TP63 is implicated in apoptotic dysregulation in melanoma

PhDCutaneous melanoma is an aggressive malignancy accounting for 4% of skin cancers but 80% of all skin-cancer related deaths. Its incidence is rapidly rising and advanced disease is notoriously treatment-resistant. The role of apoptosis in melanoma pathogenesis and chemoresistance is poorly characterised. Mutations in TP53 occur infrequently and are not critical for tumour development, yet the TP53 apoptotic pathway is abrogated; this may alternatively result from TP53 pathway defects or from alterations in other members of the TP53 family, including the TP53 homologue, TP63. The hypothesis of this thesis was that TP63 has an anti-apoptotic role in melanoma and is responsible for mediating chemoresistance. The primary aims were to investigate the biological role of TP63 in melanoma, to explore regulation of p63 expression and to understand its role in apoptosis and dysregulation of the TP53 apoptotic pathway in melanoma. Although p63 was not expressed in primary melanocytes, upregulation of both p63 mRNA and protein was observed in melanoma cell lines and tissue samples. This is the first report of significant p63 expression in this lineage. Furthermore, aberrant cytoplasmic p63 expression significantly correlated with poor overall outcome in melanoma patients. Multiple possible mechanisms were demonstrated to regulate TP63 expression in melanoma, including epigenetic modulation, microRNA regulation of gene transcription and proteosome-dependent stability of p63 protein. In response to genotoxic stress, endogenous p63 isoforms were stabilised in both nuclear and mitochondrial subcellular compartments. Translocation of p63 to the mitochondria occurred through a co-dependent process with p53 but accumulation of wt-p53 in the nucleus was inhibited by p63. Using RNAi technology, both isoforms of p63 (TA and ΔNp63) were demonstrated to confer chemoresistance in melanoma. In addition, the truncated variant, ΔNp63, was enriched in a subset of melanomas expressing CD133, pointing to an anti-apoptotic role for p63 in putative cancer stem cells in this aggressive tumour. Taken together, these data suggest that in melanoma, p63 is an oncogene which contributes to dysregulation of wt-p53 function and has an important role in mediating chemoresistance. Ultimately, these observations may provide the rationale for novel approaches aimed at sensitising advanced melanoma to chemotherapeutic agents

Developing a national artificial intelligence-assisted skin cancer pathway

The AI Skin Cancer Consortium seeks to progress integration of artificial intelligence (AI) into the skin cancer referral pathway to promote rapid diagnosis of skin cancer and reassurance with benign lesions. In contrast to other fields of medicine, such as radiology, dermatology has lacked standardization in data acquisition, which is required for high-quality, reproducible and interoperable AI algorithm performance. Beginning in 2021, the consortium has made substantial progress towards defining a national pathway, technology architecture and data flows. We describe a standardized approach to acquisition of macroscopic and dermoscopic images, and technical and clinical metadata in a DICOM (Digital Imaging and Communications in Medicine) format, currently acquired in outpatient imaging centres and in general practice. In order to develop a transparent competitive environment for testing of this standardized National Health Service (NHS) pipeline, the consortium created a Small Business Research Initiative funded via a government agency. Three companies were awarded funding for this two-phase programme, from 15 applicants. These industry partners tested the pipeline within a trusted research environment (TRE), using real-world data. All industry partners were able to evaluate skin lesion images in combination with interoperable clinical metadata and run existing algorithms in the TRE. We report progress on this competition and also on the process of creating a national database, to permit competitive testing performance of different algorithms with specific clinical use cases. To assess the cost-effectiveness of introducing AI into the skin cancer pathway, we have also collaborated with the York Health Economics Consortium to produce a model to permit estimation of the impact of an AI triage tool to assist clinician triage. The recent vision statement from the British Association of Dermatologists encourages AI solutions intended to address a clinical unmet need and that integrates into patient pathways to enhance the service provided by healthcare professionals [https://www.bad.org.uk/clinical-services/artificial-intelligence/vision-statement-on-artificial-intelligence-ai-interventions/ (last accessed 19 March 2024)]. If the UK is to be at the forefront of skin AI, then it is imperative that the market is stimulated through use of meticulously standardized interoperable data standards with platforms that allow for transparent testing of multiple algorithms. We have successfully introduced a pipeline for safely generating standardized, high-quality images that are suitable for AI, identifying where we can achieve the greatest potential value for introducing AI into the NHS skin cancer referral pathway

