Random Dermatology MCQ - SCC

A 72-year-old female, who is 5 years post-renal transplant and on long-term immunosuppression, presents with a rapidly growing, hyperkeratotic, ulcerated plaque on her dorsal hand. A biopsy confirms a poorly differentiated invasive squamous cell carcinoma. Which of the following factors in this patient's presentation is the MOST significant independent risk factor for the development of aggressive, high-risk squamous cell carcinoma?

A) Location on the dorsal hand
B) Poor histological differentiation
C) Chronic immunosuppressive therapy
D) Patient's age and sex
E) Presence of ulceration

Correct Answer: C) Chronic immunosuppressive therapy

Explanation

This patient is a solid organ transplant recipient (OTR), which is one of the single most important risk factors for developing aggressive and potentially lethal cutaneous squamous cell carcinomas (SCC).

Key High-Risk Factor: Immunosuppression

• Mechanism: Iatrogenic immunosuppression (e.g., with azathioprine, cyclosporine, tacrolimus) to prevent graft rejection leads to decreased immune surveillance for neoplastic cells and oncogenic viruses like HPV.

• Impact: OTRs have a 65- to 250-fold increased risk of developing SCC compared to the general population. Their SCCs are notably more aggressive, with a higher risk of:

  • Local recurrence

  • Regional and distant metastasis

  • Disease-specific mortality

The other options, while relevant, are secondary to the overarching risk imposed by her immunosuppressed status:

• (A) Location on the dorsal hand: The dorsal hand is a sun-exposed site and does carry an increased risk, but this risk is dramatically amplified in an immunosuppressed host. In an immunocompetent patient, this would be a moderate-risk location.

• (B) Poor histological differentiation: This is a confirmed high-risk feature in any patient, but the aggressiveness of SCC in OTRs often occurs even with well-differentiated tumors. The immunosuppression is the primary driver.

• (D) Patient's age and sex: While age is a risk factor for skin cancer in general, it is not as significant as immunosuppression. Sex is not a major independent risk factor for SCC aggressiveness.

• (E) Presence of ulceration: Ulceration can be a sign of rapid growth and is a clinical feature of concern, but it is a consequence of the tumor's behavior. The root cause of the aggressive behavior in this case is the immunosuppression.

Management Implications:

• OTRs require lifelong, intensive dermatologic surveillance (e.g., every 3-6 months).

• Treatment often requires aggressive surgical management (e.g., Mohs surgery).

• Reduction of immunosuppression (if medically feasible) is a key part of the treatment strategy.

• Adjunctive therapies like oral retinoids (e.g., acitretin) may be used for chemoprevention.

This factor is so critical that dermatologic care is a standard part of post-transplant management protocols.