We note with interest the commentary by Pennington and Thompson (P&T) regarding our detailed update on the management of primary cutaneous melanoma in 2024 [...]

BACKGROUND:Few studies have evaluated Mohs micrographic surgery (MMS) for the treatment of squamous cell carcinoma in situ or evaluated the results by Mohs Appropriate Use Criteria. OBJECTIVE:Evaluate the clinical and surgical characteristics of squamous cell carcinoma in situ treated with MMS and categorize the results by Mohs Appropriate Use Criteria. METHODS AND MATERIALS:A single Mohs surgeon, prospective, longitudinal cohort study of all squamous cell carcinoma in situ tumors treated with MMS between April 2018 and May 2021. RESULTS:A total of 485 tumors were treated and 96.9% were primary tumors. Mean age of patients was 73.8 years; 80.6% were male. Mean tumor length, wound length, and subclinical extension were 0.98 cm, 1.58 cm, and 0.7 cm, respectively. These dimensions were lowest in Area H and highest in Area L. Mean stages to clear margins was 1.14. Area H tumors required significantly more stages than those in Areas M and L (P=0.031). CONCLUSIONS:Mean tumor and wound sizes, stages to clearance, and subclinical extension were lower than previously reported. Area H tumors required more stages to clearance than those in Areas M and L. Stages to clearance increased with increased tumor size. Curettage before surgery did not decrease the number of required stages to achieve clear tumor margins. CITATION:Steinman HK, Dixon AJ. Squamous cell carcinoma in situ on high-risk sites and with larger sizes require more stages for clearance with Mohs surgery. J Drugs Dermatol. 2025;24(5):494-497. doi:10.36849/JDD.8609.

BACKGROUND:The American Joint Committee on Cancer (AJCC) method of staging melanoma is dated and inaccurate. It ignores important prognostic melanoma features, especially the patient's age. BAUSSS is more accurate in determining survival risk for primary cutaneous melanoma patients who have no clinical or imaging evidence of nodal or distant metastases. BAUSSS is an algorithm incorporating analysis of Breslow thickness, Age, Ulceration, Subtype of melanoma, Sex and Site. These are the six features from the patient history along with the details from the melanoma pathology report that are most predictive of mortality outcome. OBJECTIVE:To develop a single-page document that allows the clinician to determine BAUSSS biomarker-predicted prognosis in consultation with the patient. METHOD:From various data sources, we developed an algorithm to predict melanoma mortality using the BAUSSS biomarker system. The single-page algorithm was made available to download at https://globalmelanoma.net/bausss-survival-chart, thus being readily available without charge to all clinicians and their patients. RESULTS:BAUSSS method of determining melanoma prognosis is more accurate and less costly than the AJCC staging system. The only surgery the patient requires is wide local excision of the primary tumour. This method of ascertaining melanoma risk does not require added surgery, costs, hospitalization, tests and anaesthesia, such as would be required if sentinel lymph node biopsy was undertaken. BAUSSS can be a useful tool in determining which primary melanoma patients are at sufficiently high risk to be considered for adjuvant drug therapy. CONCLUSIONS:We encourage clinicians to download and print in colour this single-page BAUSSS mortality prediction tool, laminate it, and use it face to face with the patient in consultations. Not only will the patient be able to recognize his/her long-term prognosis but will also be able to see how their tumour severity compares with others.

