[Show abstract][Hide abstract] ABSTRACT: The increased risk of skin cancer is well known in heart and kidney transplant recipients, but fewer data exist on liver-transplant recipients (LTRs). The aim of this study was to analyze the prevalence, clinical features and risk factors of skin cancers in LTR treated mainly with tacrolimus.
We selected LTR grafted in our hospital between January 1996 and December 2008, aged 20 years or more at the time of the study. Data were collected from the patients' medical files and with a questionnaire.
Three hundred seventy-one LTR were included. The median follow-up period was 8.2 years. The overall prevalence of skin cancers was 13.5%. The prevalence of melanoma was 1.3%. The squamous cell carcinoma to basal cell carcinoma ratio was 1:3. Both the overall cumulative patient risk of de novo skin malignancies and the squamous cell carcinoma-to-basal cell carcinoma ratio increased with time postgraft. The duration of immunosuppression was a risk factor, in addition to those common in the general population. No association was found between the primary liver disease and the development of skin cancer.
Contrasting with previous data of the literature, our findings suggest that, for a similar follow-up time, the risk of skin cancer in LTR is comparable to that of kidney transplant recipients.
[Show abstract][Hide abstract] ABSTRACT: Mammalian Target of Rapamycin (mTOR) inhibitors, such as sirolimus and everolimus, have been shown to reduce cutaneous carcinogenesis in organ-transplant recipients requiring for immunosuppressive treatment to prevent from allograft rejection. Clinical observations suggest that cutaneous squamous cell carcinomas (SCC) are more sensitive than basal cell carcinomas (BCC) to the antitumoral effect of these inhibitors. Aim: To investigate if the different response of SCC and BCC to mTOR inhibitors can be explained by differential expression of molecules involved in the mTOR signaling pathway.
The expression of phospho-mTOR was immunohistocemically studied in specimens of cutaneous SCC and BCC. Results. All 15 SCCs expressed significant cytoplasmic phospho-mTOR immunoreactivity; by contrast, 12/13 BCC were completely negative, only one BCC exhibited weak phospho-mTOR immunoreactivity.
The considerably higher expression of phospho-mTOR in SCC compared to BCC is a likely explanation for their higher sensitivity to mTOR inhibitors.
Anticancer research 09/2013; 33(9):3711-4. · 1.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Primary cutaneous posttransplant lymphoproliferative disorders (PTLD) are rare. This retrospective, multicenter study of 35 cases aimed to better describe this entity. Cases were (re)-classified according to the WHO-EORTC or the WHO 2008 classifications of lymphomas. Median interval between first transplantation and diagnosis was 85 months. Fifty-seven percent of patients had a kidney transplant. Twenty-four cases (68.6%) were classified as primary cutaneous T cell lymphoma (CTCL) and 11 (31.4%) as primary cutaneous B cell PTLD. Mycosis fungoides (MF) was the most common (50%) CTCL subtype. Ten (90.9%) cutaneous B cell PTLD cases were classified as EBV-associated B cell lymphoproliferations (including one plasmablastic lymphoma and one lymphomatoid granulomatosis) and one as diffuse large B cell lymphoma, other, that was EBV-negative. Sixteen (45.7%) patients died after a median follow-up of 19.5 months (11 [68.8%] with CTCL [6 of whom had CD30(+) lymphoproliferative disorders (LPD)] and 5 [31.2%] with cutaneous B cell PTLD. Median survival times for all patients, CTCL and cutaneous B cell PTLD subgroups were 93, 93, and 112 months, respectively. Survival rates for MF were higher than those for CD30(+) LPD. The spectrum of primary CTCL in organ transplant recipients (OTR) is similar to that in the general population. The prognosis of posttransplant primary cutaneous CD30(+) LPD is worse than posttransplant MF and than its counterpart in the immunocompetent population. EBV-associated cutaneous B cell LPD predominates in OTR.
