Diagnosis Of Actinic Keratosis Research Articles

An Update on Non-Invasive Skin Imaging Techniques in Actinic Keratosis-A Narrative Review.

Nonmelanocytic skin cancers (NMSCs) are currently the most common group of human cancers and include all tumors that are not melanomas. Increased exposure to sunlight over the past few years, the lack of regular and proper use of sunscreen, the aging of the population, and better screening techniques are the reasons for the escalation in their diagnosis. Squamous cell carcinoma (SCC) comprises nearly 37% of the tumors in this group and can originate from actinic keratosis (AK), which usually presents as pink, often scaly plaques, usually located on the face or scalp. Advances in dermatoscopy, as well as the development of other non-invasive skin imaging modalities such as high-frequency ultrasound (HFUS), reflectance confocal microscopy (RCM), and optical coherence tomography (OCT), have allowed for greatly increased sensitivity in diagnosing these lesions and monitoring their treatment. Since AK therapy is usually local, and SCCs must be removed surgically, non-invasive imaging methods enable to correctly qualify difficult lesions. This is especially important given that they are very often located on the face, and achieving an appropriate cosmetic result after treatments in this area is very important for the patients. In this review, the authors describe the use of non-invasive skin imaging methods in the diagnosis of actinic keratosis.

European consensus-based interdisciplinary guideline for diagnosis, treatment and prevention of actinic keratoses, epithelial UV-induced dysplasia and field cancerization on behalf of European Association of Dermato-Oncology, European Dermatology Forum, European Academy of Dermatology and Venereology and Union of Medical Specialists (Union Européenne des Médecins Spécialistes).

A collaboration of multidisciplinary experts from the European Association of Dermato-Oncology, the European Dermatology Forum, the European Academy of Dermatology and Venereology, and the European Union of Medical Specialists was formed to develop European recommendations on AK diagnosis and treatment, based on current literature and expert consensus. This guideline addresses the epidemiology, diagnostics, risk stratification and treatments in immunocompetent as well as immunosuppressed patients. Actinic keratoses (AK) are potential precursors of cutaneous squamous cell carcinoma (cSCC) and display typical histopathologic and immunohistochemical features of this malignancy in an early stage. They can develop into cSSC insitu and become invasive in a low percentage of cases. AK is the most frequent neoplasia in white populations, frequently occurring within a cancerous field induced by ultraviolet radiation. Since it cannot be predicted, which lesion will progress to cSCC and when treatment is usually recommended. The diagnosis of AK and field cancerization is made by clinical examination. Dermatoscopy, confocal microscopy, optical coherence tomography or line-field confocal-OCT can help in the differential diagnosis of AK and other skin neoplasms. A biopsy is indicated in clinically and/or dermatoscopically suspicious and/or treatment-refractory lesions. The choice of treatment depends on patients' and lesion characteristics. For single non-hyperkeratotic lesions, the treatment can be started upon patient's request with destructive treatments or topical treatments. For multiple lesions, field cancerization treatment is advised with topical treatments and photodynamic therapy. Preventive measures such as sun protection, self-examination and repeated field cancerization treatments of previously affected skin areas in high-risk patients are advised.

Innovation in Actinic Keratosis Assessment: Artificial Intelligence-Based Approach to LC-OCT PRO Score Evaluation.

Actinic keratosis (AK) is a common skin cancer in situ that can progress to invasive SCC. Line-field confocal optical coherence tomography (LC-OCT) has emerged as a non-invasive imaging technique that can aid in diagnosis. Recently, machine-learning algorithms have been developed that can automatically assess the PRO score of AKs based on the dermo-epidermal junction's (DEJ's) protrusion on LC-OCT images. A dataset of 19.898 LC-OCT images from 80 histologically confirmed AK lesions was used to test the performance of a previous validated artificial intelligence (AI)-based LC-OCT assessment algorithm. AI-based PRO score assessment was compared to the imaging experts' visual score. Additionally, undulation of the DEJ, the number of protrusions detected within the image, and the maximum depth of the protrusions were computed. Our results show that AI-automated PRO grading is highly comparable to the visual score, with an agreement of 71.3% for the lesions evaluated. Furthermore, this AI-based assessment was significantly faster than the regular visual PRO score assessment. The results confirm our previous findings of the pilot study in a larger cohort that the AI-based grading of LC-OCT images is a reliable and fast tool to optimize the efficiency of visual PRO score grading. This technology has the potential to improve the accuracy and speed of AK diagnosis and may lead to better clinical outcomes for patients.

