Dermatology: Practical and Conceptual Original Article | Dermatol Pract Concept. 2025;15(4):5645 1 Dermoscopy as a Predictor of Photodynamic Therapy Outcomes in Actinic Keratoses and Bowen’s Disease: Prospective Study in Solid Organ Transplant Patients Laura Bernal Masferrer1, Tamara Gracia Cazaña1, Marcial Álvarez-Salafranca1, Isabel Bernad Alonso1, Sara España Fernández de Valderrama2, Mariana Claudia Matei1, Javier Paul Ramos³, Yolanda Gilaberte1 1 Department of Dermatology, Miguel Servet University Hospital, 2IIS Aragón, Zaragoza, Spain 2 Department of Orthopedic and Trauma Surgery, Miguel Servet University Hospital, Zaragoza, Spain 3 Department of Nephrology, Miguel Servet University Hospital, Zaragoza, Spain Key words: actinic keratoses, bowen’s disease, photodynamic therapy, dermatoscopy, transplant recipients Citation: Bernal Masferrer L, Gracia Cazaña T, Álvarez-Salafranca M, et al. Dermoscopy as a Predictor of Photodynamic Therapy Outcomes in Actinic Keratoses and Bowen’s Disease: Prospective Study in Solid Organ Transplant Patients. Dermatol Pract Concept. 2025;15(4):5645. DOI: https://doi.org/10.5826/dpc.1504a5645 Accepted: June 17, 2025; Published: October 2025 Copyright: ©2025 Bernal Masferrer et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Laura Bernal Masferrer, Paseo Fernando el Católico 48, principal derecha, Zaragoza, España. ORCID ID: 0000-0002-8328-6678). E-mail: laurabermas@gmail.com Introduction: Solid organ transplant recipients (SOTRs) have a significantly higher risk of developing cutaneous squamous cell carcinoma. Identifying predictive markers for response to non-surgical treat- ments such as photodynamic therapy (PDT) may help optimize management strategies. Objectives: To evaluate the association between dermatoscopic features in actinic keratoses (AK) and Bowen’s disease (BD) and response to PDT in SOTRs. Methods: A prospective observational study was conducted, including 35 SOTRs with clinically and histologically confirmed AK or BD treated with methyl aminolevulinate-PDT. Thirteen dermatoscopic features were analyzed to assess their correlation with treatment response. Results: Response rates were 62.5% for AK and 89.47% for BD. Among the dermatoscopic features evaluated, white structureless areas in AK and rosettes in BD were significantly associated with resis- tance to PDT. Conclusions: Dermoscopy may serve as a valuable tool to predict PDT response in SOTRs with AK and BD, potentially improving patient selection and treatment outcomes. ABSTRACT 2 Original Article | Dermatol Pract Concept. 2025;15(4):5645 Introduction Actinic keratoses (AK) and in situ squamous cell carcinoma (SCC) are considered precursor lesions of invasive cutane- ous squamous cell carcinoma (cSCC). Their development is influenced by cumulative exposure to ultraviolet (UV) radi- ation, advanced age, immunosuppression, and other factors [1-3]. Given their high incidence linked to an ageing popula- tion and prolonged sun exposure, early treatment is essential to prevent progression to invasive cSCC [4]. Solid organ transplant recipients (SOTRs) represent a particularly complex group, with a 65-fold increased risk of developing cSCC [1]. This heightened risk is intrinsically linked to immunosuppression and the use of specific treat- ments for transplant maintenance such as calcineurin inhib- itors. Therefore, early diagnosis and effective treatment are especially crucial for this population [2]. Photodynamic therapy (PDT) has emerged as a valid, ef- fective, and repeatable treatment for AK and Bowen’s disease (BD) or in situ cSCC. Compared to cryotherapy, PDT offers the added advantage of treating the cancerization field [2,3]. However, PDT’s indirect immunomodulatory action may be less effective in transplant patients, potentially reducing its efficacy and explaining the lower success rates observed compared to immunocompetent patients [2]. In this context, diagnostic tools like dermoscopy not only aid in the early and accurate recognition of lesions but may also provide valuable insights into the effectiveness of treat- ments such as PDT, particularly in patients with unique clin- ical characteristics like transplant recipients. Dermoscopy is a non-invasive technique that has become an essential tool for clinicians in identifying these lesions. Dermoscopic patterns associated with AK and BD have been shown to increase diagnostic sensitivity, and their disappear- ance has been correlated with lesion resolution [4,5]. How- ever, only one study has investigated the possible relationship between dermoscopic signs of AK and response to PDT [6], while another focused on basal cell carcinoma (BCC) [7]. To our knowledge, no study has explored these correlations in BD or in SOTRs. The aim of this study was to identify dermoscopic signs associated with the response to conventional PDT in BD and daylight PDT in AK in SOTRs. Materials