Post-transplant Kaposi's Sarcoma Research Articles

BI06 The rising incidence of post-transplant Kaposi sarcoma in organ transplant recipients in a single-centre cohort: should we be routinely screening?

BI06 The rising incidence of post-transplant Kaposi sarcoma in organ transplant recipients in a single-centre cohort: should we be routinely screening?

Evaluating Kaposi Sarcoma in Kidney Transplant Patients: A Systematic Review and Meta-Analysis.

Kaposi's sarcoma (KS) is a malignancy that commonly appears as lesions on the skin or mucosal surfaces but can also develop in other organs. This cancer is usually caused by the human herpesvirus 8 (HHV-8), recently known as Kaposi's sarcoma-associated herpesvirus (KSHV). KS is rare in the general population but can develop in kidney transplant recipients with varying incidence due to immunocompromised status from immunosuppression. The main aim of the present systematic review was to identify the prevalence and treatment of KS in kidney transplant patients. PubMed, Cochrane Library, and Google Scholar databases were searched for studies until October 2023. Full-text studies with similar research objectives were included, while non-English articles, reviews, case reports, ongoing clinical trials, and studies evaluating KS in HIV patients or after other solid organ transplants were excluded. All studies were observational; therefore, methodological quality was assessed using the Newcastle-Ottawa Scale. The statistical analyses were performed with the Comprehensive Meta-Analysis (CMA) software (Biostat, Inc.Englewood, NJ). The pooled analysis from the 15 studies includedshowed that KS develops in 1.5% of kidney transplant recipients and is more prevalent in African (1.7%) and Middle Eastern (1.7%) recipients than in Western recipients (0.07%). KS was also significantly more prevalent among male recipients than female recipients (OR: 2.36; p < 0.0001). Additionally, cyclosporine-based immunosuppression accounts for most KS incidences (79.6%) compared to azathioprine-based immunosuppression (28.2%). Furthermore, reduction or withdrawal of immunosuppression alone resulted in 47.8% KS complete remissions. Post-kidney transplantation KS is more frequent among males and patients of Middle Eastern and African origin. However, the gender difference may be attributed to most patients undergoing kidney transplants being male. Therefore, if gender balance is considered in future studies, then the difference might be insignificant. Based on our results, we can concur that the mainstay treatment for post-transplant KS is reduction or withdrawal of immunosuppression. However, the patients should be closely monitored to avoid KS recurrence and kidney rejection. Furthermore, there is an increased risk for KS with the use of cyclosporine-based immunosuppression. However, this does not mean that the withdrawal of this immunosuppression agent might result in improved KS outcomes because the withdrawal of azathioprine with or without cyclosporine reduction has also led to improved outcomes.

Effectiveness and safety of conventional systemic treatments in classical and endemic Kaposi sarcoma: A multicentric retrospective study of 110 patients.

e21584 Background: Apart from post-transplant Kaposi sarcoma (KS), 2 major subtypes of non-HIV-related KS are described: classical Kaposi sarcoma (CKS) in patients originated from Mediterranean countries and endemic KS (EKS) in patients of sub-Saharan Africa origin. Some patients with aggressive EKS or CKS require systemic treatments among which liposomal anthracycline (LA), taxanes and, to a lesser extent, low dose interferon (LDI) are generally recommended as first lines. Recently, anti-PD1 have shown promising results in an early phase II trial. At the dawn of a turning point in therapeutic era, we aim to map the effectiveness and safety of the main conventional systemic treatments usually available in KS. Methods: We performed a national multicentric retrospective study including all patients receiving a systemic treatment for a histologically proven KS between January 1st 2013 to July 1st 2019. HIV infected patients and patients treated with immunosuppressive drugs were excluded. Overall response was defined as a decrease of more than 50% of lesion area and serious adverse events encompassed grade 3 and 4 toxicity. Results: A total of 110 patients were included. Sixty-nine had CKS (62.7%) and 41 had EKS (37.2) with a median age at diagnosis of 69 (IQR: 57-77) and 41 years (37-59) (p = 0.011), respectively. At the time of diagnosis, EKS was associated with greater systemic involvement compared with CKS (36.6% vs 14.9%, p = 0.017). First-line therapy was initiated within a median of 13.8 months (2.9-43) after KS diagnosis. The 3 main regimens were taxanes (27.3%), LA (19.1%) and LDI (19.1%) with response rates of 82.8%, 80% and 52.6% (p = 0.063), respectively. The cumulative incidence of a second line of treatment in the first 2 years of follow-up was 49.5% (CI95% 38.7-59.4), without significant difference according to the different regimens. Toxicity, regardless of grade, was reported more frequently with LDI (55.3%) and taxanes (47.8%) than with LA (30.4%) (p = 0.035). Poor tolerability led to discontinuation of LDI more frequently than LA (OR = 4.17, p = 0.048), without difference for taxanes. There was no difference in serious adverse events between the 3 main regimens. CKS and EKS didn’t differ regarding overall response rate or time to next treatment regardless of treatment regimens. However, response rates tended to decrease as the lines went on for EKS (from 77.5% in 1st to 33.3% in 3rd line, p = 0.005), in contrast to CKS who maintained a sustained response, with more frequent systemic involvement (56% vs 25.4%, p = 0.002) during EKS course. Conclusions: Herein, we highlight LA, taxanes and LDI are safe and effective treatments for non-immunodeficient KS. Furthermore, EKS differed from CKS, occurring in younger patients, with more frequent systemic involvement and response loss through therapeutic lines, emphasizing the need to evaluate new agents in this form of KS.