An Actinic Keratosis Auxiliary Diagnosis Method Based on an Enhanced MobileNet Model.

Actinic keratosis (AK) is a common precancerous skin lesion with significant harm, and it is often confused with non-actinic keratoses (NAK). At present, the diagnosis of AK mainly depends on clinical experience and histopathology. Due to the high difficulty of diagnosis and easy confusion with other diseases, this article aims to develop a convolutional neural network that can efficiently, accurately, and automatically diagnose AK. This article improves the MobileNet model and uses the AK and NAK images in the HAM10000 dataset for training and testing after data preprocessing, and we performed external independent testing using a separate dataset to validate our preprocessing approach and to demonstrate the performance and generalization capability of our model. It further compares common deep learning models in the field of skin diseases (including the original MobileNet, ResNet, GoogleNet, EfficientNet, and Xception). The results show that the improved MobileNet has achieved 0.9265 in accuracy and 0.97 in Area Under the ROC Curve (AUC), which is the best among the comparison models. At the same time, it has the shortest training time, and the total time of five-fold cross-validation on local devices only takes 821.7 s. Local experiments show that the method proposed in this article has high accuracy and stability in diagnosing AK. Our method will help doctors diagnose AK more efficiently and accurately, allowing patients to receive timely diagnosis and treatment.

Classification of Images of Skin Lesion Using Deep Learning

Skin cancer is among common and rapidly increasing human malignancies, which can be diagnosed visually. The diagnosis begins with preliminary medical screening and by dermoscopic examination, histopathological examination, and proceeding to the biopsy. This screening and diagnosis can be automated using machine learning tools and techniques. Artificial neural networks are helping a lot in medical diagnosis applications. In this research, skin images are classified into 7 different classes of skin cancer using deep learning methodology, then analyzed the results w.r.t to their respective precision, recall, support, and accuracy to find its practical applicability. This model is efficient in comparison to the detection of skin cancer with human eyes. Human eyes detection can be 79% accurate at most. Thus, having a scientific method of diagnosis can help the doctors and practitioners to accurately identify the cancer and its type. The model provides 80% accuracy on average for all 7 types of skin diseases, thus being more reliable than human eye examination. It will help the doctors to diagnose the skin diseases more confidently. The model has only 2 misclassified predictions for Basal cell carcinoma and Vascular lesions. However, Actinic keratosis diagnosis is most accurately predicted.

Refusal of Retreatment With Topical 5-Fluorouracil Among Patients With Actinic Keratosis: Qualitative Analysis.

Actinic keratosis (AK) is a common premalignant skin lesion, and topical 5-fluorouracil (5-FU) is commonly used in field-directed therapy. However, 5-FU is associated with frequent local skin reactions. This study aimed to qualitatively assess experiences among patients with AK who refuse retreatment with 5-FU. Semistructured interviews were conducted with 10 adult participants who had received treatment with 5-FU for AK between January 1, 2017, and January 1, 2020, and refused future treatment with 5-FU. Results were analyzed using qualitative research methods. Although most participants had low concern upon having received a diagnosis of AK, most felt that treatment is very important. When initiating treatment with 5-FU, most cited recommendation by their health care professionals as the primary motivator and initially had low concern regarding treatment. The side effects associated with treatment were physically and psychosocially burdensome for most participants and led to temporary lifestyle adjustments. After treatment, most did not believe that their health care provider prepared them for treatment or were unsure. While half of the participants felt that 5-FU helped treat AKs, half were either unsure, due to premature discontinuation, or did not think that 5-FU treated their AKs. 5-FU is one of the most commonly prescribed treatments for AKs, yet most patients experienced both a physical and psychosocial burden with the treatment. Inability to assess efficacy due to premature discontinuation secondary to 5-FU-related reactions is common, and shared decision-making, navigating treatment options, and taking into account patient preferences may be critical to help assure better adherence and outcomes. Although our study was limited by input from participants who refused future treatment with 5-FU, most stated that they would still continue to seek treatment for AKs in the future and would consider other topical treatments, especially if associated with a milder tolerability profile.