Developing a national artificial intelligence-assisted skin cancer pathway

The AI Skin Cancer Consortium seeks to progress integration of artificial intelligence (AI) into the skin cancer referral pathway to promote rapid diagnosis of skin cancer and reassurance with benign lesions. In contrast to other fields of medicine, such as radiology, dermatology has lacked standardization in data acquisition, which is required for high-quality, reproducible and interoperable AI algorithm performance. Beginning in 2021, the consortium has made substantial progress towards defining a national pathway, technology architecture and data flows. We describe a standardized approach to acquisition of macroscopic and dermoscopic images, and technical and clinical metadata in a DICOM (Digital Imaging and Communications in Medicine) format, currently acquired in outpatient imaging centres and in general practice. In order to develop a transparent competitive environment for testing of this standardized National Health Service (NHS) pipeline, the consortium created a Small Business Research Initiative funded via a government agency. Three companies were awarded funding for this two-phase programme, from 15 applicants. These industry partners tested the pipeline within a trusted research environment (TRE), using real-world data. All industry partners were able to evaluate skin lesion images in combination with interoperable clinical metadata and run existing algorithms in the TRE. We report progress on this competition and also on the process of creating a national database, to permit competitive testing performance of different algorithms with specific clinical use cases. To assess the cost-effectiveness of introducing AI into the skin cancer pathway, we have also collaborated with the York Health Economics Consortium to produce a model to permit estimation of the impact of an AI triage tool to assist clinician triage. The recent vision statement from the British Association of Dermatologists encourages AI solutions intended to address a clinical unmet need and that integrates into patient pathways to enhance the service provided by healthcare professionals [https://www.bad.org.uk/clinical-services/artificial-intelligence/vision-statement-on-artificial-intelligence-ai-interventions/ (last accessed 19 March 2024)]. If the UK is to be at the forefront of skin AI, then it is imperative that the market is stimulated through use of meticulously standardized interoperable data standards with platforms that allow for transparent testing of multiple algorithms. We have successfully introduced a pipeline for safely generating standardized, high-quality images that are suitable for AI, identifying where we can achieve the greatest potential value for introducing AI into the NHS skin cancer referral pathway

Exfoliative cytology for diagnosing basal cell carcinoma and other skin cancers in adults

