Assessment of the association of myofibroblasts and structural components of the extracellular matrix with histopathological parameters of actinic cheilitis and lower lip squamous cell carcinoma.

BACKGROUND: To evaluate the presence of myofibroblasts (MFs) in the development of lip carcinogenesis, through the correlation of clinical, histomorphometric and immunohistochemical parameters, in actinic cheilitis (ACs) and lower lip squamous cell carcinomas (LLSCCs). METHODS: Samples of ACs, LLSCCs, and control group (CG) were prepared by tissue microarray (TMA) for immunohistochemical TGF-ß, α-SMA, and Ki-67 and histochemical hematoxylin and eosin, picrosirius red, and verhoeff van gieson reactions. Clinical and microscopic data were associated using the Mann-Whitney, Kruskal-Wallis/Dunn, and Spearman correlation tests (SPSS, p < 0.05). RESULTS: ACs showed higher number of α-SMA+ MFs when compared to CG (p = 0.034), and these cells were associated with the vertical expansion of solar elastosis (SE) itself (p = 0.027). Areas of SE had lower deposits of collagen (p < 0.001), immunostaining for TGF-ß (p < 0.001), and higher density of elastic fibers (p < 0.05) when compared to areas without SE. A positive correlation was observed between high-risk epithelial dysplasia (ED) and the proximity of SE to the dysplastic epithelium (p = 0.027). LLSCCs showed a higher number of α-SMA+ MFs about CG (p = 0.034), as well as a reduction in the deposition of total collagen (p = 0.009) in relation to ACs and CG. There was also a negative correlation between the amount of α-SMA+ cells and the accumulation of total collagen (p = 0.041). Collagen and elastic density loss was higher in larger tumors (p = 0.045) with nodal invasion (p = 0.047). CONCLUSIONS: Our findings show the possible role of MFs, collagen fibers, and elastosis areas in the lip carcinogenesis process.

Actinic conjunctivitis and its relationship with prurigo in an indigenous population from the Highlands of Chiapas, Mexico.

PURPOSE: Actinic conjunctivitis (AC), along with cheilitis (AChe), is part of the clinical spectrum of actinic prurigo (AP), a rare photo dermatosis that affects high-risk populations. We analyzed the clinical manifestations and onset of actinic conjunctivitis (AC), and its relationship with prurigo (AP) in a susceptible population. METHODS: This prospective observational cohort study was performed on Indigenous populations from the highlands of Chiapas, Mexico. Thorough dermatological and ophthalmological examinations were performed in patients attending a primary health care center. The clinical features, labor and environmental factors, onset timing, and clinical staging of AC and AP were analyzed. RESULTS: Of the 2913 patients studied, 54 patients (108 eyes) (1.8%) had AC, and 14 patients (25.9%) had AP. The mean age at diagnosis was 36.18 ± 18.52 years (6-70 years). The mean residential altitude was 1884 ± 434.2 m above sea level. Mean self-reported sun exposure was 5.14 ± 3.1 h a day (0.5-12 h). A total of 90.7% reported exposure to biomass fuels during cooking, and 50% to farm animals. AC was the sole manifestation in 70% of the cases. All patients had nasal and temporal photo-exposed conjunctiva. Among the eyes, 12.9% were classified as stage-1, 64.8% as stage-2, and 22.2% stage-3. A total of 83.3% of the patients had hyperpigmented lesions, and 35.1% had evaporative dry eye disease. CONCLUSIONS: AC may be the initial or sole manifestation of AP. Most AC cases (87%) were initially observed at the advanced stages of the disease. Although solar exposure was not associated with late AC stages, a positive association was found with farm animal exposure. Evaporative dry eye associated with meibomian gland dysfunction has not been previously reported in patients with AC.

The scientometric characteristics of cheilitis researched by multidisciplinary specialists: A comparative study.