Skin Cancer Development Is Strongly Associated with Actinic Keratosis in Solid Organ Transplant Recipients: A Danish Cohort Study

Background and Objectives: Solid organ transplant recipients (SOTRs) are at increased risk of skin cancer and suffer from greater disease-specific morbidity and mortality. To risk stratify the expanding SOTR population for more targeted skin cancer screening, a detailed understanding of risk factors is needed. Using combined clinical and pathological data to capture prevalence of actinic keratosis (AK) and skin cancer, this study aimed to identify risk factors of skin cancer development in a Danish SOTR cohort. Methods: The trial comprised a retrospective cohort study of patients attending organ transplant clinics at the dermatological departments of Bispebjerg and Gentofte Hospitals in Copenhagen, Denmark, between 2009 and 2021. In addition to pathology records, AK prevalence was determined by review of electronic medical records (EMRs) of SOTR visits which specifically included descriptions of clinical AK. Prevalence of skin cancer, here defined as basal cell carcinoma (BCC), squamous cell carcinoma (SCC) (invasive or in situ), or melanoma (invasive or in situ), was determined by EMR and pathology code review. Additional data extracted from EMRs included age, sex, Fitzpatrick skin type, transplantation date and type, and immunosuppressive therapy. The effect of risk factors on skin cancer was calculated by Cox proportional hazards regression. Results: A total of 822 SOTRs were included with a mean follow-up duration of 10.8 years (SD 2.4 years). A skin dysplasia diagnosis was identified in 30% (n = 250) of the population, consisting of either AK (22%; n = 177), skin cancer (23%; n = 186) or both (14%; n = 113). An AK diagnosis predicted both SCC (odds ratio [OR]: 31.5 [95% CI: 9.8–100.6], p < 0.0001) and BCC development (OR: 2.3 [95% CI: 1.6–3.3], p < 0.0001), with AKs diagnosed an average 3.1 years before the first SCC (p < 0.0001). Correspondingly, while the risk of SCC in SOTRs without AK was 1.4% 25 years after transplantation, SOTRs with AKs had a 23% SCC risk only 10 years posttransplant. Other identified risk factors included Fitzpatrick skin type I (BCC: OR: 2.4 [95% CI: 1.2–5.0], p = 0.018; SCC: 3.2 [95% CI: 1.2–8.2], p = 0.016) and transplantation duration >15 years (BCC: OR: 1.8 [95% CI: 1.2–2.7], p = 0.007). No significant association between skin cancer development and sex or immunosuppressive regimen was shown. Conclusion: Keratinocyte carcinoma is strongly associated with an AK diagnosis in SOTRS and should prompt intensified skin cancer screening in affected individuals.

Risk of squamous cell carcinoma in immunosuppressed patients with voriconazole-related actinic keratosis.

Voriconazole is commonly administered for a long period to patients receiving immunosuppressive therapy. Although voriconazole potentially induces skin cancers in association with sun exposure, this has not yet been examined in detail in a single ethnic patient group. Therefore, the present study investigated the risk of developing squamous cell carcinoma (SCC) in Japanese patients with voriconazole-related actinic keratosis (AK) and the prognosis of Japanese patients with voriconazole-related SCC. We retrospectively examined 37 Japanese patients with AK, including five voriconazole-treated patients (mean age, 57.9 ± 16.3years) and 32 non-treated patients (74.9 ± 9.2years), and 18 Japanese patients with SCC, including four voriconazole-treated patients (55.4 ± 16.7years) and 14 non-treated patients (74.1 ± 10.7years). Among the 37 patients with AK, SCC developed in five, including four with a history of treatment with both voriconazole and immunosuppressive agents, independent of AK progression. In these four patients, the mean period from the diagnosis of AK to that of SCC was 13.8 ± 11.6months. Kaplan--Meier analyses showed that the risk of developing SCC was significantly higher in patients with both voriconazole and immunosuppressants/corticosteroid-treated patients with AK than in non-voriconazole-treated patients with AK (the Log-rank test, p < 0.001). The analyses also showed that the mortality rate was significantly higher in patients with both voriconazole and immunosuppressants/corticosteroid-treated patients with SCC than in non-voriconazole-treated patients with SCC (p=0.018). The present results suggest that voriconazole-related AK precedes the development of cutaneous SCC and voriconazole-related SCC leads to a poor prognosis under the immunosuppressive condition.

