D. Cerimele

Kaposi's Sarcoma Associated with Previous Human Herpesvirus 8 Infection in Kidney Transplant Recipients

ABSTRACT This study investigates the prevalence of human herpesvirus 8 (HHV-8) infection in kidney transplant patients, evaluating the risk of HHV-8 transmission via transplantation and the association between pre- and posttransplantation HHV-8 infection and the subsequent development of Kaposis sarcoma (KS). Immunofluorescence and an enzyme immunoassay were used to determine HHV-8 seroprevalence in 175 patients awaiting kidney transplantation and 215 controls who were attending our clinic for other reasons. All patients in the study came from central or southern Italy. Seroprevalence was similar in both groups (14.8 versus 14.9%), with no significant difference between the rates for male and female patients. Of the 175 patients, 100 were tested for anti-HHV-8 antibodies at various times during follow-up. During follow-up, seroprevalence increased from 12% on the date of transplantation to 26%. This increase was paralleled by an age-related increase in seroprevalence in the control group. During follow-up from 3 months to 10 years after transplantation, KS was diagnosed in seven patients (4.0%). Six of these patients were positive for HHV-8 prior to transplantation. Overall, 23.0% of patients who were HHV-8 positive before transplantation developed KS, whereas only 0.7% of seronegative patients developed the disease (relative risk, 34.4; 95% confidence interval, 4.31 to 274.0). This finding suggests that the key risk factor for KS is infection prior to transplantation and that antibody detection in patients awaiting transplantation could be useful in identifying patients at high risk for KS. In patients from geographic areas with a high prevalence of HHV-8, serological tests on donors may be less important.

Kaposi's sarcoma in renal-transplant recipients: experience at the Catholic University in Rome, 1988-1996.

BACKGROUND The incidence of Kaposis sarcoma (KS) in patients transplanted at the Organ Transplant Center of Catholic University in Rome appears to have increased in recent years. OBJECTIVE To describe the clinical characteristics of KS in a group of transplant recipients. METHODS Over 8 years, a total of 302 renal-transplant recipients were followed. When KS was suspected, histology and staging procedures were performed. RESULTS Ten cases of KS have been diagnosed (8 males, 2 females; age 46.4 +/- 9.4 years); 4 of them were on triple therapy. All the patients were HIV-1 seronegative. The onset of KS occurred 3 months to 4 years after transplantation (21.1 +/- 17.6 months). The disease was limited to the skin in 6 cases and involved internal organs in the remaining 4. Four patients experienced complete remission of the disease following reduction of the immunosuppressive therapy. CONCLUSION The high incidence of KS in this population (2.98%), as compared to that reported in other transplant patient groups, suggests that, besides viral infection, genetic predisposition may play a pathogenetic role. However, immunosuppression is the leading factor in transplant patients.

HLA and Multiple Skin Carcinomas

The presence of HLA-associated genetic factors in patients with multiple skin carcinomas was investigated. 43 patients affected by multiple basal and squamous cell carcinomas and 220 healthy age-matched controls were typed for 72 HLA-A, B, C, DR antigens. A negative association of B-17 (mostly B-58) and a positive association of Cw-3 and DR-1 was observed in patients with multiple basal cell carcinomas; a similar negative association with B-58 and positive association with DR-1 was seen in patients with squamous cell carcinomas. The results of this study suggest the presence of resistance factors to the development of skin cancers associated with B-17 (B-58) antigen.

High prevalence of Werner's syndrome in Sardinia. Description of six patients and estimate of the gene frequency.

SummarySeveral patients with Werners syndrome in a large family group in Sardinia were ascertained three years ago and reported briefly by Rabbiosi and Borroni (1979). Since then two sisters from a second family and a single case from a third family were ascertained. The three families originated from the Northern part of Sardinia and no connection between them was found. We provide a detailed clinical description of six of these patients and attempt to estimate the prevalence and the gene frequency of Werners syndrome in Sardinia. The prevalence was calculated as 1:94,914 for the two districts of Sassari and Nuoro and as 1:202,766 for the whole island. This is the highest prevalence thus far ascertained. Using Dahlbergs formula we obtained an estimate of the gene frequency q=0.003288 and thus a frequency of Werners syndrome of 1:92,515. A more rigorous estimate gave a gene frequency q=0.001483 and thus a frequency of Werners syndrome of 1:454,505, but because of the small sample size this estimate should be taken with caution.

High Prevalence of Microproteinuria, an Early Index of Renal Impairment, in Patients with Diffuse Psoriasis

Heavy reversible proteinuria induced by antihypertensive treatment with low doses of captopril has recently been reported by our group in psoriatic patients. To ascertain whether an increased permeability of the glomerular basal membrane of psoriatics can lead to an enhanced urinary excretion of albumin independently from the presence or absence of coexisting diabetes or hypertension, the latter parameter was measured in 39 patients affected by diffuse psoriasis. A high prevalence of microalbuminuria was observed in diabetic and hypertensive psoriatics. Moreover, a direct correlation was found between the diastolic blood pressure (BP) values and the urinary excretion of albumin in the entire group of psoriatics, thus suggesting systemic hypertension as one of the factors responsible for proteinuria in these patients. However, more than 50% of normotensive psoriatics showed an enhanced excretion of albumin. Since microalbuminuria has been indicated as a reliable index to predict the development of renal impairment, the finding of an enhanced albumin loss in psoriatics represents a further risk factor in these patients, who are particularly susceptible to experience cardiovascular complications.

