What are the diagnosis, differentials, and management options for skin cancers?

Skin Cancer: Diagnosis, Differentials, and Management

Diagnosis and Screening

Visual skin examination remains the primary screening method, though the USPSTF concludes evidence is insufficient to recommend routine screening in asymptomatic adults without risk factors. 1 However, this does not apply to high-risk patients who warrant regular surveillance.

Clinical Examination Techniques

• ABCDE rule for melanoma assessment: Asymmetry, Border irregularity, nonuniform Color, Diameter >6mm, and Evolution over time 1
• "Ugly duckling" sign: Identify pigmented lesions that appear different from other moles on the patient 1
• Dermatoscopy improves diagnostic accuracy beyond naked eye examination and should be used when available 2
• Biopsy of suspicious lesions is required for definitive diagnosis 1

High-Risk Populations Requiring Surveillance

• Patients with personal history of any skin cancer (BCC, SCC, or melanoma) 1, 3
• Fair skin, light-colored eyes, red/blond hair 1
• History of frequent sunburns, extensive UV exposure, or indoor tanning bed use 1
• Multiple or atypical moles 1
• Family history of skin cancer 1
• Immunosuppressed patients, including solid organ transplant recipients 1

Major Skin Cancer Types and Key Differentials

Melanoma

Melanoma accounts for only 1% of skin cancers but causes the majority of skin cancer deaths, with 5-year survival ranging from 99.5% for localized disease to 31.9% for distant-stage disease. 1

• Acral lentiginous melanoma is the most common type in Black populations, occurring on palms, soles, or under nails—areas not frequently sun-exposed 1
• Differentiate from benign nevi using ABCDE criteria and dermatoscopy 1
• Consider lentigo maligna melanoma in chronically sun-damaged skin, which carries 35% risk of another cutaneous malignancy within 5 years 3

Squamous Cell Carcinoma (SCC)

• Presents as indurated, keratinizing, or crusted tumor that may ulcerate 4
• May arise in chronic wounds, scars, burns, or pre-existing epidermoid cysts 4
• Often preceded by actinic keratoses (premalignant lesions) on sun-exposed areas 1, 5
• Mortality data for SCC may be significantly underestimated 1

Basal Cell Carcinoma (BCC)

• Most common skin neoplasm, usually easily cured with local excision 5
• Rarely metastasizes but can cause significant local destruction if untreated 5
• Patients have 40.7% 5-year and 59.6% 10-year probability of developing another non-melanoma skin cancer 3

Critical Differentials Requiring Biopsy

Any chronic lesion unresponsive to standard therapy requires biopsy to exclude malignancy, particularly with marked asymmetry, rapid growth, ulceration, or indurated irregular borders. 4

• Sebaceous carcinoma: Must be excluded in chronic unresponsive eyelid lesions, especially with conjunctival cicatricial changes 4
• Inflamed epidermoid cyst vs. abscess: Longstanding nodule with recent inflammation containing keratinous debris suggests cyst; rapid onset without pre-existing mass suggests abscess 4
• Actinic keratoses: Premalignant lesions that may progress to SCC, though inadequate evidence exists that treating all AKs prevents invasive SCC 1

Management Strategies

Melanoma Treatment

Surgical excision of the primary tumor with appropriate margins plus sentinel lymph node biopsy for staging is the standard approach. 1

• Immunotherapy and targeted therapy for advanced melanoma 1
• Nivolumab (anti-PD-1 immunotherapy) is FDA-approved for unresectable or metastatic melanoma and adjuvant treatment 6

Squamous Cell Carcinoma Treatment

Surgical excision offers the best long-term cure rates and should be first-line for most SCCs. 1

• Mohs micrographic surgery for high-risk lesions (recurrent, poorly defined borders, high-risk anatomic sites) 1
• Radiotherapy provides comparable cure rates and may give superior cosmetic/functional results for lesions on lip, nasal vestibule, nose, and ear 1
• Cryosurgery only for small, histologically confirmed SCC in experienced hands; not appropriate for recurrent disease 1
• Electrodesiccation and curettage for selected low-risk lesions 1

