Skin Cancer
Disease Details
Family Health Simplified
- Description
- Skin cancer is a disease in which malignant (cancer) cells form in the tissues of the skin.
- Type
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Skin cancer encompasses several types, including melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC).
Type of genetic transmission:
Skin cancer can result from a combination of genetic and environmental factors. While the majority of cases are sporadic and caused by UV exposure, there are hereditary syndromes like familial melanoma, which follow an autosomal dominant pattern of inheritance. These hereditary forms often involve mutations in specific genes such as CDKN2A for melanoma and PTCH1 for basal cell carcinoma in the context of basal cell nevus syndrome (Gorlin syndrome). - Signs And Symptoms
- There are a variety of different skin cancer symptoms. These include changes in the skin that do not heal, ulcering in the skin, discolored skin, and changes in existing moles, such as jagged edges to the mole, enlargement of the mole, changes in color, the way it feels or if it bleeds. Other common signs of skin cancer can be painful lesion that itches or burns and large brownish spot with darker speckles.
- Prognosis
- The mortality rate of basal-cell and squamous-cell carcinoma is around 0.3%, causing 2000 deaths per year in the US. In comparison, the mortality rate of melanoma is 15–20% and it causes 6500 deaths per year.: 29, 31 Even though it is much less common, malignant melanoma is responsible for 75% of all skin cancer-related deaths.The survival rate for people with melanoma depends upon when they start treatment. The cure rate is very high when melanoma is detected in early stages, when it can easily be removed surgically. The prognosis is less favorable if the melanoma has spread to other parts of the body. As of 2003 the overall five-year cure rate with Mohs' micrographic surgery was around 95 percent for recurrent basal cell carcinoma.Australia and New Zealand exhibit one of the highest rates of skin cancer incidence in the world, almost four times the rates registered in the United States, the UK and Canada. Around 434,000 people receive treatment for non-melanoma skin cancers and 10,300 are treated for melanoma. Melanoma is the most common type of cancer in people between 15 and 44 years in both countries. The incidence of skin cancer has been increasing. The incidence of melanoma among Auckland residents of European descent in 1995 was 77.7 cases per 100,000 people per year, and was predicted to increase in the 21st century because of "the effect of local stratospheric ozone depletion and the time lag from sun exposure to melanoma development."
- Onset
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Onset: Skin cancer can develop over several years, often appearing as a new, unusual growth or changes in an existing mole or lesion on the skin.
Nan: (Your request might not be clear; could you clarify what specific information you're seeking related to "nan"?) - Prevalence
- Prevalence of skin cancer varies globally, but it's one of the most common types of cancer. In the United States, approximately 1 in 5 people will develop skin cancer by the age of 70. Cases are more frequently diagnosed in fair-skinned populations and typically rise with increased exposure to ultraviolet (UV) radiation from the sun or tanning beds. The most common types are basal cell carcinoma, squamous cell carcinoma, and melanoma, with melanoma being the most dangerous form.
- Epidemiology
- Skin cancers result in 80,000 deaths a year as of 2010, 49,000 of which are due to melanoma and 31,000 of which are due to non-melanoma skin cancers. This is up from 51,000 in 1990.More than 3.5 million cases of skin cancer are diagnosed annually in the United States, which makes it the most common form of cancer in that country. One in five Americans will develop skin cancer at some point of their lives. The most common form of skin cancer is basal-cell carcinoma, followed by squamous cell carcinoma. Unlike for other cancers, there exists no basal and squamous cell skin cancers registry in the United States.
- Intractability
- Skin cancer is not inherently intractable. Many forms of skin cancer, particularly when detected early, can be effectively treated and managed. Treatments might include surgical removal, radiation therapy, and topical medications. However, advanced cases or aggressive forms like melanoma can be more challenging to treat. Early detection and prompt intervention are critical for a better prognosis.
- Disease Severity
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Skin cancer severity can range from mild to severe, depending on the type and stage:
1. **Basal Cell Carcinoma (BCC)**: Generally the least severe, slow-growing, and rarely metastasizes. If untreated, it can cause local tissue damage.
