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Dear Editor, Patients with superficial basal cell carcinoma (sBCC) may be offered several treatment options including surgery, imiquimod, 5-fluorouracil (5-FU) or photodynamic therapy (PDT).1,2 Patient decision aids (PDAs) are tools to assist patients and physicians in shared decision making; a recent study showed that patients with BCC would like to participate in decision making.3 Stacey I et al i . provided evidence showing that PDAs helped patients improve knowledge of their disease and possible treatments, and perform risk assessment.4 Junn I et al i . recently described the development of a paper-based PDA for patients with sBCC with limited life expectancy that weighs the benefits and risks of treatments vs. watchful waiting.5 We describe the development of a digital PDA for all patients with sBCC. Information on cryotherapy and electrodesiccation and curettage was not included, because these treatments are reserved for patients who desire quick treatment. From the dermatology department of a university hospital (MUMC+), 21 patients (minimum 18 years old) with a history of sBCC were invited for the focus group; eight patients were included (three men and five women). [Extracted from the article]

Background A recent noninferiority randomized trial showed that in terms of clinical effectiveness imiquimod was superior and topical fluorouracil noninferior to methylaminolaevulinate photodynamic therapy (MAL-PDT) for treatment of superficial basal-cell carcinoma (sBCC). Although it was expected that MAL-PDT would be more costly than either cream, a full cost-effectiveness analysis is necessary to determine the balance between effectiveness and costs. Objective To determine whether imiquimod or topical fluorouracil are costeffective treatments for sBCC compared with MAL-PDT. Methods An economic evaluation was performed from a healthcare perspective. Data on resource use and costs were collected alongside the randomized clinical trial. The incremental cost-effectiveness ratio was expressed as the incremental costs per additional patient free of tumour recurrence. Results At 12 months follow-up, the total mean costs for MAL-PDT were €680, for imiquimod cream €526 and for topical fluorouracil cream €388. Both imiquimod and topical fluorouracil were cost-effective treatments compared with MAL-PDT. Comparing costs and effectiveness of both creams led to a incremental investment of €4451 to achieve an additional patient free of tumour recurrence. The acceptability curve showed that, for a threshold value of €4451, the probability of imiquimod being more cost-effective than topical fluorouracil was 50%. Conclusion Based on the 12 months follow-up results, imiquimod and topical fluorouracil cream are more cost-effective than MAL-PDT for treatment of sBCC. Hence, substituting MAL-PDT with either imiquimod or topical fluorouracil results in cost savings; these savings will be larger for topical fluorouracil. Longterm follow-up effectiveness data are necessary to confirm the cost-effectiveness of imiquimod vs. topical 5-fluorouracil cream. [ABSTRACT FROM AUTHOR]

BACKGROUND: Basal-cell carcinoma (BCC) is the most common form of skin cancer and its incidence is still rising worldwide. Surgery is the most frequently used treatment for BCC, but large randomised controlled trials with 5-year follow-up to compare treatment modalities are rare. We did a prospective randomised controlled trial to compare the effectiveness of surgical excision with Mohs' micrographic surgery (MMS) for the treatment of primary and recurrent facial BCC. METHODS: Between Oct 5, 1999, and Feb 27, 2002, 408 primary BCCs (pBCCs) and 204 recurrent BCCs (rBCCs) in patients from seven hospitals in the Netherlands were randomly assigned to surgical excision or MMS. Randomisation and allocation was done separately for both groups by a computer-generated allocation scheme. Tumours had a follow-up of 5 years. Analyses were done on an intention-to-treat basis. The primary outcome was recurrence of carcinoma, diagnosed clinically by visual inspection with histological confirmation. Secondary outcomes were determinants of failure and cost-effectiveness. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN65009900. FINDINGS: Of the 397 pBCCs that were treated, 127 pBCCs in 113 patients were lost to follow-up. Of the 11 recurrences that occurred in patients with pBCC, seven (4.1%) occurred in patients treated with surgical excision and four (2.5%) occurred in patients treated with MMS (log-rank test chi(2) 0.718, p=0.397). Of the 202 rBCCs that were treated, 56 BCCs in 52 patients were lost to follow-up. Two BCCs (2.4%) in two patients treated with MMS recurred, versus ten BCCs (12.1%) in ten patients treated with surgical excision (log-rank test chi(2) 5.958, p=0.015). The difference in the number of recurrences between treatments was not significant for pBCC, but significantly favoured MMS in rBCC. In pBCC, Cox-regression analysis showed no significant effects from risk factors measured in the study. In rBCC, aggressive histological subtype was a significant risk factor for recurrence in the Cox-regression analysis. For pBCC, total treatment costs were euro1248 for MMS and euro990 for surgical excision, whereas for rBCC, treatment costs were euro1284 and euro1043, respectively. Dividing the difference in costs between MMS and surgical excision by their difference in effectiveness leads to an incremental cost-effectiveness ratio of euro23 454 for pBCC and euro3171 for rBCC. INTERPRETATION: MMS is preferred over surgical excision for the treatment of facial rBCC, on the basis of significantly fewer recurrences after MMS than after surgical excision. However, because there was no significant difference in recurrence of pBCC between treatment groups, treatment with surgical excision is probably sufficient in most cases of pBCC. [ABSTRACT FROM AUTHOR]

