Cutaneous squamous-cell carcinoma (cSCC), also known as squamous-cell carcinoma of the skin or squamous-cell skin cancer, is one of the three principal types of

skin cancer Skin cancers are cancers that arise from the Human skin, skin. They are due to the development of abnormal cells (biology), cells that have the ability to invade or metastasis, spread to other parts of the body. It occurs when skin cells grow ...

, alongside

basal-cell carcinoma Basal-cell carcinoma (BCC), also known as basal-cell cancer, basalioma, or rodent ulcer, 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. ...

and

melanoma Melanoma is the most dangerous type of skin cancer; it develops from the melanin-producing cells known as melanocytes. It typically occurs in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In very rare case ...

. cSCC typically presents as a hard lump with a scaly surface, though it may also present as 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 sloughin ...

. Onset and development often occurs over several months. Compared to basal cell carcinoma, cSCC is more likely to spread to distant areas. When confined to the

epidermis The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and Subcutaneous tissue, hypodermis. The epidermal layer provides a barrier to infection from environmental pathogens and regulates the ...

, the outermost layer of the skin, the pre-invasive or ''

in situ is a Latin phrase meaning 'in place' or 'on site', derived from ' ('in') and ' ( ablative of ''situs'', ). The term typically refers to the examination or occurrence of a process within its original context, without relocation. The term is use ...

'' form of cSCC is termed Bowen's disease. The most significant risk factor for cSCC is extensive lifetime exposure to

ultraviolet radiation Ultraviolet radiation, also known as simply UV, is electromagnetic radiation of wavelengths of 10–400 nanometers, shorter than that of visible light, but longer than X-rays. UV radiation is present in sunlight and constitutes about 10% of t ...

from sunlight. Additional risk factors include prior scars, chronic wounds,

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

, lighter skin susceptible to sunburn, Bowen's disease, exposure to

arsenic Arsenic is a chemical element; it has Symbol (chemistry), symbol As and atomic number 33. It is a metalloid and one of the pnictogens, and therefore shares many properties with its group 15 neighbors phosphorus and antimony. Arsenic is not ...

radiation therapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a therapy, treatment using ionizing radiation, generally provided as part of treatment of cancer, cancer therapy to either kill or control the growth of malignancy, malignant cell (biology), ...

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 released from the mouth, as is generally done with pipes and cigars. The practice is believed to hav ...

, poor immune system function, previous basal cell carcinoma, and HPV infection. The risk associated with UV radiation correlates with cumulative exposure rather than early-life 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 h ...

have emerged as a significant source of UV radiation. Genetic predispositions, 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 su ...

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. Inherite ...

, also increase susceptibility to cSCC. The condition originates from

squamous cells Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial (mesothelial) tissues line the outer surfaces of many ...

located in 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 animal coverings, such as the arthropod exoskeleton, have different ...

's upper layers. Diagnosis typically relies on skin examination, and is confirmed through

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 day ...

. Research, both ''in vivo'' and ''in vitro'', indicates a crucial role for the

upregulation In biochemistry, in the biological context of organisms' regulation of gene expression and production of gene products, downregulation is the process by which a cell decreases the production and quantities of its cellular components, such as R ...

FGFR2 Fibroblast growth factor receptor 2 (FGFR-2) also known as CD332 (cluster of differentiation 332) is a protein that in humans is encoded by the ''FGFR2'' gene residing on chromosome 10. FGFR2 is a receptor for fibroblast growth factor. FGFR-2 is ...

, part of the

fibroblast growth factor receptor The fibroblast growth factor receptors (FGFR) are, as their name implies, receptors that bind to members of the fibroblast growth factor (FGF) family of proteins. Some of these receptors are involved in pathological conditions. For example, a po ...

immunoglobin family, in cSCC cell progression.

