Skin Cancer: Types, Causes, Symptoms, Diagnosis and Treatment — Overview, Diagnosis & Treatment Options | MyMedicPlus

Skin cancer is the most common cancer in humans, with more new diagnoses annually than all other cancers combined. In the United States alone, approximately 5.4 million cases of non-melanoma skin cancer are treated each year, and approximately 100,000 new cases of melanoma are diagnosed annually. The three major types are: basal cell carcinoma (BCC), the most common cancer of any type, accounting for approximately 75-80% of skin cancers; squamous cell carcinoma (SCC), accounting for approximately 15-20%; and melanoma, accounting for approximately 1-4% of skin cancers but responsible for the vast majority of skin cancer deaths. BCC and SCC are collectively referred to as keratinocyte carcinomas or non-melanoma skin cancers (NMSC). Merkel cell carcinoma and dermatofibrosarcoma protuberans (DFSP) are rare but clinically important additional primary skin malignancies. BCC rarely metastasizes but can be locally destructive. SCC has metastatic potential, particularly for high-risk variants. Melanoma, arising from melanocytes, is highly aggressive and responsible for approximately 8,000 deaths annually in the US despite representing only a small fraction of new cases.

Ultraviolet (UV) radiation — from both sunlight (UVA and UVB) and artificial sources such as indoor tanning beds — is the dominant causative factor for BCC, SCC, and melanoma. UV radiation causes characteristic C→T and CC→TT pyrimidine dimer mutations (UV signature mutations) in tumor suppressor genes including TP53 (SCC, BCC) and in oncogenes. UV exposure explains the anatomical distribution of skin cancers (sun-exposed areas: head, neck, hands, arms) and the markedly elevated risk in fair-skinned individuals with low melanin photoprotection. Tanning bed use increases melanoma risk by approximately 75% and increases BCC and SCC risk substantially — tanning beds are classified as Group 1 carcinogens (IARC). Other risk factors include a history of prior skin cancers or precancerous lesions (actinic keratoses for SCC), chronic immunosuppression (organ transplant recipients have approximately 100-fold increased risk of SCC), chronic wound or scar skin changes (Marjolin's ulcer for SCC), HPV infection (certain genital SCC), arsenic exposure (Bowen's disease and SCC), Gorlin syndrome (germline PTCH1 mutations, hundreds of lifetime BCCs), xeroderma pigmentosum (XP, defective nucleotide excision repair), and familial atypical mole-melanoma (FAMM) syndrome.

Basal cell carcinoma most commonly presents as a pearly, translucent, or pink papule or nodule with telangiectasias (small dilated blood vessels) on the surface — particularly on the face, ears, and neck. It may have a central depression, ulceration, or a rolled, waxy border. Pigmented BCC can be dark brown or black, mimicking melanoma. Superficial BCC appears as a flat, erythematous, scaly patch. SCC presents as a rough, thickened, or scaly papule, plaque, or nodule — often on chronically sun-damaged skin bearing actinic keratoses. It may ulcerate, bleed, or develop a hyperkeratotic crust. SCC arising in old scars, wounds, or burns can be aggressive. Melanoma characteristically presents as a new or changing pigmented lesion meeting the ABCDE criteria (Asymmetry, Border irregularity, Color variation, Diameter greater than 6 mm, Evolving). Nodular melanoma may present as a rapidly growing dark or amelanotic (non-pigmented) nodule — the most dangerous presentation because it lacks classic pigmented features. Subungual melanoma presents as dark discoloration under a nail. Desmoplastic melanoma is often amelanotic and may resemble a scar. Any skin lesion that bleeds spontaneously, fails to heal, or changes in character over weeks to months requires dermatological evaluation and biopsy.

Dermoscopy (polarized light epiluminescence microscopy) substantially improves clinical diagnostic accuracy for pigmented lesions and BCC compared to naked-eye examination alone, reducing unnecessary biopsies while increasing sensitivity for melanoma detection. Excisional biopsy (complete removal of the suspicious lesion with 1-3 mm margins) is the preferred biopsy technique for suspicious melanocytic lesions, as it provides complete histological assessment without sampling error. Shave biopsy is appropriate for typical BCC and SCC. Punch biopsy is used for flat or large lesions where complete excision is impractical. Staging of melanoma follows AJCC 8th edition TNM criteria: T (Breslow thickness in mm, presence of ulceration, mitotic rate), N (regional nodal metastasis by sentinel lymph node biopsy for T1b and above), M (distant metastasis — lung, liver, brain, bone). Sentinel lymph node biopsy (SLNB) is the standard nodal staging procedure for melanomas 0.8 mm or thicker. LDH elevation is a staging parameter (M1d) and prognostic biomarker. BRAF V600E/K mutation testing by PCR or NGS is essential for all Stage III-IV melanoma. PD-L1 IHC, NRAS, KIT, and NF1 mutations are additional molecular tests. CT/PET/CT/MRI for distant staging in advanced melanoma.

