Humane Papillomvirus-assoziierte Warzen bei organtransplantierten Patienten

Human papillomaviruses infect the squamous epithelia of the skin and cause warts, and are occasionally found in squamous cell carcinomas. Since cell-mediated immunity plays a crucial role in the control of HPV-infections, organ transplant recipients, unable to mount an adequate T-helper 1 cell-mediated immune surveillance, frequently develop widespread and resistant induced warts. Skin tumors, especially squamous cell carcinomas, are the most common post-transplantation neoplasm. Warts, actinic keratoses and invasive squamous cell carcinomas are known to develop at the same time in the areas. The role of HPV in the development of invasive squamous cell carcinoma under immunosuppression, remains to be elucidated in respect to common risk factors and increased numbers of warts potentially indentifing patients at increased risk for carcinoma. We prospectively studied 1690 organ transplant recipients in the dermatology clinic at the Charité University Hospital in Berlin, to evaluate risk factors being involved in the development of HPV-induced warts and to assess a potential association of with the development of non-melanoma skin cancers in this population. The cumulative incidence of warts steadily increased throughout the post-transplant years. The presence of more than 10 verrucae was associated with the development of actinic keratoses, invasive squamous cell carcinoma and basal cell carcinoma. This study shows clear evidence that certain risk factors of skin carcinogenesis in organ transplant recipient such as increased age at transplantation, a high dose of immunosuppression related to a specific type of graft and use of azathioprine or cyclosporine are strongly associated with an increased incidence of warts. Furthermore, HPV-induced verrucae vulgares could be used as a potential predictor for the development of coincidental non melanoma skin cancer in organ transplant recipients and therefore could serve as an early identification marker of skin cancer high-risk patients. The challenging management of warts in organ transplantation patients is reviewed.     

Cutaneous squamous cell carcinomas and papillomaviruses in renal transplant recipients: a clinical and molecular biological study.

Papillomaviruses are strongly implicated in squamous cell carcinomas arising on mucosal surfaces of normal individuals, and in the skin carcinomas of epidermodysplasia verruciformis suffers. Renal transplant recipients often have numerous skin warts and, in Australia particularly, a very high risk of developing cutaneous squamous cell carcinoma. To determine the magnitude of this risk, and to test whether papillomaviruses are specifically associated with these cancers, we examined 188 renal transplant recipients for skin cancers and tested 235 biopsy specimens of (histologically proven) squamous cell carcinomas for the presence of viral DNA. The risk of developing squamous cell carcinoma increased with duration of transplant: the probability being 25% after 9.5 years (standard error = 1.3 years) rising to 50% at 20.6 years (standard error 6.8 years). Factors which did not appear to affect the risk of tumour development included the patients sex and their skin type. However the age at transplant significantly altered the risk with patients transplanted at greater than 35 years developing tumours about four times more rapidly than patients less than or equal to 35 years. Extensive hybridisation tests for the presence of papillomavirus DNA in squamous cell carcinomas were negative, as was the polymerase chain reaction amplification method using general L1 gene oligonucleotide primers. Our data do not support a role for papillomavirus in the maintenance of cutaneous squamous cell carcinoma.     

Human papillomavirus type 1-associated squamous cell carcinoma in a heart transplant recipient.

The occurrence of squamous cell carcinomas in organ transplant recipients with warts represents a good model to study viral carcinogenesis. Most of the cases were reported in renal transplant recipients. We present the case of a heart transplant recipient in whom multiple common warts, preepitheliomatous keratoses, and squamous cell carcinomas developed. The warts began 4 years after the transplantation and the first carcinoma occurred 2 years after the warts, all the lesions being on sun-exposed areas. Histologic signs of human papillomavirus infection were seen in all premalignant and malignant lesions. Furthermore, human papillomavirus type 1 DNA was detected by in situ molecular hybridization within one of the carcinomas. Human papillomaviruses, along with other carcinogenic factors, play an important role in the development of carcinomas, and benign types could be implicated. Further studies are required to evaluate the frequency of cutaneous malignant neoplasms in heart transplant recipients as compared with renal transplant recipients.     