Background: Maximizing survival for patients with primary cutaneous melanomas (melanomas) depends on an early diagnosis and appropriate management. Several new drugs have been shown to improve survival in high-risk melanoma patients. Despite well-documented guidelines, many patients do not receive optimal management, particularly when considering patient age. Objective: to provide an update on melanoma management from the time of the decision to biopsy a suspicious skin lesion. Methods: We reviewed melanoma-management research published between 2018 and 2023 and identified where such findings impact and update the management of confirmed melanomas. Pubmed, Google Scholar, Ovid and Cochrane Library were used as search tools. Results: We identified 81 publications since 2017 that have changed melanoma management; 11 in 2018, 12 in 2019, 10 in 2020, 12 in 2021, 17 in 2022 and 18 in 2023. Discussion: Delayed or inaccurate diagnosis is more likely to occur when a partial shave or punch biopsy is used to obtain the histopathology. Wherever feasible, a local excision with a narrow margin should be the biopsy method of choice for a suspected melanoma. The Breslow thickness of the melanoma remains the single most important predictor of outcome, followed by patient age and then ulceration. The BAUSSS biomarker, (Breslow thickness, Age, Ulceration, Subtype, Sex and Site) provides a more accurate method of determining mortality risk than older currently employed approaches, including sentinel lymph node biopsy. Patients with metastatic melanomas and/or nodal disease should be considered for adjuvant drug therapy (ADT). Further, high-risk melanoma patients are increasingly considered for ADT, even without disease spread. Invasive melanomas less than 1 mm thick are usually managed with a radial excision margin of 10 mms of normal skin. If the thickness is 1 to 2 mm, select a radial margin of 10 to 20 mm. When the Breslow thickness is over 2 mm, a 20 mm clinical margin is usually undertaken. In situ melanomas are usually managed with a 5 to 10 mm margin or Mohs margin control surgery. Such wide excisions around a given melanoma is the only surgery that can be regarded as therapeutic and required. Patients who have had one melanoma are at increased risk of another melanoma. Ideal ongoing management includes regular lifelong skin checks. Total body photography should be considered if the patient has many naevi, especially when atypical/dysplastic naevi are identified. Targeted approaches to improve occupational or lifestyle exposure to ultraviolet light are important. Management also needs to include the consideration of vitamin D supplementary therapy.

Journal of the European Academy of Dermatology and VenereologyEarly View LETTER TO THE EDITOR BAUSSS biomarker further validated as a key risk staging tool for patients with primary melanoma This article relates to: Online tools for predicting melanoma survival: Including sentinel node status as a variable improves prediction accuracy Serigne N. Lo, Alexander H. R. Varey, Mary-Ann El Sharouni, Richard A. Scolyer, John F. Thompson, Volume 38Issue 2Journal of the European Academy of Dermatology and Venereology pages: e182-e184 First Published online: October 14, 2023 Anthony J. Dixon, Corresponding Author Anthony J. Dixon [email protected] orcid.org/0000-0001-8071-7199 Australasian College of Cutaneous Oncology, Docklands, Victoria, Australia Correspondence Anthony J. Dixon, Australasian College of Cutaneous Oncology, 1101/5 Caravel Lane, Docklands, VIC 3008, Australia. Email: [email protected]Search for more papers by this authorAthanassios Kyrgidis, Athanassios Kyrgidis orcid.org/0000-0003-3896-0309 Aristotle University of Thessaloniki, Thessaloniki, GreeceSearch for more papers by this authorMichael Sladden, Michael Sladden orcid.org/0000-0001-7281-2444 University of Tasmania, Launceston, Tasmania, AustraliaSearch for more papers by this authorAlexander Nirenberg, Alexander Nirenberg orcid.org/0000-0001-8645-5388 Australasian College of Cutaneous Oncology, Docklands, Victoria, AustraliaSearch for more papers by this authorHoward K. Steinman, Howard K. Steinman orcid.org/0000-0002-0333-2882 Campbell University, Buies Creek, North Carolina, USASearch for more papers by this authorHarvey Smith, Harvey Smith