Basal cell carcinoma: Mohs micrographic surgery is the gold standard for high-risk BCC (large size, aggressive histological subtype, recurrent, immunosuppressed patient, or cosmetically critical site), achieving cure rates of approximately 98-99%. Standard excision with 4 mm margins is appropriate for low-risk BCC. Topical imiquimod or 5-fluorouracil is used for superficial BCC in low-risk locations. For locally advanced or metastatic BCC: vismodegib (Smoothened/hedgehog pathway inhibitor) or sonidegib achieve response rates of approximately 50-60%; cemiplimab is approved for BCC refractory to hedgehog inhibitors. Squamous cell carcinoma: Mohs surgery is preferred for high-risk SCC; standard excision with 4-6 mm margins for low-risk. Adjuvant radiation therapy for high-risk features (perineural invasion, lymph node involvement, positive margins). Cemiplimab is approved for locally advanced and metastatic SCC, achieving response rates of approximately 50%. Pembrolizumab is an alternative. Melanoma: wide local excision with margins based on Breslow depth (0.5 cm for in situ, 1 cm for T1-T2, 2 cm for T3-T4) is definitive surgery. SLNB for staging and nodal management. Adjuvant therapy for resected Stage IIB/IIC (pembrolizumab, significantly reduces recurrence risk) and Stage III (nivolumab, pembrolizumab, or dabrafenib+trametinib for BRAF V600E). Metastatic melanoma first-line: nivolumab plus ipilimumab (CheckMate 067: ~45% 5-year OS), pembrolizumab monotherapy (KEYNOTE-006), or relatlimab plus nivolumab (LAG-3 + PD-1 dual blockade, RELATIVITY-047). BRAF-mutated melanoma: dabrafenib plus trametinib or encorafenib plus binimetinib — response rate approximately 65-70%. Intracranial melanoma metastases: stereotactic radiosurgery for limited lesions, combined with systemic immunotherapy or targeted therapy.

Sun protection is the single most effective preventive strategy for all three major skin cancer types. Daily application of broad-spectrum SPF 30 or higher sunscreen to all sun-exposed skin, wearing UV-protective clothing and wide-brimmed hats, seeking shade during peak UV hours (10 am to 4 pm), and completely avoiding indoor tanning beds collectively reduce UV exposure and skin cancer incidence. The US Preventive Services Task Force (USPSTF) recommends counseling about sun protection behaviors for fair-skinned individuals aged 6 months to 24 years. Regular self-skin examination — monthly head-to-toe inspection for new or changing lesions using the ABCDE criteria — combined with annual full-body dermatological examination is recommended for individuals at elevated risk (personal or family history of skin cancer, many moles, fair skin, significant sun history, immunosuppression). High-risk groups such as organ transplant recipients under chronic immunosuppression require more frequent dermatological surveillance — every 6 months — given their markedly elevated SCC risk. Actinic keratoses (AK), which are precancerous SCC precursors, should be treated with cryotherapy, photodynamic therapy, or topical fluorouracil or imiquimod to prevent progression to invasive SCC. Nicotinamide (vitamin B3, 500 mg twice daily) reduced new AK and NMSC in immunocompetent high-risk patients in the ONTRAC trial.

Any skin lesion meeting one or more of the ABCDE criteria should be evaluated by a dermatologist within 4 weeks — particularly a mole or dark spot that is new, changing, growing, or bleeding. Any non-healing sore, ulcer, or crust on the skin that has been present for more than 4-6 weeks requires dermatological evaluation and biopsy to exclude SCC or BCC. A pearly, translucent, or pink bump on the face, especially near the nose, ears, or lips, should be evaluated for BCC. New dark discoloration appearing under a fingernail or toenail — particularly a broad dark band that widens over time or is associated with nail plate destruction — requires urgent biopsy by a dermatologist or surgeon to exclude subungual melanoma. Organ transplant recipients, patients on long-term immunosuppressive therapy (methotrexate, cyclosporine, biologics), and individuals with a personal history of skin cancer should see a dermatologist every 6 months for full-body skin surveillance. Any individual with a first-degree relative diagnosed with melanoma under age 50, or a family history of multiple melanomas, should undergo genetic counseling and regular dermatological surveillance.

BCC: over 98% cure rate with appropriate treatment. SCC: over 90% 5-year survival for localized disease; approximately 50% for nodal disease. Melanoma: over 99% 5-year survival for Stage I; approximately 65% for Stage III; approximately 25-30% for Stage IV (dramatically improved from historical 5-10% with modern immunotherapy). Approximately 20-30% of Stage IV melanoma patients treated with nivolumab/ipilimumab are alive at 10 years. The prognosis for Skin Cancer: Types, Causes, Symptoms, Diagnosis and Treatment varies depending on severity at diagnosis, the patient's overall health, and how promptly treatment is initiated. With early diagnosis and appropriate management, many patients achieve good outcomes and maintain quality of life. Regular follow-up with healthcare providers is essential to monitor progress, adjust treatment as needed, and detect any complications early. Adherence to prescribed treatments and lifestyle modifications significantly improves long-term prognosis.