Background: Early accurate detection of all skin cancer types is essential to guide appropriate management and to reduce morbidity and improve survival. Basal cell carcinoma (BCC) is usually localised to the skin with potential to infiltrate and damage surrounding tissue, while cutaneous squamous cell carcinoma (cSCC) and melanoma have a much higher potential to metastasise and ultimately lead to death. Exfoliative cytology is a non–invasive test that uses the Tzanck smear technique to identify disease by examining the structure of cells obtained from scraped samples. This simple procedure is a less invasive diagnostic test than a skin biopsy, and for BCC has the potential to provide an immediate diagnosis that avoids an additional visit to clinic to receive skin biopsy results. This may benefit patients scheduled for either Mohs micrographic surgery or non–surgical treatments such as radiotherapy. A cytology scrape can never give the same information as a skin biopsy, however, so it is important to know more about which skin cancer situations it may be helpful.Objectives: The primary objective was to determine the diagnostic accuracy of exfoliative cytology for the detection of basal cell carcinoma (BCC) in adults. Secondary objectives were to determine diagnostic accuracy for the detection of i) cutaneous squamous cell carcinoma, ii) invasive melanoma and atypical intraepidermal melanocytic variants, and iii) any skin cancer, including keratinocyte skin cancer, invasive melanoma and atypical intraepidermal melanocytic variants, or any other skin cancer.Search methods: We undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; EMBASE; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We also studied the reference lists of published systematic review articles.Selection criteria: Studies evaluating exfoliative cytology in adults with lesions suspicious for BCC, cSCC or melanoma, compared with a reference standard of histological confirmation.Data collection and analysis: Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS-2). Where possible we estimated summary sensitivities and specificities using the bivariate hierarchical model.Main results: This review reports on nine studies with a total of 1655 lesions including 1120 BCCs (14 datasets), 401 lesions with 44 cSCCs (two datasets), and 200 lesions with 10 melanomas (one dataset). Three of these datasets (one each for BCC, melanoma, and any malignant condition) were derived from one study which also performed a direct comparison with dermoscopy. Studies were of moderate to poor quality providing inadequate descriptions of participant selection, thresholds used to make cytological and histological diagnoses, and blinding. Reporting of patients’ prior referral pathways was particularly poor, as were descriptions of the cytodiagnostic criteria used to make diagnoses. No studies evaluated the use of exfoliative cytology as a primary diagnostic test for detecting BCC or other skin cancers in lesions suspicious for skin cancer. Pooled data from seven studies using standard cytomorphological criteria (but various stain methods) to detect BCC in patients with a high clinical suspicion of BCC estimated the sensitivity and specificity of exfoliative cytology as 97.5% (95% CI: 94.5 to 98.9%) and 90.1% (95% CI: 81.1 to 95.1%) respectively. When applied to a hypothetical population of 1000 clinically suspected BCC lesions with a median observed BCC prevalence of 86%, exfoliative cytology would miss 21 BCCs and would lead to 14 false positive diagnoses of BCC. No false positive cases were histologically confirmed to be melanoma. Insufficient data are available to make summary statements regarding the accuracy of exfoliative cytology to detect melanoma or cSCC, or its accuracy compared to dermoscopy.Authors' conclusions: The utility of exfoliative cytology for the primary diagnosis of skin cancer is unknown, as all included studies focused on the use of this technique for confirming strongly suspected clinical diagnoses. For the confirmation of BCC in lesions with a high clinical suspicion, there is evidence of high sensitivity and specificity for exfoliative cytology. Since decisions to treat low riskBCCs are unlikely in practice to require diagnostic confirmation given that clinical suspicion is already high, exfoliative cytology might be most useful for cases of BCC where the treatments being contemplated require a tissue diagnosis (e.g. radiotherapy). The small number of included studies, poor reporting and varying methodological quality means that no strong conclusions can currently be drawn to guide clinical practice. Despite insufficient data on the use of cytology for cSCC or melanoma, it is unlikely that cytology would be useful in these scenarios since preservation of the architecture of the whole lesion that would be available from a biopsy provides crucial diagnostic information. Given the paucity of good quality data, appropriately designed prospective comparative studies may be required to evaluate both the diagnostic value of exfoliative cytology by comparison to dermoscopy, and its confirmatory value in adequately reported populations with a high probability of BCC scheduled for further treatment requiring a tissue diagnosis

Dermatofibrosarcoma Protuberans Re-excision and Recurrence Rates in the Netherlands Between 1989 and 2016

Dermatofibrosarcoma protuberans is a rare soft tissue tumour with a very low (less than 0.5%) rate of metastasis. Rates of re-excision and recurrence were determined using data from the Netherlands Cancer Registry between 1989 and 2016. Of the 1,890 instances of dermatofibrosarcoma protuberans included, 87% were treated with excision, 4% with Mohs micrographic surgery, and 9% otherwise or unknown. Linked pathology data were retrieved for 1,677 patients. Half of all excisions (847/1,644) were incomplete and 29% (192/622) of all re-excisions were incomplete. The cumulative incidence of a recurrence was 7% (95% confidence interval (CI) 6–8) during a median followup of 11 years (interquartile range (IQR) 6–17). AfterMohs micrographic surgery (n = 34), there were no recurrencesduring a median follow-up of 4 years (IQR 3–6). Due to the high rate of incomplete excisions and recurrences after excision, this study supports the European guideline, which recommends treating dermatofibrosarcoma protuberans with Mohs micrographic surgery in order to decrease the rate of recurrence

