Squamous Cell Carcinoma SQUAMOUS CELL CARCINOMA by Justina April 17, 2024 April 17, 2024 A+A- Reset 47 Squamous cell carcinoma (SCC), also known as cutaneous squamous cell carcinoma (CSCC), ranks as the second most prevalent type of skin cancer, often attributed to sun exposure, trailing behind basal cell carcinoma. It originates in the squamous cells found in the outer layer of the skin, called the epidermis. Typically, SCCs develop in areas of the skin that are frequently exposed to sunlight, such as the head, arms, and legs. However, they can also emerge in regions with mucous membranes, such as the mouth, lungs, and anus. Squamous cells, which form the outer layer of the skin, undergo a constant turnover process, shedding old cells and generating new ones. However, if these cells undergo mutations and accumulate abnormally, it can lead to the formation of a tumor. SCC typically progresses slowly, making early detection and treatment relatively straightforward. However, unlike some other skin cancers, SCC has the potential to spread to surrounding tissues, bones, and nearby lymph nodes if left untreated, complicating treatment strategies. Causes of Squamous Cell Carcinoma Mutation to the p53 Gene: Squamous cell carcinoma is primarily triggered by a mutation in the p53 gene. This gene plays a crucial role in regulating cell division and replication to replace aging cells. Essentially, p53 acts as a tumor suppressor, ensuring that cells reproduce at an appropriate rate. However, exposure to ultraviolet (UV) radiation from the sun or indoor tanning beds is the primary culprit behind p53 gene mutations. These rays gradually inflict damage on the skin, triggering uncontrolled growth of squamous cells, a process that can ultimately lead to SCC. This is particularly pertinent for individuals with lower levels of melanin, the natural pigment responsible for skin, hair, and eye color, as they are more susceptible to UV-induced skin damage. However, it’s essential to recognize that SCC can affect anyone, regardless of their sun exposure habits. Surprisingly, up to 65% of all skin cancer cases in individuals with dark skin comprise SCC. This underscores the importance of understanding that UV exposure isn’t the sole determinant of SCC risk. While UV rays serve as the primary instigator of SCC, various other factors contribute to the likelihood of its development. Health conditions impacting the immune system and daily activities also play a role in increasing SCC risk. Therefore, maintaining awareness of these risk factors and adopting preventive measures remains crucial in mitigating the chances of SCC occurrence. Effects of p53 Mutation: When the p53 gene mutates, cells lose their proper instructions for replication. Consequently, squamous cells start dividing and replicating excessively, leading to the formation of tumors such as bumps, lumps, or lesions on or within the body. Spread of Squamous Cell Carcinoma Cutaneous squamous cell carcinoma typically does not spread (metastasize) to other body parts. However, if metastasis does occur, it progresses slowly and can pose life-threatening risks if left untreated. Any changes observed in the skin should prompt immediate consultation with a healthcare provider to rule out or address potential concerns. Early detection and intervention are critical in managing squamous cell carcinoma effectively. Prevalence: In the United States alone, over 1 million people are diagnosed with squamous cell carcinoma annually. Notably, the incidence of SCC has surged by about 200% over the past three decades. Types of Squamous Cell Carcinoma In Situ: This type is confined to the top layer of the skin, indicating early-stage SCC. Cutaneous: This type affects the superficial layer of the skin, either remaining confined to the top layer (in situ) or extending beyond it. Metastatic: In cases where SCC metastasizes, it spreads from the skin to other parts of the body. Although rare, this can occur if SCC remains undetected or untreated. Risk Factors Squamous cell carcinoma can afflict anyone, with certain factors increasing susceptibility: Older Age: The risk of SCC tends to increase with advancing age (Age 65 or older). While most commonly diagnosed in individuals over 50, the incidence of SCC has been rising among those younger than 50. Male Gender: Individuals assigned male at birth (AMAB) are at a higher risk of developing SCC compared to females. Fair Complexion: People with fair skin are more susceptible to SCC due to lower levels of melanin, which provides natural protection against UV radiation. Eye and Hair Color: Blue, green, or gray eyes, as well as blonde or red hair, are associated with a higher risk of SCC. Sun Exposure: Spending prolonged periods outdoors in the sun, especially without adequate protection, increases the risk of SCC. History of Sunburns: Previous episodes of sunburns, as well