Background/purpose: Cheilitis is a relatively common lip disease with many etiologies and causes including concomitant mucocutaneous or systemic diseases, which needs multidisciplinary communication. The purpose of this study was to compare the scientometric characteristics of cheilitis publications by multidisciplinary specialists. Materials and methods: All the papers on cheilitis were comprehensively retrieved from the Scopus database, and divided into three groups (dermatologists, stomatologists, and other scholars). Results: There were 478 and 241 papers on cheilitis published by dermatologists and stomatologists, respectively. The total citation count was 5838 and the h index was 36 for cheilitis publications by dermatologists, and the total count was 2983 and the h index was 27 for cheilitis publications by stomatologists. Interestingly, we observed that dermatologists preferentially concerned contact cheilitis/dermatitis and plasma cell cheilitis, while stomatologists preferentially concerned cheilitis-related lip neoplasms including squamous cell carcinoma, dysplasia, and precancerous conditions. The most common disorder researched by both dermatologists and stomatologists was actinic cheilitis. The keywords such as patch test, cosmetic, edema, drug efficacy, toothpaste, lipstick, allergens, and granulomatous inflammation were common in dermatologists' publications; while the keywords such as protein expression, metabolism, risk factor, prevalence, malignant transformation, and carcinogenesis were common in stomatologists' publications. Conclusion: This study for the first time reported the scientometric characteristics of cheilitis as an interdisciplinary disease researched by specialists. It highlights that cheilitis-related specialists through reciprocal collaboration and communication will improve the patients' outcomes.

Multiple noninvasive auxiliary tests-assisted photodynamic therapy in actinic cheilitis: A case report.

Actinic cheilitis (AC) is recognized as the most common precursor lesion of squamous cell carcinoma (SCC) of the lip, with a higher risk of invasiveness and metastasis. Early accurate diagnosis and appropriate therapy are essential to prevent carcinogenesis and progression of AC. Topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT), a non-surgical and minimally invasive modality, has been proposed as an effective treatment for oral potentially malignant diseases (OPMDs) and oral cancers. Herein, we report a 64-year-old female patient with AC on the lower lip who received 3 sessions of ALA-PDT with an interval of 1 week. Multiple noninvasive auxiliary tests including autofluorescence imaging, toluidine blue staining, and aneuploidy with DNA image cytometry (DNA-ICM) using brushing from screening through diagnosis, treatment, and follow-up. The patient successfully showed a complete response with no adverse effects and no evidence of recurrence at the 20-month follow-up. Noninvasive auxiliary tests assisted PDT is attractive and well-tolerated and may have synergistic effects against AC.

Desordens orais potencialmente malignas: o que o cirurgião-dentista precisa saber? / Oral potentially malignant disorders: what do dentists need to know?

Introdução:as desordens orais potencialmente malignas (DOPMs) são condições que podem preceder o aparecimento do câncer em cavidade bucal. Objetivo: descrever os principais aspectos clínicos, histológicos e tratamento da leucoplasia, eritroplasia, queilite actínica e líquen plano oral. Metodologia: trata-se de uma revisão da literatura atual, em que foram consultados artigos nas bases do MEDLINE/PUBMED e Biblioteca Virtual em Saúde, publicados nos últimos 10 anos. Os descritores foram localizados usando o vocabulário controlado do MeSH, sendo eles: Leukoplakia; Erythroplakia, Actinic cheilitis, Oral lichen planus, Diagnosis, Therapeutics. Resultados: asapresentações clínicas das DOPMs são diversas. A leucoplasia é a mais comum e deve ser distinguida da leucoplasia verrucosa proliferativa que tem uma apresentação clínica generalizada e uma tendência à recorrência após a excisão; a eritroplasia, embora rara, tem maior chance de malignização. A queilite actínica acomete com frequência o lábio inferior, tem forte relação com exposição solar e pode progredir para o carcinoma escamocelular labial; o líquen plano oral tem uma variedade de apresentações clínicas, sendo a forma reticular a mais comum. O tipo erosivo, atrófico ou bolhoso é acompanhado de sintomatologia dolorosa variável. A biópsia é essencial para confirmar a suspeita clínica das DOPMs e o encaminhamento oportuno para um especialista é indicado. Conclusão: as DOPMs podem ser encontradas durante o exame bucal, possibilitando assim, o diagnóstico precoce, e o correto encaminhamento a um especialista e a intervenção adequada, podendo reduzir a taxa de progressão dessas condições para câncer.