Line-field confocal optical coherence tomography (LC-OCT) is a new technology for skin cancer diagnostics. However, the interobserver agreement (IOA) of known image markers of keratinocyte carcinomas (KC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), as well as precursors, SCC in situ (CIS) and actinic keratosis (AK), remains unexplored. This study determined IOA on the presence or absence of 10 key LC-OCT image markers of KC and precursors, among evaluators new to LC-OCT with different levels of dermatologic imaging experience. Secondly, the frequency and association between reported image markers and lesion types, was determined. Six evaluators blinded to histopathologic diagnoses, assessed 75 LC-OCT images of KC (21 SCC; 21 BCC), CIS (12), and AK (21). For each image, evaluators independently reported the presence or absence of 10 predefined key image markers of KCs and precursors described in an LC-OCT literature review. Evaluators were stratified by experience-level as experienced (3) or novices (3) based on previous OCT and reflectance confocal microscopy usage. IOA was tested for all groups, using Conger's kappa coefficient (κ). The frequency of reported image marker and their association with lesion-types, were calculated as proportions and odds ratios (OR), respectively. Overall IOA was highest for the image markers lobules (κ = 0.68, 95% confidence interval (CI) 0.57;0.78) and clefting (κ = 0.63, CI 0.52;0.74), typically seen in BCC (94%;OR 143.2 and 158.7, respectively, p < 0.001), followed by severe dysplasia (κ = 0.42, CI 0.31;0.53), observed primarily in CIS (79%;OR 7.1, p < 0.001). The remaining seven image-markers had lower IOA (κ = 0.06-0.32) and were more evenly observed across lesion types. The lowest IOA was noted for a well-defined (κ = 0.07, CI 0;0.15) and interrupted dermal-epidermal junction (DEJ) (κ = 0.06, CI -0.002;0.13). IOA was higher for all image markers among experienced evaluators versus novices. This study shows varying IOA for 10 key image markers of KC and precursors in LC-OCT images among evaluators new to the technology. IOA was highest for the assessments of lobules, clefting, and severe dysplasia while lowest for the assessment of the DEJ integrity., (© 2024. The Author(s).)

Introduction: Basal cell carcinoma (BCC) is treated with local surgery or noninvasive treatment modalities. If a BCC remains untreated, it can develop into a locally advanced BCC or a metastatic BCC., Case Presentation: Here we report in detail the management of three complex advanced BCC (aBCC) after treatment failure with vismodegib. On all tumors, next generation DNA sequencing in the Center for Personalized Cancer Treatment-02 (CPCT-02) study was performed; subsequently, patients were included in the Drug Rediscovery Protocol (DRUP) trial, in which treatment was started with commercially available targeted anticancer drugs based on the molecular tumor profile. All patients showed partial response or stable disease following treatment with second line PD-1 inhibitors with an average duration of response of 12.3 months., Discussion/conclusion: Immunotherapy can be a treatment option for aBCC resistant to hedgehog pathway inhibitor treatment. However, despite the high tumor mutational burden of aBCCs, immunotherapy does not always lead to a long response. Rechallenge or combining treatment of hedgehog inhibitors and PD-1 inhibitors by parallel or alternating cycles may be a strategy to lengthen the treatment response., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

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 in situ 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., (© 2024 European Academy of Dermatology and Venereology.)