Human papillomavirus infection and skin cancer risk in organ transplant recipients

Warts and squamous cell carcinomas are important cutaneous complications in organ transplant recipients. The role of infection with human papillomaviruses (HPV) in the development of cutaneous squamous cell carcinoma is still unclear. An extremely diverse group of HPV types, mainly consisting of epidermodysplasia-verruciformis (EV)-associated HPV types, can be detected in benign, premalignant, and malignant skin lesions of organ transplant recipients. Frequently, there are multiple HPV types present in single skin biopsies. Typically, the prevalence of viral warts rises steadily after transplantation and a strong association exists between the number of HPV-induced warts and the development of skin cancer. The interval between the transplantation to the development of warts is clearly shorter than the interval from transplantation to the diagnosis of the first skin cancer. A comparison of transplant recipients with and without skin cancer, however, showed an equally high prevalence of EV-HPV DNA in keratotic skin lesions in both groups of patients and the detection rate and spectrum of HPV infection in hyperkeratotic papillomas, actinic keratoses, and squamous cell carcinomas was also similar. HPV DNA can frequently be detected in patients with hyperproliferative disorders like psoriasis and antibodies against HPV in patients with regenerating skin (e.g., after extensive second degree burns). Latent infection with EV-HPV seems to be widespread. The hair follicle region might be the reservoir of EV-HPV. The E6 protein from a range of cutaneous HPV types effectively inhibits apoptosis in response to UV-light induced damage. It is therefore conceivable that individuals who are infected by EV-HPV are at an increased risk of developing actinic keratoses and squamous cell carcinomas, possibly by chronically preventing UV-light induced apoptosis.     

p53 immunoreactivity in non-melanoma skin cancer from immunosuppressed and immunocompetent individuals: a comparative study of 246 tumours

p53 immunoreactivity was examined in 132 cutaneous non-melanoma tumours from renal transplant recipients and in 114 histologically matched specimens from immunocompetent individuals. Skin lesions examined included 52 viral warts, 50 clysplastic keratoses, 51 intraepidermal carcinomas (IEC), 50 invasive squamous cell carcinomas (SCC) and 43 basal cell carcinomas (BCC). Overall, 51% (51/101) pre-malignant skin lesions and 45% (42/93) non-melanoma skin cancers (NMSC) showed p53 immunoreactivity, with extensive (> 50% cells positive) p53 staining in 27% (27/101) of pre-malignant and 20% (19/93) of malignant lesions. 17% (9/52) viral warts showed p53 immunoreactivity, but this was limited to focal or basal p53 staining. p53 immunoreactivity in all tumours was less in transplant than in non-transplant patients and this reached statistical significance for SCCs (p = 0.03).     

Sun habits in kidney transplant recipients with skin cancer: a case-control study of possible causative factors

Organ transplant recipients are frequently affected by skin cancer, which might also be a major cause of long-term mortality. Excessive sun exposure is considered to be a factor in the aetiology, but uncertainty about the importance of this and other proposed risk factors remains. The purpose of this study was to investigate sun behaviour before and/or after the transplantation in kidney transplant recipients with or without cutaneous squamous cell carcinoma. A nested, population-based, case-control study was carried out on 95 kidney transplant recipients who had contracted cutaneous squamous cell carcinoma after the transplantation and on an accurately matched control population of 154 kidney transplanted patients. Information on sun exposure before and after the transplantation, skin type, use of sunbeds, warts, etc., was obtained from a questionnaire which contained 38 detailed questions. The differences between cases and control subjects were not significant for sun exposure before or after the transplantation, sun protective measures, number of sunburns, outdoor occupation, smoking habits or use of sunbeds. Compared to patients with skin type IV, the cutaneous squamous cell carcinoma odds ratio was 3.0 (95% CI = 1.3-7.0) for skin type I + II. Patients with light blond or red hair colour also had a higher odds ratio than those with dark hair, 3.2 (95% CI = 1.2-8.2), and patients with warts after the transplantation had a higher odds ratio than those without, 2.2 (95% CI = 1.2-4.2). In conclusion, poor tanning ability rather than the amount of sun exposure is associated with the development of cutaneous squamous cell carcinoma in kidney transplant recipients and warts appearing after the transplantation indicate increased risk.     

