Squamous-cell carcinoma

Squamous-cell carcinoma (SCC) is a carcinomatous cancer occurring in multiple organs. These

include 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).
Despite the common name, these are unique cancers with large differences in manifestation and
prognosis.

Contents
[hide]

 1 Classification

o 1.1 Terminology

o 1.2 Related conditions

 2 Signs and symptoms

 3 Cause

o 3.1 HPV

o 3.2 By region

 3.2.1 Skin

 3.2.2 Head and neck cancer

 3.2.3 Esophagus

 3.2.4 Lung

 3.2.5 Penis

 3.2.6 Prostate

 3.2.7 Vagina and cervix

 3.2.8 Bladder

 4 Diagnosis

 5 Management

 6 Epidemiology of squamous-cell carcinoma of the skin

 7 Epidemiology of squamous-cell cancer not involving the skin

 8 See also

 9 External links

 10 References
Classification
[1]:473
Squamous-cell carcinoma may be classified into the following types:

 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.

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

Signs and symptoms

Symptoms are highly variable depending on the involved organs.

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.

 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)
Cause

HPV
[2] [3]
Human papilloma virus has been associated with SCC of the oropharynx, lung, fingers, and
anogenital region.

By region
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
[4]
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
[5]
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
[6]
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 (i.e., 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
[citation needed]
time, systemic chemotherapy is used exclusively for patients with metastatic disease.

Australian scientist Professor Ian Frazer, one of the developers of the HPV vaccine, says that
animal tests have been effective in preventing squamous-cell carcinoma in animals, and there
[7]
may be a human vaccine against this kind of skin cancer within the decade.
Head and neck cancer

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

[8]
Ninety percent of cases of head and neck cancer (cancer of the mouth, nasal cavity,
nasopharynx, 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 withsurgery (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.
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
Main article: Squamous-cell lung carcinoma

Photograph of a squamous-cell carcinoma. Tumour is on the left, obstructing the bronchus (lung). Beyond
the tumour, the bronchus is inflamed 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

[9]
called erythroplasia of Queyrat. 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 ofvaginal cancer.

Bladder

Most bladder cancer is transitional cell, but bladder cancer associated with Schistosomiasis is
often squamous-cell carcinoma.

Diagnosis
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 inadequate biopsy might be read as actinic
keratosis with follicular involvement. A deeper biopsy down to the dermis or subcutanous 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.

Management

Most squamous-cell carcinomas are removed with surgery. A few selected cases are treated
with topical medication. Surgical excision with a free margin of healthy tissue is a frequent
treatment modality. Radiotherapy, given as external beam radiotherapy or
as brachytherapy (internal radiotherapy), can also be used to treat squamous-cell carcinomas.

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-
[10]
cell carcinoma of the mouth, throat, and neck. An equivalent method of
the CCPDMA standards can be utilized by a pathologist in the absence of a Mohs-trained
physician. Radiation therapy often used afterward in high risk cancer or patient types.

Electrodessication and curettage or 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.

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
[11]
hormone called afamelanotide (formerly CUV1647) to provide photoprotection for organ
[12][13]
transplant patients against squamous-cell carcinoma of the skin and actinic keratosis.
Epidemiology of squamous-cell carcinoma of the skin

Age-standardized death from melanoma and other skin cancers per 100,000 inhabitants in 2004.[14]
no data
less than 0.7
0.7-1.4
1.4-2.1
2.1-2.8
2.8-3.5
3.5-4.2
4.2-4.9
4.9-5.6
5.6-6.3
6.3-7
7-7.7
more than 7.7

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 predisposed to cutaneous malignancy. In certain
geographic locations, exposure to arsenic in well water or from industrial sources may
[4]
significantly increase the risk of SCC.

Epidemiology of squamous-cell cancer not involving the skin

These are discussed under the heading of Cause and include exposure to factors such as
smoking, alcohol, betel nut (combination of the betel leaf and arecanut), carcinogens, human
papilloma virus or hpv, and chronic esophageal reflux disease (GERD) risks.