Basal cell nevus syndrome (BCNS) is an inherited disorder characterized mainly by the development of basal cell carcinomas (BCCs) at an early age. BCNS is caused by heterozygous small-nucleotide variants (SNVs) and copy-number variants (CNVs) in the Patched1 ( PTCH1 ) gene. Genetic diagnosis may be complicated in mosaic BCNS patients, as accurate SNV and CNV analysis requires high-sensitivity methods due to possible low variant allele frequencies. We compared test outcomes for PTCH1 CNV detection using multiplex ligation-probe amplification (MLPA) and digital droplet PCR (ddPCR) with samples from a BCNS patient heterozygous for a PTCH1 CNV duplication and the patient's father, suspected to have a mosaic form of BCNS. ddPCR detected a significantly increased PTCH1 copy-number ratio in the index patient's blood, and the father's blood and tissues, indicating that the father was postzygotic mosaic and the index patient inherited the CNV from him. MLPA only detected the PTCH1 duplication in the index patient's blood and in hair and saliva from the mosaic father. Our data indicate that ddPCR more accurately detects CNVs, even in low-grade mosaic BCNS patients, which may be missed by MLPA. In general, quantitative ddPCR can be of added value in the genetic diagnosis of mosaic BCNS patients and in estimating the recurrence risk for offspring.

Optical coherence tomography (OCT), a non-invasive diagnostic modality, may replace biopsy for diagnosing basal cell carcinoma (BCC) if a high-confidence BCC diagnosis can be established. In other cases, biopsy remains necessary to establish a histopathological diagnosis and treatment regimen. It is, therefore, essential that OCT assessors have a high specificity for differentiating BCC from non-BCC lesions. To establish high-confidence BCC diagnoses, specific morphological BCC characteristics on OCT are used. This study aimed to review several cases of non-BCC lesions that were misclassified as BCC by experienced OCT assessors, thereby providing insight into the causes of these misclassifications and how they may be prevented. The study population consisted of patients who had a histopathologically-verified non-BCC lesion. Patients from Maastricht University Medical Center+ from February 2021 to April 2021 were included in the study. Two independent OCT assessors assessed OCT scans. One OCT assessor recorded the presence or absence of validated morphological BCC characteristics. A false-positive OCT test result was defined as certainty of BCC presence in a non-BCC lesion. The frequency of misclassifications and the presence or absence of morphological BCC features are discussed. A total of 124 patients with non-BCC lesions were included. Six patients were misclassified by both OCT assessors and are discussed in more detail. Histopathological diagnoses were squamous cell carcinoma (n = 2/21), actinic keratosis (n = 2/29), squamous cell carcinoma in situ/Bowen's disease (n = 1/16), or interphase dermatitis (n = 1/4). In all misclassified cases, multiple, apparent morphological BCC characteristics on OCT were present. Most non-BCC lesions are recognized as such by OCT assessors. However, there remains a small risk that a high-confidence BCC diagnosis is established in non-BCC lesions wherein features mimicking validated BCC characteristics are present. Misclassification may be prevented by careful delineation of epidermal layers and good differentiation between dermal ovoid structures typical of BCC versus squamous cell carcinoma., (© 2023 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Background: Randomized controlled trials comparing the effectiveness of 5-fluorouracil cream, methylaminolevulinate photodynamic therapy (MAL-PDT) and surgical excision in patients with Bowen's disease are lacking., Methods: In this multicenter noninferiority trial, patients with a histologically proven Bowen's disease of 4-40 mm were randomly assigned to excision with 5 mm margin, 5% 5-fluorouracil cream twice daily for 4 weeks, or 2 sessions of MAL-PDT with 1 week interval. The primary outcome was the proportion of patients with sustained clearance at 12 months after treatment. A noninferiority margin of 22% was used., Results: Between May 2019 and January 2021, 250 patients were randomized. The proportion of patients with sustained clearance was 97.4% (75/77) after excision, 85.7% (66/77) after 5-fluorouracil, and 82.1% (64/78) after MAL-PDT. Absolute differences were -11.7% (95% CI -18.9 to -4.5; P = .0049) for 5-fluorouracil versus excision and -15.4% (95% CI -23.1 to -7.6; P = .00078) for MAL-PDT versus excision. Both noninvasive treatments significantly more often led to good or excellent cosmetic outcome., Conclusions: Based on our predefined noninferiority margin of 22%, 5-fluorourcail is noninferior to excision and associated with better cosmetic outcome. For MAL-PDT noninferiority to excision cannot be concluded. Therefore, 5-fluorouracil should be preferred over excision and MAL-PDT in treatment of Bowen's disease., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: This study evaluates whether using a patient decision aid (PDA) for