Use of topical immunomodulators in organ transplant recipients

Solid organ transplant recipients are a growing population at increased risk for the development of cutaneous premalignant and malignant lesions, resulting in significant morbidity and mortality. Topical immunomodulators, in particular imiquimod, have shown efficacy in the management of multiple malignant, precancerous, and viral conditions. The ability to locally induce an immune response, presumably against tumor and viral antigens, and induce apoptosis makes topical immunomodulators a promising therapeutic option in organ transplant recipients. Although limited, data have begun to accumulate on the use of imiquimod in transplant patients for the management of superficial, nodular, and infiltrative basal cell carcinomas; in situ and invasive squamous cell carcinomas; condyloma acuminata; and common warts. As more experience is gathered, the role of imiquimod and other topical immunomodulators in the care of OTRs will be clarified. The authors reviewed the existing data on the use of topical imiquimod in OTRs with mention of its presumed mechanisms of action and other immunomodulators with potential efficacy against cancerous and precancerous lesions.     

TP53 polymorphism of exon 4 at codon 72 in cutaneous squamous cell carcinoma and benign epithelial lesions of renal transplant recipients and immunocompetent individuals: lack of correlation with human papillomavirus status

A common polymorphism at codon 72 of exon 4 encoding either arginine or proline has been shown to confer a susceptibility to the development of skin tumor in renal transplant recipients. Moreover, this polymorphism may affect proteolytic degradation of p53 promoted by E6 protein from mucosal human papillomaviruses and represent a risk factor for human-papillomavirus-induced carcinogenesis. In this study, we analyzed the human papillomavirus presence and the TP53 allele distribution in cutaneous squamous cell carcinoma of renal transplant recipients and immunocompetent patients. Fifty-three squamous cell carcinomas from 40 renal transplant recipients, 50 benign epithelial skin lesions from 50 renal transplant recipients with no history of skin cancer, 51 squamous cell carcinomas from immunocompetent patients, and 29 blood samples from immunocompetent individuals without skin cancer were investigated. Human papillomavirus DNA was detected using polymerase chain reaction performed with two pairs of primers (MY09-MY11 and FAP59-FAP64). TP53 allele distribution was studied by denaturing gradient gel electrophoresis assay, followed by sequencing analysis. Human papillomavirus DNA was detected in 64% of squamous cell carcinoma and 79% of benign epithelial lesions from renal transplant recipients (NS) and only in 37% of squamous cell carcinoma from immunocompetent patients (p < 0.05). Mucosal oncogenic human papillomavirus types were predominant in squamous cell carcinoma from both renal transplant recipients and immunocompetent patients. Rate of arginine homozygosity in squamous cell carcinoma from renal transplant recipients was significantly higher (83%) than in immunocompetent patients with or without squamous cell carcinoma (60% and 59%, respectively). Our results suggest that TP53 arginine/arginine genotype could represent a potential risk factor for the development of squamous cell carcinoma in renal transplant recipients compared to immunocompetent patients. No association between TP53 arginine/arginine genotype and human papillomavirus status could be determined, however.     

Hauterkrankungen bei organtransplantierten Patienten

In Germany 3273 visceral organs were transplanted in the year 2000. Together with patients grafted abroad, it is estimated that between 70,000 and 100,000 organ transplant patients are currently living in Germany. With the provision of lifelong immunosuppression the survival-time of these patients can exceed more than 20 years. In the first year following transplantation special emphasis is given to the prevention of viral, bacterial and fungal infections. Regular dermatological screening can provide early diagnosis of even systemic infections. An increased incidence of skin cancer parallels the extended survival rates of grafted patients. Within the first 5 years of immunosuppression 40% of these patients develop pre-malignant skin tumors such as actinic keratoses, dysplastic nevi, squamous cell carcinomas and basal cell carcinomas. Squamous cell carcinomas show an aggressive biology and an uncommon clinical morphology. The increased incidence of cancer is now responsible for a mortality rate of 5-8% in grafted patients. Against a background of lifelong immunosuppression, other risk factors include sun exposure and infections with oncogenic viruses. The rapidly growing numbers of allograft recipients as well as the rising long term survival rates of these patients demand the provision of high quality interdisciplinary and dermatological care in this field.     