Blue scales on an “iced” scalp

Although the diagnosis of actinic keratosis (AK) is mainly clinical, dermoscopy is a highly useful and accurate diagnostic technique. The dermoscopic features of AK include the strawberry pattern with white areas, keratotic, follicular openings, a pseudonetwork, and rosettes [1]. An 82-year-old male with a personal history of type 3 autoimmune polyglandular syndrome and hypertension was referred to the dermatology department due to the presence of scaly lesions located on the scalp and forehead. A physical examination revealed asymptomatic, keratotic lesions on the forehead and in the occipital region (Fig. 1a). The patient denied the application of any product except toning shampoo for white hair. Interestingly, the lesions had a blue, superficial scale, although they clinically resembled AK. Dermoscopy evidenced an erythematous background with multiple, arctic-blue, keratotic plugs (Fig. 1b). Moreover, a superficial excision of one of the lesions was performed, evidencing solar elastosis and a chronic dermal infiltrate, as well as basal keratinocytes with loss of polarity, presenting with irregular nuclei (Fig. 2). Thus, the clinical and pathological correlation confirmed the diagnosis of AK. The lesions were treated with cryotherapy leading to their resolution. Figure 1: (a) Clinical presentation of the cutaneous lesions: numerous bluish-gray, scaly lesions in the occipital area; the patient confirmed using toning shampoo for white hair containing Acid Violet 43. (b) Dermoscopy of one of the lesions: an erythematous background, as well as numerous arctic-blue, keratotic plugs; the blue scale compatible with the iceberg sign present in AK neglecta. Figure 2: Solar elastosis and a chronic dermal infiltrate, as well as basal keratinocytes with loss of polarity presenting with irregular nuclei; findings compatible with the clinical suspicion of AK; no basophilic amorphous material present in the stratum corneum (H&amp;E, 20×). Blue AK has been termed AK neglecta while the dermoscopic blue coloration the iceberg sign [2,3]. The latter is described to be caused both by sunscreens containing titanium dioxide [3] or shampoos containing Acid Violet (present in the shampoo that the patient used) [2]. Moreover, this exogenous pigmentation may easily be removed with alcohol [3]. Histologically, a basophilic amorphous material on the stratum corneum is described to be present [2]. A lack of this finding in our case might have been explained due to the 10% formol used to preserve the biopsy, eliminating the pigment. Recognizing this presentation is essential due to the widespread use of toning shampoos and sunscreens among the elder population.

Classifying Actinic Keratosis: What the Reality of Everyday Clinical Practice Shows Us.

Difficulties faced by clinicians in routine clinical practice when selecting the appropriate treatment for patients with actinic keratosis (AK) include: the independent evaluation of AK lesions, the absence of a standardized definition of field cancerization (FC), and the lack of a reproducible classification to grade the entire AK-affected area. Moreover, to assess the severity of AK, most guidelines rely on lesion count, which is often not reproducible among specialists. The present work has 2 main objectives: first, to review and highlight some of the issues clinicians tackle when classifying and monitoring AK lesions and the status of FC, looking in more detail at some of the most commonly used clinical scales for classifying AK lesions. Second, we pose questions that we encounter in daily clinical practice, and whose answers or comments help to deal with cases of AK, facilitating the work of clinicians: How should we approach AK diagnosis? How do the challenges of clinical studies on the evaluation of treatment efficacy translate into clinical practice? We review the literature on the clinical classifications and management of AK, and propose how to guide the diagnosis, management, and monitoring of patients with AK. J Drugs Dermatol. 2022;21(8):845-849. doi:10.36849/JDD.6704.

Dermoscopy and Reflectance Confocal Microscopy in Actinic Keratosis, Intraepithelial Carcinoma, and Invasive Squamous Cell Carcinoma.

Patients with multiple actinic keratosis (AK), have pre-neosplastic abnormalities, constituting the sites of new tumors, this region is called the cancerization field. Due to the risk of malignant transformation, rigorous evaluation, follow-up, and treatment of the cancerization field is proposed. Recently, non-invasive diagnostic technologies such as confocal reflectance microscopy (RCM), detect AK, intraepithelial carcinomas (IEC), and SCC, without the need of repeated biopsies. There are few reports of the progression of AK assessed by dermatoscopy and RCM concomitantly. Define morphological patterns and clinical applicability of dermatoscopy and MCR examinations of the AK lesions and their degrees of progression to IEC and SCC. A retrospective cross-sectional study of dermatoscopy and RCM examinations was performed in 30 patients with histopathological diagnosis of AK (20), IEC (6), and SCC (4). In the comparative analysis of the dermatoscopic features, erythema was present in 100% of the lesions, the red pseudo-network in 75% of the AK (P=0.007), and linear and irregular vessels in 90% of the lesions of IEC/SCC. In the RCM of AK, the most striking finding was the presence of atypical honeycomb in the spinous layer, but typical in the granular layer. While the IEC/SCC group presented irregular epidermal architecture and atypical honeycomb in all epider-mal layers, it also showed a higher prevalence of individual corneocytes and nucleated cells, cellular pleomorphism, and nuclear atypia in the dermal papillae, irregular vessels within papilla, and cells with bright edges and dark central nuclei in the dermis. Dermoscopy and RCM may be considered as auxiliary methods for assessing lesions resulting from ke-ratinocyte atypia. The results of this study are consistent with published studies and it was possible to propose, with literature support, a model of progression of AK to IEC and SCC. J Drugs Dermatol. 2022;21(3):259-268. doi:10.36849/JDD.5086.

Analysis of molecular mechanisms of development of actinic keratosis: a review

Objective — to study the molecular mechanisms of the development of actinic keratosis (AK) and compare them with Bowen’s disease.&#x0D; Materials and methods. A literature review, analysis of national and international protocols for the diagnosis of AK are presented, which meet the selection criteria. We reviewed works with at least one recommendation for AK diagnostic scenario published after 2015. The systematic literature review is based on modern studies containing descriptions of molecular diagnostics of certain proto-oncogenes to establish the final diagnosis. Interdisciplinary guidelines were also reviewed to further explore all possible diagnostic criteria.&#x0D; Results and discussion. Until now, the molecular mechanisms of AK development have not been fully studied and grouped into a single review. In most of the sources, only p53 protein was mentioned as the main transcription factor regulating apoptosis. However, recent studies prove a sufficient influence of CD95, which, like p53, induces apoptosis and plays a leading role in the development of AK. All precancerous and malignant neoplasms of the skin arise due to mutations in cells, which cause a violation of apoptosis, but there are still no recommendations and a clear diagnostic algorithm that will allow to quickly establish the final diagnosis and make a choice in favor of this or another method of treatment.&#x0D; Conclusions. AK and Bowen’s disease are different stages in the development of the same malignant process, differing in the proliferative activity of cells and the expression of proto-oncogenes CD95, bcl-2, and p16 which can be used as differential diagnostic markers. Thanks to early diagnosis, it is possible to choose the most suitable treatment option, with consideration for modern protocols.

28521 Frequency of procedural and medical treatments for actinic keratosis

Actinic keratosis (AK) is a common dermatologic diagnosis with the potential of malignant transformation. Treatment options include destructive therapies, such as cryotherapy, and topical medications, such as 5-fluorouracil (5-FU), imiquimod, and ingenol mebutate. Historically, destructive procedures have remained the standard of care. There have been limited updates on AK management practices; we determined the frequency of procedural and medical treatments of AK. We assessed visits from the 2009 to 2016 National Ambulatory Medical Care Survey to quantify the use of cryotherapy, topical 5-fluorouracil, imiquimod, ingenol and topical aminolevulonic acid (as a proxy for photodynamic therapy). There were an estimated 11.5 (10.6, 12.4) million visits with a primary diagnosis of AK. One or more of the studied treatments were identified at 47.1% (42.5, 51.6) of visits. Of visits with some kind of AK treatment, cryotherapy was used in 90.6% (81.5, 99.7) of visits, while 5-fluorouracil, imiquimod, and ingenol were prescribed at 4.06% (2.20, 5.92), 5.00% (1.65, 8.36) and 0.16% (0, 0.33) of all visits (respectively). Photodynamic therapy was used at 0.90% (0.25, 1.55) of all visits with treatment. Despite the expansion of treatment options, cryotherapy remains the standard of care. Future development of therapies with improved tolerability and patient compliance as well as alternate payment models have the potential to change the standard of practice.