American Journal of Transplantation 05/2013; · 6.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Organ transplant recipients (OTR) are at increased risk of cutaneous squamous cell carcinoma, which may be related to reactivation of human papillomavirus (HPV) infections. Measurement of change in HPV antibodies after transplantation would help to explore this hypothesis. We measured antibodies to 34 HPV types on up to six occasions over 18 months in 441 OTRs from five European countries. At baseline (mean 24 days after transplantation), 80% of all OTRs were seropositive to at least one HPV type. The beta HPV genus had the highest seroprevalence (45%). For most HPV genera baseline seroprevalence peaked between 40 and 59 years old. Most OTRs retained their serostatus over time and antibody levels were stable. Seroprevalence in immunosuppressed OTRs is stable in the 18 months immediately after transplantation. Thus there is no short-term evidence that immunosuppression leads to new or reactivated skin infection with HPV sufficient to induce antibodies.
[Show abstract][Hide abstract] ABSTRACT: The aims of the study were to assess the risk of HHV8 transmission resulting from organ transplantation, and related morbidity in liver, heart and kidney transplant recipients. Donor and recipient serologies were screened between January 1, 2004 and January 1, 2005 using HHV8 indirect immunofluorescence latent assay (latent IFA) and indirect immunofluorescent lytic assay (lytic IFA). Recipients negative for latent IFA with a donor positive for at least one test were sequentially monitored for HHV8 viremia and underwent serological tests over a period of 2 years. The results showed that among 2354 donors, HHV8 seroprevalence was 9.9% (lytic IFA) and 4.4% (latent IFA). A total of 454 organ recipients (281 renal, 116 liver and 57 heart) were monitored over a 2-year period. Seroconversion was observed in 12 patients (cumulative incidence 28%) whose donor had positive latent IFA and in 36 patients (cumulative incidence 29%) whose donors were positive only for lytic IFA, without differences across types of transplants. Positive HHV8 viremia was detected in only 4 out of 89 liver transplant recipients during follow-up and not in recipients of other types of transplant. Two liver transplant recipients and one kidney transplant recipient developed KS. In conclusion, although HHV8 transmission is a frequent event after organ transplantation, HHV8-related morbidity is rather rare but can be life threatening. Donor screening is advisable for monitoring HHV8 seronegative liver transplant recipients.
American Journal of Transplantation 10/2012; · 6.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Data on post-graft cutaneous cryptococcosis (CC) are rare. The objective was to delineate the epidemiological, clinical, diagnostic, therapeutic features of CC in organ transplant recipients. We compared cases from a cohort of 3,670 transplanted adults with cases from a regional cryptococcosis registry including 122 patients. Four CC were diagnosed in the transplanted cohort (1‰) corresponding in the regional registry to 33% of the 12 cases of cryptococcosis after transplantation, while among the 110 non-grafted patients, only five cryptococcosis were cutaneous (4%). CC appeared as a single (3 patients) ulcer or nodule over 1cm in size in an uncovered body zone, on average 13 months post-graft. 3 patients had concomitant opportunistic infections or a recent increase in their immunosuppression. All CC after transplantation were localized exclusively to the skin, raising the question of the mode of contamination (through the skin or the lungs). Evidence of dissemination is difficult because of the poor sensitivity of diagnostic tests. Fluconazole was the treatment of choice in association with immunosuppressive treatment tapering.
European journal of dermatology : EJD. 09/2012; 22(5):651-7.
[Show abstract][Hide abstract] ABSTRACT: Transplant recipients in whom cutaneous squamous-cell carcinomas develop are at high risk for multiple subsequent skin cancers. Whether sirolimus is useful in the prevention of secondary skin cancer has not been assessed.
In this multicenter trial, we randomly assigned transplant recipients who were taking calcineurin inhibitors and had at least one cutaneous squamous-cell carcinoma either to receive sirolimus as a substitute for calcineurin inhibitors (in 64 patients) or to maintain their initial treatment (in 56). The primary end point was survival free of squamous-cell carcinoma at 2 years. Secondary end points included the time until the onset of new squamous-cell carcinomas, occurrence of other skin tumors, graft function, and problems with sirolimus.