patients with superficial basal-cell carcinoma (sBCC) results in a decreased decisional conflict level and increased knowledge., Methods: In a prospective multicentre study, patient groups were included before and after implementation of a PDA. Decisional conflict levels were compared directly after making the treatment decision, measured once as the mean score on the decisional conflict scale (DCS). Higher scores correspond with higher conflict levels (0-100). Secondary outcomes were knowledge on treatment options, recognizing a BCC, and risk factors for developing a BCC measured on an adapted version of a validated knowledge questionnaire for melanoma patients, and patient satisfaction with the PDA., Results: Data was available for 103 patients in the control-group and 109 in the PDA-group. The mean DCS score in the control-group was 22.78 (SD 14.76) compared to 22.34 (SD 14.54) in the PDA-group; the decrease was non-significant (p = 0.828). The average percentage correct answers on the knowledge questionnaire increased from 76.5% in the control-group to 80.5% in the PDA-group (p = 0.044). According to the majority of patients in the PDA-group (73.7%) the PDA had added value., Conclusion: Using the PDA had no significant effect on decisional conflict levels, but increased overall knowledge on relevant issues concerning sBCC., Practice Implications: The PDA can be used as an informational tool by patients with sBCC., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Recurrent/residual basal cell carcinoma (BCC) after topical treatment may not be visible during clinical and dermatoscopic examination (CDE). Optical coherence tomography (OCT) may detect these subclinical recurrences or residues., Objective: To compare the diagnostic accuracy of CDE with that of CDE combined with OCT (CDE-OCT) for detecting recurrent/residual BCC after topical treatment of superficial BCC., Methods: In this diagnostic cohort study, the suspicion level for recurrence or residue was recorded on a 5-point confidence scale. All patients with high suspicion of recurrence or residue based on CDE and/or CDE-OCT were referred for punch biopsy. Patients with a low suspicion on CDE and CDE-OCT were asked to (voluntarily) undergo a control biopsy. Histopathologic results of the biopsy were used for verification of CDE and CDE-OCT diagnoses (gold standard)., Results: This study included 100 patients. A histopathologic recurrent/residual BCC was found in 20 patients. For recurrence or residue detection, sensitivity was 100% (20 of 20) for CDE-OCT and 60% (12 of 20) for CDE (P = .005) and specificity was 95% for CDE-OCT and 96.3% for CDE (P = .317). The area under the curve for CDE-OCT (0.98) was significantly higher than that for CDE (0.77) (P = .001)., Limitations: Results are based on 2 OCT assessors., Conclusion: Compared with CDE alone, CDE-OCT results in a significantly higher ability to detect recurrent/residual BCCs after topical treatment., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Basal cell nevus syndrome is a rare, autosomal dominant disorder, predominantly caused by a mutation in the PTCH1 gene. As basal cell carcinomas and keratocysts are the most common abnormalities, dermatologists, orofacial maxillary surgeons, and dentists play a key role in patient care. From the age of 8, screening for odontogenic keratocysts with an orthopantomogram or MRI is recommended every other year. The intensity increases to annual screening after the development of the first odontogenic keratocyst. If BCNS is caused by an underlying SUFU mutation, screening is not indicated since there are no reports of odontogenic keratocyst in these patients to date. Radiation exposure by, for example, computed tomography, should be minimized as it induces new BCCs. Regular follow-up by a dermatologist for early diagnosis and treatment of (multiple) BCC's is recommended for life.

Basal cell nevus syndrome (BCNS) is a rare genetic disorder accompanied by a broad variety of tumours, of which basal cell carcinomas and odontogenic keratocysts are the most common. BCNS is caused by a germline or postzygotic mutation in either PTCH1 or SUFU As BCNS is a rare disease, it is difficult to establish whether less frequently occurring tumours are actually part of the syndrome. In this study, the molecular mechanism behind four extracutaneous tumours in patients with BCNS was elucidated. A leiomyoma of the testis and meningioma were confirmed to be associated with BCNS in two patients by presence of a second mutation or loss of heterozygosity in PTCH1 In a meningioma of a patient with a mosaic postzygotic PTCH1 mutation an association could not be conclusively confirmed. SUFU was probably not involved in the development of a thyroid carcinoma in a patient with a germline SUFU mutation. Hence, we have proven that meningioma and leiomyoma of the testis are rare extracutaneous tumours that are part of BCNS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Conflicts of interest Dr K. Mosterd participated in an advisory board for Michelson Diagnostics. Drs Wolswijk, Adan, and Nelemans have no conflicts of interest to declare.