Reflectance confocal microscopy for diagnosising keratinocyte skin cancers in adults

Background Early accurate detection of all skin cancer types is important to guide appropriate management and to improve morbidity and survival. Basal cell carcinoma (BCC) is usually a localised skin cancer but with potential to infiltrate and damage surrounding tissue, whereas squamous cell carcinoma (cSCC) and melanoma are higher risk skin cancers with the potential to metastasise and ultimately lead to death. When used in conjunction with clinical or dermoscopic suspicion of malignancy, or both, reflectance confocal microscopy (RCM) may help to identify those eligible for non-surgical treatment without the need for a diagnostic biopsy, particularly in people with suspected BCC. Any potential benefit must be balanced against the risk of any misdiagnoses. Objectives 1) To determine the diagnostic accuracy of RCM for the detection of BCC, cSCC, or any skin cancer in adults with a) suspicious lesion and b) lesions that are difficult to diagnose (equivocal); and 2) to compare its accuracy with that of usual practice (visual inspection or dermoscopy, or both). Search methods We undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; EMBASE; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists and published systematic review articles. Selection criteria Studies of any design that evaluated the accuracy of RCM alone, or RCM in comparison to visual inspection or dermoscopy, or both, in adults with lesions suspicious for skin cancer compared with a reference standard of either histological confirmation or clinical follow-up, or both. Data collection and analysis Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS-2). We contacted authors of included studies where information related to the target condition or diagnostic threshold were missing. We estimated summary sensitivities and specificities using the bivariate hierarchical model. For computation of likely numbers of true positive, false positive, false negative, and true negative findings in the'Summary of findings' tables, summary sensitivity and specificity estimates were applied to lower quartile, median and upper quartiles of the prevalence observed in the study groups. We also investigated the impact of observer experience. Main results Ten studies reporting on a total of 11 study cohorts were included. All 11 cohorts reported data for the detection of BCC, including 2037 lesions (464 with BCC); and four cohorts reported data for the detection of cSCC, including 834 lesions (71 with cSCC). Only one study also reported data for the detection of BCC or cSCC using dermoscopy, limiting comparisons between RCM and dermoscopy. Studies were at high or unclear risk of bias across almost all methodological quality domains, and were of high or unclear concern regarding applicability of the evidence. Selective participant recruitment, unclear blinding of the reference test, and exclusions due to image quality or technical difficulties were observed. It is unclear whether studies are representative of populations eligible for testing with RCM, and test interpretation was often undertaken using images, remotely from the patient and the interpreter blinded to clinical information that would normally be available in practice. Meta-analysis found RCM to be more sensitive but less specific for the detection of BCC in studies of participants with equivocal lesions (sensitivity 94%, 95% CI 79% to 98%; specificity 85%, 95% CI 72% to 92%; n = 3 studies) compared to studies that included any suspicious lesion (sensitivity 76%, 95% CI 45% to 92%; specificity 95%, 95% CI 66% to 99%; n = 4 studies), although confidence intervals were wide. At the median prevalence of disease of 12.5% observed in studies including any suspicious lesion, applying these results to a hypothetical population of 1000 lesions results in 30 BCCs missed with 44 false positive results (lesions misdiagnosed as BCCs). At the median prevalence of disease of 15% observed in studies of equivocal lesions, 9 BCCs would be missed with 128 false positive results in a population of 1000 lesions. Across both sets of studies, up to 15% of these false positive lesions were observed to be melanomas mistaken for BCCs. There was some suggestion of higher sensitivities in studies with more experienced observers. Summary sensitivity and specificity could not be estimated for the detection of cSCC due to paucity of data. Authors' conclusions There is insufficient evidence for the use of RCM for the diagnosis of BCC or cSCC in either population group. A possible role for RCM in clinical practice is as a tool to avoid diagnostic biopsies in lesions with a relatively high clinical suspicion of BCC. The potential for, and consequences of, misclassification of other skin cancers such as melanoma as BCCs requires further research. Importantly, data are lacking that compare RCM to standard clinical practice (with or without dermoscopy)

