, also known as epidermoid carcinoma or squamous carcinoma, is a common cancer that develops in the cells of the...){kind=link}
Squamous cell carcinoma (SCC), also known as epidermoid carcinoma or squamous carcinoma, is a common cancer that develops in the cells of the skin layers (epidermis) and mucosa. Mucosa refers to the lining present in your mouth (and associated structures like pharynx/larynx), respiratory tract, and digestive tract. Studies show that there is a high global prevalence of SCC, and the numbers have increased dangerously over the past years, increasing the medical burden.
Individuals exposed to UV rays (from sunlight) have a higher risk of developing cutaneous (skin) squamous cell carcinoma. Males are about two times more likely to develop SCC than women. Doctors adopt different types of strategies, like chemotherapy and surgical excision, to treat the carcinomas. Early diagnosis and treatment are key to a better prognosis.
Types Of Squamous Cell Carcinoma
Several different types of SCC exist in nature. Carcinomas are broadly classified based on the region involved.
Cutaneous SCC (cSCC)
This is the most common type of squamous cell carcinoma, which arises in the top layer of the skin, i.e., epidermis. Most prevalent sites of cutaneous carcinoma are the face, neck, lips, hands, and arms. Skin carcinoma is further divided into different types.
In SCC in situ, cancer cells involve only the outermost skin layers, while invasive SCC is characterized by deeper invasion of the skin layers. Keratocanthomas present with dome-shaped lesions, and verrucous carcinomas are rare and appear as wart-like growths.
Head And Neck SCC
Squamous cell carcinomas arising in the head and neck region are usually aggressive and hard to treat. Oral squamous cell carcinomas can develop on the inner side of the cheeks, lips, and tongue. You may develop carcinomas on the mucosa of the pharynx, larynx, and nasal sinuses, too.
Erythematous, ulcerated lesion of oral squamous cell carcinoma on the patient’s tongue.
Pulmonary SCC
The mucosal lining of your respiratory system can also fall prey to uncontrolled division of the cells. It is a common type of non-small cell carcinoma of the lung. You may also develop squamous carcinomas in the esophageal (gut) lining.
Genital And Anal SCCs
Vaginal, cervical, and vulvar linings can develop SCC and are often associated with Human Papillomavirus (HPV) infection. You may develop SCC in the anal lining, too. HPV vaccination can help prevent some of these SCCs.
Progression Of Cancer
Based on the progression and spread of the cancer, SCC is divided into the following types:
- In situ: Limited to the top layer of skin.
- Cutaneous: Invasive SCC extending deeper into the dermis or subcutis.
- Metastatic: Cancer has spread to other parts of the body.
Squamous Cell Carcinoma Symptoms
Cancerous growths may have different presentations on the skin and mucosa. In the vast majority of cases, cancerous growths are not painless and non-itchy. Therefore, we divide symptoms into skin (cutaneous) and mucosal.
Cutaneous Symptoms
In the vast majority of cases, carcinomas arise on skin that is exposed to the sun. Thus, you will find most cancerous lesions on the scalp, hands (especially the back side), lips, and ears. Cancerous lesions do not heal with conventional therapies, which is a feature distinguishing them from non-cancerous lesions.
Bumps:
Several patients report having a non-healing, rough bump/growth on the skin, which tends to crust (like a scab). The skin-colored lesions can also bleed and may show rapid growth. In a clinical case, an 83-year-old male presented with an aggressively growing eye bump that was diagnosed as SCC.
Erythematous (red) papule (raised skin lesion) of squamous cell carcinoma on the patient’s leg. Image courtesy of Kelly Nelson, M.D., made available by theNational Cancer Institute
Crater Bumps:
Sometimes, the cancerous skin bumps may have a unique appearance (especially in keratocanthoma-type lesions). The bumps are higher than the adjacent skin, and there is a depression in the middle of the lesion, giving it a crater-like appearance.
Scaly Patches:
Patients have reported flat and scaly patches that are carcinomatous. The patches are red-colored (erythematous) and can be 1 inch (2.5 centimeters) in size. As per reports, the most frequent clinical presentation of SCC in situ is an erythematous sclay patch which is barely noticed by the patients.
Mucosal
The presentations of squamous cell carcinoma in the mucosa differ slightly from skin lesions. The following types of lesions are frequently seen in the mucosal linings of the body:
Oral Ulcer And Sores:
Non-healing sores of the oral region are frequently associated with oral squamous cell carcinoma. Patients often experience red/white patches and non-healing ulcers on the tongue, cheek, and lips. Doctors have identified specific oral lesions as oral potentially malignant disorder (OPMD) that can transform into squamous cell cancers. In some cases, the oral sore heals but comes back again.
Wartlike Growths:
A rare variant of the squamous cell carcinoma is verrucous carcinoma, which affects the skin and mucosal linings of the mouth and genitals. It is a slow-growing cancer that appears as a cauliflower-like or wart-like growth. According to a case study, verrucous carcinoma of the foot can mimic a plantar wart and lead to misdiagnosis.
