WHO2004

The incidence of squamous cell carcinoma continues to rise around the world. A recent study estimated that there are between 180,000 and 400,000 cases of SCC in the United States in 2013. Risk factors for 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 60 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 skin or those chronically exposed to UV radiation. Squamous cell carcinoma of the skin can be found on all areas of the body but is most common on frequently sun-exposed areas, such as the face, legs and arms. Solid organ transplant recipients (heart, lung, liver, pancreas, among others) are also at a heightened risk of developing aggressive, high-risk SCC. There are also a few rare congenital diseases predisposed to cutaneous malignancy. In certain geographic locations, exposure to arsenic in well water or from industrial sources may significantly increase the risk of SCC.

Additional images

File:Biopsy proven Squamous Cell Carcinoma- 2014-05-27 05-13.jpg, Biopsy-proven squamous cell carcinoma File:Squamous-carcinoma-of-dorsum-of-hand.jpg, Squamous carcinoma of dorsum of hand File:Bowen11.jpg, SCC ''in situ'' (''Bowen's disease''). File:Squamous_Cell_Carcinoma,_Right_Upper_Cheek.png, Squamous Cell Carcinoma, Right Upper Cheek; Lesion outlined in blue marker with a dashed line prior to biopsy

References

External links

DermNet NZ: Squamous cell carcinoma
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