Mutations In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosi ...

in the TPL2 gene leads to overexpression of FGFR2, which activates the

mTORC1 mTORC1, also known as mammalian target of rapamycin complex 1 or mechanistic target of rapamycin complex 1, is a protein complex that functions as a nutrient/energy/redox sensor and controls protein synthesis. mTOR Complex 1 (mTORC1) is comp ...

and

AKT Protein kinase B (PKB), also known as Akt, is the collective name of a set of three serine/threonine-specific protein kinases that play key roles in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, tra ...

pathways in primary and metastatic cSCC cell lines. Utilization of a "pan FGFR inhibitor" has shown to reduce

cell migration Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryogenesis, embryonic development, wound healing and immune system, immune responses all require the orchestrated movemen ...

and proliferation in cSCC ''in vitro'' studies. Preventive measures against cSCC include minimizing exposure to ultraviolet radiation and the use of

sunscreen Sunscreen, also known as sunblock, sun lotion or sun cream, is a photoprotection, photoprotective topical product for the Human skin, skin that helps protect against sunburn and prevent skin cancer. Sunscreens come as lotions, sprays, gels, fo ...

. Surgical removal is the typical treatment method, employing simple excision for minor cases or

Mohs surgery Mohs surgery, developed in 1938 by 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, the ...

for more extensive instances. Other options include

cryotherapy Cryotherapy, sometimes known as cold therapy, is the local or general use of low temperatures in medical therapy. Cryotherapy can be used in many ways, including whole body exposure for therapeutic health benefits or may be used locally to treat ...

and

. For cases with distant metastasis,

chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

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, th ...

may be employed. As of 2015, approximately 2.2 million individuals globally were living with cSCC at any given time, constituting about 20% of all skin cancer cases. In the United States, approximately 12% of males and 7% of females are diagnosed with cSCC at some point in their lives. While prognosis remains favorable in the absence of metastasis, upon distant spread the

five-year survival rate 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 surv ...

is markedly reduced to ~34%. In 2015, global deaths attributed to cSCC numbered around 52,000. The average age at diagnosis is approximately 66 years. Following successful treatment of an initial cSCC lesion, there is a substantial risk of developing subsequent lesions.

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 cutaneous squamous-cell carcinoma. * The lesion caused by cSCC is often

asymptomatic Asymptomatic (or clinically silent) is an adjective categorising the medical conditions (i.e., injuries or diseases) that patients carry but without experiencing their symptoms, despite an explicit diagnosis (e.g., a positive medical test). P ...

* 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 lesion, skin. It may have a rounded, pointed or flat top, and may have a umbilication, dip. It can appear with a Peduncle (anatomy), stalk, be thread-like or look warty. It can be soft or firm a ...

, 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. . Actin ...

(solar keratoses) * The tumor grows relatively slowly

Spread

* Unlike

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

metastasis Metastasis is a pathogenic agent's spreading 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, ...

. * Risk of metastasis is higher clinically in SCC arising in scars, on the lower lips, ears, 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, presence of

lymphovascular invasion Lymphovascular invasion (LVI or lymphovascular space invasion) is the invasion of a cancer to the blood vessels and/or lymphatics. Terminology Lymph: A clear or white fluid that travels through vessels, moves within tissues and work to keep all t ...

, poorly differentiated cell architecture on histology, or thickness greater than 6 mm.

Causes

Cutaneous squamous-cell carcinoma is the second-most common cancer of the skin (after basal-cell carcinoma, 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 ...

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. cSCC represents about 20% of the non-melanoma skin cancers; 80-90% of cSCCs 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 cSCC cases are located on exposed skin, and are often the result of

ultraviolet Ultraviolet radiation, also known as simply UV, is electromagnetic radiation of wavelengths of 10–400 nanometers, shorter than that of visible light, but longer than X-rays. UV radiation is present in sunlight and constitutes about 10% of ...

exposure. cSCC usually occurs on portions of the body commonly exposed to the sun; the face, ears, neck, hands, or arms. The primary sign is a growing bump that may have a rough, scaly surface, and flat, reddish patches. Unlike basal-cell carcinoma, cSCC carries a higher risk of

than does basal-cell carcinoma, 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 includ ...

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

glans The glans (, : 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 of the g ...