Survival free of cutaneous squamous-cell carcinoma was significantly longer in the sirolimus group than in the calcineurin-inhibitor group. Overall, new squamous-cell carcinomas developed in 14 patients (22%) in the sirolimus group (6 after withdrawal of sirolimus) and in 22 (39%) in the calcineurin-inhibitor group (median time until onset, 15 vs. 7 months; P=0.02), with a relative risk in the sirolimus group of 0.56 (95% confidence interval, 0.32 to 0.98). There were 60 serious adverse events in the sirolimus group, as compared with 14 such events in the calcineurin-inhibitor group (average, 0.938 vs. 0.250). There were twice as many serious adverse events in patients who had been converted to sirolimus with rapid protocols as in those with progressive protocols. In the sirolimus group, 23% of patients discontinued the drug because of adverse events. Graft function remained stable in the two study groups.
Switching from calcineurin inhibitors to sirolimus had an antitumoral effect among kidney-transplant recipients with previous squamous-cell carcinoma. These observations may have implications concerning immunosuppressive treatment of patients with cutaneous squamous-cell carcinomas. (Funded by Hospices Civils de Lyon and others; TUMORAPA ClinicalTrials.gov number, NCT00133887.).
New England Journal of Medicine 07/2012; 367(4):329-39. · 54.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bacillary angiomatosis (BA) is a rare vasculoproliferative disorder due to Bartonella henselae (BH) or Bartonella quintana. It can involve many organs, including the skin, and has been mainly reported in patients with acquired immunodeficiency syndrome. In organ transplant recipients (OTR), this disorder remains misdiagnosed and therapeutic guidelines are nonexistent. We report 3 cases of BA with skin involvement in OTR and review similar cases from the literature. BA manifests on the skin with violaceous lesions mimicking Kaposi sarcoma, and is associated with fever, lymphadenopathy, and liver, spleen, or lung nodules. Bartonellosis infections in OTR are due to BH, the agent causing cat-scratch disease (CSD), but BA comprises histologically a prominent vascular proliferation, which is usually lacking in CSD. Cultures and serologic tests are poorly reliable for the diagnosis, which relies on demonstration of BH within the lesions. A history of cat exposure exists in most cases and pediatric OTR are at higher risk. Prevention consists of regular use of a flea-control product in cats and prompt cleaning of scratches. Our cases highlight several original features of this rare condition, which could potentially improve the management of BA in OTR.
[Show abstract][Hide abstract] ABSTRACT: Viral skin infections are commonly present in organ transplant recipients (OTR). In this study, we aimed to identify factors associated with human papillomavirus (HPV) infections in OTR. Patients with solid-organ transplants were recruited from the outpatient nephrology and dermatology clinics in five European countries. Only patients with no current or past skin cancer were included in this analysis. Serum samples were analysed for antibodies to the L1 proteins of 26 cutaneous and two genital HPV types from five phylogenetic genera (α, β, γ, μ and ν). The most consistent association was found between recreational sun exposure and the seroprevalence of all tested genera, except α. The antibody presence of any β type was higher among people who had been transplanted at least 23 years prior to participation than in those who had been transplanted for less than 7 years. The prevalence of two γ-HPV types (60 and 65) and three β-HPV types (15, 38 and 49) was associated with time since transplantation. The presence of a high number of warts was associated with the presence of any μ-PV or ν-PV types, and having greater than 50 keratotic skin lesions was almost significantly associated with the presence of antibodies to two or more γ-PV. Discrepancies in the results of the present study, as well as in previous reports, may depend on different methodologies and on geographical variations. Our results also indicate that further research with more standardized methods is needed to clarify the role of cutaneous HPV in OTR.
