Factors associated with an increased risk of developing squamous cell carcinoma (SCC) of the skin following diagnosis of chronic lymphocytic leukemia (CLL) included prior history of SCC of the skin, aggressive CLL at diagnosis, and treatment with T-cell immunosuppressive therapy, according to findings of a study published in the Journal of the American Academy of Dermatology.

Although findings from previously conducted studies have shown an association between CLL and the development of basal cell carcinoma and squamous cell carcinoma (SCC) of the skin, as well as more aggressive SCC in individuals with CLL compared with those without CLL, the etiology of this increased risk has not been well established.

This analysis included 1269 adult patients with newly diagnosed CLL and no prior history of lymphoma included in the Mayo Clinic CLL Resource database between 2002 and 2015.

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At diagnosis, the median patient age was 63 years, and all patients were White. Only 6% had Rai Stage III/IV disease, and according to the CLL-International Prognostic Index (IPI), 34%, 44%, 18%, and 4% had low-, intermediate-, high-, and very high-risk disease, respectively. Thirteen percent (13%) and 4.8% of patients had a prior history of nonmelanoma skin cancer and SCC, respectively.

Of the 545 patients with available genetic data, the median SCC-polygenetic risk score (SCC-PRS), which corresponds to a weighted average number of genes associated with SCC, was 1.47.

At a median follow-up of 7 years, 124 patients were diagnosed with least 1 SCC after CLL diagnosis, corresponding to an incidence rate at 5 years for development of SCC following CLL diagnosis of 8.7%.

Univariate analyses showed increasing 10-year age group (hazard ratio [HR], 1.62;

95% CI, 1.36-1.92), male sex (HR, 1.67; 95% CI, 1.10-2.54), higher CLL-IPI category (HR, 1.42; 95% CI, 1.13-1.80) and prior history of any skin cancer (HR, 4.80; 95% CI, 3.37-6.83) were significantly associated with development of SCC in patients with CLL. On multivariable analysis, the latter 3 factors remained independently associated with risk of SCC in the setting of CLL.

“The fact that prior history of skin cancer was a strong risk factor to predict SCC in CLL patients will enable clinicians to better counsel an individual patient and their risk in developing SCC,” the study authors noted.

For the subgroup of patients with SCC-PRS scores, univariate analyses including this parameter showed it to also be significantly associated with development of SCC following CLL diagnosis (HR, 2.58; 95%CI, 1.50-4.43), and multivariable analysis supported its independent association with SCC risk in CLL patients.

In addition, on multivariable analysis (after adjusting for age, sex and prior history of SCC), treatment with T-cell immunosuppressive therapy was significantly associated with development of SCC following diagnosis of CLL (HR, 2.29; 95% CI, 1.47-3.55).

Some of the limitations of this study mentioned by the study authors included missing data such that only 360 patients were fully characterized according to sex, prior history of skin cancer, CLL-IPI category, and SCC-PRS score. In addition, since all patients were White, the results of this study may only be applicable to individuals of that race.

In their concluding remarks, the study authors opined that “future studies should develop prediction models that include both CLL-specific and SCC-specific factors; this may lead to improved screening and counseling guidelines for newly diagnosed CLL patients.”


Kleinstern G, Rishi A, Achenback SJ, et al. Delineation of clinical and biological factors associated with cutaneous squamous cell carcinoma amongst chronic lymphocytic leukemia patients.J Am Acad Dermatol. Available online July 15, 2020. doi: 10.1016/j.jaad.2020.06.1024

This article originally appeared on Cancer Therapy Advisor