NCCN Squamous Cell Carcinoma Guidelines

Overview / Definition Squamous cell carcinoma (SCC) is a malignant neoplasm arising from keratinocytes in the epidermis. It is characterized by uncontrolled proliferation of squamous cells and can present in various forms, including in situ and invasive disease. SCC is the second most common type of skin cancer, following basal cell carcinoma. Epidemiology SCC accounts for approximately 20-30% of non-melanoma skin cancers and has a rising incidence globally. The lifetime risk of developing SCC is approximately 11% for men and 8% for women in the United States. Key factors influencing its epidemiology include: Increased exposure to ultraviolet (UV) radiation Chronic immunosuppression (e.g., organ transplant recipients) History of actinic keratosis or prior skin cancers Human papillomavirus (HPV) infection Pathophysiology / Mechanism The development of SCC involves a complex interplay of genetic, environmental, and immunological factors. The primary mechanism is UV-induced DNA damage, leading to mutations in key genes such as TP53, CDKN2A, and HRAS. These mutations result in loss of cell cycle regulation, promoting uncontrolled cell division and tumor formation. Clinical Presentation Clinically, SCC can present in various forms: In situ SCC (Bowen's disease): Presents as a localized, erythematous, scaly plaque. Invasive SCC: May appear as a firm, raised nodule or an ulcerated lesion with a keratotic surface. Variants: Include poorly differentiated, keratoacanthoma-like, and spindle cell SCC. Common sites of occurrence include sun-exposed areas such as the face, ears, neck, and hands. Diagnosis / Workup The diagnosis of SCC is primarily made through: Clinical Examination: Assessing the lesion's characteristics and history. Biopsy: Punch, shave, or excisional biopsy to confirm the diagnosis and evaluate the depth of invasion. Imaging: Consideration of CT or MRI for high-risk lesions or suspected metastasis. Histopathological examination will reveal atypical keratinocyte