Diagnosis and treatment of classic and iatrogenic Kaposi's sarcoma: Italian recommendations.

Kaposi's sarcoma (KS) is a lymphangioproliferative disorder associated with Human herpesvirus 8 (HHV8) infection. Four clinical subtypes are recognized: classic, endemic, epidemic (HIV-related) and iatrogenic. KS diagnosis is based on clinical features, histopathological assessment, and HHV8 serology. Classic KS is usually skin-limited and has a chronic course, while the iatrogenic variant may show mucosal, nodal or visceral involvement. Clinical staging is fundamental to guide the management. Localized disease may be treated with different local therapies, even if there are no randomized trials comparing these different modalities. Aggressive, disseminated KS and cases with visceral involvement usually require systemic chemotherapy, most commonly vinblastine, bleomycin or paclitaxel. Iatrogenic KS needs immunosuppression tapering/withdrawal and, if possible, switch to m-TOR inhibitors in post-transplant KS. The present work by a panel of Italian experts provides guidelines on KS diagnosis and management based on a critical review of the literature and a long and extensive personal experience.

Succès du traitement par paclitaxel d’une rechute viscérale d’un sarcome de Kaposi après transplantation rénale

We report the observation of a patient who presented with post-transplant Kaposi's sarcoma after a delay of eight months with a dual cutaneous and palatal localisation. The reduction in immunosuppressive treatment and the introduction of Rapamune® allowed good clinical progress initially with regression of the skin lesions. He subsequently presented later a skin relapse with visceral localisation. Chemotherapy was conducted based on weekly paclitaxel infusions allowing partial remission and maintenance of renal graft function with good clinical tolerance.

Trends in Kaposi's Sarcoma Morbidity: A Retrospective Cohort Study of Heart and Lung Transplant Recipients.

Data on post-transplant Kaposi’s sarcoma in heart and lung transplant recipients are sparse. This study examined the incidence of biopsy-proven post-transplant Kaposi’s sarcoma in thoracic organ recipients over a period of 20 years. As mammalian target of rapamycin inhibitors were introduced in 2006 as optional maintenance immunosuppressive therapy, the overall results were analysed and stratified into 2 groups: 1996 to 2005 and 2006 to 2016. A total of 867 transplant recipients met the study criteria. Post-transplant Kaposi’s sarcoma was diagnosed in 7 (0.81%) patients. Five cases (0.19% of transplant recipients) were recorded in 1996 to 2005 and 2 (0.03% of transplant recipients) in 2006 to 2016 (p = 0.04). Multivariable logistic regression analyses identified the following as risk factors: period of transplantation (odds ratio (OR) 4.844, 95% confidence interval (95% CI) 1.156–20.291), age at transplantation (OR 1.066, 95% CI 0.992–1.145), and North African origin (OR 7.282, 95% CI 12.55–42.254). This study found a decreased incidence of post-transplant Kaposi’s sarcoma over the last 20 years, mainly attributed to the change in immunosuppressive therapy.

