The incidence of skin cancer is very low in our country, but it is one of the common malignant tumors among Caucasians, exceeding the sum of all other malignant tumors. In the southern regions of Australia, the incidence of skin cancer reaches at least 650 per 100,000, while among Caucasians in the United States, the incidence is as high as 165 per 100,000—100 times higher than in our country. Among skin cancers, basal cell carcinoma is the most common, accounting for over 60%. The early manifestations of various types of skin cancer often appear as erythematous skin lesions accompanied by scaly desquamation or crust formation. Visual inspection alone is not only insufficient to distinguish histological types but also easily confused with benign skin conditions such as psoriasis or eczema. Pathological examination is often required for a definitive diagnosis. Whether treated with surgery, radiotherapy, or other methods, skin cancer has a very high cure rate, exceeding 90%.

bubble_chart Etiology

Common causes of the disease include: ①Daily exposure to ultraviolet (UV) radiation: There is sufficient evidence supporting that UV radiation, combined with the interaction of melanin protection and immune system function, leads to the development of skin cancer. Measurements of human skin under sunlight show that the areas receiving the highest UV exposure are the head, face, back of the neck, and hands, and squamous cell carcinoma almost exclusively occurs in these regions. The carcinogenic mechanism of UV radiation may involve photochemical alterations to cellular DNA structure, simultaneous damage to the surface antigen structure of lymphocytes, and a reduction in immune function, collectively contributing to skin cancer development under the influence of other promoting factors. ②Chemical carcinogens: Approximately 100 years after Percivall first described scrotal skin cancer in chimney sweeps, it was discovered that workers frequently exposed to arsenic compounds, tar, and asphalt were prone to developing skin cancer. Chemical carcinogenesis can be divided into two stages: initiation and promotion. The initiation stage is closely linked to exposure to specific substances or carcinogens, resulting in irreversible cellular changes related to genetics. The promotion stage requires repeated exposure to the agent and is time-dependent; prolonged absence of exposure may reverse the process, preventing cancer formation. The interval between initiation and promotion is critical, determining whether skin cancer develops or not. ③Ionizing radiation: In the past, skin cancer often arose from radiation-induced xerosis in radiology workers due to inadequate protective measures. However, with advancements in radiological equipment and techniques, particularly enhanced safety protocols, occupational skin cancer has largely disappeared. Nonetheless, cases of skin cancer developing years later within radiation fields can still occur in some patients who underwent radiotherapy. ④Chronic irritation and inflammation: Malignant skin tumors may develop and progress in areas of chronic ulceration, scar formation, fistulas, or sinuses. In certain Asian populations, habits such as chewing tobacco or betel nuts increase the risk of squamous cell carcinoma in the oral or lip regions. ⑤Other factors: During immunosuppression, when immune system function is compromised, skin cancer may develop. For example, the use of immunosuppressive drugs can facilitate its occurrence. Viral carcinogens—many viruses can induce cancer in animal hosts, and certain subtypes of human papillomavirus (HPV) are known to trigger skin cancer in humans.

(1) Basal cell carcinoma 80% of skin cancers are basal cell carcinomas. With early diagnosis and appropriate treatment, it can be completely cured. According to its histological morphology, it can be divided into the following three types: ① Subepidermal basal cell carcinoma: The surface skin may be intact or accompanied by an ulcer. There is a cystic cavity formed in the center of the cancer nest, and the cancer cells around the cystic cavity often undergo vacuolar degeneration. The cancer cells may exhibit tubular or glandular structures, arranged in cords, networks, or islands. ② Superficial ulcerative basal cell carcinoma: Often multiple, the cancer nests appear as solid masses, nests, or cords, infiltrating from the basal layer into the deeper layers. ③ Basal squamous cell carcinoma: The tumor consists of two components, namely squamous cell carcinoma nests and keratin pearls within the basal cell carcinoma.