2. **Squamous Cell Carcinoma (SCC)**: More aggressive than BCC, can metastasize if not treated early, particularly in high-risk patients.
3. **Melanoma**: The most severe form, highly aggressive with a high potential for metastasis. Early detection and treatment are crucial for a better prognosis.
Severity is assessed based on factors like tumor size, depth of invasion, metastasis, and overall patient health. Each case requires individualized evaluation and treatment planning. - Healthcare Professionals
- Disease Ontology ID - DOID:4159
- Pathophysiology
- A malignant epithelial tumor that primarily originates in the epidermis, in squamous mucosa or in areas of squamous metaplasia is referred to as a squamous-cell carcinoma.Macroscopically, the tumor is often elevated, fungating, or may be ulcerated with irregular borders. Microscopically, tumor cells destroy the basement membrane and form sheets or compact masses which invade the subjacent connective tissue (dermis). In well differentiated carcinomas, tumor cells are pleomorphic/atypical, but resembling normal keratinocytes from prickle layer (large, polygonal, with abundant eosinophilic (pink) cytoplasm and central nucleus).Their disposal tends to be similar to that of normal epidermis: immature/basal cells at the periphery, becoming more mature to the centre of the tumor masses. Tumor cells transform into keratinized squamous cells and form round nodules with concentric, laminated layers, called "cell nests" or "epithelial/keratinous pearls". The surrounding stroma is reduced and contains inflammatory infiltrate (lymphocytes). Poorly differentiated squamous carcinomas contain more pleomorphic cells and no keratinization.A molecular factor involved in the disease process is mutation in gene PTCH1 that plays an important role in the Sonic hedgehog signaling pathway.
- Carrier Status
- Skin cancer is not typically associated with a genetic "carrier status" in the same way some other hereditary conditions are. While certain genetic mutations can increase an individual's risk for developing skin cancer (such as mutations in the CDKN2A gene for melanoma), having these mutations does not mean someone is a "carrier" in the traditional sense, as skin cancer is not a recessive genetic disorder. Instead, these genetic factors may predispose an individual to skin cancer, often in combination with environmental factors like UV exposure.
- Mechanism
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Skin cancer is primarily caused by DNA damage in skin cells, often as a result of exposure to ultraviolet (UV) radiation from the sun or tanning beds.
### Mechanism:
1. **DNA Damage**: UV radiation penetrates the skin and causes direct DNA damage.
2. **Mutation Accumulation**: DNA repair mechanisms attempt to correct the damage, but errors can occur, leading to mutations.
3. **Cellular Transformation**: These mutations can activate oncogenes or inactivate tumor suppressor genes, leading to uncontrolled cell growth.
4. **Tumor Development**: Accumulation of such cells leads to the formation of malignant tumors.
### Molecular Mechanisms:
1. **P53 Pathway**: UV radiation can result in mutations in the p53 tumor suppressor gene, which normally regulates cell cycle and apoptosis. Dysfunctional p53 can lead to unregulated cell proliferation.
2. **PTCH1 and SMO Genes**: In basal cell carcinoma, mutations in the PTCH1 gene, a part of the hedgehog signaling pathway, are common. This leads to the activation of the SMO protein and uncontrolled cell division.
3. **BRAF Mutations**: In melanoma, mutations in the BRAF gene, which encodes a serine/threonine-protein kinase involved in directing cell growth, are frequently observed. The most common mutation is V600E.
4. **NRAS Mutations**: Mutations in the NRAS gene can also contribute to melanoma by activating the MAPK/ERK signaling pathway, promoting cell proliferation and survival.
