Delineation of clinical and biological factors associated with cutaneous squamous cell carcinoma among patients with chronic lymphocytic leukemia

Geffen Kleinstern, Abdul Rishi, Sara J. Achenbach, Kari G. Rabe, Neil E. Kay, Tait D. Shanafelt, Wei Ding, Joe F. Leis, Aaron D. Norman, Timothy G. Call, James R. Cerhan, Sameer A. Parikh, Christian L. Baum, Susan L. Slager

Research output: Contribution to journalArticlepeer-review


Background: The incidence of cutaneous squamous cell carcinoma (SCC) in patients with chronic lymphocytic leukemia (CLL) is significantly higher compared with age- and sex-matched controls. Objective: To evaluate the association of factors associated with SCC risk. Methods: Clinical CLL and SCC data were obtained from Mayo Clinic CLL Resource and self-reported questionnaires among patients with newly diagnosed CLL. We computed the CLL International Prognostic Index (CLL-IPI) from CLL prognostic factors, and a polygenic risk score from SCC susceptibility variants. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Among 1269 patients with CLL, the median follow-up was 7 years, and SCC subsequently developed in 124 patients. Significant associations with SCC risk were history of skin cancer (HR=4.80; 95% CI: 3.37-6.83), CLL-IPI (HR=1.42; 95% CI: 1.13-1.80), and polygenic risk score (HR=2.58; 95% CI: 1.50-4.43). In a multivariable model, these factors were independent predictors (C statistic = 0.69; 95% CI: 0.62-0.76). T-cell immunosuppressive treatments were also associated with SCC risk (HR=2.29; 95% CI: 1.47-3.55; adjusted for age, sex, and prior SCC). Limitations: The sample size decreases when combining all risk factors in a single model. Conclusion: SCC risk includes history of skin cancer, an aggressive disease at time of CLL diagnosis, receiving T-cell immunosuppressive treatments, and high polygenic risk score. Future studies should develop prediction models that include these factors to improved screening guidelines.

Original languageEnglish
Pages (from-to)1581-1589
Number of pages9
JournalJournal of the American Academy of Dermatology
Issue number6
StatePublished - Dec 2020
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2020 American Academy of Dermatology, Inc.


  • chronic lymphocytic leukemia
  • cutaneous squamous cell carcinoma

ASJC Scopus subject areas

  • Dermatology


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