as the presence of precancerous skin lesions or a history of skin cancer, elevate the risk of SCC. Tanning Bed Use: Regular use of tanning beds, which emit artificial UV radiation, contributes to the development of SCC. Chemical Exposure: Long-term exposure to chemicals such as arsenic, found in water sources, is linked to an increased risk of SCC. Medical Conditions: Conditions such as Bowen’s disease, human papillomavirus (HPV) infection, human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS), or a weakened immune system heighten the risk of SCC. Radiation Exposure: Previous exposure to radiation, either for medical purposes or occupational exposure, can predispose individuals to SCC. Inherited DNA Conditions: Certain inherited genetic conditions can raise the risk of developing SCC. Tobacco Use: Smoking, chewing tobacco, or using snuff increases the risk of SCC, especially in the oral cavity. Skin Injury: Severe burns or other traumatic injuries to the skin can increase the likelihood of SCC development. Heavy Alcohol Use: Excessive alcohol consumption is associated with an elevated risk of SCC, particularly in combination with other risk factors. Chronic Mouth Irritation: Factors such as cavities, overuse of mouthwash, or the use of betel quid (a combination of betel leaf, areca nut, and slaked lime) can lead to chronic irritation of the mouth tissues, increasing the risk of oral SCC. Symptoms and Signs of Squamous Cell Carcinoma Symptoms: Texture Changes: You might notice a rough-feeling bump or growth on your skin, which could crust over like a scab and bleed. Depressions: The growth may be higher than the surrounding skin but have a depression in the middle. Non-Healing Wounds: Persistent wounds or sores that fail to heal properly or recur after healing. Flat, Red, Scaly Areas: These areas on the skin may appear flat, scaly, and red, typically larger than about 1 inch (2.5 centimeters). Signs: Actinic Keratosis: Dry, itchy, scaly bumps or lumps with a different color from the surrounding skin. Cheilitis: Lesions on the lower lip characterized by pale, dry, and cracked tissue, often accompanied by a burning sensation upon sun exposure. Leukoplakia: White or pale spots observed in the mouth, on the tongue, gums, or cheeks. Affected Areas of the Body Skin: Most commonly affected by SCC. Oral Cavity: Including the mouth, tongue, and throat. Facial Features: SCC can develop on the face, lips, nose, ears, eyelids, and scalp. Esophagus: SCC may occur in the stomach. Extremities: Hands, arms, and legs. Anal Cavity: SCC can also manifest in this area. Stages of Squamous Cell Carcinoma Upon diagnosis, your healthcare provider will assign a stage to identify the extent of cancer in your body. This guides the treatment decisions. The stages of squamous cell carcinoma are as follows: Stage 0: Cancer is confined to the top layer of the skin (epidermis), also known as squamous cell carcinoma in situ. Stage I (1): Cancer affects both the top and middle layers of the skin (epidermis and dermis). Stage II (2): Cancer involves the top and middle skin layers and may extend to nerves or deeper skin layers (epidermis, dermis, and subcutis). Stage III (3): Cancer has spread beyond the skin to the nearby lymph nodes. Stage IV (4): Cancer has metastasized to other parts of the body, including organs like the liver, lungs, or brain. While SCC can occur on any part of the body, it tends to be more prevalent in areas exposed to sunlight or those with mucous membranes. Regular skin checks and prompt medical attention for any suspicious growth or changes are crucial for early detection and treatment. Diagnosis of Squamous Cell Carcinoma Physical Examination: Your healthcare provider will conduct a thorough physical examination of the affected area. He/she will assess the size, shape, and location of any lumps or lesions. They will also inquire about your medical history and symptoms, including: When you first noticed the lump or lesion. Any changes in size since its initial appearance. Presence of pain or itching. Diagnostic Tests: Skin Biopsy: This involves the removal of a small tissue sample from the affected area for microscopic examination. The biopsy helps confirm the presence of squamous cell carcinoma. Imaging Tests: Your healthcare provider may recommend imaging tests such as a CT scan or MRI to assess the size of the carcinoma beneath the skin and determine if it has spread to other parts of the body, particularly the lymph nodes. Treatment Options for Squamous Cell Carcinoma Cryosurgery: This involves freezing the cancer cells to destroy them. Photodynamic Therapy (PDT): Utilizing blue light and light-sensitive agents to eliminate cancer from the skin. Curettage and Electrodesiccation: Scraping off the cancerous lump with a curette (spoon-like instrument) followed by burning the area with an electric needle. Excision: Surgically