Stuff I Worry About: High-Risk Squamous Cell Carcinoma and High-Risk Patients

Christian Baum, MD

Professor and Vice-Chair of Dermatology, Mayo Clinic Rochester, Minnesota

December 2023

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Dr. Baum presented information about tumor- and patient-specific risk factors for cutaneous squamous cell carcinoma (cSCC).

First, Dr. Baum noted that the cSCC incidence in the US is increasing, with an estimated 180,000–520,000 new cases annually and a metastatic rate of 2–5%. Patients with bulky nodal disease have higher recurrence rates and lower overall survival rates than those with a lower burden of nodal disease. Consequently, early detection may reduce mortality.

Second, Dr. Baum described cSCC tumor characteristics and risk factors. cSCC follows a typical metastatic pattern. Most regional recurrence involves the head and neck. Disease-specific death is typically preceded by regional recurrence. Tumor-specific risk factors include tumor size >2 cm, invasion beyond the subcutaneous fat, and perineural invasion >0.1 mm. According to the Brigham and Women’s Hospital Staging System, patients with ≥2 risk factors have a 15–20% risk of nodal metastasis.

Third, Dr. Baum discussed patient-specific risk factors for cSCC, including organ transplant, hematopoietic cell transplantation (HCT), and non-Hodgkin’s lymphoma/chronic lymphocytic leukemia (NHL/CLL). Organ transplant recipients have a 65–250-fold increased risk for cSCC, and the metastatic rate is 3.5 times greater than that for the general population. Heart and lung transplant recipients have worse outcomes compared to recipients of other organs due to increased levels of immunosuppression. Dr. Baum emphasized that any painful or tender lesion in an organ transplant recipient needs to be biopsied.

Patients with NHL/CLL have an 8-fold increased risk for cSCC. The risk of nodal metastasis is higher in CLL patients with higher-stage CLL.

HCT patients have an 18-fold increased risk for cSCC. The median time to cSCC diagnosis after HCT is 2–7 years. cSCC risk factors in HCT patients include: age <55 years at transplantation, chronic graft versus host disease (GvHD), immunosuppression for >2 years, azidothymidine (AZT) immunosuppression, and total body irradiation. If a patient has had >6 tumors in a year and is on AZT for immunosuppression, Dr. Baum recommends a conversation with the transplant doctors about possible alternatives. AZT is a known carcinogen for keratinocytes. Total body irradiation before HCT leads to a 50-fold increased risk of cSCC. Patients with allogeneic transplants tend to have worse outcomes compared to those with autologous transplants.

To conclude, Dr. Baum emphasized that patients at highest risk for cSCC are those with heart and lung transplants, any organ transplant, multiple tumors in a year, CLL requiring treatment, GvHD, and AZT treatment.