utaneous squamous cell carcinoma (SCC) is a malignant neoplasm deriving from epidermal keratinocytes. In the general population, SCC is the second most common form of keratinocyte carcinoma after basal cell basal cell carcinoma, 1,2 and in organ transplant recipients SCC is the most common skin cancer. [1][2][3][4][5][6][7][8][9][10][11] Previous studies 12-15 report a risk for nodal metastasis of 1.9% to 4.0% and a risk for diseasespecific death of 1.5% to 2.1% in the general population.The number of solid organ transplants and long-term survival in organ transplant recipients have increased over the 5 decades as a result of progress in both surgical techniques and drug-induced immunosuppression. 16 Notwithstanding the clear benefits of successful allograft transplantation, organ transplant recipients experience important adverse effects from long-term immunosuppressive medication, including a 10-fold increased risk for malignant neoplasms overall. 17,18 In particular, solid organ transplant recipients have a 65-fold to 250-fold higher incidence of SCC compared with those who have not received transplants. After transplantation, 20% to 75% of solid organ transplant recipients are affected by at least 1 SCC within 20 years. 8,19 After a first invasive SCC, multiple subsequent SCCs will develop in 60% to 80% of these patients within 3 years. The risk of SCC increases over time, with the incidence increasing to 40% to 60% at 20 years after transplantation. 20,21 Cutaneous SCC is also associated with a more aggressive behavior and a higher risk of metastasis and death in solid organ transplant recipients than in the general population. 6,7,22 The rate of metastasis in solid organ transplant recipients is reported to be 5% to 8%. 23 IMPORTANCE Squamous cell carcinoma (SCC) is the most frequent malignant neoplasm found in solid organ transplant recipients and is associated with a more aggressive disease course and higher risk of metastasis and death than in the general population.OBJECTIVES To report the clinicopathologic features of and identify factors associated with aggressive SCC in solid organ transplant recipients.METHODS This retrospective multicentric case series included 51 patients who underwent solid organ transplantation and were found to have aggressive SCC, defined by nodal or distant metastasis or death by local progression of primary SCC. Standard questionnaires were completed by the researchers between

Summary Background Epidemiological studies indicate that gene–environment interactions play a role in atopic dermatitis (AD). Objectives To review the evidence for gene–environment interactions in AD aetiology, focusing on filaggrin (FLG) loss‐of‐function mutations. Methods A systematic search from inception to September 2018 in Embase, MEDLINE and BIOSIS was performed. Search terms included all synonyms for AD and filaggrin/FLG; any genetic or epidemiological study design using any statistical methods were included. Quality assessment using criteria modified from guidance (ROBINS‐I and Human Genome Epidemiology Network) for nonrandomized and genetic studies was completed, including consideration of power. Heterogeneity of study design and analyses precluded the use of meta‐analysis. Results Of 1817 papers identified, 12 studies fulfilled the inclusion criteria required and performed formal interaction testing. There was some evidence for FLG–environment interactions in six of the studies (P‐value for interaction ≤ 0·05), including early‐life cat ownership, older siblings, water hardness, phthalate exposure, higher urinary phthalate metabolite levels (which all increased AD risk additional to FLG null genotype) and prolonged breastfeeding (which decreased AD risk in the context of FLG null genotype). Major limitations of published studies were the low numbers of individuals (ranging from five to 94) with AD and FLG loss‐of‐function mutations and exposure to specific environmental factors, and variation in exposure definitions. Conclusions Evidence on FLG–environment interactions in AD aetiology is limited. However, many of the studies lacked large enough sample sizes to assess these interactions fully. Further research is needed with larger sample sizes and clearly defined exposure assessment. Linked Comment: Park and Seo. Br J Dermatol 2020; 183:411.

Background The risk of cutaneous squamous cell carcinoma (cSCC) is significantly increased in organ transplant recipients (OTRs). Clearance of actinic keratoses (AKs) is generally regarded as a surrogate biomarker for cSCC prevention. OTR-cSCC chemoprevention with topical AK treatments has not been investigated in randomized controlled trials (RCTs), although there is evidence that 5% 5fluorouracil (5-FU) may be chemoprotective in immunocompetent patients. Objectives To assess the feasibility, activity and evaluation outcomes relevant to the design of a future phase III RCT of topical cSCC chemoprevention in OTRs. Methods OTRs with 10 or more AKs in predefined areas were randomized 1 : 1 : 1 to topical 5-FU, 5% imiquimod (IMIQ) or sunscreen (sun-protective factor 30+) in a phase II, open-label RCT over 15 months. Feasibility outcomes included proportions of eligible OTRs randomized, completing treatment and willing to be re-treated. AK activity [AK clearance, new AK development, patientcentred outcomes (toxicity, health-related quality of life, HRQoL)] and evaluation methodology (clinical vs. photographic) were assessed. Results Forty OTRs with 903 AKs were randomized. All feasibility outcomes were met (56% of eligible OTRs were randomized; 89% completed treatment; 81% were willing to be re-treated). AK activity analyses found 5-FU and IMIQ were superior to sunscreen for AK clearance and prevention of new AKs. 5-FU was more effective than IMIQ in AK clearance and prevention in exploratory analyses. Although toxicity was greater with 5-FU, HRQoL outcomes were similar. Conclusions Trials of topical AK treatments in OTRs for cSCC chemoprevention are feasible and AK activity results support further investigation of 5-FU-based treatments in future phase III trials.

Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of non-Hodgkin lymphomas characterized by an infiltration of malignant monoclonal T lymphocytes into the skin. Mycosis fungoides (MF), the most common subtype, and the rarer Sézary syndrome (SS), are considered the classical forms of CTCL, which, because of a varying presentation and lack of genetic and immunophenotypical markers, can often have a delayed diagnosis. With skin-directed topical treatment being the mainstay of therapy in the early stages, there is an absence of long-term curative therapies for advanced disease. Recent insight into the pathogenesis of CTCL has identified new potential therapeutic targets including the monoclonal antibody therapies, brentuximab vedotin and mogamulizumab. Brentuximab vedotin, an anti-CD30 antibody-drug conjugate, received extended approval by the US FDA in 2017 to include primary cutaneous anaplastic large-cell lymphoma and CD30-expressing MF. Mogamulizumab, an anti-CCR4 antibody, received FDA approval in 2018 for relapsed or refractory MF and SS. Further targets and therapies continue to be investigated, including the monoclonal antibody therapy alemtuzumab, an anti-CD52 antibody, and the immune checkpoint blockade therapies, pembrolizumab and nivolumab. These new and emerging targets and therapies may lead to a promising broadening of CTCL treatment options in the future.

No abstract

No abstract

Click https://www.wileyhealthlearning.com/ced.aspx for the corresponding questions to this CME article.

No abstract