orcid.org/0000-0002-9433-6212 Oxford Dermatology, Mt Hawthorn, Perth, Western Australia, AustraliaSearch for more papers by this authorChristopher B. Zachary, Christopher B. Zachary orcid.org/0000-0002-5883-5188 Department of Dermatology, University of California Irvine, Irvine, California, USASearch for more papers by this authorStuart Anderson, Stuart Anderson orcid.org/0000-0002-4998-8713 Maffra Medical Group, Maffra, Victoria, AustraliaSearch for more papers by this authorUlrike Leiter-Stöppke, Ulrike Leiter-Stöppke orcid.org/0000-0002-8019-1577 Center for Dermatooncology, Department of Dermatology, Eberhard Karls University, Tuebingen, GermanySearch for more papers by this authorCaterina Longo, Caterina Longo orcid.org/0000-0002-8218-3896 Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy Azienda Unità Sanitaria Locale – IRCCS di Reggio Emilia, Skin Cancer Center, Reggio Emilia, ItalySearch for more papers by this authorZoe Apalla, Zoe Apalla orcid.org/0000-0002-9255-8196 Aristotle University of Thessaloniki, Thessaloniki, GreeceSearch for more papers by this author Anthony J. Dixon, Corresponding Author Anthony J. Dixon [email protected] orcid.org/0000-0001-8071-7199 Australasian College of Cutaneous Oncology, Docklands, Victoria, Australia Correspondence Anthony J. Dixon, Australasian College of Cutaneous Oncology, 1101/5 Caravel Lane, Docklands, VIC 3008, Australia. Email: [email protected]Search for more papers by this authorAthanassios Kyrgidis, Athanassios Kyrgidis orcid.org/0000-0003-3896-0309 Aristotle University of Thessaloniki, Thessaloniki, GreeceSearch for more papers by this authorMichael Sladden, Michael Sladden orcid.org/0000-0001-7281-2444 University of Tasmania, Launceston, Tasmania, AustraliaSearch for more papers by this authorAlexander Nirenberg, Alexander Nirenberg orcid.org/0000-0001-8645-5388 Australasian College of Cutaneous Oncology, Docklands, Victoria, AustraliaSearch for more papers by this authorHoward K. Steinman, Howard K. Steinman orcid.org/0000-0002-0333-2882 Campbell University, Buies Creek, North Carolina, USASearch for more papers by this authorHarvey Smith, Harvey Smith orcid.org/0000-0002-9433-6212 Oxford Dermatology, Mt Hawthorn, Perth, Western Australia, AustraliaSearch for more papers by this authorChristopher B. Zachary, Christopher B. Zachary orcid.org/0000-0002-5883-5188 Department of Dermatology, University of California Irvine, Irvine, California, USASearch for more papers by this authorStuart Anderson, Stuart Anderson orcid.org/0000-0002-4998-8713 Maffra Medical Group, Maffra, Victoria, AustraliaSearch for more papers by this authorUlrike Leiter-Stöppke, Ulrike Leiter-Stöppke orcid.org/0000-0002-8019-1577 Center for Dermatooncology, Department of Dermatology, Eberhard Karls University, Tuebingen, GermanySearch for more papers by this authorCaterina Longo, Caterina Longo orcid.org/0000-0002-8218-3896 Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy Azienda Unità Sanitaria Locale – IRCCS di Reggio Emilia, Skin Cancer Center, Reggio Emilia, ItalySearch for more papers by this authorZoe Apalla, Zoe Apalla orcid.org/0000-0002-9255-8196 Aristotle University of Thessaloniki, Thessaloniki, GreeceSearch for more papers by this author First published: 20 February 2024 https://doi.org/10.1111/jdv.19889Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Open Research DATA AVAILABILITY STATEMENT Lifemath data are publicly available at http://www.lifemath.net/cancer/. Lo et al. SLNB positivity risk data are publicly available at www.melanomarisk.org. REFERENCES 1Lo SN, Varey AHR, El Sharouni MA, Scolyer RA, Thompson JF. Online tools for predicting melanoma survival: including sentinel node status as a variable improves prediction accuracy. J Eur Acad Dermatol Venereol. 2023; 38: e182–e184. PubMedWeb of Science®Google Scholar 2Zabor EC, Coit D, Gershenwald JE, McMasters KM, Michaelson JS, Stromberg AJ, et al. Variability in predictions from online tools: a demonstration using internet-based melanoma predictors. Ann Surg Oncol. 2018; 25(8): 2172–2177. 10.1245/s10434-018-6370-4 PubMedWeb of Science®Google Scholar 3Dixon A, Steinman HK, Kyrgidis A, Smith H, Sladden M, Zouboulis C, et al. Online prediction tools for melanoma survival: a comparison. J Eur Acad Dermatol Venereol. 2023; 37: 1999–2003. 