Evaluation of human papillomavirus type 5 on frozen sections of multiple lesions from transplant recipients with in situ hybridization and non-isotopic probes.

Transplant recipients are at high risk to develop multiple cutaneous lesions after grafting. The frequency of the potentially oncogenic human papillomavirus (HPV) type 5 DNA was evaluated in cutaneous lesions taken from sun-exposed areas in transplant recipients (92 lesions and 5 samples from normal skin) and compared with a nontransplanted population (22 lesions and 7 samples from normal skin) using in situ hybridization and biotinylated probes to HPV types 1, 2, 5, 16 and 18. HPV type 5 DNA was identified in 8/92 cutaneous lesions of transplanted recipients: 3 warts, 1 case of seborrheic keratosis, 2 actinic keratoses and 2 keratoacanthomas. HPV type 5 DNA was not detected in 27 malignant tumors (8 basal cell carcinomas and 19 squamous cell carcinomas) from transplant recipients. HPV DNA type 5 was detected in only 1 case of squamous cell carcinoma from the general population. The presence of HPV DNA 5 was confirmed with Southern blotting in 2 out of 6 cases from transplant recipients. The reaction was negative with the squamous cell carcinoma from nontransplant recipients. These data indicate that the presence of HPV DNA type 5 is not very frequent; it can be detected with in situ hybridization and nonisotopic probe, which is easier to handle than Southern blot.     

Langerhans cells, inflammation markers and human papillomavirus infections in benign and malignant epithelial tumors from transplant recipients.

Organ transplant recipients frequently develop warts which progress toward premalignant or malignant lesions after a rather long grafting period. The local immune responses of such lesions (warts, condyloma acuminata, actinic keratoses, Bowen, basal and squamous cell carcinomas) was studied in 32 frozen skin specimens taken from 15 male transplant recipients and compared to similar lesions from the normal population. We studied the expression of T cell subsets, Langerhans cell phenotype, HLA class 1 (beta 2-microglobulin), HLA class 2 (DR antigen), and intercellular adhesion molecule 1 (ICAM 1). The presence of HPV infection was also considered, using in situ hybridization with biotinylated probes in order to examine the correlation with immunological markers. In the dermis, the lesions from grafted patients showed a moderate to intense inflammatory reaction of HLA-DR-positive cells. Most of these cells were CD4+ and CD8+ without any predominance of a single T cell subset. In the epidermis, most lesions were characterized by a reduced number of CD1-positive cells; this was concomitant with a decrease or a loss of beta 2-microglobulin expression by epithelial cells. HLA-DR antigen was not expressed by keratinocytes or tumoral cells in any specimen; ICAM 1 antigen was observed in a few cases. The expression of these markers was similarly modified with or without the presence of HPV DNA. Conversely, most lesions from non-immunocompromised patients, except warts, showed intense inflammatory reactions, with a predominance of CD4-positive cells and large foci of ICAM 1-positive cells. Expression of activation markers by keratinocytes occurred mainly in condylomas and squamous cell carcinomas. In the normal population, HPV infection was only detected in papilloma lesions. These data indicate, in lesions from grafted patients, a lack of effective immune response with partial inhibition of activation markers expressed by keratinocytes. It is conceivable that immunosuppressive treatment with solar exposure may also be responsible for the local immune deficiency and thus for the conversion of benign warts toward malignant lesions in grafted patients.     

Interleukin-10 promoter polymorphisms and susceptibility to skin squamous cell carcinoma after renal transplantation

After organ transplantation, susceptibility to cancer is multifactorial, especially for skin carcinomas. Risk factors may include genetic susceptibilities, such as the control of cytokine production. Interleukin-10 is a cytokine that is implicated in tumorigenesis, and it has been shown that polymorphisms in its gene promoter correlate with differential amounts of production. The aim of this study was to investigate a possible association between interleukin-10 gene promoter polymorphisms and the occurrence of skin carcinomas after renal transplantation. Seventy kidney transplant recipients who developed a squamous cell carcinoma or a basal cell carcinoma were examined for polymorphisms in the interleukin-10 gene promoter using polymerase chain reaction based methods. Single base pair mutations were studied at positions -1082, -819, and -592. These patients were compared to 70 healthy controls and to 70 matched renal transplant recipients without cancer. The interleukin-10 secretion capability was tested in a subgroup of 40 of these patients by in vitro stimulation of peripheral mononuclear cells. Interleukin-10 genotypes and haplotypes were differently distributed in kidney transplant recipients who developed a skin carcinoma, but especially a squamous cell carcinoma, with an increased frequency of the GCC haplotype and a decreased frequency of the ATA haplotype. Subsequently, we found a shift in the predicted phenotypes from the low production phenotype to the high production phenotype. Secretion of interleukin-10 was strongly correlated to the production predicted phenotype, and tended to be higher in patients who developed a squamous cell carcinoma than in the others. These results indicate that interleukin-10 gene polymorphisms and interleukin-10 production capability may contribute to the development of skin squamous cell carcinomas after renal transplantation.     

Basal cell carcinomas developing in solid organ transplant recipients: clinicopathologic study of 176 cases

OBJECTIVE: To assess the clinicopathologic features of basal cell carcinomas developing in organ transplant recipients. DESIGN: Case series. SETTING: University department of dermatology. PATIENTS: One hundred forty-six (7.2%) of 2029 transplant recipients followed up in our department who developed 176 histologically proven basal cell carcinomas. One hundred fifty-three random samples of basal cell carcinomas excised from nonimmunosuppressed patients served as controls. MAIN OUTCOME MEASURES: Clinical data were gathered from the medical records. Histologic slides were retrospectively reexamined. RESULTS: Basal cell carcinomas developed an average of 6.9 years after transplantation, sooner after heart than kidney transplantation, and showed a relative predilection for heart allograft recipients. The mean age of transplant recipients with basal cell carcinomas was significantly lower than that of controls (54.6 vs 69.8 years), especially for recipients of renal transplants, and a male preponderance was found (male-female ratio, 4.8:1 vs 1.3:1). In both groups, basal cell carcinomas were predominantly found on the head and neck, but extracephalic locations were significantly more frequent in transplant recipients (37.5%) than controls (24.5%). Histologically, superficial basal cell carcinomas were more frequent in transplant recipients than controls (33.6% vs 14.4%). The density of the peritumoral cell infiltrate was lower in tumors from transplant recipients compared with controls. The tumor thickness and the presence of epidermal ulceration did not differ significantly between the 2 groups. CONCLUSIONS: Basal cell carcinomas in transplant recipients show some clinicopathologic differences from their "ordinary" counterparts, namely, a younger age at development, male preponderance, more frequent distribution in extracephalic sites, and higher frequency of superficial subtypes.     

Human papillomavirus infections in a group of renal transplant recipients

One hundred and twenty renal transplant recipients were investigated. Fifty-eight (48%) were found to have warts, 13 (11%) keratoses and six (5%) to have, or recently to have had cancers. The longer the time of immunosuppression, the greater the prevalence of warts; of those patients who had had their transplant for at least 5 years, 87% had warts. Those with a graft survival time of 10 years or more are at special risk of warts, keratoses and malignancy. Five (10%) of 50 women had genital warts, four of whom had internal lesions (vaginal, cervical or anal) and one developed a carcinoma of the vulva. These findings indicate the advisability of colposcopy for all female renal transplant recipients, a high risk group. Eighty-eight specimens from 42 patients were examined by DNA restriction enzyme analysis and cross hybridization for the presence and type of human papillomavirus (HPV). HPV DNA was detected in 66% of the warts examined, HPV2 and HPV4 occurring most often and HPV1 and HPV3 only infrequently. In sequential specimens from common hand warts of one individual, an HPV was found which could not be precisely identified but was related to HPV4. HPV16 was detected in a vaginal wart from one patient and an HPV6-related virus in a vulval wart of another. HPV DNA of an unknown type was demonstrated in one of 11 keratoses examined. With the probes used to examine the few samples of skin cancers available, HPV16 was found in a squamous cell carcinoma of the vulva, and faint bands from an unidentified type of HPV were detected in two squamous cell carcinomata from a patient's hand. One woman had plaque lesions morphologically and histologically resembling those found in epidermodysplasia verruciformis (EV). HPV5 was identified in these lesions. This is only the third reported case of HPV5, previously thought to be unique to EV, in a renal transplant recipient.     

