Solid organ transplant recipients (SOTRs) are a population of patients with drastically increased rates for keratinocytic and adnexal skin cancers, including squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Merkel cell carcinoma (MCC), malignant melanoma (MM), and Kaposi sarcoma (KS). The cumulative incidence of skin cancer and skin cancer-specific mortality in SOTRs have recently been estimated to, respectively, over 1.4 per 100 person-years and 35.27 per 100 000 person-years (higher than breast cancer and colon cancer in SOTRs). Among SOTRs, general factors associated with increased risk for skin cancer development include a history of malignant or premalignant lesions, a history of chronic ultraviolet (UV) exposure, a history of human papillomavirus (HPV) infection, Fitzpatrick skin phototypes I through III, advanced age, increased duration and intensity of iatrogenic immunosuppression, and CD4 lymphocytopenia. Some specific pretransplantation conditions with end-organ failure, such as cholestatic liver disease and polycystic kidney disease, are also correlated with an increased risk of skin cancer in SOTRs.

SCC is the predominant skin cancer arising in transplant recipients (with an occurrence 65- to 250-fold more than the general population), while MM produces the highest disease-specific mortality in this group of patients (11.48 per 100 000 person-years compared to 4.94 per 100 000 person-years for SCC). Factors associated with mortality include White race, male sex, advanced age, and thoracic transplantation.

Iatrogenic immunosuppression and an altered neoplastic microenvironment are important pathophysiological considerations for SCC in SOTRs. Immunomodulating agents in transplant recipients act synergistically with UV radiation and lead to increased mutational burden, leading to development of actinic keratoses (AKs) and Bowen disease, with consequent malignant transformation.

SCC in SOTRs may present multifocally, with precursor multifocal Bowen disease and lesions also distributed in normally photoprotected areas (ie, truncal and anogenital skin). SCC in immunosuppressed patients (including SOTRs) presents with twice the rate for metastatic disease than in immunocompetent individuals, and metastatic SCC in SOTRs portends a poorer prognosis than in the general population, with significantly higher rates for locoregional relapses and lower rates for subsequent survival.

BCC also occurs more frequently in transplant recipients than other patients, although its prevalence is significantly lesser than SCC. SCC-to-BCC ratio is estimated to be 5:1 in this population of patients. Clinicopathologic features and prognosis of BCC in SOTRs are identical to BCC in the general population.

MCC presents with a 5- to 24-fold increased risk in SOTRs and favors male patients. A review of cases in renal transplant recipients suggested that Merkel cell polyomavirus (MCPyY) is not the principal etiological factor for MCC in transplant recipients as most cases were MCPyV-negative, and that MCC in such patients predominantly arises from SCC. Although occurring much less frequently than SCC, MCC features a specifically aggressive clinical course in SOTR, with a 4- and 12-fold increase, respectively, in progression and specific mortality when compared to the general population.

It has been postulated that immunosuppressing agents may induce unconventional mutations or activate alternate signaling pathways leading to development of MM, as MM arising in SOTRs has been found to have lower BRAF-V600E mutation rates than MM in immunocompetent individuals. In rare cases, MM may be derived directly from the organ donor. Clinical presentation of MM in SOTRs does not differ from the general population. However, prognosis for MM in transplant recipients appears to be significantly worse than in nontransplanted controls, with higher overall and MM-specific 3-year mortality in SOTRs. Factors associated with poorer prognosis are higher Breslow depths and more aggressive immunosuppressive regimens (ie, in patients with cardiac transplantation). In a 2008 multicenter retrospective analysis, outcomes for T1-T2 MM were similar in SOTRs than in the general population, but outcomes for T3 and T4 tumors were significantly worse.

The risk for iatrogenic KS in transplanted populations is up to 500-fold the risk for classic KS in the general population, and KS accounts for over 5% of all malignancies in transplanted recipients. Iatrogenic KS displays a 3:1 male-to-female ratio, and patients have a 5-year survival rate of around 69%, contrasting with the 17:1 male-to-female ratio and slowly progressive or indolent clinical course of classic KS. Among SOTRs, hepatic transplant recipients are more likely to develop KS. Systemic glucocorticoids are especially important for the development of iatrogenic KS as they indirectly upregulate proliferation of endothelial KS cells. Human herpesvirus (HHV)-8 reactivation and transmission through grafting are likely mechanisms leading to KS in SOTRs. Prognosis depends on tolerability for reduction of immunosuppression and is worse in patients with visceral involvement (especially in patients with pulmonary KS).

The Skin and Ultraviolet Neoplasia Transplant Risk Assessment Calculator (SUNTRAC) stratifies SOTRs into 4 risk groups, according to ethnicity, sex, age at transplantation, pretransplantation skin cancer history, and transplantation type. Stratification by SUNTRAC scores accurately predict the average 5- and 10-year risk for SCC, MCC, and MM, as well as optimal screening frequency for each group. SUNTRAC as a tool has been externally validated in a large European cohort.

Related topics: cutaneous SCC, infiltrating BCC, nodular BCC, non-AIDS-associated Kaposi sarcoma, melanoma, Merkel cell carcinoma, pigmented BCC, SCC in situ, superficial BCC