removing the cancer from the skin and stitching the area back together. Mohs Surgery: Removing layers of cancer-affected skin, commonly used for facial cancers. Systemic Chemotherapy: Employing powerful medications to eradicate cancer cells throughout the body. Medications for Squamous Cell Carcinoma Topical Creams: Imiquimod or 5-fluorouracil-containing skin creams target squamous cell carcinoma located in the top layer of the skin (epidermis). Immunotherapy: Drugs such as cemiplimab-rwlc (Libtayo®) and pembrolizumab (Keytruda®) are used to treat advanced or surgically untreatable forms of squamous cell carcinoma. Side Effects of Treatment Cosmetic Changes: The most common side effect is cosmetic alterations to the skin, including scarring, following cancer removal. Immunotherapy Side Effects: Individuals undergoing immunotherapy should be aware of potential side effects associated with these drugs. Recovery Timeline Healing time varies depending on individual factors such as the size, shape, and location of the cancer, as well as the type of treatment received. On average, most people experience recovery within two to four weeks after cancer removal treatment. Follow-up appointments with healthcare providers are essential to monitor healing progress and ensure successful cancer removal. Complications of Squamous Cell Carcinoma If left untreated, squamous cell carcinoma can progress and potentially lead to severe complications, including: Spread and Tissue Damage: The cancer can spread from its original site, invading surrounding healthy tissue and organs, causing damage and functional impairment. Life-Threatening Situations: In rare instances, untreated squamous cell carcinoma can become life-threatening, particularly under certain circumstances, such as: Large or Deep Tumors: When the cancerous growth is sizable or extends deeply into the skin layers, the risk of complications and adverse outcomes increases. Involvement of Mucous Membranes: Squamous cell carcinoma affecting mucous membranes, such as the lips, can pose heightened risks due to the proximity to vital structures and potential for rapid spread. Organ Transplant Recipients: Individuals who have undergone organ transplantation are at increased risk of complications from squamous cell carcinoma, as immunosuppressive medications used to prevent organ rejection can weaken the body’s ability to fight cancer. Weakened Immune System: Certain medical conditions, such as certain types of leukemia, can compromise the immune system’s function, making individuals more susceptible to cancer progression and complications. Prevention of Squamous Cell Carcinoma While it’s not possible to prevent all types of squamous cell carcinoma, you can take proactive measures to lower your risk by: Limiting Sun Exposure: Avoid prolonged periods in the sun, especially during peak hours when UV radiation is strongest (10 a.m. to 4 p.m.). Steering Clear of Tanning Beds: Refrain from using tanning beds, as they emit harmful UV radiation that can damage the skin. Sunscreen Use: Apply broad-spectrum sunscreen with an SPF of 30 or higher whenever you’re outdoors, even on cloudy days. Protective Clothing and Accessories: Wear clothing with UPF protection, along with sunglasses and wide-brimmed hats to shield yourself from UV rays. Smoking Cessation: Quit smoking to reduce your risk of developing squamous cell carcinoma, as smoking is a known risk factor. Chemical Exposure: Avoid exposure to harmful chemicals without wearing appropriate personal protective equipment (PPE). Regular Skin Exams: Keep an eye on any changes in your skin and promptly report any suspicious moles, lumps, or sores to your healthcare provider or dermatologist. Outlook and Prognosis Positive Prognosis: Most cases of squamous cell carcinoma have a favorable outlook and high survival rates, especially with early diagnosis and treatment. Prevention of Recurrence: Regular follow-up appointments with your healthcare provider are crucial to monitor for any signs of recurrence. Additionally, practicing sun protection measures can help prevent future occurrences. When to Seek Medical Attention Any concerning changes in your skin, including new lumps, moles, or non-healing sores, warrant a visit to your healthcare provider. Schedule annual skin check appointments with your dermatologist to monitor for any suspicious changes. Report any side effects or complications from treatment, such as pain, bleeding, or itching, to your healthcare provider promptly. Sources Skin Cancer Foundation Mayo Clinic Cleveland Clinic MD Anderson Cancer Center Dana-Farber Cancer Institute American Cancer Society Asian Pacific Journal of Cancer Prevention Penn Medicine Abramson Cancer Center Memorial Sloan Kettering Cancer Center Duke University Medicine National Cancer Institute. Johns Hopkins Medicine. 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