Cumulative incidence and risk factors for cutaneous squamous cell carcinoma metastases in organ transplant recipients: The Skin Care in Organ Transplant Patients in Europe-International Transplant Skin Cancer Collaborative metastases study, a prospective multicenter study.

INTRODUCTION: Solid organ transplant recipients (SOTRs) are believed to have an increased risk of metastatic cutaneous squamous cell carcinoma (cSCC), but reliable data are lacking regarding the precise incidence and associated risk factors. METHODS: In a prospective cohort study, including 19 specialist dermatology outpatient clinics in 15 countries, patient and tumor characteristics were collected using standardized questionnaires when SOTRs presented with a new cSCC. After a minimum of 2 years of follow-up, relevant data for all SOTRs were collected. Cumulative incidence of metastases was calculated by the Aalen-Johansen estimator. Fine and Gray models were used to assess multiple risk factors for metastases. RESULTS: Of 514 SOTRs who presented with 623 primary cSCCs, metastases developed in 37 with a 2-year patient-based cumulative incidence of 6.2%. Risk factors for metastases included location in the head and neck area, local recurrence, size > 2 cm, clinical ulceration, poor differentiation grade, perineural invasion, and deep invasion. A high-stage tumor that is also ulcerated showed the highest risk of metastasis, with a 2-year cumulative incidence of 46.2% (31.9%-68.4%). CONCLUSIONS: SOTRs have a high risk of cSCC metastases and well-established clinical and histologic risk factors have been confirmed. High-stage, ulcerated cSCCs have the highest risk of metastasis.

Nephrogenic Systemic Fibrosis with Osseous Metaplasia in a Kidney-Pancreas Transplant Patient.

A French (Caucasian) woman with a history of nonobstructive hypertrophic cardiopathy, type 1 diabetes mellitus, cataract, and ante-hypophysary insufficiency had undergone multiple magnetic resonance imaging (MRI) studies. She had developed end-stage renal disease (ESRD) and had undergone hemodialysis for 10 years before receiving a kidney-pancreas allotransplantation at the age of 48 years. She received antithymocyte globulins as induction immunosuppression and steroids (5 mg/d), mycophenolate mofetil (2 g/d), and tacrolimus (5 mg/d) as maintenance immunosuppression. Following transplantation, she underwent a cerebral MRI with injection of a gadolinium-based contrast agent (GBCA) in the work-up for Schwartz-Bartter syndrome. Shortly thereafter, she progressively developed cutaneous infiltration, sclerosis, and hyperpigmentation on her extremities and back (Figure 1), firm nodules on the thighs and the right hand, and confluent papules on the back, all of which were asymptomatic. She had no facial involvement, sclerodactyly, periungual telangiectasias, Raynaud syndrome, or arthralgias. Histologic examination showed mild epidermal hyperplasia and a thickened dermis containing several fibroblasts and some histiocytes (Figure 2a). The alcian blue stain revealed increased dermal mucin deposits (Figure 3b). Remarkably, several round-to-ovoid, well-limited yellowish collagenous structures containing basophilic (elastic) fibers were seen in the dermis (Figures 2b, 2c, 3a, and 4a). These "elasto-collagenous balls" stained blue with Masson's trichrome stain (Figure 4c); the orcein stain confirmed the presence of elastic fibers within them (Figure 4b). Some orange-yellow elasto-collagenous balls contained osteocytes, indicative of osseous metaplasia (Figure 5); these were von Kossa stain-positive, highlighting calcium deposition (Figure 4d). Immunohistochemically, the dermal fibroblasts were variably CD34-positive. Factor XIIIa+ dermal dendrocytes and histiocytic, occasionally multinucleated, CD68+ cells were also seen. (SKINmed. 2022;20:145-148).

Consensus-Based Recommendations on the Prevention of Squamous Cell Carcinoma in Solid Organ Transplant Recipients: A Delphi Consensus Statement.

IMPORTANCE: There is a paucity of evidence to guide physicians regarding prevention strategies for cutaneous squamous cell carcinoma (CSCC) in solid organ transplant recipients (SOTRs). OBJECTIVE: To examine the development and results of a Delphi process initiated to identify consensus-based medical management recommendations for prevention of CSCC in SOTRs. EVIDENCE REVIEW: Dermatologists with more than 5 years' experience treating SOTRs were invited to participate. A novel actinic damage and skin cancer index (AD-SCI), consisting of 6 ordinal stages corresponding to an increasing burden of actinic damage and CSCC, was used to guide survey design. Three sequential web-based surveys were administered from January 1, 2019, to December 31, 2020. Pursuant to Delphi principles, respondents thoroughly reviewed all peer responses between rounds. Supplemental questions were also asked to better understand panelists' rationale for their responses. FINDINGS: The Delphi panel comprised 48 dermatologists. Respondents represented 13 countries, with 27 (56%) from the US. Twenty-nine respondents (60%) were Mohs surgeons. Consensus was reached with 80% or higher concordance among respondents when presented with a statement, question, or management strategy pertaining to prevention of CSCC in SOTRs. A near-consensus category of 70% to less than 80% concordance was also defined. The AD-SCI stage-based recommendations were established if consensus or near-consensus was achieved. The panel was able to make recommendations for 5 of 6 AD-SCI stages. Key recommendations include the following: cryotherapy for scattered actinic keratosis (AK); field therapy for AK when grouped in 1 anatomical area, unless AKs are thick in which case field therapy and cryotherapy were recommended; combination lesion directed and field therapy with fluorouracil for field cancerized skin; and initiation of acitretin therapy and discussion of immunosuppression reduction or modification for patients who develop multiple skin cancers at a high rate (10 CSCCs per year) or develop high-risk CSCC (defined by a tumor with approximately ≥20% risk of nodal metastasis). No consensus recommendation was achieved for SOTRs with a first low risk CSCC. CONCLUSIONS AND RELEVANCE: Physicians may consider implementation of panel recommendations for prevention of CSCC in SOTRs while awaiting high-level-of-evidence data. Additional clinical trials are needed in areas where consensus was not reached.