These molecular changes disrupt normal cellular regulation, leading to the development and progression of skin cancer. - Treatment
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Treatment is dependent on the specific type of cancer, location of the cancer, age of the person, and whether the cancer is primary or a recurrence. For a small basal-cell cancer in a young person, the treatment with the best cure rate (Mohs surgery or CCPDMA) might be indicated. In the case of an elderly frail man with multiple complicating medical problems, a difficult to excise basal-cell cancer of the nose might warrant radiation therapy (slightly lower cure rate) or no treatment at all. Topical chemotherapy might be indicated for large superficial basal-cell carcinoma for good cosmetic outcome, whereas it might be inadequate for invasive nodular basal-cell carcinoma or invasive squamous-cell carcinoma. In general, melanoma is poorly responsive to radiation or chemotherapy.
For low-risk disease, radiation therapy (external beam radiotherapy or brachytherapy), topical chemotherapy (imiquimod or 5-fluorouracil) and cryotherapy (freezing the cancer off) can provide adequate control of the disease; all of them, however, may have lower overall cure rates than certain type of surgery. Other modalities of treatment such as photodynamic therapy, epidermal radioisotope therapy, topical chemotherapy, electrodesiccation and curettage can be found in the discussions of basal-cell carcinoma and squamous-cell carcinoma.
Mohs' micrographic surgery (Mohs surgery) is a technique used to remove the cancer with the least amount of surrounding tissue and the edges are checked immediately to see if tumor is found. This provides the opportunity to remove the least amount of tissue and provide the best cosmetically favorable results. This is especially important for areas where excess skin is limited, such as the face. Cure rates are equivalent to wide excision. Special training is required to perform this technique. An alternative method is CCPDMA and can be performed by a pathologist not familiar with Mohs surgery.
In the case of disease that has spread (metastasized), further surgical procedures or chemotherapy may be required.Treatments for metastatic melanoma include biologic immunotherapy agents ipilimumab, pembrolizumab, nivolumab, cemiplimab; BRAF inhibitors, such as vemurafenib and dabrafenib; and a MEK inhibitor trametinib. - Compassionate Use Treatment
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Compassionate use treatment and off-label or experimental treatments for skin cancer can be important options for some patients.
1. **Compassionate Use Treatment**: This refers to the use of unapproved drugs or therapies outside of clinical trials for patients with serious or immediately life-threatening conditions who have no other treatment options. In the context of skin cancer, it could involve the use of investigational drugs that are still in the trial phase. Patients usually need to meet specific criteria and get approval from regulatory authorities, such as the FDA in the United States.
2. **Off-Label Treatments**: These are treatments that are used in a manner not specified in the FDA’s approved packaging label. For skin cancer, this could involve using drugs approved for other types of cancer or conditions. For example, certain immunotherapy or targeted therapy drugs approved for other cancers might be used off-label for advanced skin cancers.
3. **Experimental Treatments**: Experimental treatments are those that are still being studied in clinical trials and are not yet approved for general use. These might include new forms of immunotherapy, gene therapy, or novel targeted therapies specifically aimed at treating skin cancer. Participating in clinical trials can provide access to these cutting-edge treatments.
Patients interested in these options typically need to discuss them with their oncologist to weigh benefits, risks, and suitability based on their individual condition. - Lifestyle Recommendations
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For skin cancer, here are some lifestyle recommendations to help reduce the risk:
1. **Sun Protection**:
- Use broad-spectrum sunscreen with an SPF of at least 30.
- Wear protective clothing, such as long-sleeved shirts, pants, and wide-brimmed hats.
- Seek shade, especially between 10 a.m. and 4 p.m. when the sun's rays are strongest.
- Avoid tanning beds and sunlamps.
2. **Regular Skin Checks**:
- Perform monthly self-examinations to check for new or changing moles, freckles, or spots.
- Schedule annual skin exams with a dermatologist, especially if you have a family history of skin cancer or other risk factors.
3. **Healthy Diet**:
- Eat a balanced diet rich in fruits, vegetables, and omega-3 fatty acids to support overall skin health.
- Stay hydrated by drinking plenty of water.
4. **Avoid Smoking**:
- Smoking can damage your skin and increase the risk of many types of cancers, including skin cancer.
5. **Be Aware of Medications**:
- Some medications can increase your sensitivity to sunlight. Consult your doctor about any potential side effects.