10.1111/jdv.19219 CASPubMedWeb of Science®Google Scholar 4Soong SJ, Ding S, Coit D, Balch CM, Gershenwald JE, Thompson JF, et al. Predicting survival outcome of localized melanoma: an electronic prediction tool based on the AJCC Melanoma Database. Ann Surg Oncol. 2010; 17(8): 2006–2014. 10.1245/s10434-010-1050-z PubMedWeb of Science®Google Scholar 5Callender GG, Gershenwald JE, Egger ME, Scoggins CR, Martin RC 2nd, Schacherer CW, et al. A novel and accurate computer model of melanoma prognosis for patients staged by sentinel lymph node biopsy: comparison with the American Joint Committee on Cancer model. J Am Coll Surg. 2012; 214(4): 608–617; discussion 17–19. 10.1016/j.jamcollsurg.2011.12.027 PubMedWeb of Science®Google Scholar 6El Sharouni MA, Stodell MD, Ahmed T, Suijkerbuijk KPM, Cust AE, Witkamp AJ, et al. Sentinel node biopsy in patients with melanoma improves the accuracy of staging when added to clinicopathological features of the primary tumor. Ann Oncol. 2021; 32(3): 375–383. 10.1016/j.annonc.2020.11.015 PubMedWeb of Science®Google Scholar 7Morton DL, Thompson JF, Cochran AJ, Mozzillo N, Nieweg OE, Roses DF, et al. Final trial report of sentinel-node biopsy versus nodal observation in melanoma. N Engl J Med. 2014; 370(7): 599–609. 10.1056/NEJMoa1310460 CASPubMedWeb of Science®Google Scholar 8Nahm FS. Receiver operating characteristic curve: overview and practical use for clinicians. Korean J Anesthesiol. 2022; 75(1): 25–36. 10.4097/kja.21209 PubMedWeb of Science®Google Scholar Early ViewOnline Version of Record before inclusion in an issue ReferencesRelatedInformation

BackgroundMelanoma disease patterns vary with patient age.AimTo evaluate sentinel lymph node biopsy (SLNB) in managing melanoma at differing patient ages.MethodsOnline prediction tools were applied to compare SLNB positivity (SLNB+) and survival risk at patient ages 20-80. Tubingen melanoma data were used to determine variations in the hazard ratio of SLNB+ for mortality at different patient ages.ResultsRegardless of tumour thickness, predicted SLNB+ rates were markedly higher than mortality rates for 20-year-old patients. For 80-year-old patients, it is the opposite.DiscussionIf 1000 20-year-olds with a 0.4 mm thickness non-ulcerated melanoma underwent SLNB, 100 would likely be positive. If all 100 were to be offered adjuvant drug therapy (ADT), fewer than three more melanoma deaths in those 1000 patients would be avoided. In total, 97 patients would have received medication they may never have needed. If 1000 80-year-olds with a 3 mm thickness non-ulcerated melanoma underwent SLNB, only 40 would likely be positive. In total, 274 patients would be predicted to die of melanoma, 245 being SLNB negative and 29 SLNB+. ADT linked to SLNB+ could deny treatment to 89% of these high-risk patients.LimitationsThe authors relied on published risk data.ConclusionSLNB has poor specificity at predicting mortality in young melanoma patients and poor sensitivity in older patients. SLNB is not indicated in managing cutaneous melanoma for patients under 40 or over 60 years of age. Many such patients could be managed with wide local excision alone in their clinician's office-based practice. For all cutaneous melanoma patients at all ages, linking ADT to BAUSSS biomarker, (an algorithm of Breslow thickness, age, ulceration, subtype, sex and Site) rather than SLNB+ is likely more appropriate. BAUSSS provides a more accurate melanoma-specific mortality risk assessment for patients without burdening them with added surgery, hospitalization, costs or morbidity risk.

Journal of the European Academy of Dermatology and VenereologyEarly View LETTER TO THE EDITOR Age-associated metastatic potential of melanoma in lymph nodes: A preliminary gene association study C. C. Zouboulis, Corresponding Author C. C. Zouboulis [email protected] orcid.org/0000-0003-1646-2608 Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodor Fontane and Faculty of Health Sciences Brandenburg, Dessau, Germany Correspondence C. C. Zouboulis, Departments of Dermatology, Venereology, Allergology and Immunology, Staedtisches Klinikum Dessau, Brandenburg Medical School Theodor Fontane and Faculty of Health Sciences Brandenburg, Auenweg 38, 06847 Dessau, Germany. Email: [email protected]Search for more papers by this authorA. J. Dixon, A. J. Dixon