Figure 1. Patients enrolled. Cumulative incidences of nonmelanoma skin cancer (NMSC) after organ transplant. A, Organ transplant recipients (OTRs) enrolled (N = 225) and squamous cell carcinomas (SCCs) that developed within 8 years after transplant. B, Cumulative incidence of the first NMSC SCC and basal cell carcinoma (BCC) after transplant.
Figure 2. Acceleration from first to second squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) in organ transplant recipients (OTRs) (N = 225) but not in immunocompetent controls. Total annual numbers of the nonmelanoma skin cancer (NMSC) SCC (A) and BCC (B) following transplant. Identical filling patterns depict NMSC within the same solid organ transplant group in the same year and across years. Time interval in months from transplant (TPL) to first SCC and from first to second, second to third, and third to fourth SCC in OTRs (n = 5) and immunocompetent (Im’cpt) patients (n = 10) (C) and from TPL to first BCC and from first to second, second to third, and third to fourth BCC in OTRs (n = 4) and Im’cpt controls (n = 10) (D). * P < .05. † P < .01.
Muehleisen B, Pazhenkottil A, French LE, Hofbauer GFL. Nonmelanoma skin cancer in organ transplant recipients: increase without delay after transplant and subsequent acceleration. JAMA Dermatol. doi:10.1001/jamadermatol.2013.3115
eFigure 1. Patient Age at Transplantation and at Diagnosis of Non-Melanoma Skin Cancer
eFigure 2. Transplanted Organs
Customize your JAMA Network experience by selecting one or more topics from the list below.
Muehleisen B, Pazhenkottil A, French LE, Hofbauer GFL. Nonmelanoma Skin Cancer in Organ Transplant Recipients: Increase Without Delay After Transplant and Subsequent Acceleration. JAMA Dermatol. 2013;149(5):618–620. doi:10.1001/jamadermatol.2013.3115
Author Affiliations: Departments of Dermatology (Drs Muehleisen, Pazhenkottil, French, and Hofbauer) and Radiology (Dr Pazhenkottil), University Hospital Zurich, Zurich, Switzerland.
Organ transplant recipients (OTRs) have a 60- to 250-fold increased risk for cutaneous squamous cell carcinoma (SCC) and a 10-fold increased risk for basal cell carcinoma (BCC).1 It is still unclear, however, how fast after transplant these tumors arise. To develop risk-adjusted clinical follow-up in OTRs, we investigated the incidence of first and subsequent nonmelanoma skin cancers (NMSCs) in OTRs.
Following approval by the local ethical committee, clinical information from 225 OTRs who underwent transplant at the University Hospital Zurich, Zurich, Switzerland, with complete follow-up in a special consultation for OTRs at the Department of Dermatology for at least 8 years after transplant was retrieved from medical charts. None of these patients had NMSC before transplant. In addition, clinical information from 10028 NMSCs in immunocompetent control patients was retrieved from the dermatohistopathology archive database, and clinical information from medical charts was also retrieved in a subset of 10 immunocompetent patients with multiple SCC or BCC. Histological diagnoses of NMSC were all made by board-certified dermatopathologists. GraphPad Prism software v5.0 (GraphPad) was used for statistical analysis. P <.05 was considered significant.
The mean (SD) age at transplant was 41.99 (14.3) years (n = 255) (eFigure 1A). Transplanted organs included 130 kidneys, 53 livers, 35 lungs, and 7 hearts (eFigure 2).
Of 225 OTRs, 24 (10.7%) developed 1 SCC or more and 17 (7.6%) developed 1 BCC or more within 8 years (Figure 1A). Cumulative incidence for the first NMSC rose linearly and without delay after transplant and was similar between SCC and BCC (P = .18, log-rank test) (Figure 1B).
Squamous cell carcinoma in OTRs developed earlier (mean [SD] years, 56.2 [15.5]; SCC, n = 53) than in immunocompetent controls (73.9 [12.9] years; SCC, n = 2531; P < .01, t test). Similarly, BCC occurred earlier in OTRs (58.8 [15.2] years; BCC, n = 35) than in immunocompetent patients (67.2 [14.1] years; BCC, n = 7497; P < .01) (eFigure 1B).