Introduction: Oral Potentially Malignant Disorders (OPMDs) are conditions that may precede the onset of cancer in the oral cavity. Objective: To describe the main clinical features, histological aspects and treatment of leukoplakia, erythroplakia, actinic cheilitis and oral lichen planus. Methodology: this is a review of the current literature, in which articles in the databases of MEDLINE/PUBMED and the Virtual Health Library, published in the last 10 years, were consulted. The descriptors were located using the MeSH controlled vocabulary, namely: Leukoplakia; Erythroplakia, Actinic cheilitis, Oral lichen planus, Diagnosis, Therapeutics. Results:the clinical presentations of OPMDs are diverse. Leukoplakia is the most common and must be distinguished from proliferative verrucous leukoplakia which has a generalized clinical presentation and a tendency to reoccur after excision; erythroplakia, although rare, has a greater chance of becoming malignant. Actinic cheilitis frequently affects the lower lip, is strongly related to sun exposure and can progress to labial squamous cell carcinoma; oral lichen planus has a variety of clinical presentations, with the reticular form being the most common. The erosive, atrophic or bullous type is accompanied by different levels of pain. Biopsy is essential to confirm the clinical suspicion of OPMDs and timely referral to a specialist is indicated. Conclusion: OPMDs can be found during oral examination, thus enabling early diagnosis, correct referral to a specialist and appropriate intervention, which may reduce the rate of progression of these conditions to cancer.

Clinicopathological Analysis of Actinic Cheilitis: A Systematic Review with Meta-analyses.

BACKGROUND: This systematic review aimed to conduct a complete investigation of the demographic aspects, clinicopathological features, degrees of epithelial dysplasia, and malignant transformation rate of actinic cheilitis. METHODS: The study was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered in the International Prospective Register of Systematic Reviews (CRD42020201254). A search without year and language restrictions was performed using PubMed/MEDLINE, Embase, Virtual Health Library, Scopus, Web of Science, and gray literature. Studies that provided information on patients with actinic cheilitis were included, excluding those with general information on other diseases or other types of cheilitis. Risk of bias was explored using the Joanna Briggs Institute tool. Narrative and quantitative data syntheses were performed using meta-analyses and subgroup analyses. Association tests were also performed. RESULTS: Thirteen studies (728 patients) were included. The most prevalent clinical signs were dryness (99%), blurred demarcation between the lip vermilion and skin (82%), scaling (69%), and atrophy (69%). Regarding epithelial dysplasia, a prevalence of mild dysplasia (34.2%), followed by moderate (27.5%), and severe (14.9%). The malignant transformation rate was 14%. Crusts, ulcerations, and erythematous areas were associated with lip carcinoma (p < 0.001), and scaling was associated with actinic cheilitis (p < 0.001). CONCLUSIONS: This study revealed several features of actinic cheilitis, providing an overview of the disease. It is suggested that new studies help develop policy guides for the standardization of clinical criteria, enabling more rigorous and homogeneous analysis of actinic cheilitis.

Laminin Immunostaining in Biopsies as a Useful Biomarker of Early Invasion in Actinic Cheilitis and Differential Diagnosis Between Actinic Cheilitis and Lip Cancer: New Insights.

BACKGROUND: Squamous cell carcinoma of the lip (LSCC) and oral cavity can be life-threatening if not diagnosed early. Precancerous lesions like actinic cheilitis (AC), can transform into LSCC. Laminin is a fundamental component for basement membrane (BM) and its integrity may prevent neoplastic invasion. Therefore, laminin immunostaining of BM may be useful in identifying early invasion in actinic cheilitis and thus in the differential diagnosis between AC and invasive LSCC or high-grade epithelial dysplasia (ED). MATERIALS AND METHODS: Biopsies from 46 patients with oral lesions were histologically analyzed and immunohistochemically stained for laminin-1. RESULTS: AC was diagnosed in 34 patients and LSCC in 12 patients, including 3 patients with AC and concomitant high-grade ED/in situ carcinoma. Laminin-1 immunostaining revealed intense and linear expression of the BM in AC with low-grade ED. Loss of laminin expression was observed in LSCC. Intracellular laminin expression in parabasal cells was noted in AC with high-grade ED/in situ carcinoma. CONCLUSION: Laminin immunostaining could be useful in identifying AC cases suspected of early invasion. It could also contribute to the histopathological differential diagnosis between AC with low- and high-grade ED and between AC and invasive LSCC. The findings of this study provide new insights into the mechanism involved in the progression process of AC into LSCC, encouraging preclinical studies that may document the stochastic role of laminin in this process.

