Published in Dermatology Journal Scan / Research · March 24, 2022 Non-Keratinocyte Skin Cancer Risk Among Solid Organ Transplant Recipients in the US JAMA Dermatology

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.

JAMA Dermatology

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

JAMA Dermatol 2022 Mar 09;[EPub Ahead of Print], MR Sargen, EK Cahoon, KJ Yu, MM Madeleine, Y Zeng, JR Rees, CF Lynch, EA Engels 

Written by

 

 

Melissa Pugliano-Mauro MD

The increased risk of skin cancer as well as its cause of morbidity and mortality among solid organ transplant recipients (SOTRs) is well-known. This has been best studied and described with keratinocyte carcinomas. This original article helps to fill a gap in our knowledge by focusing on identifying risk factors and the spectrum of disease due to nonkeratinocyte skin cancers.  

Linked data from the national transplant registries and 32 cancer registries were used to identify standardized incidence ratios to assess risk of nonkeratinocyte carcinomas in SOTRs relative to the general population. Thereafter, Poisson regression models were applied to calculate incidence rate ratios to identify specific risk factors for the development of these nonkeratinocyte carcinomas.

There was a twofold increased risk for the diagnosis nonkeratinocyte carcinomas in SOTRs in comparison with the general population. Melanoma, with the greatest risk associated with amelanotic and nodular variants, was the most common nonkeratinocyte carcinoma (61.8%). This was followed by Merkel cell carcinoma (MCC; 14%), Kaposi sarcoma (KS; 7.8%), sebaceous carcinoma (7.1%), and cutaneous lymphomas (4.5%; with the greatest increased risk associated with anaplastic large-cell lymphoma and diffuse large B-cell lymphoma).

The risk for the development of nonkeratinocyte carcinomas was elevated in the following settings: viruses (MCC, KS, extranodal natural killer/T-cell lymphoma); UVR exposure (non-Hispanic White race and ethnicity, living in an area with a higher incidence of UVR exposure at time of transplantation, and personal history of posttransplant diagnosis of a keratinocyte carcinoma); and immunosuppression (time since transplantation ≥10 years, transplant number, intensity of immunosuppression captured by organ transplanted). The risk for melanoma, MCC, and nonsebaceous adnexal skin cancers (NSACs) increased up to three- to fourfold after a diagnosis of a UVR-related keratinocyte carcinoma (BCC and SCC).

Altogether, 46.1% of the diagnoses of melanoma, MCC, sebaceous carcinoma, and NSACs occurred on the head and neck, whereas KS preferentially occurred on the lower extremity. In addition, what sets KS apart from the other tumors is that the risk of KS was greatest in the first year after transplantation in contrast to the other nonkeratinocyte carcinomas studied, which were more likely to occur further out from transplantation.

Male sex, older age at transplantation, age ≥65 years, and factors associated with UVR exposure (as above) were independently associated with a greater risk for multiple skin cancer types. Therefore, these SOTRs may benefit from increased skin cancer surveillance, and these findings support modifications to screening guidelines.

Treatment with mTOR inhibitors was not only associated with a reduced incidence of melanoma (25% decreased risk) but also an increased risk of MCC. This raises the possibility and consideration of this class of immunosuppressive medication to be utilized as chemoprevention for melanoma and must be weighed against the potential increased risk of MCC.

TAKE-HOME MESSAGE

• This population-based cohort study investigated the risk of solid organ transplant recipients (SOTRs) developing non-keratinocyte skin cancers. SOTRs have a twofold increased risk of non-keratinocyte skin cancer compared with the general population. Melanoma, Merkel cell carcinoma (MCC), Kaposi sarcoma (KS), and sebaceous carcinoma are the most common identified in the study. Virus-associated cancers (KS and MCC) carried the highest incident ratios compared with the general population. Factors, such as old age at transplant, male sex, and UV radiation exposure were associated with a higher risk of skin cancer.

• The findings indicate that oncogenic viruses, UV exposure, and immunosuppression increase the risk of SOTRs developing non-keratinocyte skin cancers.

–  Joshua R. Ortego, MD

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Benjamin Hidalgo-Matlock
Skin Care Physicians of Costa Rica

Clinica Victoria en San Pedro: 4000-1054
Momentum Escazu: 2101-9574

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