orcid.org/0000-0001-8071-7199 Australasian College of Cutaneous Oncology, Melbourne, Victoria, AustraliaSearch for more papers by this authorH. K. Steinman, H. K. Steinman Campbell University, Buies Creek, North Carolina, USASearch for more papers by this authorM. Sladden, M. Sladden University of Tasmania, Launceston, Tasmania, AustraliaSearch for more papers by this authorA. Kyrgidis, A. Kyrgidis orcid.org/0000-0003-3896-0309 Aristotle University of Thessaloniki, Thessaloniki, GreeceSearch for more papers by this author C. C. Zouboulis, Corresponding Author C. C. Zouboulis [email protected] orcid.org/0000-0003-1646-2608 Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodor Fontane and Faculty of Health Sciences Brandenburg, Dessau, Germany Correspondence C. C. Zouboulis, Departments of Dermatology, Venereology, Allergology and Immunology, Staedtisches Klinikum Dessau, Brandenburg Medical School Theodor Fontane and Faculty of Health Sciences Brandenburg, Auenweg 38, 06847 Dessau, Germany. Email: [email protected]Search for more papers by this authorA. J. Dixon, A. J. Dixon orcid.org/0000-0001-8071-7199 Australasian College of Cutaneous Oncology, Melbourne, Victoria, AustraliaSearch for more papers by this authorH. K. Steinman, H. K. Steinman Campbell University, Buies Creek, North Carolina, USASearch for more papers by this authorM. Sladden, M. Sladden University of Tasmania, Launceston, Tasmania, AustraliaSearch for more papers by this authorA. Kyrgidis, A. Kyrgidis orcid.org/0000-0003-3896-0309 Aristotle University of Thessaloniki, Thessaloniki, GreeceSearch for more papers by this author First published: 13 February 2024 https://doi.org/10.1111/jdv.19850Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Open Research DATA AVAILABILITY STATEMENT The data that support the findings of this study are available from the corresponding author upon reasonable request. Data sets related to this article are hosted at the Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/) data repositories GSE8401 and GSE43081. REFERENCES 1Ribero S, Stucci LS, Marra E, Marconcini R, Spagnolo F, Orgiano L, et al. Effect of age on melanoma risk, prognosis and treatment response. Acta Derm Venereol. 2018; 98: 624–629. 10.2340/00015555-2944 CASPubMedWeb of Science®Google Scholar 2Menefee DS, McMasters A, Pan J, Li X, Xiao D, Waigel S, et al. Age-related transcriptome changes in melanoma patients with tumor-positive sentinel lymph nodes. Aging. 2020; 12: 24–24939. 10.18632/aging.202435 Google Scholar 3Makrantonaki E, Brink TC, Zampeli V, Elewa RM, Mlody B, Hossini AM, et al. Identification of biomarkers of human skin ageing in both genders: Wnt signalling – a label of skin ageing? PLoS One. 2012; 7:e50393. 10.1371/journal.pone.0050393 CASPubMedWeb of Science®Google Scholar 4Mulder EEAP, Dwarkasing JT, Tempel D, van der Spek A, Bosman L, Verver D, et al. Validation of a clinicopathological and gene expression profile model for sentinel lymph node metastasis in primary cutaneous melanoma. Br J Dermatol. 2021; 184: 944–951. 10.1111/bjd.19499 CASPubMedWeb of Science®Google Scholar 5Farrow NE, Holl EK, Jung J, Gao J, Jung S-H, Al-Rohil RN, et al. Characterization of sentinel lymph node immune signatures and implications for risk stratification for adjuvant therapy in melanoma. Ann Surg Oncol. 2021; 28: 3501–3510. 10.1245/s10434-020-09277-w PubMedWeb of Science®Google Scholar 6Egger ME, Xiao D, Hao H, Kimbrough CW, Pan J, Rai SN, et al. Unique genes in tumor-positive sentinel lymph nodes associated with nonsentinel lymph node metastases in melanoma. Ann Surg Oncol. 2018; 25: 1296–1303. 10.1245/s10434-018-6377-x PubMedWeb of Science®Google Scholar 7Netanely D, Leibou S, Parikh R, Stern N, Vaknine H, Brenner R, et al. Classification of node-positive melanomas into prognostic subgroups using keratin, immune, and melanogenesis expression patterns. Oncogene. 2021; 40: 1792–1805. 10.1038/s41388-021-01665-0 CASPubMedWeb of Science®Google Scholar 8Bozdogan O, Guresci S, Öcalan DT, Bozdogan N. Kindlin-3 and RA SSF6 are probable biomarkers for predicting metastasis in cutaneous melanoma. Pol J Pathol. 2021; 72: 237–244. 10.5114/pjp.2021.111774 PubMedWeb of Science®Google Scholar 9Xie R, Li B, Jia L, Li Y. Identification of core genes and pathways in melanoma metastasis via bioinformatics analysis. Int J Mol Sci. 2022; 23: 794. 10.3390/ijms23020794 CASPubMedWeb of Science®Google Scholar 10Jakub JW, Weaver AL, Meves A. Association of tumor molecular factors with in-transit metastasis in primary cutaneous melanoma. Int J Dermatol. 2022; 61: 1117–1123. 10.1111/ijd.16141 CASPubMedWeb of Science®Google Scholar Early ViewOnline Version of Record before inclusion in an issue ReferencesRelatedInformation