Basal Cell Carcinoma Treatment

• Surgical excision remains standard 5
• Mohs micrographic surgery for high-risk or cosmetically sensitive areas 1
• Radiation therapy, electrodesiccation and curettage, or photodynamic therapy for selected cases 1

Actinic Keratoses Management

Treatment decisions should be individualized based on lesion characteristics, patient risk factors, symptoms, and preferences—observation without treatment is acceptable for many patients. 1

• Lesion-directed treatments: Cryotherapy, curettage and cautery for individual lesions 1
• Field-directed treatments: Topical therapies (5-fluorouracil), chemical peels, or photodynamic therapy (PDT) for multiple lesions or field cancerization 1, 5
• Patients with ≥10 AKs have threefold higher risk of SCC and warrant more aggressive treatment and shorter follow-up intervals 1

High-Risk SCC Requiring Multidisciplinary Care

Patients with high-risk SCC or clinically involved lymph nodes should be reviewed by a multiprofessional oncology team including dermatologist, pathologist, trained surgeon, clinical oncologist, and oncology nurses. 1

• High-risk features: Depth >6mm (lip) or >8mm (cutaneous), poorly differentiated, perineural invasion, recurrent disease 1
• Elective prophylactic lymph node dissection is not routinely recommended due to lack of compelling evidence of benefit over morbidity 1

Follow-Up Protocols

Post-BCC Follow-Up

Annual skin cancer screening for all BCC patients, with examinations every 6-12 months during the first 2 years when recurrence risk is highest. 3

• Counsel on skin self-examination and sun protection strategies 3
• BCC patients have increased melanoma risk (RR 1.99 for men, 2.58 for women) 3

Post-SCC Follow-Up

Patients with high-risk SCC should be observed for 5 years, as 95% of local recurrences and metastases occur within this timeframe. 1

• At least annual full-body skin examination, adjusting frequency based on individual risk 1
• Clinical assessment of regional lymph node basins for high-risk lesions 1
• Patient self-examination instruction is essential 1

Post-Melanoma Follow-Up

Clinical examinations every 3 months during first 3 years, then every 6-12 months thereafter. 3

• Imaging not necessary for thin primary melanomas 3
• Consider ultrasound of lymph nodes, CT, or PET/PET-CT for high-risk patients (thick tumors, post-metastasis treatment) 3
• Teach lifelong regular self-examination of skin and peripheral lymph nodes 3

Prevention Strategies

Sun Protection Recommendations

All patients should minimize sun exposure during peak UV hours (10 AM-4 PM), seek shade, wear protective clothing with wide-brimmed hats, use sunglasses blocking 99% UV-A/UV-B, and apply broad-spectrum sunscreen SPF >15. 7

• Completely avoid sunlamps and tanning beds, which are classified as carcinogenic 7
• Sunscreen should be used in combination with other protective measures, not as sole protection 7
• Sun protection is necessary even on cloudy days 7

Chemoprevention

Oral nicotinamide shows early evidence for reducing SCC risk in patients with history of keratinocyte carcinoma, though more study is needed. 1

• Topical and oral retinoids are NOT recommended for reducing skin cancer risk in non-transplant patients 1, 7
• Acitretin may have a role in solid organ transplant recipients with ≥10 keratotic lesions 1
• Dietary supplements (selenium, β-carotene) are not recommended 7

Common Pitfalls to Avoid

• Missing sebaceous carcinoma in chronic unresponsive eyelid lesions—always biopsy unilateral unresponsive lesions 4
• Misdiagnosing inflamed epidermoid cyst as simple abscess leads to inappropriate antibiotic use without addressing cyst wall, resulting in recurrence 4
• Inconsistent follow-up during first 1-2 years when recurrence risk is highest 3
• Relying solely on sunscreen without implementing other protective measures 7
• Using cryotherapy for SCC without prior biopsy confirmation or in recurrent disease 1
• Failing to educate patients about self-examination techniques 3