Journal of General Virology 09/2011; 93(Pt 1):165-74. · 3.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There is increasing evidence of an association between human papillomaviruses (HPV) of the beta-genus (beta-PV) and the development of cutaneous squamous cell carcinoma (SCC). The viral DNA load may be an important determinant of pathogenicity, but there are currently no baseline epidemiological data relating to load in people without SCC. We investigated DNA-loads of eight beta-PV types previously associated with risk of SCC. We collected eyebrow hairs from immunocompetent people (ICP) and organ transplant recipients (OTR), determined load by quantitative PCR and obtained demographic, phenotypic, and sun exposure information. Viral loads for ICP from Australia (n = 241) and Italy (n = 223) and OTR from across Europe (n = 318) spanned seven orders of magnitude. The median loads for all types were below one viral DNA copy per 60 cells and were highest for HPV5, HPV8 and HPV20. None of the populations had consistently higher viral loads for all 8 types. However, a higher proportion of OTR were in the top deciles of viral load distributions for six of the eight beta-PV types examined. In a nested analysis of Italian OTR and ICP, this finding was significant for six beta-PV types and cumulative load. Increasing age was significantly associated with higher viral loads in Australia, and there was a weak trend for higher loads with the time elapsed since transplantation in the OTR. We observed a wide distribution of beta-PV loads with OTR significantly more likely to have the highest viral loads. Thus, viral loads may be an important contributor to the higher risk of SCC in OTR.
Medical Microbiology and Immunology 07/2011; 201(2):117-25. · 3.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We examined the association between betapapillomavirus (betaPV) infection and cutaneous squamous cell carcinoma (SCC) in organ transplant recipients. A total of 210 organ transplant recipients with previous SCC and 394 controls without skin cancer were included. The presence of 25 betaPV types in plucked eyebrow hairs was determined using a human papillomavirus (HPV) DNA genotyping assay, and antibodies for the 15 most prevalent betaPV types were detected using multiplex serology. We used multivariate logistic regression models to estimate associations between various measures of betaPV infection and SCC. BetaPV DNA was highly prevalent (>94%) with multiple types frequently detected in both groups. We found a significant association between SCC and the concordant detection of both antibodies and DNA for at least one betaPV type (adjusted OR 1.6; 95% CI 1.1;2.5). A borderline-significant association with SCC was found for HPV36 (adjusted OR 2.4; CI 1.0;5.4), with similar associations for HPV5, HPV9 and HPV24. These data provide further evidence of an association between betaPV infection and SCC in organ transplant recipients. Confirmation of a betaPV profile predictive of risk for SCC may pave the way for clinically relevant pretransplant HPV screening and the development of preventive and therapeutic HPV vaccination.
American Journal of Transplantation 07/2011; 11(7):1498-508. · 6.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Basosquamous cell carcinoma (BSCC) is a poorly known tumor showing pathological features of both basal and squamous cell carcinomas. BSCC has never been specifically studied in organ transplant recipients (OTRs).
We sought to study the clinicopathologic features of BSCC in OTRs and compare them with BSCC from nongrafted patients.
Tumors diagnosed as BSCC were re-evaluated pathologically and immunohistochemically for the expression of the human epithelial antigen to confirm the diagnosis. The clinicopathologic features of BSCC in OTRs were compared with 30 BSCC obtained from nongrafted patients.
In our cohort of 3520 OTRs, 12 patients (0.34%) developed BSCC after a mean postgraft delay of 13.2 years, ie, later than other skin carcinomas. As compared with control patients, the age of OTRs with BSCC and the tumor thickness were significantly lower. BSCC were located on the head/neck in both groups in more than 75% of cases. No metastases developed in OTRs (mean follow-up 2.8 years). During the follow-up period (mean 16 years), OTRs with BSCC developed up to 220 additional premalignant and malignant skin tumors. After the diagnosis of BSCC, two patients developed lymph node metastasis of distinct squamous cell carcinoma.
This is a single-center, retrospective study.
BSCC is a rare tumor, even in OTRs who are at high risk of carcinomas. Its incidence (0.34%) is comparable with that of cutaneous lymphomas and melanomas, and much lower than that of other nonmelanoma skin cancers. Contrary to previous reports, BSCC do not seem to behave more aggressively than other nonmelanoma skin cancers.