High frequency ultrasound for the diagnosis of skin cancer in adults

Background: Early accurate detection of all skin cancer types is essential to guide appropriate management and to improve morbidity and survival. Melanoma and squamous cell carcinoma (SCC) are high risk skin cancers which have the potential to metastasise and ultimately lead to death, whereas basal cell carcinoma (BCC) is usually localised with potential to infiltrate and damage surrounding tissue. Anxiety around missing early curable cases needs to be balanced against inappropriate referral and unnecessary excision of benign lesions. Ultrasound is a non-invasive imaging technique which relies on the measurement of sound wave reflections from the tissues of the body. At lower frequencies, the deeper structures of the body such as the internal organs can be visualised, while high frequency ultrasound (HFUS) with transducer frequencies of at least 20MHz, has a much lower depth of tissue penetration but produces a higher resolution image of tissues and structures closer to the skin surface. Used in conjunction with clinical or dermoscopic examination of suspected skin cancer, or both, HFUS may offer additional diagnostic information compared to other technologies. Objectives: To determine the diagnostic accuracy of HFUS to assist in the diagnosis of (a) melanoma and intraepidermal melanocytic variants, (b) cutaneous squamous cell carcinoma (cSCC), and (c) basal cell carcinoma (BCC) in adults. Search methods: We undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; EMBASE; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists and published systematic review articles. Selection criteria: Studies evaluating HFUS (>= 20 MHz) in adults with lesions suspicious for melanoma, cSCC or BCC, compared with a reference standard of histological confirmation or clinical follow-up. Data collection and analysis: Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS-2). Due to scarcity of data and poor quality of studies, no meta-analysis was undertaken for this review. For illustrative purposes, estimates of sensitivity and specificity were plotted on coupled forest plots. Main results: Six studies were included, providing 29 datasets, 20 for diagnosis of melanoma (1125 lesions and 242 melanomas) and 9 for diagnosis of BCC (993 lesions and 119 BCCs). No data relating to the diagnosis of cSCC were identified. Studies were generally poorly reported limiting judgements of methodological quality. Half of studies did not set out to establish test accuracy and all should be considered preliminary evaluations of the potential usefulness of HFUS. There were particularly high concerns for applicability of findings due to selective study populations and data driven thresholds for test positivity. Studies reporting qualitative assessments of HFUS images excluded up to 22% of lesions (including some melanomas) due to them not being visualised by the test. Derived sensitivities for qualitative HFUS characteristics were at least 83% (95% CI 75% to 90%) for the detection of melanoma; the combination of three features (lesions appearing hypoechoic, homogenous and well defined) demonstrating 100% sensitivity in two studies, with variable corresponding specificities of 33% (95% CI 20% to 48%) and 73% (95% CI 57% to 85%) (Lower limits of the 95% CIs for sensitivities were 94% and 82% respectively). Quantitative measurement of HFUS outputs in two studies enabled decision thresholds to be set to achieve 100% sensitivity; specificities were 93% (95% CI 77% to 99%) and 65% (95% CI 51% to 76%). It was not possible to make summary statements regarding HFUS accuracy for the diagnosis of BCC due to highly variable sensitivities and specificities. Authors' conclusions: Insufficient data are available on the potential value of HFUS in the diagnosis of melanoma or BCC. Given the between study heterogeneity, unclear to low methodological quality and limited volume of evidence, no implications for practice can be drawn. The main value of the preliminary studies included may be in provision of guidance on the possible components of future diagnostic rules for diagnosis of melanoma or BCC using HFUS that require future evaluation. A prospective evaluation of HFUS added to visual inspection and dermoscopy alone in a standard health care setting with a clearly defined and representative population of participants would be required for a full and proper evaluation of accuracy

Exfoliative cytology for the diagnosis of basal cell carcinoma and other skin cancers in adults