and Methods A prospective observational clinical practice study was con- ducted. The study population consisted of SOTRs referred from the Nephrology and Cardiology Transplant Clinics to the specialized transplant skin cancer unit at Miguel Servet University Hospital between January 2022 and December 2023. Patients had to meet the following inclusion criteria: aged 18 years or older; solid organ transplant recipient; diag- nosed with at least five Grade I or II Olsen AKs within a field of cancerizations or histologically confirmed in situ SCC; eligible for treatment with MAL-PDT and having provided informed consent to participate (Annex II); no hypersensi- tivity to any component of Metvix®; no photodermatosis diagnosis. Exclusion criteria were: allergic to any treatment compo- nent; refused treatment with PDT; did not provide consent to participate in the study; unable to complete treatment or follow-up; had undergone treatment for non-melanoma skin cancer (NMSC) within the previous three months. A baseline biopsy was performed for all patients to con- firm clinical diagnoses, accompanied by clinical and der- moscopic photography (DermLite Handyscope 2020). The study was approved by the Ethics Committee of the Autono- mous Community of Aragon (CEICA) EPA22/0007. Treatment Protocols For BD patients, two sessions of conventional PDT were con- ducted. Lesions were first curetted, followed by application of 16% methyl aminolevulinate (MAL, Metvix®, Galderma). After three hours of occlusive incubation, the area was illu- minated using a red diode device (Aktilite CL 128, Galderma Nordic AB, Sweden) at 37 J/cm² for eight minutes from a dis- tance of 10 cm. The second session was conducted 7–14 days later [8]. For AK patients, one session of daylight PDT was conducted. Lesions were curetted, followed by MAL 16% ap- plication. Patients were then exposed to sunlight for two hours, after which the photosensitizer residue was removed [9]. Outcome Measures Three months post-treatment, lesion biopsies were repeated to confirm histological clearance or persistence. Dermo- scopic evaluations were conducted by a blinded observer (M.A.S) using pre-treatment dermoscopic photographs. The evaluated dermoscopic signs included superficial scales, thick white-yellow scales, white circles, white structureless areas, erythema, rosettes, red pseudonetwork or perifollic- ular vessels, strawberry pattern, glomerular vessels, hairpin vessels, irregular linear vessels, erosions, and ulcerations [4]. Treatment response was assessed clinically and histologi- cally three months post-treatment. Follow-up visits were con- ducted over the subsequent 12 months, with persistent lesions excised. Statistical Analysis Qualitative variables are presented as absolute numbers and percentages. Chi-squared tests (Chi²) were used for group comparisons, with statistical significance defined as P<0.05. Statistical analyses were performed using SPSS® software (version 25.1). Original Article | Dermatol Pract Concept. 2025;15(4):5645 3 Results A total of 35 patients were included in the study: 16 with at least five Grade I or II Olsen AKs and 19 with BD, all with histopathological confirmation. Complete response rates were 62.5% for AK and 89.47% for BD. Among the dermoscopic features analyzed, only the ab- sence of rosettes in BD and the absence of white structureless areas in AK were significantly associated with response to PDT. No other dermoscopic structure showed a statistically significant correlation with treatment response. The statisti- cal analysis of all dermoscopic structures is summarized in Tables 1 and 2. Discussion Photodynamic therapy (PDT) is considered the most ef- fective treatment for actinic keratoses (AK) in solid organ transplant recipients (SOTRs) [10]. Our study achieved sim- ilar results in terms of clinical and histological effectiveness. Table 1. Statistical Analysis of Dermoscopic Structures in Bowen’s Disease and Response to Photodynamic Therapy. Variable Response No response p-value Superficial scales Yes No 7 (41.2%) 10(58.8%) 1 (50%) 1 (50%) 1.00 0.81 White-yellow scales Yes No 10 (58.8%) 7 (42.1%) 1 (50%) 1 (50%) 1.00 0.81 White circles Yes No 1 (5.3%) 16 (94.1%) 0 (0%) 2 (100%) 1.00 0.72 White structureless areas Yes No 3(17.6%) 14 (82.4%) 1 (50%) 1 (50%) 0.38 0.28 Erythema Yes No 16 (94.1%) 1 (5.3%) 2 (100%) 0 (0) 1.00 0.72 Rosettes Yes No 0 (0%) 17 (100%) 1 (50%) 1 (50%) 0.10 0.003 Red pseudonetwork Yes No 5 (31.6%) 12 (70.6%) 1 (50%) 1 (50%) 1.00 0.55 “Strawberry pattern” Yes No 4 (23.5%) 13 (76.5%) 1 (50%) 1 (50%) 0.46 0.42 Glomerular vessels Yes No 8 (47.1%) 9 (52.9%) 1 (50%) 1 (50%) 1.00 0.93 Hairpin vessels Yes No 2 (11.8%) 15 (88.2%) 0 (0) 2 (100%) 1.00 0.60 Linear irregular vessels Yes No 1 (5.3%) 16 (94.1%) 0 (0) 2 (100%) 1.00 0.72 Erosions Yes No 1 (5.3%) 16 (94.1%) 0 (0) 2 (100%) 1.00 0.72 Ulceration Yes No 0 (0) 17 (100%) 0 (0) 2 (100%) - 4 Original Article | Dermatol Pract Concept. 