Total annual numbers of NMSC were variable without an upward or downward trend and with a mean of 6.6 SCCs (2.9%) and 4.4 BCCs (1.9%) per year (Figure 2A and B). An analysis of organ transplant groups revealed a trend toward earlier occurrence of SCC in the strongly immunosuppressed heart and lung OTRs (combined, n = 42) compared with the less immunosuppressed liver and kidney OTRs (combined, n = 183) (heart and lung OTRs, 7 SCCs in years 1-4 and 4 SCCs in years 5-8; kidney and liver OTRs, 16 SCCs in years 1-4 and 26 SCCs in years 5-8; P = .18, Fisher exact test) (Figure 2A and B).
Of interest, subsequent NMSC in OTRs with several NMSCs showed accelerated carcinogenesis: In OTRs with multiple SCC (n = 5), the first SCC developed after a mean (SEM) of 36.6 (9.4) months, whereas the second SCC occurred after only another 4.0 (1.3) months, (P = .008, Kruskal-Wallis with Dunn post hoc test). In control immunocompetent patients with multiple SCCs (n = 10), the time interval to a second, third, or fourth SCC remained constant (Figure 2C). Organ transplant recipients with multiple BCCs (n = 4) had a first BCC after a mean (SEM) of 47.5 (6.8) months and the second BCC already after another 12.5 (1.0) months (P = .048) (Figure 2D). There was a trend toward shorter time intervals in OTRs than in immunocompetent patients from the first to second SCC (4.0 [1.3] vs 12.5 [3.74] months; P = .14); from the second to third SCC (6.0 [2.3] vs 10.6 [1.92] months; P = .16) (Figure 2C); and from the first to second BCC (12.5 [0.96] vs 20.0 [3.63] months; P = .23) (Figure 2D).
We aimed to determine how fast after organ transplant the incidence of NMSC increases. Age at time of transplant and at occurrence of NMSC in our cohort compared well with published data.1
While some previous publications reported a linear increase of the NMSC cumulative incidence,2 others indicated a low or even unchanged risk in the first years, followed by a marked increase after 5 to 10 years.3 Our study demonstrated a linear increase of the cumulative incidence of first SCC and BCC without delay after transplant and a constant accrual of total annual SCC and BCC over the first 8 years.
Several other studies have described an increased risk for subsequent NMSC in OTRs, reporting a cumulative 3-year incidence for a second NMSC ranging between 22% and 52%.4,5 Herein, we demonstrated that the risk for subsequent NMSC in OTRs was not only increased overall but also accelerated with intervals shrinking between the first and subsequent NMSC. Even though OTRs received skin checks more frequently after a first NMSC, we do not believe that earlier detection of subsequent NMSC in OTRs accounted for that acceleration because clinically and histologically first NMSC had similar tumor stages at the time of diagnosis as subsequent NMSC and because a trend toward shorter time intervals in OTRs was observed not only from first to second but also from second to third NMSC. Nonmelanoma skin cancers after transplant should be considered a marker for increased subsequent NMSC risk in OTRs and be integrated into the clinical algorithms for the follow-up in OTR specialty clinics.
Correspondence: Dr Hofbauer, Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland (email@example.com).
Accepted for Publication: November 29, 2012.
Author Contributions: Drs Pazhenkottil, Muehleisen, and Hofbauer had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Muehleisen and Hofbauer. Acquisition of data: Muehleisen and Pazhenkottil. Analysis and interpretation of data: Muehleisen, Pazhenkottil, French, and Hofbauer. Drafting of the manuscript: Muehleisen and Hofbauer. Critical revision of the manuscript for important intellectual content: Pazhenkottil, French, and Hofbauer. Statistical analysis: Muehleisen. Obtained funding: Hofbauer. Administrative, technical, and material support: Muehleisen, Pazhenkottil, Hofbauer. Study supervision: Pazhenkottil, French, Hofbauer.
Conflict of Interest Disclosures: None reported.
Funding/Support: This study was supported in part by Baugarten Stiftung.
Additional Contributions: Tamara Gachter, MD, assisted in extracting histological data.
Create a personal account or sign in to: