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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.

Transplant recipients develop numerous benign and malignant cutaneous and mucosal lesions in which histological signs of human papillomavirus (HPV) infection are observed. To investigate the role of HPV and c-myc and c-Ha-ras cellular oncogenes' activation in transplanted patients lesions, we used in situ hybridization with biotinylated probes and Southern blot to detect HPV and oncogenes DNA. We analyzed 36 lesions from grafted patients: 11 common warts, 10 actinic keratoses, 13 squamous cell carcinomas and 2 anogenital papillomas. With in situ hybridization, HPV DNA was detected in 14/36 lesions, 10 of which contained several HPV types. Benign and potentially oncogenic HPV types were detected in warts as well as in squamous cell carcinomas. The Southern blot technique confirmed the distribution of HPV types. Group specific viral antigen was detected in 12 lesions, mainly warts. C-Ha-ras oncogene was amplified in 13 lesions and c-myc oncogene in 10 lesions, 9 of which showed both oncogene amplification. The results obtained with in situ hybridization for c-myc gene amplification were confirmed with the Southern blot technique in 11/14 cases. Ras and/or myc amplification was more frequent in squamous cell carcinomas and anogenital papillomas than in warts and actinic keratoses. The amplification was not always linked to the presence of HPV DNA; however, it was more frequent in lesions infected by potentially oncogenic HPV types than in lesions containing only benign HPV types. Myc and p21 oncoproteins were respectively localized in the nucleus and on the membrane of epithelial cells by immunofluorescence. Most lesions showed a good concordance between the detection of oncogene DNA and proteins. Our results suggest than c-Ha-ras and c-myc cellular oncogenes' activation and HPV infection could play a role in the cancerization of cutaneous lesions from transplant recipients.

Oral hairy leukoplakia (OHL) is seen almost exclusively in patients infected with HIV. A case is reported of OHL occurring in a patient who was seronegative for HIV and who had a renal graft. This occurred following an increase in his treatment with immunosuppressive drugs.

The authors studied the skin disorders in 50 hemodialyzed patients. Pruritus appears to be the main dermatological feature by the frequency of its occurrence and by its unpleasant and even intolerable effects. This sign is more frequent among long time dialyzed patients and seems to be due to 2 factors: high urea blood concentration and secondary hyperparathyroidism. Calcinosis cutis is less frequent than pruritus. It seems to have the same origin and can be considered in the more general picture of the metastatic calcinosis in patients with renal failure and secondary hyperparathyroidism. Hypermelanosis, exceptional in the chronic renal insufficiency patients before hemodialysis, is present in 41% of our group. It is more obvious in the long time dialyzed patients. The nail disorders are mostly the absence of lunula (30%), related to the anaemia, and the half and half nail (36%) that seems specific of the severe azotaemia. Skin dryness (30%) and ichthyosis (10%) can be related to the pruritus. Alopecia, drug reactions and prurigo seems to have a particular indidence. Two patients presented bullous eruptions localized in sunlight exposed areas of skin. The clinical, histological and immunological aspect was identical to that observed in the Porphyria Cutanea Tarda but all the porphyrin levels in the urine and faeces were normal.

In the context of a study of cutaneous problems seen in chronic renal failure patients on intermittent haemodialysis, the authors noted bullous eruptions very similar to late onset cutaneous porphyria. The bullae occur during the summer and are situated on exposed areas, in particular the head and neck. There is skin fragility and the bullae are transient, giving place to erosions and later to atrophic scarring. Even pseudo-miliary cysts have been observed. Histology reveals a sub-epidermal bulla, the basis of which consists of spiky papillary dermis. Immunofluorescence show immunoglobulin deposits in the vessels and basal membrane. All porphyrin measurements are negative. This disorder may be due to the presence of a non-porphyrinogenic photo-sensitising substance, found in certain types of plastic tubing.

The authors studied by electron microscope, the sun-exposed skin of the back of the hand from three heavily hemodialysed patients with a porphyria cutanea tarda-like bullous skin disease. The vascular impairment, like that of PCT, closely resembles that seen during medicamentous phototoxic processes. The connective tissue is infiltrated by large granulo-filamentous masses and the fibroblasts are secretory in appearance. At the dermal-epidermal junction, the abnormalities are important, with a diffuse infiltration of the upper dermis by a hyalin substance, probably resulting in a collagen degeneration and cellular necrosis. The aetiological factors are uncertain, as no common medicamentous factor appeared in our patients, and as the plasticizers used in the hemodialysis tubes probably played no part.

Eccrine syringofibroadenoma is a rare tumor considered to originate from the excretory portion of the eccrine sweat gland. A new case of this lesion, whose acrosyringeal differentiation was underlined by an immunohistological study using antibodies to keratin and involucrin, is reported herein.

Unlabelled: 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)

Four cases of Kaposi's sarcoma in recipients of renal transplants are reported. The 4 patients of Italian origin were male. Kaposi's sarcoma, began during pre-transplantation haemodialysis, then extended in one of the patients; in the remaining 3 patients it developed 20 months on average after transplantation. All patients were receiving an immunosuppressive treatment (azathioprine, systemic corticosteroids, anti-lymphocyte serum). Kaposi's sarcoma was located in the skin and mucosae, sometimes in lymph nodes and viscera. In 2 patients the cutaneous and mucosal lesions responded well to vindesine: in the other two patients withdrawal of the immunosuppressive therapy had no effect on the course of the disease. This study highlights the multiple factors involved in the development of Kaposi's sarcoma, notably immunosuppression and the ethnic factor.

In this study, 100 hemodialyzed patients were examined for pseudo-porphyria cutanea tarda, which was first described in 1975. Pseudo-porphyria cutanea tarda was found in 16%. Our main concern was the analysis of the etiological factors; none of the hypotheses so far put forward--a medicinal agent, an hepatic disorder, or some factor relating to the material used in the dialysis--has been confirmed. On the other hand, this condition occurred in patients with the longest interval since dialysis, and who were more often than not completely anuretic. These facts would seem to indicate that this is part of a premature ageing process which is common in these patients.