Possible role of ALDH1 and CD44 in lip carcinogenesis

Abstract Lip squamous cell carcinoma (LSCC) accounts for 12% of all head and neck cancers. It is caused by chronic exposure to ultraviolet light solar radiation and related to previous actinic cheilitis (AC). This study aimed to investigate the immunostaining of the putative cancer stem cells (CSC) markers ALDH1 and CD44 in AC (n=30) and LSCC (n=20). ALDH1 positivity was found to be statistically higher in LSCC than in AC lesions (p=0.0045), whilst CD44 expression was statistically higher in AC than in LSCC lesions (p=0.0155). ALDH1+ cells in AC lesions were associated with specific clinical features: a younger age (<60 years old), the female gender, white skin, not smoking or consuming alcohol, and a fast evolution, and not associated with the chronic exposure to UV radiation (p<0.0001). CD44 positivity was associated with patients who were male, feoderm, smoked, consumed alcohol, underwent occupational exposure to UV-radiation, and demonstrated lesions with log-time evolution (p<0.0001). ALDH1 + cells were associated with mild dysplasia using a system from the World Health Organization (WHO), and with a low risk of malignant transformation, according to the binary system (p<0.0001). CD44+ cells were also associated with moderated dysplasia, according to the WHO system. In LSCC, ALDH1 + cells were positively associated with patients who were older (≥ 60 years old), smokers, and with those who consumed alcohol (p<0.0001). CD44 + cells in LSCC were associated with older (≥ 60 years old) patients as well, but also with female patients, white skin, non-smokers, and individuals who did not consume alcohol (p<0.0001), all of whom showed distinct patterns in pre- and malignant lesions of both markers. Additionally, in LSCC, both ALDH1 and CD44 staining were associated with smaller tumor sizes (T1/T2; p<0.0001). In summary, although both ALDH1 and CD44 were associated with the presence of dysplasia in AC lesions, the present findings suggest that ALDH1 and CD44 may be activated by different etiopathogenic pathways, predominantly in distinct steps of oral carcinogenesis. CD44 would thus be more significantly related to the potentially malignant lesion, while ALDH1 would be closely linked to malignancy.

Diagnostic study of actinic cheilitis by reflectance confocal microscopy / 口腔疾病防治

Objective @#To explore the clinical application value of reflectance confocal microscopy(RCM) in the diagnosis of actinic cheilitis(AC).@*Methods@#After approval by the hospital ethics committee and informed consent given by the patients, from October 2020 to July 2022, 17 patients who were diagnosed with actinic cheilitis in the Ninth People's Hospital affiliated with Shanghai Jiao Tong University School of Medicine were retrospectively analyzed. The white keratotic lesions of the lips were scanned with reflectance confocal microscopy, and the image characteristics were summarized and analyzed, including epithelial hyperplasia/atrophy, hyperkeratosis, inflammatory cell infiltration, blood vessel dilatation, solar elastosis, atypical keratinocytes, widening of intercellular spaces, degeneration of basal cell layer, and pigmentation. We used the sample compliance rate to measure the correlation between RCM parameters and histopathological diagnostic criteria for AC and kappa concordance analysis to calculate the concordance between RCM and pathological diagnosis. @* Results@# Under RCM, the sample correct rates for epithelial hyperplasia/atrophy, hyperkeratosis, inflammatory cell infiltration, vasodilation, and solar elastosis were 76.5%, 100%, 100%, 64.7%, and 70.6%, the sample accuracy compared with pathological diagnosis was 82.4%, 47.1%, 94.1%, 88.2% and 76.5%, respectively. We also observed that 100%, 88.2%, 76.5%, and 88.2% of AC patients showed RCM features of atypical keratinocytes, widening of intercellular spaces, degeneration of the basal cell layer, and pigmentation, respectively. The kappa value of hyperkeratosis and inflammatory cell infiltration was 1. The kappa value of blood vessel dilatation was 0.645. @* Conclusion @#Reflectance confocal microscopy is noninvasive and versatile and has clinical application value in the diagnosis of actinic cheilitis.