2025;15(4):5645 Table 2. Statistical Analysis of Dermoscopic Structures in Actinic Keratoses and Response to Photodynamic Therapy. Variable Response No response p-value Superficial scales Yes No 6 (60%) 4 (40%) 2(33.3%) 4(66.7%) 0.60 0.30 White-yellow scales Yes No 3 (30%) 7 (70%) 3 (50%) 3 (50%) 0.60 0.42 White circles Yes No 0 (0%) 10 (100%) 0 (0%) 6 (100%) - White structureless areas Yes No 0(0%) 10 (100%) 2(33.3%) 4(66.7%) 0.12 0.05 Erythema Yes No 9 (90%) 1 (10%) 6 (100%) 0 (0) 1.00 0.42 Rosettes Yes No 2 (20%) 8 (80%) 0 (0%) 6 (100%) 0.50 0.24 Red pseudonetwork Yes No 6 (60%) 4 (40%) 2(33.3%) 4(66.7%) 0.60 0.30 “Strawberry pattern” Yes No 3 (30%) 7 (70%) 1(16.7%) 5(83.3%) 1.00 0.55 Glomerular vessels Yes No 1 (10%) 9 (90%) 0 (0%) 6 (100%) 1.00 0.42 Hairpin vessels Yes No 0 (0%) 10 (100%) 0 (0) 6 (100%) - Linear irregular vessels Yes No 0 (0%) 10 (100%) 0 (0) 6 (100%) - Erosions Yes No 0 (0%) 10 (100%) 0 (0) 6 (100%) - Ulceration Yes No 0 (0) 10 (100%) 0 (0) 6 (100%) - Dragieva et al. conducted a prospective study involving 17 SOTRs with 129 AK lesions. The patients received two con- secutive treatments (one with methyl aminolevulinate [MAL] and the other with placebo), resulting in complete resolution in 13 patients and partial response in three others [11]. The clinical response of some patients is summarized in Figure 1. For Bowen’s disease (BD), Antonetti et al. conducted a systematic review, reporting clinical response rates of 88–100% with MAL-PDT in immunocompetent patients. They hypothesized that efficacy could be maintained in immunosuppressed individuals, which aligns with our find- ings, though current evidence remains limited [12]. Our study analyzed dermoscopic signs in AK and BD lesions in SOTRs and their association with PDT response. Rosettes correspond histopathologically to hyperkerato- sis within follicular openings interspersed with a normal peripheral stratum corneum [13]. Meanwhile, white struc- tureless areas represent hyperkeratosis and parakeratosis overlying dysplastic epidermis [4]. Both features are indica- tors of lesion keratinization and hyperkeratosis, potentially Original Article | Dermatol Pract Concept. 2025;15(4):5645 5 Figure 1. Photographs of the lesions before the treatment with MAL-PDT (A) and after three months of the treatment (B). In the first two pictures we can see the white structureless areas associated with the lack of response to PDT. hindering photosensitizer penetration and reducing treat- ment effectiveness. Zalaudek et al. proposed that white structureless areas could also signal lesion progression to invasive SCC, with vertical growth increasing lesion thickness and complicating dermal penetration. Lesion thickness is a key predictor of resistance to PDT [14]. In a study by Lee et al. [5], the most frequent der- moscopic findings in AK lesions were superficial scales (79.4%) and red pseudonetwork pattern (73.5%). Fol- lowing treatment with PDT, imiquimod, or cryother- apy, most dermoscopic structures disappeared in tandem with histological clearance. However, superficial scales persisted in 20.6% of cases and red pseudonetwork pattern in 14.7%, even when histological atypia was absent. Similarly, Mun et al. concluded that the disappearance of vascular pat- terns in BD lesions correlated with treatment success, while their persistence indicated histological disease presence [15]. Wang et al. identified red pseudonetwork pattern as positive predictors of PDT response in AK, whereas mi- croerosions and white structureless areas were negatively associated. However, their findings are not fully compara- ble to ours due to methodological differences, including the use of cryotherapy or CO2 laser as neoadjuvant treatments, higher photosensitizer concentrations (20% aminolevulinic acid vs. 16% MAL in our study), and fluences exceeding three times the standard (100–120 J/cm² vs. 37 J/cm²). Nev- ertheless, both studies identified white structureless areas as predictors of treatment resistance [6]. This study has some limitations, including a relatively small sample size from a single center, which may affect generalizability. Moreover, dermoscopic evaluation was per- formed by a single observer, which may introduce observer bias or limit the reproducibility of the findings. Despite these limitations, the prospective design and histological confir- mation strengthen the reliability of the findings. Conclusions To summarize, photodynamic therapy (PDT) is an effective treatment for actinic keratoses (AK) and Bowen’s disease (BD) in solid organ transplant recipients (SOTRs), with re- sponse rates of 62.5% and 89.47%, respectively. Among the dermoscopic features evaluated, the presence of rosettes in BD and white structureless areas in AK were negatively cor- related with treatment response. 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