Risk of Kaposi's Sarcoma-Associated Herpes Virus Transmission From Donor Allografts Among Italian Posttransplant Kaposi's Sarcoma Patients

AbstractKaposi's sarcoma–associated herpesvirus (KSHV) is a newly discovered herpes virus found in all forms of Kaposi's sarcoma (KS) including KS among immunosuppressed transplant patients. It is unknown whether this virus is transmitted by organ transplantation or is reactivated during immunosuppression among those patients infected before transplantation. To investigate the risk of KSHV transmission during organ transplantation, we conducted a case-control study of transplant recipients with and without KS matched to their respective donors. Sera were collected at time of transplantation and tested in a randomized and blinded fashion using four KSHV serologic assays testing for antibodies to both latent and lytic phase antigens. Ten (91%) of 11 organ recipients who developed KS were seropositive prior to transplantation by one or more of the assays compared with two (12%) of 17 control organ recipients (OR = 75, 95% CI = 4.7, 3500). KS cases were more likely to have been born in southern Italy where KS is endemic than the recipient controls or either donor group. Only four (36%) of 11 donors to case patients and three (18%) of 17 donors to control patients were seropositive (P = .38, two-tailed Fisher's exact test). KSHV transmission could not be ruled out for the single KS patient seronegative at transplantation and clear evidence for organ-related transmission was found for another KS patient outside of the case-control study. Antibodies to KSHV are detectable in the sera from most transplant recipients before initiation of immunosuppressive treatment suggesting that KS among immunosuppressed transplant patients is primarily due to virus reactivation. KSHV transmission, however, from an infected allograft can occur, and our study reports the first documented case of person-to-person transmission of KSHV.

Italian guidelines for the diagnosis and treatment of classic and iatrogenic Kaposi's sarcoma

Kaposi's sarcoma (KS) is a lymphangioproliferative disorder associated with human herpesvirus 8 (HHV8) infection. Four clinical subtypes are recognized: classic, endemic, epidemic (HIV-related) and iatrogenic. KS diagnosis is based on clinical features, histopathological assessment, and HHV8 serology. Classic KS is usually skin-limited and has a chronic course, while the iatrogenic variant may show mucosal, nodal or visceral involvement. Clinical staging is fundamental to guide the management. Localized disease may be treated with different local therapies, even if there are no randomized trials comparing these different modalities. Aggressive, disseminated KS and cases with visceral involvement usually require systemic chemotherapy, most commonly vinblastine, bleomycin or paclitaxel. Iatrogenic KS needs immunosuppression tapering/withdrawal and, if possible, switch to m-TOR inhibitors in post-transplant KS. The present work by a panel of Italian experts provides guidelines on KS diagnosis and management based on a critical review of the literature and a long and extensive personal experience.

Donor-derived human herpesvirus 8 and development of Kaposi sarcoma among 6 recipients of organs from donors with high-risk sexual and substance use behavior.

Kaposi sarcoma (KS) can develop following organ transplantation through reactivation of recipient human herpesvirus 8 (HHV‐8) infection or through donor‐derived HHV‐8 transmission. We describe 6 cases of donor‐derived HHV‐8 infection and KS investigated from July 2018 to January 2020. Organs from 6 donors, retrospectively identified as HHV‐8‐positive, with a history of drug use disorder, were transplanted into 22 recipients. Four of 6 donors had risk factors for HHV‐8 infection reported in donor history questionnaires. Fourteen of 22 organ recipients (64%) had evidence of posttransplant HHV‐8 infection. Lung recipients were particularly susceptible to KS. Four of the 6 recipients who developed KS died from KS or associated complications. The US opioid crisis has resulted in an increasing number and proportion of organ donors with substance use disorder, and particularly injection drug use history, which may increase the risk of HHV‐8 transmission to recipients. Better awareness of the risk of posttransplant KS for recipients of organs from donors with HHV‐8 infection risk could be useful for recipient management. Testing donors and recipients for HHV‐8 is currently challenging with no validated commercial serology kits available. Limited HHV‐8 antibody testing is available through some US reference laboratories and the Centers for Disease Control and Prevention.