Ten-Year Follow-up of Persons With Sun-Damaged Skin Associated With Subsequent Development of Cutaneous Squamous Cell Carcinoma

Risk of cutaneous squamous cell carcinoma (cSCC) after the diagnosis of actinic keratosis (AK) has not been studied during long follow-up periods. To estimate the risk up to 10 years and identify risk factors for cSCC development. This longitudinal cohort study, performed from January 1, 2009, to February 29, 2020, examined Kaiser Permanente Northern California patients with AK and control patients matched 1:1 on age, sex, race/ethnicity, medical center, and date of the initial diagnosis plus 30 days in the patients with AK. Patients with AK and control participants were followed up for up to 10 years for incidence of cSCC. Incident cSCC was obtained from pathologic data, and subdistribution hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards regression analysis, accounting for competing risks, calendar year, demographic factors, and number of AKs. The study included 220 236 patients with AK and 220 236 matched control patients (mean [SD] age, 64.1 [12.2] years; 231 248 [52.5%] female). After losses to follow-up were accounted for, risk of cSCC increased with each year of follow-up by 1.92% (95% CI, 1.89%-1.95%) in patients with AK and 0.83% (95% CI, 0.81%-0.85%) in matched control patients (subdistribution HR, 1.90; 95% CI, 1.85-1.95). However, among patients 49 years or younger, those diagnosed with AK were nearly 7 times more likely to be diagnosed with cSCC than those without AK (HR, 6.77; 95% CI, 5.50-8.32). At 10 years, the cumulative incidence of cSCC reached 17.1% (95% CI, 16.9%-17.4%) in patients with AK and 5.7% (95% CI, 5.5%-5.9%) in control patients. Increased numbers of AKs were modestly associated with increased cSCC risk (≥15 AKs vs 1 AK: subdistribution HR, 1.89; 95% CI, 1.75-2.04). Older patients had much higher risk of cSCC than younger patients (compared with those ≤49 years of age at AK diagnosis; ≥80 years of age: subdistribution HR, 8.18; 95% CI, 7.62-8.78). Other than AK, risk factors for cSCC included older age, White race (a proxy for skin type), history of basal cell carcinoma, and male sex. Risk decreased between 2009 and 2019 (2018-2019 vs 2009-2010: subdistribution HR, 0.67; 95% CI, 0.63-0.72). The results of this longitudinal cohort study can be used to develop recommendations to increase early detection of cSCC. Additional research is needed to understand the effect of AK treatment on cSCC risk and outcomes of cSCC.

The Usefulness of Teledermatology in Monitoring the Efficacy and Safety of a Topical Treatment for Actinic Keratosis

We recently reported that teledermatology (TD) is valid and reliable in the diagnosis of actinic keratosis (AK) and field cancerization (Sola-Ortigosa et al., 2020). Although AK is mostly treated by dermatologists, primary care physicians (PCPs) participate in the management and follow-up (de Berker et al., 2017; Lowell et al., 2001). Topical AK treatments usually produce local skin reactions (LSRs) that lead to unscheduled dermatological consultations and treatment withdrawal. We hypothesized that TD could be used for monitoring topical AK therapy in the primary care setting, thus reducing treatment-related referrals.

P53 immunostaining in skin biopsies may assist the diagnosis of actinic keratosis

P53 immunostaining in skin biopsies may assist the diagnosis of actinic keratosis

Diagnostic Accuracy of Dermoscopy of Actinic Keratosis: A Systematic Review.

Dermoscopy is a tool that aids clinicians in the diagnosis of actinic keratosis; however, few diagnostic accuracy studies have determined its sensitivity and specificity for this diagnosis. Determine the diagnostic accuracy of dermoscopy on actinic keratosis. A systematic review was conducted on EMBASE, PubMed, Scopus and the Cochrane Central Registry of Controlled Trials from inception to August 2019. We screened 485 titles and abstracts. Two studies comprising 219 actinic keratoses were eligible for qualitative analysis. The number and heterogeneity of included studies limited a quantitative analysis. Studies that focus specifically on the diagnostic accuracy of dermoscopy for actinic keratosis are lacking.

The diagnostic value of in vivo reflectance confocal microscopy in actinic keratosis.