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

in males, M or the

vulva In mammals, the vulva (: vulvas or vulvae) comprises mostly external, visible structures of the female sex organ, genitalia leading into the interior of the female reproductive tract. For humans, it includes the mons pubis, labia majora, lab ...

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 A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It ...

or the oral mucosa. Genetically, cSCC tumors harbor high frequencies of 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 transcription factor protein that is often mutated in human cancers. The p53 proteins (originally thou ...

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 packa ...

chromatin remodeling complex PBRM1, DNA-repair deubiquitinase USP28, and

NF-κB Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a family of transcription factor protein complexes that controls transcription (genetics), transcription of DNA, cytokine production and cell survival. NF-κB is found i ...

signaling regulator CHUK. A significant proportion of cSCC and its precursor lesions carry UV-induced

mutations. In fact, these mutations are present in up to 90% of cSCC cases. The detection of p53 mutations in precursor lesions indicates that this could be an early event in the development of squamous cell carcinoma.

Immunosuppression

People who have received solid organ transplants are at a significantly increased risk of developing

squamous-cell carcinoma Squamous-cell carcinoma (SCC), also known as epidermoid carcinoma, comprises a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the ...

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 cSCC, with hazard ratios as high as 250 being reported, versus 40 for basal cell carcinoma. The incidence of cSCC development increases with time posttransplant. Heart and lung transplant recipients are at the highest risk of developing cSCC due to more intensive immunosuppressive medications used. Cutaneous squamous-cell carcinoma in individuals on immunotherapy or who have lymphoproliferative disorders (e.g.

leukemia Leukemia ( also spelled leukaemia; pronounced ) is a group of blood cancers that usually begin in the bone marrow and produce 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 cSCC, 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

antimetabolite An antimetabolite is a chemical that inhibits the use of a metabolite, which is another chemical that is part of normal metabolism. Such substances are often similar in structure to the metabolite that they interfere with, such as the antifolat ...

s azathioprine and mycophenolic acid have an intermediate risk profile.

Diagnosis

Diagnosis is confirmed via

of the tissue or tissues suspected to be affected by SCC. 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 actinic keratosis 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.

Histological characteristics

Histopathologically, the epidermis in cSCC ''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 cSCC. 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 cSCC ''in situ'', when not having invaded through the

basement membrane The basement membrane, also known as base 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 epithelial tis ...

. Depending on source, it is classified as precancerous or cSCC ''in situ'' (technically cancerous but non-invasive). In cSCC ''in situ'' (Bowen's disease), atypical

squamous cell Epithelium or epithelial tissue is a thin, continuous, protective layer of Cell (biology), cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial (Mesothelium, mesothelial) tissues line ...

s 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 equipment, 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 ...

, 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, cSCC ''in situ'', high magnification, demonstrating an intact basement membrane. Image:Bowen disease (1).jpg, cSCC ''in situ'' Image:Bowen disease (2).jpg, cSCC ''in situ'' Image:Bowen disease (3).jpg, cSCC ''in situ'' Image:Bowen disease (4).jpg, cSCC ''in situ'' Erythroplasia of Queyrat is a particular type of Bowen's disease that can arise on the

in males, and the

in females. It mainly occurs in uncircumcised males, over the age of 40.

Invasive disease

In invasive cSCC, 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 squamous-cell carcinoma of the skin File:Micrograph of invasive squamous cell carcinoma - 150x.jpg, Superficially invasive cutaneous squamous-cell carcinoma. These lesions often do not show the marked pleomorphism and atypical nuclei of cSCC ''in situ'', but manifest 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 cSCC.

Degree of differentiation

File:Micrograph of well-differentiated and invasive squamous-cell carcinoma.jpg, Well-differentiated (yet invasive) cSCC, showing prominent keratinization. It may form pearl-like structures where dermal nests of keratinocytes attempt to mature in a layered fashion. Well-differentiated cSCC 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 cSCC 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 infiltrated cords through the dermis. Poorly differentiated cSCC has greatly enlarged pleomorphic nuclei showing 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 cSCC, 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 cutaneous squamous-cell carcinoma found insufficient evidence to demonstrate whether it was effective.