Background: Early accurate detection of all skin cancer types is essential to guide appropriate management and to reduce morbidity and improve survival. Basal cell carcinoma (BCC) is usually localised to the skin with potential to infiltrate and damage surrounding tissue, while cutaneous squamous cell carcinoma (cSCC) and melanoma have a much higher potential to metastasise and ultimately lead to death. Exfoliative cytology is a non–invasive test that uses the Tzanck smear technique to identify disease by examining the structure of cells obtained from scraped samples. This simple procedure is a less invasive diagnostic test than a skin biopsy, and for BCC has the potential to provide an immediate diagnosis that avoids an additional visit to clinic to receive skin biopsy results. This may benefit patients scheduled for either Mohs micrographic surgery or non–surgical treatments such as radiotherapy. A cytology scrape can never give the same information as a skin biopsy, however, so it is important to know more about which skin cancer situations it may be helpful. Objectives: The primary objective was to determine the diagnostic accuracy of exfoliative cytology for the detection of basal cell carcinoma (BCC) in adults. Secondary objectives were to determine diagnostic accuracy for the detection of i) cutaneous squamous cell carcinoma, ii) invasive melanoma and atypical intraepidermal melanocytic variants, and iii) any skin cancer, including keratinocyte skin cancer, invasive melanoma and atypical intraepidermal melanocytic variants, or any other skin cancer. Search methods: We undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; EMBASE; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We also studied the reference lists of published systematic review articles. Selection criteria: Studies evaluating exfoliative cytology in adults with lesions suspicious for BCC, cSCC or melanoma, compared with a reference standard of histological confirmation. Data collection and analysis: Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS-2). Where possible we estimated summary sensitivities and specificities using the bivariate hierarchical model. Main results: This review reports on nine studies with a total of 1655 lesions including 1120 BCCs (14 datasets), 401 lesions with 44 cSCCs (two datasets), and 200 lesions with 10 melanomas (one dataset). Three of these datasets (one each for BCC, melanoma, and any malignant condition) were derived from one study which also performed a direct comparison with dermoscopy. Studies were of moderate to poor quality providing inadequate descriptions of participant selection, thresholds used to make cytological and histological diagnoses, and blinding. Reporting of patients’ prior referral pathways was particularly poor, as were descriptions of the cytodiagnostic criteria used to make diagnoses. No studies evaluated the use of exfoliative cytology as a primary diagnostic test for detecting BCC or other skin cancers in lesions suspicious for skin cancer. Pooled data from seven studies using standard cytomorphological criteria (but various stain methods) to detect BCC in patients with a high clinical suspicion of BCC estimated the sensitivity and specificity of exfoliative cytology as 97.5% (95% CI: 94.5 to 98.9%) and 90.1% (95% CI: 81.1 to 95.1%) respectively. When applied to a hypothetical population of 1000 clinically suspected BCC lesions with a median observed BCC prevalence of 86%, exfoliative cytology would miss 21 BCCs and would lead to 14 false positive diagnoses of BCC. No false positive cases were histologically confirmed to be melanoma. Insufficient data are available to make summary statements regarding the accuracy of exfoliative cytology to detect melanoma or cSCC, or its accuracy compared to dermoscopy. Authors' conclusions: The utility of exfoliative cytology for the primary diagnosis of skin cancer is unknown, as all included studies focused on the use of this technique for confirming strongly suspected clinical diagnoses. For the confirmation of BCC in lesions with a high clinical suspicion, there is evidence of high sensitivity and specificity for exfoliative cytology. Since decisions to treat low risk BCCs are unlikely in practice to require diagnostic confirmation given that clinical suspicion is already high, exfoliative cytology might be most useful for cases of BCC where the treatments being contemplated require a tissue diagnosis (e.g. radiotherapy). The small number of included studies, poor reporting and varying methodological quality means that no strong conclusions can currently be drawn to guide clinical practice. Despite insufficient data on the use of cytology for cSCC or melanoma, it is unlikely that cytology would be useful in these scenarios since preservation of the architecture of the whole lesion that would be available from a biopsy provides crucial diagnostic information. Given the paucity of good quality data, appropriately designed prospective comparative studies may be required to evaluate both the diagnostic value of exfoliative cytology by comparison to dermoscopy, and its confirmatory value in adequately reported populations with a high probability of BCC scheduled for further treatment requiring a tissue diagnosis