Randomized Clinical Trial of Conventional versus Indoor Daylight Photodynamic Therapy for Treatment of Actinic Cheilitis.

INTRODUCTION: Actinic cheilitis (AC) is the biologic precursor of invasive squamous cell carcinoma (SCC) of the vermilion, and different treatment options have been investigated, but their efficacy is hampered by local inflammation, pain and slow recovery. Daylight photodynamic therapy (dl-PDT) has been demonstrated to represent a valuable treatment option for AC, but its feasibility is limited by weather conditions and latitude. METHODS: Our study proposed to compare the efficacy and tolerability of conventional photodynamic therapy (c-PDT) and indoor daylight photodynamic therapy (idl-PDT) with a white LED lamp for the treatment of AC. Sixteen patients were enrolled in the study: 8 (50%) treated with c-PDT and 8 (50%) treated with idl-PDT. All patients completed the study protocol. RESULTS: Both idl-PDT and c-PDT were demonstrated to be highly effective in terms of reduction of the cumulative lesional area and severity of the clinical score. Neither treatment was inferior to the other. The inflammatory reaction and the pain scores were milder with idl-PDT, whereas the cosmetic outcome was not different. CONCLUSION: The present findings confirm that idl-PDT can represent a valid therapeutic strategy for AC patients as well, despite the procedural difficulties and the risk of poor tolerability related to the body site.

Actinic cheilitis: Proposal of a clinical index

Background: Actinic cheilitis is a potentially malignant lesion most commonly found in the lower lip of individuals with chronic exposure to ultraviolet radiation. The aim of this study was to develop and to test a clinical indexthat can be used to assess the severity of actinic cheilitis.Material and Methods: The clinical index of actinic cheilitis was applied to 36 patients. An incisional biopsy wasobtained to grade oral epithelial dysplasias following the World Health Organization (WHO) and binary systems,and to evaluate their association with clinical characteristics by Fisher’s exact test (P<0.05). The accuracy of theindex was evaluated based on sensitivity, specificity, positive and negative predictive values, and receiver operating curve.Results: The blurring between the border of the lip and the skin was significantly associated with cases withoutdysplasia/mild epithelial dysplasia (P=0.041) and with low risk of malignancy (P=0.005). Ulcers and crusts weresignificantly associated with moderate/severe epithelial dysplasia (P=0.002 and P=0.012, respectively) and highrisk of malignancy (P=0.005 and P=0.045, respectively). Erosion showed a significant association only with highrisk cases of malignancy (P=0.024). The cut-off values of the diagnostic test showing the best performance were10 for the WHO grading system and 11 for the binary system.Conclusions: The index cut-offs with the highest accuracy were considered indicators for a biopsy. Erosion, ulceration and crusts were associated with more severe oral epithelial dysplasias. (AU)

Photodynamic Therapy with 5-Aminolevulinic Acid Patch for the Treatment of Actinic Keratosis.

Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) is an emerging treatment option in the care of actinic keratosis (AK). A self-adhesive 5-ALA patch was recently developed that allows a precise PDT procedure. Here, we review the current literature and report the findings of our case series that observed the outcomes and safety of 5-ALA patch PDT. Ten patients with a total of 40 AKs were treated with a single session of conventional or daylight PDT using 5-ALA patch at the Department of Dermatology and Venereology, Sapienza University of Rome or at the European Institute of Oncology, Milan, Italy. Complete response was observed in three patients, while partial response was seen in seven patients. Overall tolerability was good or excellent, with local adverse events observed in four patients. This is the first case series reported where the 5-ALA patch was applied using daylight PDT, and its efficacy and tolerability in the treatment of AK were demonstrated. In conclusion, the self-adhesive 5-ALA patch is a convenient application of PDT that provides a well-tolerated and effective treatment option with satisfactory cosmetic outcomes.

