What is the updated protocol for diagnosis and management of basal cell carcinoma?

Updated Protocol for Diagnosis and Management of Basal Cell Carcinoma

Risk Stratification Framework

The National Comprehensive Cancer Network (NCCN) stratification system should be used to classify all BCCs as either low-risk or high-risk, as this directly determines treatment approach. 1

High-Risk Features (any one qualifies as high-risk):

• Location in Area H (central face, eyelids, eyebrows, periorbital skin, nose, lips, chin, mandible, preauricular/postauricular skin, temple, ear, genitalia, hands, feet) - regardless of size 1
• Tumor ≥20 mm in Area L (trunk/extremities) or ≥10 mm in Area M (cheeks, forehead, scalp, neck) 1
• Poorly defined clinical borders 1
• Recurrent tumor 1
• Aggressive histologic subtypes: infiltrative, morpheaform, basosquamous, sclerosing, micronodular 1, 2
• Perineural invasion 1
• Immunosuppression or prior radiation therapy site 1

Low-Risk Features:

• Nodular or superficial histologic pattern 1
• Well-defined borders 1
• Primary tumor 1
• Area L <20 mm or Area M <10 mm 1

Diagnostic Protocol

Biopsy Technique Selection

Punch biopsy or deep shave biopsy extending into the reticular dermis are the recommended techniques, with the critical requirement being adequate depth to detect infiltrative components. 1, 2, 3

Key technical requirements:

• Biopsy must extend deep into the reticular dermis, as aggressive subtypes may only be present at deeper advancing margins 2, 3
• Superficial tangential shaves are inadequate and lead to underestimation of risk 3
• Deep shave (saucerization) technique must penetrate deep into dermis 3
• Punch biopsy provides full-thickness tissue through dermis into subcutaneous fat 3

When to obtain multiple or repeat biopsies:

• Suspected recurrent tumor, deep invasion, or aggressive features warrant multiple scouting biopsies or more extensive tissue resection 1, 2
• Repeat biopsy if initial specimen shows tumor transection at the base 1, 3
• Repeat biopsy if clinical suspicion suggests aggressive features but histology shows only superficial/nodular subtype 3

Essential Clinical Information for Pathology Requisition

The following must be provided to the pathologist 1, 3:

• Patient age and biological sex 1
• Precise anatomic location 1, 3
• Primary versus recurrent lesion 1, 3
• Clinical size of lesion 1, 3
• History of immunosuppression 1, 3
• History of prior radiation therapy 1, 3

Required Pathology Report Elements

The pathology report should include 1:

• Specific histologic subtype(s) detected 1
• Invasion beyond reticular dermis 1
• Perineural invasion 1
• Notation if deeper invasion cannot be ruled out due to tumor transection 1

Treatment Protocol

Low-Risk BCC

Surgical excision with 4-mm clinical margins and histologic margin assessment is the recommended treatment for low-risk primary BCC. 1

Alternative options for appropriately selected low-risk superficial BCC:

• Curettage and electrodesiccation (C&E) for low-risk tumors in non-terminal hair-bearing locations, with 5-year cure rates of 91-97% 1, 4
• Topical 5% imiquimod for superficial BCC 5
• Topical 5% fluorouracil for superficial BCC 6, 5
• Photodynamic therapy for superficial BCC and thin nodular BCC 5, 7
• Cryotherapy for appropriately selected low-risk lesions 7

High-Risk BCC

Mohs micrographic surgery is the treatment of choice for high-risk BCC, achieving 5-year disease-free rates exceeding 98%. 1, 2, 4

Specific indications for Mohs surgery:

• All infiltrative, morpheaform, sclerosing, or micronodular subtypes 2
• Location in Area H (high-risk anatomic sites) 1, 2
• Recurrent tumors 2
• Tumors with poorly defined clinical margins 1
• Tumors with perineural invasion 1

Standard excision may be considered for select high-risk tumors, but strong caution is advised when selecting treatment without complete margin assessment. 1 The multicenter RCT comparing Mohs with standard excision showed recurrence rates of 3% at 2.5 years increasing to 12.2% at 10 years following standard excision, with 56% of recurrences identified beyond 5 years. 1

Locally Advanced or Metastatic BCC

Hedgehog pathway inhibitors (vismodegib or sonidegib) should be offered to patients with locally advanced BCC that has recurred following surgery or who are not candidates for surgery and radiation, and for metastatic BCC. 8, 5

Vismodegib dosing: 150 mg orally once daily until disease progression or unacceptable toxicity 8

Critical safety considerations for vismodegib:

• Verify pregnancy status within 7 days prior to initiating therapy 8
• Females of reproductive potential must use effective contraception during therapy and for 24 months after final dose 8
• Males must use condoms during therapy and for 3 months after final dose 8
• Can cause embryo-fetal death or severe birth defects 8
• Withhold for up to 8 weeks for intolerable adverse reactions 8

Radiation therapy may be considered when surgery is contraindicated or refused, particularly in elderly patients, though recurrence rates are higher than surgical excision 2, 5

Post-Treatment Surveillance

Patients who develop one BCC are at significantly increased risk of developing subsequent BCCs at other sites, necessitating long-term full-body skin surveillance. 2, 4

Follow-up intensity considerations:

• Long-term follow-up is particularly important for high-risk BCC subtypes, high-risk anatomic sites, multiple BCCs, and patients with nevoid basal cell carcinoma syndrome 5
• Recurrences are frequently diagnosed beyond 5 years following definitive treatment due to slow growth rate 1
• Recurrent lesions carry higher risk of further recurrence and should be managed with Mohs surgery 2

Critical Pitfalls to Avoid

• Never perform superficial tangential shave biopsy - this misses aggressive subtypes at deeper margins 3
• Never treat high-risk BCC without complete margin assessment - incomplete excision leads to high recurrence rates 1
• Never underestimate subclinical extension of infiltrative BCC - lesions appear deceptively small clinically while harboring extensive finger-like outgrowths 2
• Basosquamous carcinomas must be managed as squamous cell carcinomas due to higher metastatic potential 4