Management

Most cutaneous 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 A resection margin or surgical margin is the edge or "margin" of apparently non-tumorous tissue around a tumor that has been surgically removed, called " resected", in surgical oncology. The resection is an attempt to remove a cancer tumor so th ...

of healthy tissue is a frequent treatment modality. Radiotherapy, given as

external beam radiotherapy External beam radiation therapy (EBRT) is a form of radiotherapy that utilizes a high-energy collimated beam of ionizing radiation, from a source outside the body, to target and kill cancer cells. The radiotherapy beam is composed of particl ...

or as

brachytherapy Brachytherapy is a form of radiation therapy where a sealed radiation, radiation source is placed inside or next to the area requiring treatment. The word "brachytherapy" comes from the Ancient Greek, Greek word , meaning "short-distance" or "s ...

(internal radiotherapy), can also be used to treat cSCC. There is little evidence comparing the effectiveness of different treatments for non-metastatic cSCC. Cosibelimab (Unloxcyt) was approved for medical use in the United States in December 2024, for the treatment of adults with metastatic cutaneous squamous cell carcinoma or locally advanced cutaneous squamous cell carcinoma who are not candidates for curative surgery or curative radiation.

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 ...

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 a material medium. This includes: * ''electromagnetic radiation'' consisting of photons, such as radio waves, microwaves, infr ...

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

radiotherapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a treatment using ionizing radiation, generally provided as part of cancer therapy to either kill or control the growth of malignant cells. It is normally delivered by a linear particle ...

can also be a standalone option in treating cSCC. 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 Naturally occurring rhenium (75Re) is 37.4% 185Re, which is stable (although it is predicted to decay), and 62.6% 187Re, which is unstable but has a very long half-life (4.12×1010 years). Among elements with a known stable isotope, only indium a ...

. The radiation source is enclosed in a compound which is applied to a thin protection foile directly over the lesion. 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 cSCC is 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 cSCC ''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 used in treating acne, wet age-related macula ...

with 5-aminolevulinic acid,

, topical

5-fluorouracil Fluorouracil (5-FU, 5-fluorouracil), 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, stoma ...

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 that 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 cSCC 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 pharmaceutica ...

(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 carcinoma 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, with a metastasis rate of 1.9-5.2% and a mortality rate of 1.5-3.4%. When it does metastasize, the most commonly involved organs are the lungs, brain, bone and other skin locations. Squamous-cell carcinoma occurring in immunosuppressed people (such as those with organ transplant, human immunodeficiency virus infection, or chronic lymphocytic leukemia) the risk of developing cSCC and having metastasis is much higher than the general population. 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.

Epidemiology

Melanoma and other skin cancers world map - Death - WHO2004

The incidence of cutaneous squamous-cell carcinoma continues to rise around the world. This is theorized to be due to several factors; including an aging population, a greater incidence of those who are immunocompromised and the increasing use of tanning beds. A recent study estimated that there are between 180,000 and 400,000 cases of cSCC in the United States in 2013. Risk factors for cSCC varies with age, gender, race, geography, and genetics. The incidence of cSCC increases with age and with those 75 years or older being at a 5-10 times increased risk of developing cSCC as compared with those who are younger than 55 years old. Males are affected with cSCC at a ratio of 3:1 in comparison to females. Those who have light skin, red or blonde hair and light colored eyes are also at increased risk. 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 cSCC. 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 cSCC.

Additional images

File:Biopsy proven Squamous Cell Carcinoma- 2014-05-27 05-13.jpg, Biopsy-proven cutaneous squamous-cell carcinoma File:Squamous-carcinoma-of-dorsum-of-hand.jpg, Squamous-cell carcinoma of the dorsum of the hand File:Bowen11.jpg, cSCC ''in situ'' (''Bowen's disease'') File:Squamous Cell Carcinoma, Right Upper Cheek.png, cSCC of the right upper cheek; lesion outlined in blue with a dashed line prior to biopsy File:Giant squamous cell carcinoma of the cheek.jpg, Giant squamous cell carcinoma of the cheek

References

External links

DermNet NZ: Squamous cell carcinoma
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