Precancerous Conditions Associated With SCC
Several different skin/mucosal abnormalities are known to transform into squamous cell cancers and are thus termed precancerous conditions. Acitinic keratosis (rough and scaly patches of skin), actinic cheilitis (scaly patches on lips) and leukoplakia (white spots in the mouth) can turn into SCC.
An erythematous (red) ulcerated lesion (SCC) on the patient’s nose can be seen. In this case, squamous cell carcinoma developed from a pre-malignant lesion of actinic keratoses. Image courtesy ofNational Cancer Institute.
Thus, they must be treated on time. Oral submucous fibrosis (OSF) is another oral, precancerous condition characterized by limited mouth opening and thick, white, fibrous bands in the oral mucosa.
Squamous Cell Carcinoma Causes
Like most cancers, squamous cell carcinoma develops due to underlying genetic mutations. In this type of skin cancer, a mutation takes place in the p53 gene, which is a tumor suppressor gene. This gene prevents the formation of cancers in the body by producing a protein (tumor suppressor protein) that halts cell division in damaged DNA. This activity prevents faulty division of the DNA.
Squamous cells are present in the outer layers of the skin. Researchers believe that UV radiation can directly cause DNA damage or harm the genetic materials through reactive oxygen species (ROS). Mutation and consequent inhibition of the p53 gene lay the foundation of cutaneous squamous cell carcinoma. However, additional alterations contribute to the progression of premalignant lesions into metastatic SCC. The abrupt cell divisions lead to the formation of skin bumps and lesions.
In the case of oral squamous cell carcinoma, chronic irritation can induce changes in the oral mucosa. Several things can irritate your mucosa and increase the propensity of SCC, including tobacco consumption and betelnut/arecanut chewing. Heavy alcohol consumption and a weak immune system can also contribute to oSCC.
Risk Factors for SCC
Clinicians have identified certain factors that increase the risk of squamous carcinoma. Healthcare providers must always carefully examine patients with these risk factors.
- Old age
- Long-term exposure to sunlight (mainly due to occupational exposure in farmers, construction workers, and gardeners, etc)
- Having light colored eyes (green, blue) and a pale complexion
- Severe sunburns
- Exposure to harmful chemicals like arsenic and those found in cigarette smoke
- Weak immune system (due to immunosuppressant drugs after organ transplant or disorders like hepatitis, HIV, etc.)
Squamous Cell Carcinoma Diagnosis
Diagnosing squamous cell carcinoma is difficult because it resembles multiple benign conditions. Your healthcare provider will start by physically examining the size, color, shape, and texture of the lesion. Non-healing lesions on cancer-prone areas raise concerns. So, your doctor will ask questions about your medical history. He will inquire about when you noticed the lesion/lump, and did you notice any changes in its size in the recent past, and if the lesion is itchy/painful. When suspected, your doctor will order an array of tests.
Diagnostic Tests
As this cancer involves skin cells, the main diagnostic test is a skin biopsy. However, doctors also take help from imaging studies in advanced cases to check the spread of cancer.
Biopsy:
In a skin biopsy, the doctor removes a small part of the skin lesion and sends it to the lab for microscopic examination. However, when doctors suspect the spread of the tumor to neighboring lymph nodes, they perform a sentinel lymph node biopsy (SLNB). The lymphatic system is a circulatory system that carries lymph fluid instead of blood. Cancers can spread to different parts of the body via the lymph.
In this technique, oncologists identify the first lymph node draining from the tumor to check for spread. Professionals inject a radioactive tracer (and a blue dye) near the tumor. Then, surgeons use a special camera, i.e., lymphoscintigraphy, to remove the tumor via a small incision. The radioactive tumor and the dye help locate the node during surgery. Modern studies support the use of SLNB in the diagnosis and management of oral SCC and high-risk cutaneous SCC of the head/neck.
Imaging Studies:
CT and MRI scans may be advised to check the size of the tumor that has penetrated deep into the layers of the skin. It also helps identify the spread of cancer to other parts of the body.
Squamous Cell Carcinoma Stages
Once the diagnosis is made, the oncologist (cancer specialist) allocates a stage to the cancer. Staging SCC helps in devising the best-suited treatment plan and predicting outcomes.
| Stages | Features |
|---|---|
| 0 | SCC in situ (in only the top layer of skin) |
| Ⅰ | In top and middle layers of skin (epidermis and dermis) |
| Ⅱ | Deeper into the skin (subcutis) and targets nerves |
| Ⅲ | Spread to nearby lymph nodes but not distant organs |
| Ⅳ | Spread to different organs (brain, liver, lungs, etc.) |
Differential Diagnosis (DD)
Multiple skin/mucosal pathologies fall under the DD of squamous cell carcinoma, including melanoma, basal cell carcinoma, lichen planus, and seborrheic keratosis, etc.
Basal Cell Carcinoma (BCC) Vs Squamous Cell Carcinoma (SCC)
BCC and SCC are the most common cancers of the skin. Both these carcinomas arise in sun-exposed skin, but there are certain evident differences between them. While SCC appears mostly as red, scaly patches, BCC forms waxy (pearly) bumps. The rate of progression of SCC is faster than compared of BCC. Moreover, there is a higher risk of spread associated with SCC than with BCC.