6. **Educate Yourself and Others**:
- Share information about the risks of UV exposure and the importance of sun protection with friends and family.
Implementing these lifestyle changes can significantly reduce the risk of developing skin cancer. - Medication
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Skin cancer treatment typically involves various approaches depending on the type and stage of cancer. Medications can include:
1. **Topical Treatments**:
- **Imiquimod**: Stimulates the immune system to attack cancer cells.
- **Fluorouracil (5-FU)**: A topical chemotherapy cream that destroys cancerous cells.
2. **Oral Medications**:
- **Vismodegib** and **Sonidegib**: Used for advanced basal cell carcinoma.
- **BRAF inhibitors (e.g., Vemurafenib, Dabrafenib)** and **MEK inhibitors (e.g., Trametinib, Cobimetinib)**: Effective in treating metastatic melanoma with specific genetic mutations.
3. **Immunotherapy**:
- **Pembrolizumab** and **Nivolumab**: Checkpoint inhibitors used for advanced melanoma.
- **Ipilimumab**: Another checkpoint inhibitor used for metastatic melanoma.
4. **Targeted Therapy**:
- **Cetuximab**: Sometimes used for squamous cell skin cancer.
These medications are prescribed based on individual patient conditions and the specifics of their cancer type and progression. - Repurposable Drugs
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Currently, research is ongoing to identify drugs that can be repurposed for the treatment of skin cancer. Some drugs initially intended for other conditions have shown promise in this area. Examples include:
1. **Metformin**: Originally used for type 2 diabetes, it has shown potential in reducing the risk of skin cancer and slowing its progression.
2. **Aspirin**: Known for its anti-inflammatory properties, aspirin has been studied for its potential to reduce the risk of developing skin cancer.
3. **Beta-blockers**: Commonly used for hypertension and heart conditions, some studies have suggested they may have a role in inhibiting skin cancer growth.
4. **Statins**: These cholesterol-lowering drugs have been investigated for their potential to reduce the risk of skin cancers, including melanoma.
It is crucial to consult a healthcare professional for appropriate diagnosis and treatment plans, as these findings are still under investigation. - Metabolites
- Metabolites associated with skin cancer can include alterations in lipid metabolism, amino acid metabolism, and energy production pathways. Specific metabolites that have been researched include lactic acid, alanine, glutamate, and various phospholipids. Metabolomic profiling aims to identify these and other small molecules, which may serve as biomarkers for early detection, prognosis, and therapeutic targets in skin cancer treatment.
- Nutraceuticals
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Nutraceuticals refer to food-derived products that provide health benefits, including the prevention and treatment of diseases. For skin cancer, certain nutraceuticals might offer protective effects:
1. **Vitamin D**: Regulates cell growth and could aid in reducing the risk of certain skin cancers.
2. **Carotenoids**: Found in fruits and vegetables, these compounds, including beta-carotene and lycopene, have antioxidant properties that may protect skin cells from UV damage.
3. **Polyphenols**: Present in green tea and other foods, polyphenols have shown potential in protecting skin from UV radiation and reducing the risk of skin cancer.
4. **Omega-3 Fatty Acids**: These may help lower inflammation and protect against skin cancer.
Research into these nutraceuticals is ongoing, and they should be considered as complementary approaches rather than primary treatments for skin cancer. Always consult a healthcare provider before starting any new supplementation. - Peptides
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Peptides and nanotechnology are emerging areas in the research and treatment of skin cancer. Peptides can function as therapeutic agents due to their ability to interfere with protein-protein interactions specific to cancer cells. They can also serve as targeting ligands to enhance the delivery of drugs to cancer cells.
Nanotechnology offers tools for better diagnosis, imaging, and treatment of skin cancer through the use of nanoparticles. These nanoparticles can be designed to deliver drugs specifically to cancer cells, minimizing damage to healthy tissue and enhancing the efficacy of the treatment. Nanoparticles can also be used for improved imaging techniques, aiding in the early detection of skin cancers.