What are the key differences between basal cell carcinoma and squamous cell carcinoma?

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Last updated: June 26, 2025View editorial policy

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From the Guidelines

Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are two distinct types of skin cancer with several key differences, primarily in their origin, growth rate, metastatic potential, and associated risk factors, as noted in studies such as 1.

Key Differences

  • BCC originates from the basal cells in the lower epidermis, typically appearing as a pearly, translucent nodule or a flat, scaly patch, often with rolled borders and visible blood vessels, and grows slowly with rare metastasis, as discussed in 1 and 1.
  • SCC, on the other hand, develops from squamous cells in the upper epidermis, presenting as a firm, red nodule or a scaly, crusted patch that may ulcerate, with a higher risk of metastasis, especially when occurring on the lips, ears, or in immunocompromised patients, as highlighted in 1 and 1.

Risk Factors and Causes

  • Both cancers are primarily caused by cumulative UV exposure, but SCC is also associated with chronic inflammation, radiation exposure, and human papillomavirus infection, as mentioned in 1 and 1.

Treatment Approaches

  • Treatment approaches differ based on cancer type, size, location, and patient factors, with options including surgical excision, Mohs surgery, radiation therapy, topical medications, and photodynamic therapy, as outlined in 1.
  • Early detection and treatment of both types are crucial for optimal outcomes, emphasizing the importance of skin cancer preventive education and regular skin examinations, as promoted in 1 and 1.

Clinical Presentation and Workup

  • The workup of both basal and squamous cell cancers begins with a history and physical examination, followed by a skin biopsy, which should include deep reticular dermis if the lesion is suspected to be more than a superficial process, as detailed in 1.
  • Imaging studies can be performed in all patients as clinically indicated for extensive disease, and fine-needle aspiration (FNA) for diagnosis should be considered in patients with squamous cell cancer and palpable regional lymph nodes, as suggested in 1.

From the Research

Key Differences Between Basal Cell Carcinoma and Squamous Cell Carcinoma

  • Basal cell carcinoma (BCC) is the most common form of skin cancer, with surgical therapies such as curettage and electrodesiccation (E and C) and surgical excision being the most commonly utilized treatments 2.
  • Squamous cell carcinoma (SCC) is another type of skin cancer, with topical imiquimod therapy being a potential treatment option for patients who are not candidates for surgical excision 3.
  • A limited immunohistochemical panel can be used to distinguish BCC from basaloid squamous cell carcinoma (bSCC), with markers such as epithelial membrane antigen (EMA), SOX2, and p16 being useful in this regard 4.
  • Basosquamous carcinoma is a rare, aggressive non-melanoma skin cancer with features that lie between those of BCC and SCC, and its diagnosis and management can be challenging 5.
  • Immunohistochemical stains such as Ber-EP4 and MOC-31 can be used to aid in the differential diagnosis between BCC and basaloid SCC, with MOC-31 being a useful marker in this regard 6.

Histologic and Immunohistochemical Characteristics

  • BCC is typically characterized by strong and diffuse staining for Ber-EP4 and MOC-31, while basaloid SCC tends to be only sporadically reactive for these markers 6.
  • EMA is positive in all bSCCs and negative in all BCCs, while SOX2 is positive in all bSCCs and in only a subset of BCCs 4.
  • p16 is positive in most bSCCs and negative in all BCCs, making it a useful marker in the differential diagnosis between these two tumors 4.

Treatment Options

  • Surgical excision remains the mainstay of therapy for low-risk non-melanoma skin cancers, including BCC and SCC 3.
  • Topical imiquimod therapy may be a useful treatment option for patients who are not candidates for surgical excision, particularly for those with superficial BCC or basaloid SCC 2, 3.
  • Mohs micrographic surgery is the gold standard for high-risk non-melanoma skin cancers, including those with aggressive histologic features or located in high-risk areas 3.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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