Journal of the American Academy of Dermatology 06/2011; 66(5):e151-7. · 4.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Human papillomaviruses (betaPV) from the beta genus cannot be classified according to their oncogenicity due to a paucity of information. This study evaluates the association between betaPV infection and cutaneous squamous cell carcinoma in conjunction with measures of UV exposure and susceptibility. We performed case-control studies in the Netherlands, Italy, and Australia, countries with profoundly different UV exposures. The presence of 25 betaPV types in eyebrow hair follicles was determined using a highly sensitive HPV DNA genotyping assay, and antibodies for the 15 most prevalent betaPV types in a total of 689 squamous cell carcinoma cases and 845 controls were detected using multiplex serology. Multivariate logistic regression models were used for case-control comparisons and interaction analyses. BetaPV DNA was detected in eyebrow hairs of more than 90% of all participants. The presence of betaPV DNA was associated with an increased risk of squamous cell carcinoma in the Netherlands (OR = 2.8; 95% CI 1.3-5.8) and Italy (OR = 1.7; 95% CI 0.79-3.6), but not in Australia (OR = 0.91; 95% CI 0.53-1.6). Seropositivity for betaPV in controls ranged between 52% and 67%. A positive antibody response against 4 or more betaPV types was associated with squamous cell carcinoma in Australia (OR = 2.2; 95% CI 1.4-3.3), the Netherlands (OR = 2.0; 95% CI 1.2-3.4) and fair-skinned Italians (OR = 1.6, 95% CI 0.94- 2.7). The association between UV susceptibility and squamous cell carcinoma was stronger in betaPV-seropositive people. These combined data support the hypothesis that betaPV may play a role in the development of cutaneous squamous cell carcinoma.
Cancer Research 12/2010; 70(23):9777-86. · 9.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Orf is a viral skin infection due to a poxvirus. It manifests as a nodule of the hands that heals spontaneously within 3-4 weeks, but may be persisting and difficult to treat in immunocompromised patients. Very few cases have been reported in transplant patients; therefore, management is not established. We report a renal transplant recipient with a rapidly growing orf which regressed after application of imiquimod and a reduction in immunosuppression without damage on his renal function. This case suggests that a rapidly growing orf in transplant patients behaves as an opportunistic infection and therefore minimization should be considered along with a topical treatment.
Transplant International 10/2010; 23(10):e62-4. · 3.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Solid organ transplant and subsequent graft survival have increased worldwide, while immunosuppression has prevented rejection with increasing success. Side effects of cutaneous infection and neoplasm, however, affect the majority of solid organ transplant recipients (OTRs). Squamous cell carcinoma of the skin (SCC) is the most common neoplasm overall following organ transplant with a risk that is 60-100 times greater than for the immunocompetent population. This review focuses on questions of ongoing debate about SCC formation in OTRs such as viral carcinogenesis, systemic photoprotection, photosensitization by drugs, the impact of immunosuppressive drugs and inflammation as a driver of carcinogenesis.
[Show abstract][Hide abstract] ABSTRACT: Warts are thought to be associated with the development of squamous cell carcinoma (SCC) in organ transplant patients. We investigated the association between the different types of warts and SCC in organ transplant patients.
A prospective multicenter case-control study was conducted. Cases were patients with a kidney or heart transplant who were referred for a SCC. Controls were organ transplant patients without SCC, individually matched for age, gender, type of organ transplant (heart or kidney), skin phototype, time from transplantation, and center. Four types of warts: flat warts, verrucae vulgares (including palmo-plantar warts and common warts), verrucous papilloma, and verrucokeratotic lesions were compared between cases and controls using conditional logistic regression.
Ninety-nine cases and 169 controls were included. In multivariate analysis, number of rejections, azathioprine, prednisolone and anti-lymphocyte anti-serum or anti-CD3 monoclonal antibodies use, cumulative sun exposure, actinic keratosis, and verrucokeratic lesions (odds ratio [OR] 16.50; 95% confidence interval [CI] 2.82-96.80) were independently associated with SCC, whereas the association with verrucous papilloma was borderline significant (OR 2.21; 95% CI 0.97-8.15). The association between the presence of at least one of these two types of warts (verruco-keratotic lesions and verrucous papilloma) and the occurrence of SCC was highly significant (OR 18.36; 95% CI 3.03-111) when these warts were located in the same area than SCC, whereas no significant association was evidenced when these warts were located in another area (OR 1.02; 95% CI 0.13-5.79).
Verrucous papilloma and mainly verrucokeratotic lesions are strongly associated with the risk of SCC in organ transplant patients, whereas the most typical types of warts: verrucae vulgares and flat warts, are not.