Actinic keratosis (AK) is a pre-neoplastic skin damage caused by sun exposure with a risk of transforming squamous cell carcinoma (SCC) ranging from 0.1%-20%, while it should be differentiated with many diseases such as seborrheic keratosis (SK), discoid lupus erythematosus (DLE), Bowen's disease, and basal cell carcinoma(BCC) et al. Reflectance confocal microscopy (RCM) as a non-invasive method is showing an increasing diagnostic accuracy. Currently, there are a few studies that summarized the characteristics of AK with RCM. The study aimed to find the diagnostic value of diagnosing actinic keratosis by reflectance confocal microscopy. A total of 92 patients with clinical suspicious diagnosis of actinic keratosis were enrolled in this study, and RCM device imaged their lesions. Fifty-three of these patients underwent skin biopsies to confirm the diagnosis. We retrospectively analyzed the results of RCM and histological diagnosis and then summarized the RCM characteristics of biopsy-confirmed lesions. Based on RCM images, 76 of 92 (82.6%) patients were diagnosed with AK, 9 of 92 (9.8%) patients could not be diagnosed by the dermatologist according to RCM. Of all 53 biopsied lesions, 42 (79.2%) were AK, 1 was seborrheic keratosis, 3 were basal cell carcinoma, three were discoid lupus erythematosus, 1 was Bowen's disease, and three were squamous cell carcinoma. The value of RCM in the diagnosis and differential diagnosis of AK is good and worthy of clinical application.

Evaluation of diagnostic criteria of actinic keratosis through reflectance confocal microscopy.

The diagnosis of actinic keratosis (AK) is based on clinical evaluation and confirmed by histopathological analysis (HA). The challenge is to establish the correct diagnosis with a minimally invasive assessment. The aim of this study is to validate the analysis of AK by reflectance confocal microscopy (RCM), a cellular resolution, noninvasive imaging method and to determine the relevant parameters for diagnosis, compared to HA, by calculating the sensitivity (S), specificity (E), positive predictive value (PPV), and negative predictive value (NPV) of each criterion. Through clinical examination, 25 AKs were selected for dermoscopy and RCM evaluation followed by shaving excision for HA. Statistical analysis was done by hypothesis tests (McNemar for binary and Wilcoxon for continuous variables). There was no significant difference between RCM and HA for 5 of the 6 parameters analyzed. The criteria that were statistically relevant were as follows: parakeratosis (p-value 0.449690; S 90%; PPV 78.26%), hyperkeratosis (p-value 0.248213; S 87.5%; E 100%; PPV 100%; NPV 25%), dyskeratosis (p-value 0.617075; S 85.71%; E 75%; PPV 94.74%; NPV 50%), spinous layer keratinocyte atypia classified as mild, moderate or severe (P-value 0.145032) and inflammation in epidermis (P-value 1.000000; S 75%; E 20%; PPV 78.95%; NPV 16.67%). RCM could not adequately measure inflammation in dermis (P-value 0.013328), despite good sensitivity (68%) and PPV (100%). RCM proved to be an effective method for the diagnosis of AK, contributing to the selection of the most appropriate treatment option.

143 Identification of actinic keratosis susceptibility loci

Actinic keratosis (AK) is a keratinocyte-derived precancerous lesion that arises on skin exposed to chronic ultraviolet radiation. AK is highly prevalent, afflicting >58 million Americans, and its treatment costs are estimated at >$1 billion per year. AK can progress to keratinocyte carcinoma, including cutaneous squamous cell carcinoma (cSCC). Genetic risk has been implicated in AK, as evidenced by a genome-wide association study (GWAS), which identified 3 susceptibility loci (IRF4, TYR, and MC1R) among Europeans. To identify additional AK-associated loci, we performed a GWAS in non-Hispanic white participants of the Kaiser Permanente Genetic Epidemiology Research on Adult Health and Aging cohort. Participants with a physician-rendered diagnosis of AK were classified as cases (n=16,251), and the non-cases (n=46,454) were assigned to the control group. Genome-wide genotype data were generated on the Affymetrix Axiom European array and imputed to the 1000 Genomes reference panel. Genetic association analysis with AK was performed using logistic regression adjusted for age, sex, and ancestry principal components, and we identified ten genome-wide significant loci for AK (P<5×10-8), including 8 novel loci. Identified loci are implicated in the pigmentation pathway (IRF4, TYR, SLC45A2, BNC2, and HERC2), the Notch signaling pathway (FOXP1), the TGF-ß pathway (SPIRE2), immune regulation (HLA), coactivating receptors including retinoid and vitamin D receptors (NCOA6), and an additional locus DLGAP4 whose biologic relevance to AK risk is currently unknown. Interestingly, some of our AK-associated loci have been previously reported to be cSCC-associated loci (IRF4, TYR, SLC45A2, BNC2, HERC2, FOXP1, and HLA), suggesting common biological pathways in keratinocyte carcinogenesis. Study findings provide new insight into the genetic basis of AK susceptibility and may help identify subjects at higher risk for developing AK and cSCC. Further studies replicating our findings in an independent cohort are needed.