ong-term survival after organ transplantation is increasing. As a result, many physicians may encounter patients who have long-term complications of transplantation. Adequate graft function requires lifelong immunosuppressive treatment, and the resultant modification of the immune system is associated with an increased risk of various cancers, particularly those involving viruses. Skin cancers are the most common malignant conditions in transplant recipients 1-4 (Table 1) and account for substantial morbidity and mortality in such patients. In this review, we discuss the most common forms of skin cancer in transplant recipients. Squamous-cell and basal-cell carcinomas account for more than 90 percent of all skin cancers in transplant recipients. 1,3,5,6 The incidence of these carcinomas increases with the duration of immunosuppressive therapy, ultimately affecting 50 percent or more of white transplant recipients. 1,5,7 For example, the cumulative incidence of skin cancer in transplant recipients in Queensland, Australia, increases from 7 percent after 1 year of immunosuppressive therapy 5 to 82 percent after 20 years. 8 Among Dutch transplant recipients, the incidence of skin cancer at one year is 0.2 percent and the long-term incidence is 41 percent. 5 Squamous-cell carcinoma is the most common skin cancer in transplant recipients, occurring 65 to 250 times as frequently as in the general population. 6,7,9 The incidence of basal-cell carcinomas is reportedly increased by a factor of 10 in transplant recipients. 7 The risk appears to increase linearly for basal-cell carcinomas and exponentially for squamous-cell carcinomas 1 ; thus, the ratio of squamous-cell to basal-cell carcinomas in patients without transplants (1:4) is reversed in transplant recipients. 1,5,10 The relative risk of squamous-cell carcinoma after transplantation is higher for men than for women, except for cancers of the lip. 9 Curiously, skin cancers appear to be extremely rare in Japanese patients with transplants. 11 The mean interval between transplantation and diagnosis of a tumor is eight years for patients who received transplants at approximately 40 years of age, 10 but is only about three years for those who received transplants after the age of 60. 1 The severity of these tumors is linked to their number. Approximately 30 to 50 percent of patients with squamous-cell carcinomas also have basal-cell carcinomas. 5,10 According to a Scandinavian study, 25 percent of patients with a first squamous-cell carcinoma will have a second lesion within 13 months, and 50 percent will have a second lesion within 3.5 years. 9 Liddington et al. reported a mean interval of 15 months between detection of the first and second cancers, and 11 months between the second and third. 12 Carcinomas are usually associated with multiple warts and premalignant keratoses, and are often associated with Bowen's disease (an intraepidermal carcinoma of the skin or mucous membranes that may progress to invasive carcinoma) and keratoacanthomas (Fig. 1A). The appearance ...

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Although the proportion of HTR developing new tumors is greater as compared with KTR, the mean number of tumors per patient is higher in KTR. This could be due to a longer immunosuppression in patients younger at transplantation.

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The skin is the main target of rejection in human hand allografts. Close clinicopathologic monitoring of the skin is the most reliable way to detect rejection in human composite tissue allografts.

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As it happens with other composite tissue allografts, close clinicopathologic monitoring of the skin (and oral mucosa) seems to be the most reliable way to detect rejection in the setting of human facial tissue allotransplantation. Apart from these rejection episodes, the skin and mucosa maintained a normal microscopic structure, paralleling functional recovery.

Vascular endothelial growth factor (VEGF), an endothelium-specific growth factor and microvessel hypermeability factor, is expressed and secreted by several kinds of cells and is implicated in angiogenesis of tumors. The present study was performed to determine the relationship between the expression of VEGF in normal skin, benign and malignant epithelial lesions and cultured keratinocytes and the proliferative activity and degree of differentiation of keratinocytes. Skin lesions were studied immunohistochemically by staining with two anti-VEGF antibodies and secretion and production of VEGF by keratinocyte cultures were evaluated using an enzyme-linked immunosorbent assay. Low to moderate VEGF expression was observed in normal epidermis. In epithelial tumors, different reactivity patterns were observed and different areas of the same tumor expressed different amounts of VEGF. A more prominent labelling occurred in proliferative layers and/or more differentiated cells of virus-induced lesions, squamous cell carcinomas and Bowen's disease, whereas basal cell carcinomas always stained weakly for VEGF. In cultured keratinocytes, the amount of cell-associated and secreted VEGF increased with time, and the constitutively produced VEGF was mostly released extracellularly. High calcium concentrations upregulated the intracellular content of VEGF but downregulated its release. Taken together, these results showed a modulated expression and release of VEGF in relation to the stage of cell differentiation and in rapidly growing or activated keratinocytes.