Diagnosis and treatment of Kaposi's sarcoma: European consensus-based interdisciplinary guideline (EDF/EADO/EORTC)

Kaposi's sarcoma (KS) is a multifocal neoplasm of lymphatic endothelium-derived cells infected with human herpesvirus 8. Four clinical subtypes are distinguished: the classic, the endemic, the epidemic subtype in HIV positive patients and the iatrogenic subtype. The diagnosis is primarily based on clinical features and confirmation by histology with immunohistochemistry. Cutaneous distribution and severity, mucosal, nodal and visceral involvement depend on the type of KS with in general indolent behaviour and chronic evolution in the classic subtype and the more severe forms in iatrogenic or epidemic subtypes. Management should aim at achieving disease control. For localised lesions, several local therapies have been developed without randomised trial comparisons. Radiotherapy, intralesional chemotherapies and electrochemotherapy have high response rates. Topical treatments—imiquimod or topical 9-cis-retinoid acid—can also be used. Systemic treatments are reserved for locally aggressive extensive and disseminated KS: the recommended first-line agents are pegylated liposomal doxorubicin (PLD) and paclitaxel. In CKS, PLD or low-dose interferon-alfa are the recommended first-line agents in younger patients. In AIDS-related KS, combination antiretroviral therapy is the first treatment option; specific systemic treatment is needed only in case of extensive disease and in the prevention and treatment of immune reconstitution inflammatory syndrome. In post-transplant KS, tapering down immunosuppressive therapy and switching to mammalian target of rapamycin (m-TOR) inhibitors are used. Follow-up schedules for patients with KS disease depend on aggressiveness of the disease.

Management of Kaposi sarcoma after solid organ transplantation: A European retrospective study

Systemic therapeutic management of post-transplant Kaposi sarcoma (KS) is mainly based on 3 axes: reduction of immunosuppression, conversion to mammalian target of rapamycin (mTOR) inhibitors, chemotherapy, or a combination of these. To obtain an overview of clinical strategies about the current treatment of KS. We conducted a multicenter retrospective cohort study including 145 solid organ transplant recipients diagnosed with KS between 1985 and 2011 to collect data regarding first-line treatment and response at 6months. Overall, 95%, 28%, and 16% of patients had reduction of immunosuppression, conversion to mTOR inhibitor, and chemotherapy, respectively. Patients treated with chemotherapy or mTOR inhibitor conversion were more likely to have visceral KS. At 6months, 83% of patients had response, including 40% complete responses. The retrospective design of the study. Currently available therapeutic options seem to be effective to control KS in most patients. Tapering down the immunosuppressive regimen remains the cornerstone of KS management.

Kaposi Sarcoma in HIV-positive Solid-Organ Transplant Recipients: A French Multicentric National Study and Literature Review.

Kaposi sarcoma is a vascular tumor related to herpesvirus-8 and is promoted by immunosuppression. For the last 15 years, human immunodeficiency virus (HIV) patients have had access to organ transplantation. The dual immunosuppression of HIV and immunosuppressive treatments might increase the risk and severity of Kaposi sarcoma. We conducted a multicentric retrospective study by collecting cases from French databases and society members of transplanted patients, among which 7 HIV-infected patients who subsequently developed Kaposi sarcoma were included. In the CRISTAL database (114 511 patients) and the DIVAT (Données Informatisées et VAlidées en Transplantation) database (19 077 patients), the prevalence of Kaposi sarcoma was 0.18% and 0.46%, respectively, in transplanted patients; these values compare with 0.66% and 0.50%, respectively, in transplanted patients with HIV. The median time from HIV infection to Kaposi sarcoma was 20 years. Kaposi sarcoma occurred during the first year after transplantation in most cases, whereas HIV viral load was undetectable. Only 2 patients had visceral involvement. Five patients were treated with conversion of calcineurin inhibitor to mammalian target of rapamycin inhibitor, and 5 patients were managed by decreasing immunosuppressive therapies. At 1 year, 4 patients had a complete response, and 3 had a partial response. In our study, Kaposi sarcoma in transplanted patients with HIV did not show any aggressive features and was treated with the usual posttransplant Kaposi sarcoma management protocol.

Outcome of second kidney transplantation in patients with previous post-transplantation Kaposi's sarcoma: A French retrospective study.

This retrospective study concerned 8 patients with post-transplantation Kaposi's sarcoma (pt-KS) after a first kidney transplant who later had a second kidney transplantation. Pt-KS was widespread, with lymph node or visceral involvement in 7 cases. Complete remission was observed in 6 cases and partial remission in 2. After the second kidney transplantation, only 2 cases showed recurrence of skin KS, one with previous complete remission of KS and one with partial remission. The mean delay between stability or complete remission of KS and retransplantation was 2.0 and 7.3years in patients with and without relapse, respectively. Both recurrent cases showed complete KS remission after tapering immunosuppression therapy and/or switching a calcineurin inhibitor to a mammalian target of rapamycin inhibitor. We compared these 8 cases to 24 controls who had undergone 2 kidney transplantations but did not have KS, matching on sex, age and phototype. Cases and controls did not differ in graft function or survival. A second kidney transplantation may be possible after pt-KS and has acceptable risk, especially after a long complete remission of pt-KS.