Laser Therapy for the Treatment of Actinic Cheilitis: A Systematic Review.

Actinic cheilitis (AC) is a chronic inflammation of the lip considered an oral, potentially malignant disorder associated with an increased risk of lip squamous cell carcinoma (SCC) development. Controversies surrounding current therapeutic modalities of AC are under debate, and the implications of laser treatment have not been specifically investigated through a systematic review design. The present study aims to evaluate the degree of evidence of laser for the treatment of AC in terms of efficacy and safety. We searched for primary-level studies published before January 2022 through MEDLINE/PubMed, Embase, Web of Science, Scopus and CENTRAL, with no limitation in publication language or date. We evaluated the methodological quality and risk of bias of the studies included using the updated Cochrane Collaboration's tool for assessing risk of bias (RoB-2). Twenty studies (512 patients) met our eligibility criteria. Laser therapy showed a complete clearance of AC in 92.5% patients, with a maximum recurrence rate of 21.43%, and a very low frequency of malignant transformation to SCC (detected in only 3/20 studies analyzed). In addition, cosmetic outcomes and patient satisfaction were described as excellent. In conclusion, our findings indicate that laser therapy is a high efficacy approach to AC.

Dermoscopic Features of Actinic Cheilitis and Other Common Inflammatory Cheilitis: A Multicentric Retrospective Observational Study by the International Dermoscopy Society.

BACKGROUND: Clinical differentiation between different cheilitis variants may be difficult. Application of mucoscopy, in addition to clinical background, could provide additional diagnostic clues facilitating initial patient management. OBJECTIVES: To determine mucoscopic clues differentiating actinic cheilitis from the main forms of inflammatory cheilitis, including eczematous cheilitis, discoid lupus erythematosus, and lichen planus of the lips. METHODS: This was a retrospective, multicenter study being a part of an ongoing project "Mucoscopy - an upcoming tool for oral mucosal disorders" under the aegis of the International Dermoscopy Society. Cases included in the current study were collected via an online call published on the IDS website (www.dermoscopy-ids.org) between January 2019 and December 2020. RESULTS: Whitish-red background was found in actinic cheilitis as well as in cheilitis due to discoid lupus erythematous and lichen planus. Polymorphous vessels were more likely to be seen in actinic cheilitis compared to other causes of cheilitis. White scales, ulceration, and blood spots predominated in actinic cheilitis and lichen planus, whereas yellowish scales typified eczematous and discoid lupus erythematous cheilitis. Radiating white lines although most common in lichen planus patients were also seen in actinic cheilitis. CONCLUSION: Despite differences in the frequency of mucoscopic structures, we have not found pathognomonic features allowing for differentiation between analyzed variants of cheilitis.

Actinic Cheilitis - From Risk Factors to Therapy.

Actinic cheilitis or solar cheilosis is considered a precursor of malignancy or even an in situ squamous cell carcinoma (SCC) of the lip, located most frequently on the lower lip. Actinic cheilitis (AC) has a higher likelihood of developing into invasive SCC of the lip, which is one of the deadliest non-melanoma skin cancers. Risk factors include chronic UV exposure, increasing age, male gender, fair phototypes, chronic scarring, immunosuppressive therapy, and tobacco use. From a clinical point of view, AC is characterized by dryness, scaling, atrophy, indistinct borders, and erosions. Ulceration and the appearance of a nodule often suggest the progression to invasive SCC. Dermoscopic examination reveals white structureless areas, scales, erosions, and white halos of the vermilion. Reflectance confocal microscopy shows disruption of the stratum corneum, parakeratosis, an atypical honeycomb pattern, solar elastosis, and dilated and tortuous blood vessels with increased blood flow. The rate of malignant transformation ranges from 10 to 30% and early diagnoses and treatment are essential in preventing the development of invasive SCC. Optimal treatment has not been established yet, but invasive and topical treatments can be tried. The present paper aims to review the existing data regarding epidemiology, risk factors, clinical picture, non-invasive imaging, diagnosis, and therapy in AC.

