Superficially Invasive Squamous Cell Carcinoma: Aggressiveness Assessment

Definition and Classification

• The National Comprehensive Cancer Network defines Superficially Invasive Squamous Cell Carcinoma (SISCCA) as anal cancer that has been completely excised, with ≤3-mm basement membrane invasion and a maximal horizontal spread of ≤7 mm (T1, NX) 1
• SISCCA is typically found incidentally during biopsy or excision of what was thought to be a benign lesion such as a condyloma, hemorrhoid, or anal skin tag 1

Risk Assessment

Low-Risk Features of SISCCA

• Superficial invasion (≤3mm depth) is a low-risk feature of SISCCA 1
• Limited horizontal spread (≤7mm) is a low-risk feature of SISCCA 1
• Well-differentiated histology is a low-risk feature of SISCCA 2, 3
• No perineural involvement is a low-risk feature of SISCCA 4, 5

Factors That Would Increase Risk

• Perineural involvement significantly increases the risk of recurrence and metastasis in SISCCA 4, 3
• Poor differentiation is associated with worse outcomes in SISCCA 3, 5
• Desmoplastic features are associated with increased risk of recurrence and metastasis in SISCCA 3, 6
• Invasion into deep reticular dermis or subcutaneous fat increases the risk of recurrence and metastasis in SISCCA 2, 3

Management Implications

• For SISCCA with histologically negative margins in carefully selected patients, local excision alone with a structured surveillance plan may represent adequate treatment, according to the National Comprehensive Cancer Network 1
• A careful surveillance plan is necessary as observational studies have reported detection of high-grade squamous intraepithelial lesions in 74% of patients after local excision 1

Clinical Outcomes

• A retrospective study of patients with completely excised invasive anal cancer, including those meeting criteria for superficially invasive disease, showed excellent outcomes with 5-year overall survival of 100% and 5-year cancer recurrence-free survival rates of 87% 1
• The National Comprehensive Cancer Network guidelines support the classification of SISCCA as a non-aggressive variant of squamous cell carcinoma 1

Important Considerations

• Although the risk of metastasis from SISCCA is negligible, the risk of recurrence depends on the presence or absence of additional risk factors, according to the National Comprehensive Cancer Network 2, 6
• Regular follow-up is essential as these lesions can recur locally, as recommended by the National Comprehensive Cancer Network 1
• The NCCN guidelines specifically categorize superficial basal cell carcinoma as non-aggressive, and the same principle applies to superficially invasive SCC, according to the National Comprehensive Cancer Network 7, 8