Outcome of pretransplant melanoma after solid organ transplantation: an observational study.

The number of patients with a history of melanoma who are awaiting a solid organ transplantation (SOT) is increasing. Few recommendations exist on the timing to transplantation after melanoma diagnosis. The aim of this study was to assess the melanoma recurrence-free survival after pretransplant melanoma (PTM). We conducted a multicenter ambispective observational study. Organ transplant recipients (OTR) with a history of PTM and complete AJCC staging were included. Thirty-seven patients (predominantly men with a renal allograft) were included. Five melanomas were in situ, 21 stage IA, 4 stage IB, 5 stage II, and 2 stage IIIB. The median post-transplantation follow-up time was 4 years. Sixty-two percent of patients were followed up more than 2 years. Recurrence-free survival since melanoma reached 89.9%, but varied significantly according to AJCC staging (P = 0.0129). Three patients presented a recurrence. Despite the rather limited sample size and a wide range of follow-up, our findings concerning the recurrence-free survival appear reassuring for in situ and stage IA PTM; accordingly, we suggest that a waiting time to transplantation is not mandatory in patients with in situ or stage IA PTM, especially whenever SOT is urgently needed. Caution is, however, needed for patients with higher stage.

Deep cutaneous fungal infections in solid-organ transplant recipients.

BACKGROUND: Deep cutaneous fungal infections (DCFIs) are varied in immunosuppressed patients, with few data for such infections in solid-organ transplant recipients (s-OTRs). OBJECTIVE: To determine DCFI diagnostic characteristics and outcome with treatments in s-OTRs. METHODS: A 20-year retrospective observational study in France was conducted in 8 primary dermatology-dedicated centers for s-OTRs diagnosed with DCFIs. Relevant clinical data on transplants, fungal species, treatments, and outcomes were analyzed. RESULTS: Overall, 46 s-OTRs developed DCFIs (median delay, 13 months after transplant) with predominant phaeohyphomycoses (46%). Distribution of nodular lesions on limbs and granulomatous findings on histopathology were helpful diagnostic clues. Treatments received were systemic antifungal therapies (48%), systemic antifungal therapies combined with surgery (28%), surgery alone (15%), and modulation of immunosuppression (61%), leading to complete response in 63% of s-OTRs. LIMITATIONS: Due to the retrospective observational design of the study. CONCLUSIONS: Phaeohyphomycoses are the most common DCFIs in s-OTRs. Multidisciplinary teams are helpful for optimal diagnosis and management.

Multiple acantholytic dyskeratotic acanthomas in a liver-transplant recipient.

Acantholytic dyskeratotic acanthoma is a rare variant of epidermal acanthoma characterized pathologically by the presence of acantholysis and dyskeratosis. Few cases have been reported until now, one of them in a heart-transplant patient. We present here a new case of this rare lesion that developed in a liver-transplant patient and review the salient features of this uncommon condition.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Immunosuppressive regimen and risk for de novo malignancies after liver transplantation for alcoholic liver disease.

BACKGROUND AND AIMS: Long-term prognosis after liver transplantation for alcoholic liver disease is impaired because of the occurrence of de novo malignancies and recurrent disease on liver graft. The aim of the present retrospective study was to evaluate the risk of de novo malignancy and to identify the predictive factors in a large cohort of liver-transplanted patients with a long follow-up in the setting of alcoholic liver disease. METHODS: All patients who underwent a first liver transplantation for alcoholic liver disease in our centre, from December 1985 to October 2010, and who survived more than 6 months were included. Survival, incidence of de novo malignancies and several clinical and biological parameters were studied. RESULTS: The study population consisted in 368 patients (284 males, median age 52.6 years). The cumulative incidence of a first solid organ de novo malignancy after LT was 8.7% at 5 years, 22.3% at 10 years, 31.5% at 15 years, and 33.1% at 20 years. Tobacco use (both past and current) was associated with a significant increased risk of de novo solid organ malignancy (HR 3.35 and 4.62, respectively), whereas immunosuppressive regimen including mTOR inhibitors (mTORi) was associated with a decreased risk (post-transplant time under mTORi-including immunosuppressive regimen was significantly longer in patients who did not present de novo malignancy (10.6% vs. 2.3%, P=1.4×10-5)). CONCLUSIONS: Our study provides additional evidence that de novo malignancies in alcoholic liver disease liver transplant patients is a major long-term complication, and that conversion from to an mTORi-including immunosuppressive regimen could reduce this risk.