Post-transplant kaposi's sarcoma: an unusual presentation and review of clinical presentation, histology and management

Abstract: Kaposi's sarcoma is an uncommon, vascular neoplasm associated with Human Herpes Virus 8 (HHV-8). An unusual case of PT-KS, presenting with pain from bilateral macular lesions on the palate, is discussed. As far as the authors are aware, this is the only reported case of a macular post-transplant Kaposi's sarcoma initially presenting with pain. The diagnosis, clinical presentation and histology are discussed, and an update on the oral presentation and management of post-transplant Kaposi's sarcoma is provided. CPD/Clinical Relevance: Post-transplant Kaposi's sarcoma is a neoplasm found in post-transplant patients that can present intra-orally, and needs to be identified early to ensure the best possible outcome for the patient.

Localized Kaposi Sarcoma

Kaposi sarcoma (KS) is a lymphoangio-proliferative disease often caused by KS associated herpes virus, also known as human herpes virus 8. There are 4 known variants of KS: Epidemic or AIDS-associated KS, Endemic or African KS, iatrogenic post transplantation KS and Mediterranean or classic KS (CKS). We report a case of CKS treated successfully by radiation therapy.

Role of HHV-8 and mTOR pathway in post-transplant Kaposi sarcoma staging.

Kaposi's sarcoma (KS) is one of the most frequent transplant related tumors. Several pathways are involved; however, the impact of the molecular phenotype associated to the tumor stage and the behavior-depending resultant therapy is still unknown. The aim of our study was to analyze the role of HHV-8 and mTOR pathway in tumor stages of skin KS after renal transplantation. Twelve renal transplant recipients with cutaneous KS from five transplant centers (1980-2007) under reduction of immunosuppression or conversion to mTOR inhibitor were included. The expression of HHV-8, PTEN, TGFβ, VEGF, phospho-mTOR, and phospho-P70S6K in tumoral tissue was analyzed. KS lesions were classified as patch, plaque, and nodule state. HHV-8 infection was found in all tissue samples. KS lesions showed high activation of VEGF, p-mTOR and p-P70S6K, low PTEN, and null TGFβ expression. The only pathway activated in a staging-dependent manner was mTOR with higher p-mTOR and p-P70S6K expression in nodule versus patch stage. KS lesions disappeared after 5.24 months in all converted patients without any recurrence in 14.05 years of mean follow-up. The activation of mTOR pathway according to KS stages supports the rational of the mTOR inhibitor in post-transplant Kaposi.

Incidence and Management of Kaposi Sarcoma in Renal Transplant Recipients: The Greek Experience

ObjectiveOne of the most common malignancies in kidney transplant recipients is Kaposi sarcoma. The incidence of Kaposi sarcoma, which develops after renal transplantation, is 400–500 times higher than that in the general population. The aims of this study were to review the experience with Kaposi sarcoma in the highest-volume transplantation Unit in Greece and to analyze clinical characteristics and response to treatment, with respect to both the patients' survival and the renal graft function. Materials and MethodsThe records of 2008 renal graft recipients between March 1983 and December 2012 were retrospectively reviewed. Kaposi sarcoma was diagnosed based on clinical, laboratory, radiological, endoscopic, and histopathologic examinations. The disease was staged according to the classification of Al-Khader et al. ResultsThe prevalence of Kaposi sarcoma was 1.2% in our renal transplant population. Of these, 1006 recipients underwent living-donor renal transplantation, whereas 1002 received their graft from deceased donors. Post-transplantation malignancy developed in 153 patients, among which, Kaposi sarcoma has been found in 24 cases. Of the 24 cases of Kaposi sarcoma, lesions were mainly cutaneous in 14 cases, visceral and cutaneous in 8, and concomitant visceral and lymph node involvement was observed in 2 patients. With regard to the final outcome, 20 patients (83.3%) showed remission of the disease, whereas 4 patients with visceral involvement (16.6%) did not respond to chemotherapy and discontinuation of immunosuppression and died. Moreover, 8 deaths occurred due to apparently unrelated causes. ConclusionsKaposi sarcoma is an important part (15.7%) of all post-transplantation neoplasias in our series. Furthermore, our findings confirmed the previously described close association between human herpesvirus-8 and post-transplantation Kaposi sarcoma. Reduction of immunosuppression or discontinuation of calcineurin inhibitors results in remission of the disease in most of the cases. Prognosis in patients with Kaposi sarcoma limited to the skin is favorable, whereas visceral involvement is associated with high mortality.