Chromosomal aberrations in lymphocyte and fibroblast cultures of patients with the sporadic type of Kaposi sarcoma

SummaryNumerical and structural chromosomal aberrations were found in metaphases from lymphocyte cultures from Sardinian patients with the sporadic type of Kaposi sarcoma, and also in fibroblasts derived from cultured biopsies of the tumoral lesions. In several cases there was evidence of clonal evolution of some of the chromosomal aberrations. The chromosomes most frequently involved in numerical aberrations were 10, 13, 15, 22 and the X and Y chromosomes, and those most frequently involved in translocations and deletions were 7, 13, 15, 22 and the X chromosomes. The hypothesis is made that in Kaposi sarcoma the chromosomal instability and clonal evolution in vivo could be modulated by the immunologic situation peculiar to the condition.

Chromosome abnormalities in tuberous sclerosis

SummaryIn fibroblasts cultured from biopsies of the skin lesions of six patients with tuberous sclerosis (TS) there was a variable but consistent degree of karyotypic variation. Premature centromere disjunction (PCD) of all or part of the chromosomes, micronuclei, an increased incidence of breaks, dicentric chromosomes and the presence of polyploid metaphases were found in all cultures. The PCD was of the type encountered in Roberts syndrome and its frequency varied from 8% to 30%. In metaphases with PCD of one and of two chromosomes, the chromosome involved were identified, and chromosome 3 was involved 21 times among 59 chromosomes with PCD. Chromosome 3 tends to be preferentially involved in dicentric formation. In lymphocyte cultures from the same patients there were no metaphases with PCD, but there was a slight increase of breaks and the presence of dicentric chromosomes, also involving chromosome 3. Polyploid metaphases were increased in some of the cases. Karyotypic variation can be considered a cellular phenotypic characteristic of TS in fibroblasts cultured from the skin lesions, and its type indicates disturbances in the mechanics of centromere division and of chromosome distribution at cell division.

Infection with Human Herpesvirus Type 8 and Kaposi’s Sarcoma in Sardinia

Background:A cross-sectional study was conducted in the provinces of Sassari (northern Sardinia, covered by a population-based cancer registry), and of Cagliari (southern Sardinia) to estimate the prevalence of infection with human herpesvirus type 8 (HHV8) and the incidence of classic Kaposi’s sarcoma (KS) among HHV8-infected individuals.Patients and Methods:Sera from 297 hospitalized persons potentially at risk of developing classic KS (i. e., those aged 50 years or older) were tested for antibodies against HHV8. HHV8 seroprevalence rates (with 95% confidence intervals—CI) and yearly incidence rates (IR/100,000) of KS were calculated according to age and sex.Results:Of tested individuals, 32.0% had antibodies against HHV8 in Sassari and 30.0% in Cagliari. Estimated IR of KS among HHV8-positive persons and KS:HHV8 ratio were two times higher in Sassari (1:3,891) than in Cagliari (1:8,114), and higher in men (1:2,846 in Sassari; 1:5,483 in Cagliari) as compared to women (1:6,827 in Sassari; 1:12,489 in Cagliari).Conclusions:Although the overall prevalence of HHV8 seemed similar in Sassari and in Cagliari, the risk of KS was higher in Sassari, suggesting that different cofactor(s), or different distribution of the same cofactor(s) between the two provinces of Sardinia, might have played a role in KS development.

Anaplastic progression of classic Kaposi's sarcoma.

We describe a case of classic Kaposis sarcoma (KS) in an Italian HIV-negative patient, with bone involvement and progression to anaplastic histotype. At the age of 22, violaceous patches of KS appeared on his feet. At the age of 50, he noted the appearance of a violaceous firm nodule on his right wrist. The lesions grew rapidly and became ulcerated. Radiotherapy led to a complete remission of symptoms. At the age of 55, a subcutaneous nodule developed on the proximal third of the right forearm associated with a wide painful edema of the right forearm and the proximal third of the right arm. The nodule enlarged rapidly, and an X-ray of the right forearm revealed the presence of a large osteolytic area of the ulna. A biopsy specimen from the right ulna showed bone erosion by a mesenchymal neoplasia with a high degree of malignancy. The right arm was amputated, and histologic examination of the surgical material confirmed the diagnosis of undifferentiated spindle-cell malignant neoplasia strongly positive for factor-VII-related antigen and CD34 antigen. Three years after surgical treatment, no recurrences have been observed.

Pityriasis Rotunda in Childhood

Abstract: Pityriasis rotunda is a rare disease characterized by round or oval patches, localized mainly on the trunk, arms, and legs. The patches are usually lighter than the surrounding skin, but sometimes may be darker, and are covered by fine, adherent scales. Two types of pityriasis rotunda have been described. Type I has been observed mainly in oriental and black patients older than 60 years of age, and is often associated with systemic disease or malignancy. Type II has been observed in white patients younger than 40 years of age, is often familial, and has never been observed in association with malignancy or internal disease. On Sardinia, a cluster of patients with type II pityriasis rotunda has been described. From 1981 until 1998, 51 cases of this disease have been observed in the Department of Dermatology, University of Sassari; 32 of them were children. The great prevalence of pityriasis rotunda on Sardinia, an island which until 40 years ago had limited contact with the Italian mainland, and the presence of a large number of familial cases suggest that type II pityriasis rotunda should be considered a genetically determined disease. The trend toward spontaneous resolution after the age of 20 years suggests that pityriasis rotunda should be considered a genodermatosis with a temporary phenotypic expression.