Cutaneous squamous cell carcinoma in patients with solid organ malignancy.
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ABSTRACT:
SUBMITTER: Johnson C
PROVIDER: S-EPMC10909743 | biostudies-literature | 2024 Jun
REPOSITORIES: biostudies-literature
Publications
Cutaneous squamous cell carcinoma in patients with solid organ malignancy.
Johnson Chandler C Groover Morgan M Granger Emily E Murad Fadi F Karn Emily E Ruiz Emily S ES
JAAD international 20231229
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Project description:Importance:Solid organ transplant recipients (SOTRs) have a 100-fold increased risk of squamous cell carcinoma (SCC), and they may develop more aggressive SCCs compared with immunocompetent individuals. Objective:To compare outcomes associated with aggressive behavior of SCC in SOTRs and high-risk immunocompetent patients. Design, Setting, and Participants:A retrospective cohort study of 58 SOTRs and 40 immunocompetent patients evaluated at the Yale Transplant Dermatology Clinic in New Haven, Connecticut, who had at least 1 SCC confirmed histopathologically between January 1, 2008, and December 31, 2015. Cumulative follow-up time for this study was 369 patient-years. Exposure:Immunosuppressive medication regimen for SOTRs. Main Outcomes and Measures:The primary outcome measure was tumor depth of SCC. Secondary outcome measures that reflected tumor aggressiveness included perineural invasion, regional metastases, nodal metastases, disease-specific death, and overall death. Results:Of the 58 SOTR study participants, 14 were women and 44 were men; the mean (SD) age was 61.3 (8.4) years. Of the 40 immunocompetent study participants, 16 were women and 24 were men; the mean (SD) age was 69.8 (10.9) years, resulting in a statistically significant difference from the SOTR group. The mean (SD) number of years that SOTRs were immunosuppressed was 14.6 (9.2) years (range, 2-37 years). The SOTR and immunocompetent groups were statistically comparable regarding race and sex, patient care, follow-up time, numbers of skin lesions, and field cancerization and chemopreventive therapies. The SOTR group had a significantly higher annual frequency of visits (mean [SD], 4 [2] vs 3 [2] office visits per patient per year, P = .02) and annual biopsy rates (mean [SD], 6 [4] vs 5 [3] biopsies per patient per year, P = .04). The SOTRs developed SCCs that did not appear to be significantly more aggressive than those found in the immunocompetent control group. These SOTRs also did not develop significantly thicker tumors than the immunocompetent control group (median [IQR] tumor depth, 1.30 [0.90-1.60] mm in 35 SOTRs vs 1.22 [1.10-1.60] mm in 20 immunocompetent patients). Conclusions and Relevance:The increased risk and the potential for aggressive behavior of SCCs in SOTRs may be successfully managed at a level comparable to that in high-risk immunocompetent individuals through close adherence to current dermatologic surveillance recommendations and a marginally lower threshold for biopsy of suspicious lesions for SOTRs.
| S-EPMC5833573 | biostudies-literature
Project description:One in twenty solid organ transplant recipients (SOTRs) will develop a highly morbid or fatal cutaneous carcinoma after transplantation. The majority of these cases develop on the head and neck and may require intervention on the part of dermatology, dermatologic surgery, otolaryngology, transplant medicine, radiation oncology, and medical oncology. In this review, we discuss the problem of cutaneous squamous cell carcinoma (cSCC) in SOTRs as well as the prognostic factors and management strategies to care for this population.