(2) Squamous cell carcinoma 20% of skin cancers are squamous cell carcinomas. Early treatment can lead to a cure, but the risk of outward spread is considerable. In the United States, the majority of deaths from skin cancer each year are due to squamous cell carcinoma. This cancer, when located on the trunk, also has a high tendency to metastasize. The cancer cells exhibit papillary, nest-like, cord-like, or glandular structures and can infiltrate into the deep dermis or subcutaneous tissue. Based on the degree of differentiation of the cancer cells, it is divided into four grades. Grade I: Differentiated mature squamous cells with intercellular bridges and cancer pearls. Cancer pearls, as characteristic structures of squamous cell carcinoma, are composed of concentrically arranged keratinized cancer cells. Grade II: The main component is prickle cells, with obvious atypia, including enlarged cell volume, uneven nuclear size, varying staining intensity, frequent mitotic figures, rare cancer pearls, and parakeratosis in their centers. Grade III: Poor cell differentiation, with most cells in the epidermal layer arranged disorderly and enlarged in volume. The nuclei are large and markedly atypical, with frequent mitotic figures, no cancer pearls, but individual cells showing dyskeratosis. Grade IV: Undifferentiated type, with no prickle cells, intercellular bridges, or cancer pearls. The cancer cells are small and spindle-shaped, with elongated and deeply stained nuclei, accompanied by necrosis and pseudoglandular structures.

1. Profuse sweating adenocarcinoma: Biopsy tissue images show skin appendage adenocarcinomas with varying degrees of differentiation. Well-differentiated types have well-developed profuse sweating gland structures, with apocrine secretion present and positive periodic acid staining. Profuse sweating adenocarcinoma can locally infiltrate and metastasize to regional lymph nodes, and sometimes patients may die from widespread tumor dissemination.

2. Eccrine carcinoma: Different histological images classify eccrine carcinoma into: eccrine porocarcinoma; tubular eccrine carcinoma; mucinous eccrine carcinoma; clear cell carcinoma; microcystic adnexal carcinoma.

3. Sebaceous gland carcinoma: Sebaceous gland carcinoma is uncommon, accounting for only 0.2% to 4.6% of all skin tumors. Histological images show some well-differentiated sebaceous gland cells forming many irregular lobules, mixed with dark-stained, polymorphic nuclei atypical sebaceous gland cells.

4. Cutaneous carcinoma in situ: The cancerous lesion is confined to the epidermal layer, with the basement membrane intact. The entire epidermal layer is thickened, containing disorderly arranged atypical cells with unclear layers, hyperkeratosis, and parakeratosis on the surface. The prickle cell layer is significantly thickened. The cells throughout the layer are enlarged and atypical, with nuclei varying in size and shape, and uneven staining intensity.

5. Extramammary Paget's disease: Large, round or oval cells with abundant and clear cytoplasm, and large, deeply stained nuclei can be seen within the epidermis. These are called Paget cells, which may be scattered or aggregated into nests, occasionally arranged in glandular structures, but all are limited below the basal layer.

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The diagnosis relies on biopsy, but requires sufficient experience from the diagnostician to identify lesions suspected of malignancy. The following conditions are highly suspicious of early malignant sexually transmitted disease changes: ① Ulcers that persist, recur intermittently, or exhibit slight bleeding. ② Solar keratosis showing bleeding, ulceration, or asymmetric nodular protrusions. ③ Previously irradiated skin, old scars, or sinuses developing ulcers or nodular protrusions. ④ Persistent red skin scars displaying grade I erosion should raise suspicion of carcinoma in situ.

