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.

Field Therapy in Solid Organ Transplant Recipients: Are We Initiating Early Enough?

Organ transplant recipients (OTRs) are at increased risk for more aggressive non-melanoma skin cancer (NMSC). Recent emphasis on field therapy has complimented the canonical surgical treatment paradigm. This retrospective analysis of survey responses by patients seen at Oregon Health and Science University from 2013-2018 offers insights into patient trends and practice gaps in caring for OTRs. All patients completed a 57-point questionnaire at their first clinic visit, which included questions regarding demographics, transplant history, dermatologic history, and use of field therapy. Of the 295 patients (mean age, 56 years; M/F: 193/102) who completed the questionnaire, field therapy was reported by 31 (11%) patients. Field therapy patients noted an overall higher AK and SCC burden, with a greater proportion of patients reporting >20 AKs and >10 SCCs. Field therapy use was sparse in the low AK/low SCC group (n=25) when compared to those reporting high AK/high SCC (n=11) burden (n=4 (16%) vs n=8 (73%), P<0.01). This data suggests that OTRs with several clinically evident AKs and/or a low number of SCCs are less likely to have been treated with field therapy modalities compared to OTRs who have developed >10 AKs or ≥6 SCCs. A delay in initiation of preventative measures or field therapy in this population, however, may be a missed opportunity for intervention. Early intervention with field therapy in particularly high-risk OTRs with a low skin cancer burden may mitigate future skin cancer development.J Drugs Dermatol. 2020;19(3): doi:10.36849/JDD.2020.4759.

Primary cutaneous Epstein-Barr virus-positive diffuse large B-cell lymphoma (DLBCL) in a patient taking fingolimod.

A 55-year-old man with relapsing-remitting multiple sclerosis on fingolimod presented to the dermatology clinic with skin lesions on the left temple and cheek. Histopathology showed a diffuse infiltrate of enlarged, atypical lymphocytes throughout the dermis with an overlying grenz zone and a subpopulation of scattered smaller lymphocytes and plasma cells. Epstein-Barr virus-encoded RNA in situ hybridization stain was positive. Based on the morphologic and immunophenotypic findings, a diagnosis of EBV-positive diffuse large B-cell lymphoma was made. This case aims to raise awareness for the dermatologist that patients on fingolimod may be at increased risk of lymphoproliferative disorders.

Incidence of and Risk Factors for Skin Cancer in Organ Transplant Recipients in the United States.

Importance: Skin cancer is the most common malignancy occurring after organ transplantation. Although previous research has reported an increased risk of skin cancer in solid organ transplant recipients (OTRs), no study has estimated the posttransplant population-based incidence in the United States. Objective: To determine the incidence and evaluate the risk factors for posttransplant skin cancer, including squamous cell carcinoma (SCC), melanoma (MM), and Merkel cell carcinoma (MCC) in a cohort of US OTRs receiving a primary organ transplant in 2003 or 2008. Design, Setting, and Participants: This multicenter retrospective cohort study examined 10 649 adult recipients of a primary transplant performed at 26 centers across the United States in the Transplant Skin Cancer Network during 1 of 2 calendar years (either 2003 or 2008) identified through the Organ Procurement and Transplantation Network (OPTN) database. Recipients of all organs except intestine were included, and the follow-up periods were 5 and 10 years. Main Outcomes and Measures: Incident skin cancer was determined through detailed medical record review. Data on predictors were obtained from the OPTN database. The incidence rates for posttransplant skin cancer overall and for SCC, MM, and MCC were calculated per 100 000 person-years. Potential risk factors for posttransplant skin cancer were tested using multivariate Cox regression analysis to yield adjusted hazard ratios (HR). Results: Overall, 10 649 organ transplant recipients (mean [SD] age, 51 [12] years; 3873 women [36%] and 6776 men [64%]) contributed 59 923 years of follow-up. The incidence rates for posttransplant skin cancer was 1437 per 100 000 person-years. Specific subtype rates for SCC, MM, and MCC were 812, 75, and 2 per 100 000 person-years, respectively. Statistically significant risk factors for posttransplant skin cancer included pretransplant skin cancer (HR, 4.69; 95% CI, 3.26-6.73), male sex (HR, 1.56; 95% CI, 1.34-1.81), white race (HR, 9.04; 95% CI, 6.20-13.18), age at transplant 50 years or older (HR, 2.77; 95% CI, 2.20-3.48), and being transplanted in 2008 vs 2003 (HR, 1.53; 95% CI, 1.22-1.94). Conclusions and Relevance: Posttransplant skin cancer is common, with elevated risk imparted by increased age, white race, male sex, and thoracic organ transplantation. A temporal cohort effect was present. Understanding the risk factors and trends in posttransplant skin cancer is fundamental to targeted screening and prevention in this population.

Putting the pieces together: necrolytic migratory erythema and the glucagonoma syndrome.

Glucagonomas are slow-growing, rare pancreatic neuroendocrine tumors. They may present with paraneoplastic phenomena known together as the "glucagonoma syndrome." A hallmark sign of this syndrome is a rash known as necrolytic migratory erythema (NME). In this paper, the authors describe a patient with NME and other features of the glucagonoma syndrome. The diagnosis of this rare tumor requires an elevated serum glucagon level and imaging confirming a pancreatic tumor. Surgical and medical treatment options are reviewed. When detected early, a glucagonoma is surgically curable. It is therefore imperative that clinicians recognize the glucagonoma syndrome in order to make an accurate diagnosis and refer for treatment.

Neoplastic/paraneoplastic dermatitis, fasciitis, and panniculitis.

The skin changes outlined in this article can be important clues to an underlying malignancy. Paraneoplastic dermatoses are skin disorders associated with an underlying neoplasm and whose course parallels that of the neoplasm. Recognizing these skin presentations leads to early diagnosis and management of the underlying malignancy. Effective treatment of the associated neoplasm often leads to improvement of the cutaneous manifestations and should be the primary focus of each patient's management.