| S-EPMC7217490 | biostudies-literature
Project description: Not available
| S-EPMC5679270 | biostudies-literature
Project description:BackgroundThe RIPK4 (receptor-interacting protein kinase 4), a member of the RIPK family, acts as an important regulator of epidermal differentiation, cutaneous inflammation, and cutaneous wound repair. However, Until now, the role of RIPK4 in tumorigenesis remains elusive. There have been no studies exploring the effects of RIPK4 on the signaling pathway in cutaneous squamous cell carcinoma (SCC). It remains unknown whether RIPK4 expression, which can affect the degree of epidermal differentiation can also influence the radiosensitivity of skin SCC. It is urgent to fully elucidate the biological mechanism by which RIPK4 promotes carcinogenesis in skin SCC and determine whether RIPK4 expression levels predicts the sensitivity to radiotherapy in skin SCC.MethodsHuman skin SCC cell line, A431, was transfected with either small interfering RNAs (siRNAs) targeting RIPK4 (siR-RIPK4) or negative control siRNA (siR-NC). Western blotting was used to detect the expression of RIPK4 and Raf/MEK/ERK pathway-related proteins. The cells were irradiated using an X-ray irradiator at 6 MV with different radiation doses (0, 2, 6, and 10 Gy). Cell proliferation analysis, colony formation assay, transwell cell migration and invasion assay, cell cycle and apoptosis analysis were conducted to investigate the effect of RIPK4 silencing on skin SCC malignancy and radiosensitivity.ResultsRIPK4 protein expression was significantly decreased in the A431 cells transfected with siR-RIPK4, compared with the A431 cells transfected with siR-NC. RIPK4 silencing facilitated the proliferation, colony formation, migration, and invasion ability of A431 cell line, while cell cycle progression or cell apoptosis were not significantly influenced. In contrast with the previous literature, Raf/MEK/ERK pathway was not effected by RIPK4 knockdown in skin SCC. RIPK4 knockdown could not reverse the radiation resistance of A431 cells to irradiation in vitro.ConclusionsIn general, although depletion of RIPK4 cannot reverse the radiation resistance of A431 cells in vitro, it parallels higher malignancy potential in cutaneous SCC. To our knowledge, this is the first report of the effects of RIPK4 expression on the Raf/MEK/ERK signaling pathway and radiosensitivity in cutaneous SCC. The better understanding of the molecular mechanism of RIPK4 in cutaneous SCC may provide a promising biomarker for skin SCC prognosis and treatment.
| S-EPMC8841032 | biostudies-literature
Project description:Background: Cutaneous squamous cell carcinoma (cSCC) is a rare complication of hidradenitis suppurativa (HS). Objectives: To conduct a systematic review and an individual patient data (IPD) meta-analysis to describe the clinical characteristics of HS patients developing cSCC and determine predictors of poor outcome. Methods: Medline/PubMed, Embase, and Web of Science were searched for studies reporting cSCC arising in patients with HS from inception to December 2019. A routine descriptive analysis, statistical hypothesis testing, and Kaplan-Meier survival curves/Cox proportional hazards regression models were performed. Results: A total of 34 case reports and series including 138 patients were included in the study. The majority of patients were males (81.6%), White (83.3%), and smokers (n = 22/27 reported) with a mean age of 53.5 years. Most patients had gluteal (87.8%), Hurley stage 3 HS (88.6%). The mean time from the diagnosis of HS to the development of cSCC was 24.7 years. Human papillomavirus was identified in 12/38 patients tested. Almost 50% of individuals had nodal metastasis and 31.3% had distant metastases. Half of the patients succumbed to their disease. Conclusions: cSCC is a rare but life-threatening complication seen in HS patients, mainly occurring in White males who are smokers with severe, long-standing gluteal HS. Regular clinical examination and biopsy of any suspicious lesions in high-risk patients should be considered. The use of HPV vaccination as a preventive and possibly curative method needs to be explored.
| S-EPMC7962537 | biostudies-literature
Project description:Although tremendous progress has been made in recent years in skin cancer care for organ transplant recipients, significant gaps remain in data-driven clinical guidelines, particularly for the treatment and prevention of cutaneous squamous cell carcinoma (cSCC), the most common malignancy among this population. In this review, we aim to summarize current knowledge around the management of cSCC and highlight the most significant gaps in knowledge that continue to pose challenges in the delivery of skin cancer care for organ transplant recipients. We suggest future directions for research that will bridge existing gaps and establish evidence-driven guidelines for primary prevention, screening and treatment of cSCC in this high-risk patient population.