BackgroundBreslow thickness, patient age and ulceration are the three most valuable clinical and pathological predictors of melanoma survival. A readily available reliable online tool that accurately considers these and other predictors could be valuable for clinicians managing melanoma patients. ObjectiveTo compare online melanoma survival prediction tools that request user input on clinical and pathological features. MethodsSearch engines were used to identify available predictive nomograms. For each, clinical and pathological predictors were compared. ResultsThree tools were identified. The American Joint Committee on Cancer tool inappropriately rated thin tumours as higher risk than intermediate tumours. The University of Louisville tool was found to have six shortcomings: a requirement for sentinel node biopsy, unavailable input of thin melanoma or patients over 70 years of age and less reliable hazard ratio calculations for age, ulceration and tumour thickness. The LifeMath.net tool was found to appropriately consider tumour thickness, ulceration, age, sex, site and tumour subtype in predicting survival. LimitationsThe authors did not have access to the base data used to compile various prediction tools. ConclusionThe LifeMath.net prediction tool is the most reliable for clinicians in counselling patients with newly diagnosed primary cutaneous melanoma regarding their survival prospects.

Journal of the European Academy of Dermatology and VenereologyEarly View LETTER TO THE EDITOR Improved methodology in determining melanoma mortality and selecting patients for immunotherapy A. J. Dixon, Corresponding Author A. J. Dixon anthony@acco.edu.au orcid.org/0000-0001-8071-7199 Australasian College of Cutaneous Oncology, Melbourne, Victoria, Australia Correspondence Anthony J. Dixon, 1109/5 Caravel Lane, Docklands, Victoria, 3008, Australia. Email: anthony@acco.edu.auSearch for more papers by this authorH. K. Steinman, H. K. Steinman Campbell University, Buies Creek, North Carolina, USASearch for more papers by this authorA. Kyrgidis, A. Kyrgidis orcid.org/0000-0003-3896-0309 Aristotle University of Thessaloniki, Thessaloniki, GreeceSearch for more papers by this authorH. Smith, H. Smith Oxford Dermatology, Perth, Western Australia, AustraliaSearch for more papers by this authorM. Sladden, M. Sladden University of Tasmania, Launceston, Tasmania, AustraliaSearch for more papers by this authorC. Zouboulis, C. Zouboulis Dessau Medical Center, Brandenburg Medical School, Dessau, GermanySearch for more papers by this authorG. Argenziano, G. Argenziano orcid.org/0000-0003-1413-8214 University of Campania, Campania, ItalySearch for more papers by this authorZ. Apalla, Z. Apalla orcid.org/0000-0002-9255-8196 Aristotle University of Thessaloniki, Thessaloniki, GreeceSearch for more papers by this authorA. Lallas, A. Lallas orcid.org/0000-0002-7193-0964 Aristotle University of Thessaloniki, Thessaloniki, GreeceSearch for more papers by this authorC. Longo, C. Longo University of Modena and Reggio Emilia, Modena, ItalySearch for more papers by this authorA. Nirenberg, A. Nirenberg Australasian College of Cutaneous Oncology, Melbourne, Victoria, AustraliaSearch for more papers by this authorC. Popescu, C. Popescu Carol Davila University of Medicine and Pharmacy, Bucharest, RomaniaSearch for more papers by this authorJ. B. Dixon, J. B. Dixon Swinburne University of Technology, Melbourne, Victoria, AustraliaSearch for more papers by this authorT. Tzellos, T. Tzellos Arctic University of Norway, Tromsø, NorwaySearch for more papers by this authorC. Zachary, C. Zachary orcid.org/0000-0002-5883-5188 University of California, Irvine, California, USASearch for more papers by this authorL. Cleaver, L. Cleaver A.T. Still University, Kirksville, Missouri, USASearch for more papers by this authorS. Anderson, S. Anderson Australasian College of Cutaneous