Spectrum of Nonkeratinocyte Skin Cancer Risk Among Solid Organ Transplant Recipients in the US

Merkelcell.org Summary

This is a study of over 444,000 persons who receive immune suppression medications to prevent the rejection of a transplanted kidney, heart, or other organ. The authors found an inceased risk of multiple cancers that are caused by sunlight and or viruses. The chance of developing Merkel cell carcinoma was 16-fold higher in such persons as compared to the general population. This study clearly indicates the importance of the immune system in preventing many types of skin cancer, including MCC. Skin cancers that are known to arise from keratinocytes (basal cell and squamous cell carcinomas) are far more common and were not included in this analysis as they are already heavily studied and known to also be strongly associated with immune suppression.

Abstract

Importance  Nonkeratinocyte skin cancers are an important cause of morbidity and mortality for immunosuppressed solid organ transplant recipients (SOTRs), but the spectrum of disease and risk factor characteristics are unknown.

Objective  To characterize the spectrum of disease and risk factors for common and rare nonkeratinocyte skin cancers in SOTRs.

Design, Setting, and Participants  This population-based cohort study included 444 497 SOTRs who underwent a transplant in the US between January 1, 1987, and December 31, 2017, using linked data from the national transplant registry and 32 cancer registries. Data analysis was conducted from April 1, 2021, to September 30, 2021.

Main Outcomes and Measures  Standardized incidence ratios (SIRs) were used to assess risk relative to the general population, and Poisson regression was used to evaluate risk factors.

Results  A total of 2380 nonkeratinocyte skin cancers were identified among 444 497 SOTRs (median age at transplant, 50 years; range, 0-96 years; 274 276 [61.7%] male; 272 241 [61.2%] non-Hispanic White). Melanoma was the most common cancer (1471 [61.8%]), followed by Merkel cell carcinoma (334 [14.0%]), Kaposi sarcoma (186 [7.8%]), sebaceous carcinoma (170 [7.1%]), and cutaneous lymphomas (108 [4.5%]). Risks were most strongly elevated for cancers associated with viruses, including Kaposi sarcoma (SIR, 20.5; 95% CI, 17.7-23.7), Merkel cell carcinoma (SIR, 16.2; 95% CI, 14.5-18.1), and extranodal natural killer/T-cell lymphoma (SIR, 44.3; 95% CI, 5.37-160). Risks were also significantly elevated for sebaceous carcinoma (SIR, 15.2; 95% CI, 13.0-17.7), anaplastic large cell lymphoma (SIR, 6.82; 95% CI, 4.53-9.85), and diffuse large B-cell lymphoma (SIR, 5.17; 95% CI, 3.28-7.76). Several characteristics were independently associated with greater risk for multiple skin cancer types, including male sex, older age at transplant, factors associated with UV radiation exposure (non-Hispanic White race and ethnicity, living in an area with higher UV radiation exposure, and posttransplant diagnosis of keratinocyte carcinoma), and increasing time since transplantation. Treatment with mammalian target of rapamycin inhibitors was associated with reduced melanoma incidence (incidence rate ratio, 0.75; 95% CI, 0.57-0.98). A total of 847 skin cancers (39.4%) occurred on the head and neck.

Conclusions and Relevance  The findings of this cohort study suggest that viruses, UV radiation exposure, and immunosuppression are associated with the development of skin cancer in SOTRs. Certain high-risk subgroups may benefit from increased skin surveillance, and treatment with mammalian target of rapamycin inhibitors could be effective for melanoma chemoprevention in the transplant population.