Rates of Second Tumor, Metastasis, and Death From Cutaneous Squamous Cell Carcinoma in Patients With and Without Transplant-Associated Immunosuppression.

Importance: Cutaneous squamous cell carcinoma (cSCC) may occur with multiple primary tumors, metastasize, and cause death both in immunocompetent and immunosuppressed patients. Objective: To study the rates of second cSCC, metastasis, and death from cSCC in patients with and without organ transplant-associated immunosuppressive treatment. Design, Setting, and Participants: This population-based, nationwide cohort study used Cancer Registry of Norway data from 47 992 individuals diagnosed with cSCC at 18 years or older between January 1, 1968, and December 31, 2020. Data were analyzed between November 24, 2021, and November 15, 2022. Exposures: Receipt of a solid organ transplant at Oslo University Hospital between 1968 and 2012 followed by long-term immunosuppressive treatment. Main Outcomes and Measures: Absolute rates of second cSCC, metastasis, and death from cSCC were calculated per 1000 person-years with 95% CIs. Hazard ratios (HRs) estimated using Cox proportional hazard regression were adjusted for age, sex, and year of first cSCC diagnosis. Results: The study cohort comprised 1208 organ transplant recipients (OTRs) (median age, 66 years [range, 27-89 years]; 882 men [73.0%] and 326 women [27.0%]) and 46 784 non-OTRs (median age, 79 years [range, 18-106 years]; 25 406 men [54.3%] and 21 378 women [45.7%]). The rate of a second cSCC per 1000 person-years was 30.9 (95% CI, 30.2-31.6) in non-OTRs and 250.6 (95% CI, 232.2-270.1) in OTRs, with OTRs having a 4.3-fold increased rate in the adjusted analysis. The metastasis rate per 1000 person-years was 2.8 (95% CI, 2.6-3.0) in non-OTRs and 4.8 (95% CI, 3.4-6.7) in OTRs, with OTRs having a 1.5-fold increased rate in the adjusted analysis. A total of 30 451 deaths were observed, of which 29 895 (98.2%) were from causes other than cSCC. Death from cSCC was observed in 516 non-OTRs (1.1%) and 40 OTRs (3.3%). The rate of death from cSCC per 1000 person-years was 1.7 (95% CI, 1.5-1.8) in non-OTRs and 5.4 (95% CI, 3.9-7.4) in OTRs, with OTRs having a 5.5-fold increased rate in the adjusted analysis. Conclusions and Relevance: In this cohort study, OTRs with cSCC had significantly higher rates of second cSCC, metastasis, and death from cSCC than non-OTRs with cSCC, although most patients with cSCC in both groups died from causes other than cSCC. These findings are relevant for the planning of follow-up of patients with cSCC and for skin cancer services.

Histopathologic reassessment of melanoma and other melanocytic skin lesions excised in 2009 and 2018-2019. / Histopatologisk revurdering av melanom og andre melanocytære hudlesjoner eksidert i 2009 og 2018­19.

BACKGROUND: Histopathological assessment of melanoma and other melanocytic skin lesions can be difficult and can vary between pathologists. MATERIAL AND METHOD: Histopathological slides of 196 melanocytic skin lesions from 2009 and 2018-2019 were obtained from the archive of the Department of Pathology at Oslo University Hospital and classified into six diagnostic categories: 1) benign nevus, 2) irregular/dysplastic nevus, i.e. dysplastic nevus with moderate atypia, 3) nevus with severe atypia, i.e. dysplastic nevus with severe atypia, 4) melanoma in situ, 5) superficial spreading or lentiginous melanoma and 6) nodular melanoma. The slides were then examined independently and blindly by three experienced pathologists and categorised in the same way. Interobserver agreement was assessed with Cohen's kappa, and agreement with the original diagnosis was assessed by the proportion of assessments in the same diagnostic category. RESULTS: The kappa values for the assessments from the three pathologists ranged from 0.45 to 0.50. The proportion of reassessments in agreement with the original diagnostic category was 85.7 % (95 % CI 75.7 to 92.1), 29.2 % (19.9 to 40.5), 27.8 % (20.9 to 36.0), 78.3 % (70.4 to 84.5), 81.2 % (73.7 to 86.9) and 93.3 % (82.1 to 97.7), respectively, i.e. highest for nodular melanoma. The proportion of reassessments in which the diagnosis was more serious or less serious than the original diagnosis was higher and lower, respectively, for slides from 2009 than for slides from 2018-2019. INTERPRETATION: The differences between the pathologists' assessments and deviations from the original diagnoses can be explained by poorly reproducible diagnostic criteria, diagnostic entities with overlapping morphology and increasing awareness of early signs of malignancy. Some evolution in diagnostic practice cannot be ruled out.

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.

Apremilast for genital erosive lichen planus in women (the AP-GELP Study): study protocol for a randomised placebo-controlled clinical trial.

BACKGROUND: Genital erosive lichen planus (GELP) is a genital subtype of lichen planus, a chronic autoimmune inflammatory disease of unknown aetiology. In women, GELP is characterised by painful vulvo-vaginal mucosal erosions and scarring, often resulting in poor sexual health and reduced quality of life. Treatment options are limited and often with little effect. Apremilast, a phosphodiesterase 4-inhibitor, has been shown to have a positive effect on psoriasis and other inflammatory skin diseases. We aim to investigate the effect and safety of peroral apremilast in women with GELP in a randomised placebo-controlled double-blinded clinical trial. METHODS: We will recruit 42 adult women with characteristic clinical and/or histological features of moderate-to-severe GELP from a specialised vulva clinic in Oslo, Norway. The patients will be randomised 1:1 to either apremilast 30 mg BID (with an initial dose titration on days 1-6) or a placebo for 24 weeks. The concomitant use of topical corticosteroids will be allowed. The primary end point will be the mean GELP score, a clinical scoring system, at week 24 in the apremilast-treated patients versus the placebo-treated patients. The secondary end points will include the mean GELP score improvement from weeks 0 to 24, patient-reported use of topical steroids, the pain score on a visual analogue scale and the number of patients with GELP score improvements at weeks 16 and 24. The Physician Global Assessment , Patient Global Assessment and selected quality of life and sexual function assessments will be recorded at weeks 0, 16 and 24. The exploratory endpoints include description of immunohistochemical changes before and after apremilast therapy, assessed in vulvar or vaginal biopsies at weeks 0 and 24. Regular follow-ups for possible adverse events will be conducted. DISCUSSION: The study design is based on experience from studies on apremilast in other inflammatory skin diseases using equivalent apremilast doses for approved indications. The trial may provide evidence for the use of apremilast in women with this burdensome genital dermatosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT0365666 . Registered on 4 September 2018.