Efficacy of photodynamic therapy in actinic cheilitis: A systematic review.

BACKGROUND: Photodynamic therapy (PDT) has gradually developed into a promising modality for actinic cheilitis (AC), and many new PDT strategies are emerging. However, comprehensive reviews evaluating the efficacy of PDT strategies for AC are lacking. OBJECTIVE: To systematically review the safety and efficacy of PDT strategies for AC. METHODS: A systematic review was conducted using three databases to compare several types of PDT for AC in terms of clinical response (CR), histopathology response (HR), cosmetic result, and adverse events. RESULTS: A total of 19 studies were included, and 292 subjects were finally enrolled. The complete CR rate of ALA-patch PDT, traditional photodynamic therapy (T-PDT), and daylight photodynamic therapy (DL-PDT) was 80.00% (24/30), 65.14% (114/179), and 76.74% (33/43), respectively. The rate of painless patients was 87.10% (27/31) in DL-PDT, whereas the rate was only 31.25% (15/48) in T-PDT. The rates of moderate and severe local phototoxicity were 47.78% (43/90) in T-PDT, 0.00% (0/23) in DL-PDT, and 21.05% (4/19) in ALA-patch PDT. CONCLUSION: Published literature suggests that ALA-patch PDT seem to achieve high complete CR rate. Besides, DL-PDT might be a well-tolerated therapy compared with T-PDT and ALA-patch PDT. However, these assumptions are made based on very limited data. It is necessary to conduct a long-term larger sample randomized controlled trial to further evaluate the efficacy and adverse events of various PDT schemes for AC.

Immunohistochemical analysis of epithelium adjacent to lip cancer: A meta-analysis.

OBJECTIVES: To identify the immunohistochemical pattern of non-tumoral epithelium adjacent to lip cancer (ANTE) to unveil molecular alterations and potential biomarkers in lip cancer patients. MATERIALS AND METHODS: A systematic search at MEDLINE, EMBASE and proceedings Web of Science, OpenGrey and WorldCat. The PICOS outline (Population: lip cancer patients; Intervention: immunostaining with biomarkers in surgical specimens; Comparisons: ANTE versus LC; Outcomes: primary-to identify the immunohistochemical pattern of peritumoral epithelium and secondary-to assess the immunoreactivity of LC epithelium; and Study design: cross-sectional, case-control and cohort studies). RESULTS: A total of 339 records were identified. Seven studies reporting on ANTE and LCs were included in the qualitative synthesis, and 4 of them (p53 immunostaining) were selected for meta-analysis. In the ANTE group, the pooled prevalence of p53 was 0.74 (95% CI: 0.66 - 0.82), while in the lip squamous cell carcinoma group this prevalence was 0.83 (95% CI: 0.75 - 0.89). CONCLUSIONS: Similar immunoexpression was found in lip epithelium adjacent to lip carcinoma, even in epithelia with normal appearance or mild histological alterations. The role of biomarkers in the follow-up of actinic cheilitis patients deserves additional clinical assessment.

Sun protection as a protective factor for actinic cheilitis: Cross-sectional population-based study.

OBJECTIVE: To determine whether sun protection is associated with lower occurrence of actinic cheilitis in adults living in a city from southern Brazil. MATERIALS AND METHODS: A multi-stage proportional sample of 404 individuals 18 years and older was obtained. Interviews and clinical examinations were conducted in participants' households. Four categories of self-reported use of sun protection were determined. Multivariable Poisson regression was used to assess the associations. RESULTS: Prevalence of actinic cheilitis was 47.1%. In the first main-effects multivariable model, AC was significantly associated with sex, age, skin colour and duration of sun exposure, but not with sun protection. However, the association between sun protection and actinic cheilitis was modified by the time of sun exposure. Among those exposed ≥4 hr/day to sun, individuals using physical protection or physical + chemical protection were 33% (prevalence ratio = 0.67, 95% confidence interval [CI] 0.47-0.94, p = .02) and 36% (PR = 0.64, 95% CI 0.47-0.94, p = .02), respectively, less likely to have actinic cheilitis than those who did not use any sun protection, adjusting for sex, age and skin colour. CONCLUSIONS: Physical and chemical sun protection were associated with lower occurrence of actinic cheilitis in individuals with greater exposure to sun.

