Skin Cancer - Midterm Notes PDF

2 1 INTEGUMENTARY – Skin Cancer/Carcinoma Skin Cancer/Carcinoma Skin cancer is one of the most common types of cancer. It includes both melanoma and non- melanoma skin cancers (NMSC), the la:er of which inclu...

2 1 INTEGUMENTARY – Skin Cancer/Carcinoma Skin Cancer/Carcinoma Skin cancer is one of the most common types of cancer. It includes both melanoma and non- melanoma skin cancers (NMSC), the la:er of which includes basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Each type has dis=nct characteris=cs, causes, and mechanisms. 1. Most Likely Cause The most common causes of skin cancer vary depending on the type. Here are the primary causes of non-melanoma and melanoma skin cancers: Basal Cell Carcinoma (BCC): o Cause: Primarily caused by exposure to ultraviolet (UV) radiaDon from sunlight or tanning beds, which leads to muta=ons in the p53 tumor suppressor gene o GeneDc Factors: Muta=ons in genes controlling cell growth and apoptosis can predispose individuals to BCC. Squamous Cell Carcinoma (SCC): o Cause: Caused by cumula=ve UV radiaDon exposure. UV light causes muta=ons in the p53 tumor suppressor gene, which affects the skin's ability to repair DNA damage. o Chronic IrritaDon: SCC can also develop from chronic wounds, burns, or scars. Melanoma: o Cause: Caused by muta=ons in melanocytes, oNen triggered by UV radiaDon. UV-induced muta=ons in oncogenes and tumor suppressor genes (like BRAF and p53) are common. o GeneDc PredisposiDon: Family history of melanoma or muta=ons in genes such as CDKN2A increase the risk. 2. Pathophysiology The pathophysiology of skin cancer varies by type but is primarily linked to DNA damage from UV radiaDon exposure. Here is an explana=on of how each type progresses: Basal Cell Carcinoma (BCC) 1. Origin: BCC arises from basal keraDnocytes located in the basal layer of the epidermis. 2. DNA Damage: UV radia=on damages DNA, par=cularly the p53 tumor suppressor gene, leading to loss of cell cycle regula=on. 3. Tumor Development: These damaged kera=nocytes begin to proliferate uncontrollably, forming nodular or ulcerated lesions on the skin, oNen with rolled edges and a central depression. 4. Growth PaVern: BCC grows slowly, infiltra=ng local =ssues rather than spreading to distant sites (it rarely metastasizes). Squamous Cell Carcinoma (SCC) 1. Origin: SCC arises from keraDnocytes of the epidermis, typically in sun-exposed areas like the head, neck, and arms. 2. DNA Damage: UV radia=on exposure causes mutaDons in p53 and other tumor suppressor genes, impairing the skin's DNA repair capacity.  2 3. Tumor Development: The kera=nocytes undergo uncontrolled prolifera=on, leading to the development of in situ SCC (Bowen's disease). If leN untreated, it may progress to invasive SCC, where the cancer invades the dermis and nearby =ssues. 4. Growth PaVern: SCC grows faster than BCC and has a higher chance of metastasis to lymph nodes. Melanoma 1. Origin: Melanoma arises from melanocytes, the pigment-producing cells of the skin. 2. DNA Damage: UV radiaDon causes muta=ons in cri=cal genes, such as BRAF and p53, which regulate the cell cycle and apoptosis. 3. Tumor Development: Muta=ons allow melanocytes to proliferate uncontrollably, forming irregular, asymmetrical pigmented lesions (ABCDE characteris=cs: Asymmetry, Border irregularity, Color varia=on, Diameter > 6mm, Evolving). 4. Metastasis: Melanoma is highly metasta=c and can spread via lymphaDc and hematogenous routes, leading to distant metastasis in the brain, liver, and lungs. 3. Disease Transmission Transmission: o Skin cancer is not a transmissible disease. o It is caused by geneDc mutaDons, oNen triggered by UV exposure, rather than an infec=ous agent. o Certain gene=c predisposi=ons (familial melanoma) may increase the risk, but this is due to hereditary muta=ons, not transmission. 4. Risk Factors Risk factors for skin cancer can be classified as modifiable (can be changed) and non-modifiable (cannot be changed) risk factors. Modifiable Risk Factors UV RadiaDon Exposure: o The most significant risk factor for all skin cancers. UV exposure from the sun or tanning beds increases the risk. o The use of sunscreen can significantly reduce this risk. Immunosuppression: o Individuals with HIV, organ transplant recipients, or those taking immunosuppressants are at higher risk. Chronic Wounds: o Chronic, non-healing wounds or scars increase the risk of developing squamous cell carcinoma (SCC). Non-Modifiable Risk Factors Age: o The risk of skin cancer increases with age due to cumula=ve UV exposure over a life=me. Skin Type: o Fair-skinned individuals with Fitzpatrick skin types I and II are at higher risk due to less melanin protec=on from UV rays.  3 GeneDc PredisposiDon: o Family history of melanoma or mutaDons in the CDKN2A gene increase the likelihood of developing melanoma Gender: o Males have a higher incidence of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Geographical LocaDon: o Living in sunny regions with high UV index exposure increases the risk of skin cancer. Summary Table Criteria Skin Cancer/Carcinoma Most Likely UV radiaDon exposure (sun, tanning beds), gene=c muta=ons (BRAF, p53, Cause CDKN2A). DNA damage → p53/BRAF mutaDons → uncontrolled proliferaDon of Pathophysiology keraDnocytes/melanocytes → tumor growth and possible metastasis【. Not transmissible. Skin cancer results from gene=c muta=ons caused by Transmission environmental factors like UV exposure. Modifiable: UV exposure, immunosuppression, chronic wounds. Non- Risk Factors Modifiable: Age, fair skin, family history, gene=c muta=ons (CDKN2A, BRAF, p53).