The role of mammalian target of rapamycin inhibitors in the management of post‐transplant malignancy

Post-transplant malignancies, which occur either de novo or as cancer recurrences, are due to chronic exposure to immunosuppressive agents and are often more aggressive than those that develop in the non-transplant setting. Mammalian target of rapamycin (mTOR) inhibitors have antitumor and immunosuppressive effects. The dual effects of this class of agents may provide adequate immunosuppression to prevent organ rejection while simultaneously reducing the risk of post-transplant malignancy. mTOR inhibitors have become established approved agents for treating renal cell carcinoma and other cancers and, as reviewed herein, accumulating experience among organ transplant recipients collectively points toward a potential to prevent the development of de novo malignancies of various types in the post-transplant period. To date, most research efforts surrounding mTOR inhibitors and cancer control in the transplant population have been in the area of skin cancer prevention, but there have also been interesting observations regarding regression of post-transplant Kaposi's sarcoma and post-transplantation lymphoproliferative disorder that warrant further study.

A Unique Herpesviral Transcriptional Program in KSHV-Infected Lymphatic Endothelial Cells Leads to mTORC1 Activation and Rapamycin Sensitivity

Immunosuppression therapy following organ transplantation is a significant factor in the development and progression of Kaposi's sarcoma-associated herpesvirus (KSHV)-induced posttransplant Kaposi's sarcoma (KS). Switching from cyclosporine to the mTOR inhibitor rapamycin is reported to promote KS regression without allograft rejection. Examining the underlying molecular basis for this clinical observation, we find that KSHV infection selectively upregulates mTOR signaling in primary human lymphatic endothelial cells (LECs), but not blood endothelial cells (BECs), and sensitizes LECs to rapamycin-induced apoptosis. Viral transcriptome analysis revealed that while infected BECs display conventional latency, KSHV-infected LECs support a radically different program involving widespread deregulation of both latent and lytic genes. ORF45, a lytic gene selectively expressed in infected LECs, is required for mTOR activation and critical for rapamycin sensitivity. These studies reveal the existence of a unique herpesviral gene expression program corresponding to neither canonical latency nor lytic replication, with important pathogenetic and therapeutic consequences.

Post renal transplantation Kaposi's sarcoma: a review of its epidemiology, pathogenesis, diagnosis, clinical aspects, and therapy

Kaposi's sarcoma (KS) is a vascular malignancy primarily involving the skin. This neoplasm occurs commonly in acquired immunodeficiency syndrome (AIDS) and post solid organ transplantation. Human herpesvirus type 8 (HHV-8) has been shown to play a causative role in AIDS-associated KS and in post renal transplantation KS. Based on a MEDLINE search, we present a review of the current information on the epidemiology, pathogenesis, diagnosis and treatment of post-transplantation KS (PT-KS) with an emphasis on renal transplantation. The different frequencies of PT-KS in different parts of the world seem to be related to seroprevalence of HHV-8 infection. Following renal transplantation and the administration of immunosuppressive therapy, HHV-8 may reactivate. The renal tubular epithelium is a site for HHV-8 latency. Rates of PT-KS in seropositive recipients and anti-HHV-8 mismatched recipients (donor+/recipient-) are approximately 13% and 4.6%, respectively. Additional risk factors for the development of PT-KS include skin color, country of birth, age at the time of transplantation, and different induction regimens including anti-thymocyte globulin, steroid, or anti-interleukin 2-receptor antagonists. Skin is the major site of involvement. Surprisingly, involvement of the transplanted organ has been reported to be extremely rare. Reduction in immunosuppressive therapy and switching to mammalian targets of rapamycin inhibitors, such as sirolimus, are effective treatments for PT-KS. In patients with no response to reduction in immunosuppressive therapy, systemic chemotherapy with different regimens has been reported to be successful. PT-KS in renal transplant patients is an important problem specifically in southern Europe and the Middle East. In the majority of patients, the diagnosis based on clinical suspicion is always essential. Clinicians should bear in mind that PT-KS may threaten graft function and hence result in rejection complications. Appropriate management increases patient survival.