Twenty-eight-year incidence and characteristics of post-transplant skin cancers: Comparative analysis of past and recent 10-year experience

Because primary skin cancers in organ transplant recipients are rare, little is known about the characteristics and risk factors for skin cancers in organ transplant recipients. We searched the Asan Medical Center database of 13 469 organ transplant recipients for cases of all skin cancers from January 1990 to December 2018. Characteristics of and risk factors for skin cancers were analyzed and compared according to the period of transplantation. Of the identified 113 patients with skin cancers, squamous cell carcinoma was the most common cancer followed by basal cell carcinoma and Kaposi sarcoma. The cumulative incidence of skin cancers at 28 years was 5.3%. Over the 10-year period from January 2009 to December 2018, the standardized incidence ratio for premalignant in situ skin lesions increased, whereas the standardized incidence ratio for skin cancers decreased. Age at transplantation and treatment with more than two immunosuppressive agents were risk factors for the development of new skin cancers in organ transplant recipients. Over the most recent 10-year period, post-transplant skin cancers have been found earlier and diversified compared with in the previous period.     

Malignant fibrous histiocytoma and atypical fibroxanthoma in renal transplant recipients

BACKGROUND: Allograft recipients are at increased risk for skin cancer. The incidence of cutaneous squamous cell carcinoma is 50-250 times higher than in the age-matched control population, and basal cell carcinoma is about 10 times more frequent. The incidence of Kaposi's sarcoma is increased 400 to 500 times over that in a control population of the same ethnic origin. However, the incidence of other types of cutaneous sarcoma in organ allograft recipients is largely unknown. CLINICAL OBSERVATION: Within a 2-year-period, we observed 2 patients with cutaneous malignant fibrous histiocytoma and 1 patient with atypical fibroxanthoma among a cohort of 642 renal transplant recipients. For comparison, the incidence for dermatofibrosarcoma protuberans which is the commonest type of cutaneous sarcoma, is 0.45/100,000 persons/year in the non-immunocompromised population. Our observation represents an incidence of 156/100,000/ year (95% confidence interval Cl 28-489/100,000/year) for cutaneous malignant fibrous histiocytoma and of 78/100,000/year (95% CI 4-368/ 100,000/year) for atypical fibroxanthoma. CONCLUSION: To our knowledge, this is the first report on an elevated incidence of cutaneous malignant fibrous histiocytoma and of atypical fibroxanthoma in renal transplant recipients. Future cohort studies on malignancies in organ allograft recipients should aim at defining this risk more exactly.     

Differences in sialyl-Tn antigen expression between keratoacanthomas and cutaneous squamous cell carcinomas

Keratoacanthoma and squamous cell carcinoma are common skin tumors, especially in immunosuppressed transplant recipients, but the distinction between these two types of epidermal neoplasia may be difficult. Sialyl-Tn (Sia-GalNAc-O-Ser/Thr) is a cell surface carbohydrate associated with hyperplasia in squamous epithelium, and correlated with poor prognosis in several human adenocarcinomas. Twenty-seven keratoacanthomas and 29 cutaneous squamous cell carcinomas were examined for the expression of sialyl-Tn and of the Ki67 epitope, the latter a marker for cell proliferation. By immunohistochemistry, basaloid tumor cells at the periphery of tumor nests showed some degree of sialyl-Tn expression in 16 keratoacanthomas (59%), while only three squamous cell carcinomas (10%) showed sialyl-Tn-positive basaloid tumor cells (p<0.001). Keratinized, differentiated tumor cells were more often sialyl-Tn-positive in keratoacanthomas (89%) than in squamous cell carcinomas (31%) (p<0.001). A striking sialyl-Tn-positivity in the basal cell layer was found in a border zone directly adjacent to most tumors of both types (88 and 88%). By immunohistochemical examination of parallel sections and by double immunofluorescence, sialyl-Tn antigen expression was primarily seen in cells that did not express Ki67, although some overlap was present. Keratoacanthomas from transplant recipients did not differ in sialyl-Tn expression compared to those from non-immunosuppressed patients. The results indicate that sialyl-Tn expression is not directly related to cell proliferation, but rather to cellular features of post-mitotic cells, and that sialyl-Tn is not associated with a malignant phenotype. Sialyl-Tn may be linked to tumor regression, as seen in keratoacanthomas.     