Clinical and dermatoscopic predictors of squamous cell carcinoma of the lips: a case-control, multicentric study.

BACKGROUND: Squamous cell carcinoma of the lip accounts for 20% of all oral carcinomas. Its diagnosis may be challenging because it clinically resembles actinic cheilitis and inflammatory lesions of the lips. OBJECTIVES: To determine clinical and dermatoscopic predictors of squamous cell carcinoma of the lip vs. other lip lesions. METHODS: Multicentre retrospective morphological study, including histologically confirmed cases of squamous cell carcinoma of the lip and controls consisting of actinic cheilitis and inflammatory lesions of the lips. Clinical and dermatoscopic images were evaluated for the presence of predefined criteria. Crude and adjusted odds ratios and corresponding 95% confidence intervals were calculated by univariate and multivariate logistic regression respectively. RESULTS: A total of 177 lip lesions were evaluated, 107 (60.5%) were squamous cell carcinomas and 70 (39.5%) were controls. The most frequent dermatoscopic criteria of lip squamous cell carcinoma were scales (100%), white halos (87.3%) and ulceration (79.4%). The majority of squamous cell carcinomas displayed polymorphic vessels (60.8%), with linear (68.6%) and hairpin (67.6%) being the most frequent types. Multivariate logistic regression analysis showed that clinical predictors of lip squamous cell carcinoma were exophytic appearance and clinical hyperkeratosis, with 43-fold and 6-fold higher probability respectively. White clods and ulceration in dermoscopy presented a 6-fold and 4-fold increased risk for squamous cell carcinoma respectively. CONCLUSIONS: A scaly lesion with exophytic growth, dermatoscopically displaying white clods, ulceration and linear and hairpin vessels is very likely a squamous cell carcinoma of the lip.

Reflectance confocal microscopy (RCM)-based criteria for progression of lower-lip squamous cell carcinoma: A prospective study.

BACKGROUND: Actinic cheilitis (AC) presents as a diffuse clinical-histopathological alteration throughout the lower lip. OBJECTIVES: To analyze AC lesions using reflectance confocal microscopy (RCM) and evaluate criteria for the early diagnosis of incipient squamous cell carcinoma (SCC). METHODS: This prospective study comprised cases of clinically diagnosed AC. RCM was performed over the entire extension of the lower lip. The sites that showed the highest degree of morphological alteration by RCM, according to established criteria for AC and SCC, were biopsied. The RCM findings and histopathology were correlated to establish the precise and early diagnosis of SCC. RESULTS: A total of 61 cases that had been clinically diagnosed with AC were included. The RCM findings that correlated independently with SCC were: nonedged papillae (sensitivity 84% and specificity 88%, p < 0.0001, and OR 42), cell-filled papillae (sensitivity 82% and specificity 93%, p < 0.0001, and OR 71.3), inflammation (sensitivity 68% and specificity 68%, p = 0.0163, and OR 4.8), large and roundish cells in the lamina propria (sensitivity 65% and specificity 100%, p < 0.0001, and OR infinity), and nests in the lamina propria (sensitivity 54% and specificity 100%, p < 0.0001, and OR infinity). An independent histopathological analysis classified the cases as partial epithelial dysplasia (25 cases, 41%) and SCC (36, 59%), and in 57 cases (94%), the results agreed with the categorization that was rendered by the RCM exam. CONCLUSIONS: RCM can be used to monitor AC cases, guide the biopsy site, and identify the early progression of AC to SCC with good sensitivity and specificity.