| S-EPMC5711582 | biostudies-literature
Project description:There have been no studies on implementing effective screening models for esophageal adenocarcinoma and squamous cell carcinoma survivors. We used a proportional subdistribution hazards model to estimate second primary malignancy risks among patients with esophageal adenocarcinoma and squamous cell carcinoma. We validated models using a bootstrap cross-validation method and performed decision curve analysis to evaluate their clinical utility. Age group and SEER historic stage were significantly associated with second primary malignancy risk after diagnosis of esophageal adenocarcinoma and squamous cell carcinoma. Saving positive lymph nodes and distant metastasis were significant factors in the adenocarcinoma group, and marital status, tumor location, and chemotherapy were significant factors in the squamous cell carcinoma group. Calibration plots show good concordance between predicted and actual outcomes except in high-probability areas for the risk of a second primary malignancy in patients with esophageal squamous cell carcinoma. Discrimination performances of the Fine-Gray models were evaluated using c-indices, which were 0.691 and 0.662 for second primary malignancies in patients with esophageal adenocarcinoma and squamous cell carcinoma, respectively. Decision curve analysis yielded a range of threshold probabilities (0.020-0.177 and 0.021-0.133 for patients with esophageal adenocarcinoma and squamous cell carcinoma, respectively) at which the clinical net benefit of the risk model was larger than those of hypothetical all-screening and no-screening scenarios. Our nomograms enable selection of patient populations at high risk for a second primary malignancy and thus will facilitate the design of prevention trials for affected populations.
| S-EPMC6738979 | biostudies-literature
Project description:BackgroundVariants at the oculocutaneous albinism 2 (OCA2)/HECT and RLD domain containing E3 ubiquitin protein ligase 2 (HERC2) locus have been associated with pigmentation phenotypes and risk of developing several types of skin cancer.ObjectivesTo evaluate OCA2/HERC2 locus variants for their impact on time to develop cutaneous squamous cell carcinoma (cSCC) in organ transplant recipients (OTRs) who are at elevated risk of developing cSCC.MethodsParticipants were solid OTRs ascertained from two centres (n = 125 and 261) with an average of 13·1 years of follow-up post-transplant. DNA was available for genotyping for all participants, in addition to medical records and questionnaire data. The Ohio State University study had a case-control design with prospective follow-up, and the University of California San Francisco study was a national cross-sectional survey with retrospective chart review.ResultsOCA2 variants rs12913832 and rs916977 were significantly associated with time to first cSCC post-transplant. OTRs homozygous for the brown-eye alleles of rs916977 (GG) and rs12913832 (AA) had significant delays of time to first cSCC post-transplant compared with individuals homozygous for the blue-eye alleles (hazard ratio 0·34, P < 0·001 and hazard ratio 0·54, P = 0·012, respectively). Both variants were highly associated with eye colour in the combined studies (P < 0·001).ConclusionsThis study is the first to show an association between OCA2/HERC2 variants and time to first cSCC post-transplant. This may impact dermatological screening recommendations for high-risk populations.
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Project description:Actinic keratosis and cutaneous squamous cell carcinoma in situ are precancerous forms of cutaneous squamous cell carcinoma. In this single-centre retrospective study, patients with histopathologically confirmed actinic keratosis (n = 121) or cutaneous squamous cell carcinoma in situ (n = 99) as their initial keratinocyte-derived lesion were compared and evaluated with regard to development of cutaneous squamous cell carcinoma during a 5-year observation period. Patients with severely dysplastic actinic keratosis or cutaneous squamous cell carcinoma in situ as their initial lesion developed cutaneous squamous cell carcinoma more rapidly than patients with actinic keratosis with mild or moderate dysplasia. With either actinic keratosis or cutaneous squamous cell carcinoma in situ as an initial lesion, advanced age, male sex, comorbidity with basal cell carcinoma, and immunosuppressive medication were associated with elevated risk of cutaneous squamous cell carcinoma development. Regarding solely patient with actinic keratosis as their initial lesion male sex, advanced age, immunosuppressive medication, location of the initial lesion, and degree of dysplasia were associated with the risk of cutaneous squamous cell carcinoma. Among patients with cutaneous squamous cell carcinoma in situ as their initial lesion, only aspirin usage was associated with increased risk of cutaneous squamous cell carcinoma. This study indicates that, among the vast and increasing population of patients with cutaneous squamous cell carcinoma precursors, male patients with immunosuppressive medication who develop basal cell carcinoma should be regarded as at heightened risk of cutaneous squamous cell carcinoma development and warrant closer surveillance.
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