For smaller lesions, excision biopsy is often performed, achieving both diagnosis and treatment in one procedure. For larger lesions, especially those requiring excision of 2–3 mm of normal skin beyond the lesion margin to meet therapeutic standards, the resulting defect may be too large and cause cosmetic issues. In such cases, punch or incisional biopsy is preferred, ensuring the sample includes the proximal edge of the lesion.

bubble_chart Treatment Measures

(I) Key Points in Treatment The appropriate treatment method is not only based on the histological type of skin cancer but also considers the anatomical location, patient age, gender, and general health status. For anatomical locations, attention should be paid to whether certain areas are prone to recurrence after surgery or whether certain areas can achieve the expected results of the treatment plan. For example, areas around the eyes, nose, and ears have high recurrence rates, so therapies with higher cure rates must be selected. Before performing surgical excision, the cosmetic appearance of the wound at the anatomical site and the skin function after excision should be considered. For prominent facial areas such as the nose, lips, cheeks, forehead, and helix, postoperative healing and scar contraction may be unacceptable. Preparations such as flaps or skin grafts should be made for prominent facial areas and functional injury sites.

The patient's general health condition should be comprehensively evaluated. For example, in cases of coagulation disorders or anticoagulant therapy, non-bleeding treatment methods such as cryotherapy, CO2 laser, or radiotherapy must be used. Elderly and frail patients or female patients may not tolerate prolonged radiotherapy, and alternatives such as curettage and electrodessication or complete surgical excision may be considered.

(II) Drug Treatment

1. Local Treatment: Mainly involves topical application, local dressing, and local injection. In earlier years, 0.5% colchicine ointment was used for topical application on tumors with good results. In recent years, 5-Fu ointment and bleomycin ointment have also achieved favorable outcomes.

(1) Bleomycin: Typically, 0.1% or 2% ointment is applied once or twice daily, generally without side effects. The ointment can be stored at room temperature for 6 months without losing potency.

(2) Fluorouracil: Clinically, 0.5% ointment is usually applied once or twice daily, showing excellent efficacy for superficial basal cell carcinoma and squamous cell carcinoma in situ.

2. Systemic Treatment

(1) Indications: Systemic chemotherapy is required for squamous cell carcinoma arising from pre-existing scars, squamous cell carcinoma at the skin-mucous membrane junction, immunocompromised patients, and cases with regional lymph node or distant metastases.

(2) BLM is more effective for proliferative-type squamous cell carcinoma. The administration method is 10mg intramuscular or intravenous injection twice weekly, with a total course of 300–400mg.

(3) PEP (Peplomycin): Not only effective against primary lesions but also achieves a response rate of about 30% in cases with lymph node metastases. Dosage: 5mg per dose, intramuscular injection six times weekly, with a one-day break, repeated 5–7 times.

(4) Combined use of DDP and ADM: The chemotherapy regimen involves intravenous infusion of DDP 75mg/m2 with hydration (large-volume fluid infusion and diuretics), followed by ADM 50mg diluted in 40ml of water for injection, administered over 5 minutes. With a 3-week interval, all patients received sufficient chemotherapy, achieving a remission rate of 87%.

(3) Curettage Treatment Dermatologists commonly use curettage and electrodessication to treat basal cell carcinoma and superficial squamous cell carcinoma. The procedure involves identifying the boundary between the tumor and the surrounding normal skin and using a curette to scrape it away. Before the procedure, ensure the curette size is appropriate—generally slightly larger than the neoplasm. During the operation, apply slight downward pressure to prevent slippage. After routine disinfection, inject a 1% procaine or lidocaine solution into the base of the basal cell carcinoma or squamous cell carcinoma to create noticeable elevation. Select a suitable curette, typically 3–4 mm in size, to excavate the lesion. Then, use a smaller curette (1–2 mm in diameter) with sharper edges to scrape the tumor bed’s periphery and base, removing any residual cancer extending into the surrounding normal tissue. Sometimes, the firmness of normal dermal tissue produces a faint gritty sound during scraping, whereas tumor tissue, being friable, is silent. After scraping, use an electrocautery device to burn the tumor bed’s periphery and base, followed by curettage to remove the charred tissue. Apply antibiotic ointment to the wound. The advantage is achieving a smooth, aesthetically pleasing wound with minimal pigmentation. The drawback is the lack of pathological examination of the margins, making it impossible to determine if residual cancer remains. Therefore, this method should be used cautiously.