Squamous Cell Carcinoma Treatment
The main aim of the treatment is to eliminate cancerous cells while keeping the healthy cells safe. Different treatment strategies have been shown to work. Treatment plans depend on several factors, like the size of the tumor, its location, and whether it has spread or not. The most commonly adopted treatment options include:
Surgical Treatments
The most effective line of treatment in case of squamous cell carcinomas is surgical intervention. Depending on the tumor factors, surgeons select from the following options:
Curretage and Electrodessication:
This modality is used to treat SCC in situ and low-risk squamous carcinomas. In this quick procedure, the surgeon scrapes off the cancerous skin layer via a spoon-shaped tool called a curette. This is followed by electrodesiccation, which uses heat from electrocautery to destroy the deeper cancerous cells. It has shown positive results with minimal recurrence.
A doctor performs electrosurgery to treat a squamous cell carcinoma tumor.
Mohs Microscopic Surgery:
Surgeons prefer this type of surgery in high-risk squamous cell carcinomas. In this very technique, the surgeon removes the cancer in a layer-by-layer manner to preserve healthy skin tissues. The procedure is carried out under microscopic guidance and offers a disease-specific survival advantage over conventional wide local excision for high-risk tumors.
Surgical Excision:
The surgeon removes the affected skin (along with some healthy skin). Oncologists now prefer minimally invasive techniques over conventional surgery due to better outcomes and fewer complications.
Non-Surgical Treatments
Non-invasive strategies are not as effective, but can still be of great help in shrinking the tumor.
Topical Therapy:
In case of superficial SCC and precancerous conditions like actinic keratosis, your doctor might advise you to use topical chemotherapeutic medications like 5-fluorouracil or an immunity-booster like imiquimod.
Cryosurgery:
It’s a famous cancer therapy that uses extreme cold to kill cancer cells. The introduction of liquid nitrogen or argon gas via a cryoprobe destroys tumorous growths. Intralesional cryosurgery effectively destroys tumor cells. Thus, it is a simple and effective alternative to surgery in SCC patients.
Photodynamic Therapy (PDT):
This is a type of phototherapy that utilizes a drug that is activated with light (photosensitizing chemical/agent) and light (from a laser/LEDs) to kill squamous cell carcinomas. When exposed to light, the photosensitizers release oxygen radicals that kill cancerous cells. It is effective in the treatment of early oral SCC.
Systemic Therapy:
Doctors usually adopt systemic therapy in cases where the cancer has spread to other organs. Chemotherapeutic drugs (like 5-fluorouracil) are given in conjunction with other therapies. Immunotherapy (e.g., cemiplimab) is used for advanced or unresectable SCC.
Radiation Therapy:
Doctors use radiation to safely kill cancerous cells. This type can be used exclusively in non-surgical candidates. However, for high-risk patients, radiotherapy can serve as an adjuvant for decreasing pain and bleeding.
Squamous Cell Carcinoma Prognosis
There is generally an excellent prognosis for squamous cell carcinoma treatment. The 5-year survival for early treated, localized cutaneous SCC is around 99%. The mortality is approximately 1-2% for cSCC, and only 3% cases metastasize to other organs.
Can you prevent SCC?
You can minimize your risk of squamous cell carcinoma by reducing your exposure to the sun. Individuals prone to developing SCC should avoid tanning beds and always use sunscreen when going outdoors. People with white skin can wear protective clothing with UPF protection. By avoiding oral irritants like cigarettes, tobacco, and betel/areca nuts, you can minimize the chances of oral SCC. You should not delay medical checkups of non-healing skin bumps and oral sores/ulcers.
Final Word
Squamous cell carcinoma is a type of cancer that affects your skin and mucosa. It is a cancer of squamous cells present in the skin/mucosal layers. Cutaneous SCC (skin type) arises in solar-exposed skin and usually presents as non-healing skin-colored bumps, crater-like bumps, or scaly patches. It is mostly seen on the head/neck region and hands. Mucosal SCC can develop in the mouth, respiratory tract, gut, and genitals/anus. This type usually presents as non-healing ulcers and sores. Sun-exposure-related precancerous conditions like actinic cheilitis and keratosis can change into SCC.
Carcinoma is believed to be caused by a mutation in the p53 gene, which is a tumor suppressor gene. Old individuals, people having occupational exposure to long-term sunlight, and those with a weak immune system are highly likely to develop SCC. Doctors diagnose skin cancer with physical examination and biopsy (sentinel lymph node biopsy is performed when the tumor spreads to the nearby lymph node).
The most effective treatment strategy is surgery. In addition to conventional surgery, we now have minimally invasive procedures like curettage and electrodessication, and Mohs microscopic surgery that are highly effective and safe. In nonsurgical management, doctors use extreme cold (cryotherapy), light (photodynamic therapy), and radiation (radiotherapy) to kill the cancerous cells. Oncologists may also advise topical or systemic anti-cancer drugs to rid you of SCC. Generally, SCC prognosis is good.
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