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.

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.

Identification of Polyomaviruses in Skin Cancers.

BACKGROUND: Polyomaviruses (PyVs) were initially described in animals. They have also been detected in humans with some evidence that could play a role in skin carcinogenesis. OBJECTIVES: This study aimed to verify the presence of PyVs in different skin tumour samples and to make clinical correlations with patients' epidemiological data from Clinics Hospital of Medical School of University of São Paulo, Brazil. METHODS: This is a cross-sectional study. A random selection was performed of 120 patients with histopathological exams of different cutaneous neoplasms equally divided into 6 groups and 20 patients with normal skin. The available skin specimens were analysed with 2 different techniques of PCR (conventional and real time) for detection of PyV DNA. Concomitantly, retrospective analysis of the respective medical records for the collection of epidemiological data was done. Analyses suitable for categorical data were used to compare the proportion of patients in each group. RESULTS: PyV DNA was found in 25.69% of the samples: 15% in basal cell carcinoma group, 15% in squamous cell carcinoma, 28.57% in melanoma, 15% in dermatofibrosarcoma protuberans, 13.33% in Kaposi sarcoma, 65% in Merkel cell carcinoma (MCC), and none in normal skin. Merkel cell PyV detection was statistically significant in MCC patients (p value <0.01), but no correlations were found between PyVs and others skin tumours. CONCLUSION: This study demonstrated the presence of PyVs in different skin tumours; however, no association of any PyVs found in any skin tumour with epidemiological data could be shown. Further studies are still needed to elucidate the mechanisms of PyVs in skin carcinogenesis.

The first observation of the association of Merkel cell polyomavirus and Merkel cell carcinoma in Brazil.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare but aggressive primary cutaneous carcinoma with high mortality rates. The present study intends to delineate the epidemiological profile of patients with MCC seen at the Clinics Hospital of the Medical School at the University of São Paulo, Brazil, and its association with Merkel cell polyomavirus (MCPyV). METHODS: This is a retrospective study. A search was performed in the hospital's medical index for all cases of MCC from January 1994 to December 2012. Among patients with MCC, the available tumoral skin specimens were analyzed with two different techniques of polymerase chain reaction (PCR) (conventional and real-time) for detection of MCPyV DNA. Additionally, paraffin-embedded samples of patients with non-MCC skin cancers were also analyzed. Analyses suitable for categorical data (i.e., x² of Fisher) were used to compare the proportion of patients in each group. RESULTS: Nineteen patients with MCC and 20 patients with non-MCC skin cancers entered the study. All MCC samples available (13) tested positive for the presence of MCPyV DNA; however, in the non-MCC skin cancer samples, the MCPyV DNA was detected in 4 of 20 samples (20%). MCPyV DNA detection rate was higher in patients with MCC than in the other group, and its analysis was statistically significant (P < 0.01). CONCLUSIONS: This study demonstrates the association of MCPyV in Brazilian patients with MCC. However, further studies are necessary to determine the exact involvement of MCPyV in MCC pathogenesis and to define the significance of viral DNA detection in non-MCC skin cancers.

Skin lesions in organ transplant recipients: a study of 177 consecutive Brazilian patients.

BACKGROUND: Skin lesions are very common among organ transplant recipients (OTR), particularly infections and tumors, because of the immunosuppressive state these patients are put in. METHODS: 177 OTR were examined. Skin lesions were categorized into neoplastic, infectious, and inflammatory diseases. RESULTS: The mean age of OTR was 52 years, the mean age at transplantation was 42.7 years, and kidney was the most common organ transplanted (72%). Skin lesions were found in 147 patients (83%). Cutaneous infections were seen in 106 patients (60%). Warts (30%) had the larger incidence and were associated with azathioprine (P = 0.026), cyclosporine (P = 0.006), and tacrolimus (P = 0.009). Superficial mycoses occurred in 16% of OTR, mostly onychomycosis, which was associated with tacrolimus (P = 0.040). Actinic keratosis (AK) occurred in 31% of patients and cutaneous tumors in 56%. Squamous cell carcinoma (SCC) was the most common tumor type affecting 36% of OTR (n = 64), with invasive SCC predominating over in situ SCC, whereas basal cell carcinoma (BCC) accounted for 17%. Both SCC and BCC were more numerous in patients' skin type I (P < 0.05). SCC was more frequent (36%) in combined kidney and liver recipients (P = 0.004), and BCC was associated with cyclosporine (P = 0.047). Inflammatory complications (acne, alopecia, hypertrichosis, and gingival overgrowth) were observed in 17.5% of patients. CONCLUSIONS: Organ transplant recipients must be regularly evaluated by dermatologists, who should be alert to the onset of infections and skin (pre)malignant diseases in these patients.