(4) Chemosurgery This method was pioneered by the American physician Mohs. After fixing the cancerous tissue with zinc chloride paste, it is horizontally excised and sent for pathological examination until the basal margins are free of cancer. However, the step of fixing the tissue with zinc chloride paste is now omitted, and fresh tissue is directly excised horizontally and continuously sent for pathological examination until the basal margins are cancer-free. This method is suitable for cases with large lesions, unclear boundaries, or recurrence after treatment.

(5) Cryotherapy Cryotherapy is suitable for skin cancers that are candidates for curettage, especially those with abundant fibrous components that make curettage difficult. It is also more suitable for cases that have recurred after curettage and radiation therapy. However, the lesions must be limited to the skin; those invading other tissues or organs are not suitable for cryotherapy. A biopsy must be performed before treatment, as no specimen is available for pathological examination after cryotherapy. The surgeon marks the tumor boundaries and treats the lesion along with 2–5 mm of surrounding normal tissue. A temperature of −20°C is optimal for ensuring tumor cell death. Thawing then begins, with slow thawing being more effective at killing tumor cells than rapid thawing. Rapid thawing is only used to prevent injury to more normal tissue.

The advantage of cryotherapy is that it results in more cosmetically appealing wounds compared to curettage, with a cure rate of 95–97%. For lesions on the eyelids, this method can still be applied as long as the eyeball is protected with a warm covering. However, the recurrence rate for scalp cancers treated with this method is high, so it is generally considered unsuitable.

(6) Radiation Therapy Both basal cell carcinoma and squamous cell carcinoma are highly sensitive to radiation therapy, yielding excellent results. Before deciding on radiotherapy, factors such as the patient's age, gender, tumor disease history, anatomical location, cure and recurrence rates, and the final cosmetic outcome must be considered.

1. Advantages of Radiation Therapy: ① Preserves tissue not involved by the tumor. ② Causes minimal injury. ③ Leaves no scars and does not alter body shape. ④ Does not form hypertrophic scars, keloids, or skin contractures. ⑤ Painless during treatment. ⑥ Minimal psychological trauma for the patient. ⑦ No hospitalization required.

2. Disadvantages of Radiation Therapy: ① Hair in the treated area may fall out and regrow poorly. ② Sweat glands in the treatment area lose function. ③ Skin atrophy, telangiectasia, depigmentation or hyperpigmentation, dryness, or keratosis may occur. ④ No tissue is available for pathological examination, and the exact tumor boundaries cannot be controlled.

(7) Laser Therapy Various lasers are commonly used in dermatology, such as carbon dioxide lasers and helium-neon lasers, each with different applications. For treating skin cancer, the carbon dioxide laser is primarily used, as it can replace electrodessication. The carbon dioxide laser emits a divergent infrared beam with a wavelength of 10,600 nm. When the beam is focused, it can vaporize skin tumors, such as basal cell carcinoma and superficial squamous cell carcinoma, causing the tumors to disappear. It can also be combined with curettage.

(8) Surgical Treatment Surgery remains one of the main methods for treating skin cancer. The extent of resection varies with the size and depth of tumor infiltration. For small, superficial, and well-defined basal cell carcinomas, a 0.5 cm margin around the tumor is usually sufficient for cure. For larger or more infiltrative lesions, a 3–5 cm margin around the primary lesion is recommended, and frozen section examination should be performed in well-equipped hospitals. The local recurrence rate for basal cell carcinoma with negative margins is 1–5%. The depth of resection depends on the tumor's infiltration; for example, superficial basal cell carcinoma on the scalp may require wide excision followed by skin grafting. If the bone membrane is involved, it should be excised along with the tumor, followed by pedicle flap transplantation and skin grafting. The resection range for squamous cell carcinoma is similar to that for basal cell carcinoma, but cases with regional lymph node metastasis require lymph node dissection.

(IX) Immunotherapy Research on the application of interferon in skin cancer treatment suggests it may become an effective future therapy. Local injection of γ₂-interferon into basal cell carcinoma tumors can provide short-term remission.