Skin tumours in the West of Scotland renal transplant population

Background Organ transplant recipients have an increased risk of skin cancers. A specialist dermatology clinic for renal transplant recipients (RTRs) was established in 2005. Objectives To analyse the type and incidence of skin cancers in prevalent patients in the West of Scotland after renal transplant, and to analyse the impact of the time since transplant and the immunosuppression regimen. Methods Skin cancer data for RTRs attending the transplant dermatology clinic over a 38‐month period were collected and recorded in the West of Scotland electronic renal patient record. Skin cancer data were intrinsically linked to each individual’s transplant and immunosuppression data. Results Overall, 610 patients attended. The median follow‐up time from the date of first transplant was 10 years. Ninety‐three patients (15·2%) had experienced a total of 368 skin cancers since transplant, and the prevalence increased with time since transplant. Basal cell carcinomas (BCCs) occurred in 74 patients (12·1%) and squamous cell carcinomas (SCCs) in 42 patients (6·9%). Three patients (0·5%) had experienced a melanoma. The SCC:BCC ratio was 0·7. Survival analysis showed significant reduction in the time to develop skin cancer in patients transplanted from 1995 onwards (P < 0·0001) and in patients who had been on triple immunosuppressant therapy at 1 year after transplant, compared with dual therapy (P < 0·0001). Conclusions This is the first study of skin cancer in prevalent Scottish RTRs. The incidence of skin cancer is high and appears to have a direct relationship to the overall burden of immunosuppression. The SCC:BCC ratio, which is lower than reports from other centres, deserves further scrutiny.     

Warts and epidermoid carcinoma after renal transplantation

Kidney transplant recipients suffer in the long-term from several cutaneous disorders linked to the transplantation. We had the opportunity to observe several patients presenting with pre-epitheliomatous keratoses and cutaneous carcinomas associated with warts. We report herein on five cases that were subjected to a clinical, histological and virological study. Material and methods. Clinical and histological report. The patients were referred to use by the Kidney Transplantation Department of the Ed. Herriot Hospital (Lyon). They were examined clinically by one of us (S.E.). Virological studies. These were performed on warts, keratoses, keratoacanthomas and squamous cell carcinomas. Human papillomavirus (HPV) antigen was detected by indirect immunofluorescence using rabbit antibodies raised against group-specific HPV antigen; viral DNA was detected by in situ molecular hybridization using biotinylated probes of types 1a, 2a, 16, 18 in all cases and type 5 in 14 lesions under stringent conditions. DNA-DNA hybrids were revealed by an alkaline phosphatase enzymatic system. Results: (a) Clinical data are summarized in table I (see fig. 1-5). (b) Histological examination (fig. 6-9) showed either unequivocal squamous-cell carcinoma or keratoacanthoma . The overall architecture of the lesions was reminiscent of keratoacanthoma; however the lower limit was frequently not sharply demarcated; in that area, cells contained large basophilic nuclei exhibiting atypical features and numerous mitoses. The majority of lesions had an histological appearance reminiscent of warts (table III), with upper epidermal keratinocytes being vacuolized and containing basophilic (c) The results of virological studies (fig. 10-13) are summarized in table III. HPV group specific antigen was detected merely in 5 out of 33 lesions; in contrast, in situ molecular hybridization showed that 25 out of 33 lesions contained HPV DNA, with 14 of them containing the potentially oncogenic types 16 and 18. Only 2 lesions were positive with the prove HPV 5. Discussion. The overall incidence of cancers in Kidney transplant recipients (3 p. 100) is about 100 times higher than in control populations (17). Cutaneous carcinomas account for about 50 p. 100 of cancers. This incidence increases with time after transplantation and sun-exposure. The delay on onset of cutaneous malignancies is relatively long (4 to 7 years) (6,7) and becomes longer with a decreasing age of the patients at the time of transplantation, as can be noted in our cases. Apart from Blohme (1), most authors have reported a prevalence of squamous over basal-cell carcinoma. None of our patients presented basal-cell carcinoma.(ABSTRACT TRUNCATED AT 400 WORDS)