Oncology, Melbourne, Victoria, AustraliaSearch for more papers by this authorS. Zagarella, S. Zagarella University of Sydney, Sydney, New South Wales, AustraliaSearch for more papers by this authorJ. M. Thomas, J. M. Thomas Formerly of Royal Marsden Hospital, London, UKSearch for more papers by this author A. J. Dixon, Corresponding Author A. J. Dixon anthony@acco.edu.au orcid.org/0000-0001-8071-7199 Australasian College of Cutaneous Oncology, Melbourne, Victoria, Australia Correspondence Anthony J. Dixon, 1109/5 Caravel Lane, Docklands, Victoria, 3008, Australia. Email: anthony@acco.edu.auSearch for more papers by this authorH. K. Steinman, H. K. Steinman Campbell University, Buies Creek, North Carolina, USASearch for more papers by this authorA. Kyrgidis, A. Kyrgidis orcid.org/0000-0003-3896-0309 Aristotle University of Thessaloniki, Thessaloniki, GreeceSearch for more papers by this authorH. Smith, H. Smith Oxford Dermatology, Perth, Western Australia, AustraliaSearch for more papers by this authorM. Sladden, M. Sladden University of Tasmania, Launceston, Tasmania, AustraliaSearch for more papers by this authorC. Zouboulis, C. Zouboulis Dessau Medical Center, Brandenburg Medical School, Dessau, GermanySearch for more papers by this authorG. Argenziano, G. Argenziano orcid.org/0000-0003-1413-8214 University of Campania, Campania, ItalySearch for more papers by this authorZ. Apalla, Z. Apalla orcid.org/0000-0002-9255-8196 Aristotle University of Thessaloniki, Thessaloniki, GreeceSearch for more papers by this authorA. Lallas, A. Lallas orcid.org/0000-0002-7193-0964 Aristotle University of Thessaloniki, Thessaloniki, GreeceSearch for more papers by this authorC. Longo, C. Longo University of Modena and Reggio Emilia, Modena, ItalySearch for more papers by this authorA. Nirenberg, A. Nirenberg Australasian College of Cutaneous Oncology, Melbourne, Victoria, AustraliaSearch for more papers by this authorC. Popescu, C. Popescu Carol Davila University of Medicine and Pharmacy, Bucharest, RomaniaSearch for more papers by this authorJ. B. Dixon, J. B. Dixon Swinburne University of Technology, Melbourne, Victoria, AustraliaSearch for more papers by this authorT. Tzellos, T. Tzellos Arctic University of Norway, Tromsø, NorwaySearch for more papers by this authorC. Zachary, C. Zachary orcid.org/0000-0002-5883-5188 University of California, Irvine, California, USASearch for more papers by this authorL. Cleaver, L. Cleaver A.T. Still University, Kirksville, Missouri, USASearch for more papers by this authorS. Anderson, S. Anderson Australasian College of Cutaneous Oncology, Melbourne, Victoria, AustraliaSearch for more papers by this authorS. Zagarella, S. Zagarella University of Sydney, Sydney, New South Wales, AustraliaSearch for more papers by this authorJ. M. Thomas, J. M. Thomas Formerly of Royal Marsden Hospital, London, UKSearch for more papers by this author First published: 14 February 2023 https://doi.org/10.1111/jdv.18951Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Early ViewOnline Version of Record before inclusion in an issue RelatedInformation

ABSTRACT:Keratoacanthoma (KA) is a cutaneous tumor with a biphasic pattern of growth. A rapidly growing phase is usually followed by involution. KA occurs on sun-damaged skin. There are many listed causative associations, which include some therapeutic agents. Debate continues as to whether KA is a variant of squamous carcinoma (SCC) or a separate entity. Reporting of KA versus SCC is markedly inconsistent. Reasons for inconsistency include overlapping microscopic criteria, variants of KA with more aggressive features, and possibly medicolegal concerns. Genetic studies have shown some differences between the 2 entities. Activation of apoptotic pathways has been demonstrated in KA. Genetic studies have shown a possible role of human polyomavirus 6 in the pathogenesis of at least some KAs. Given that some cases of KA have components that behave as conventional SCCs, KA can be considered as a low-grade variant of SCC with some genetic differences.

Steinman, Howard K. MD; Dixon, Anthony PhD, MBBS; Zachary, Christopher B. MBBS, FRCP Author Information

Merkel cell carcinoma (MCC) is an aggressive tumour with neuroendocrine differentiation. Clinically significant differences within the entity we know as MCC are apparent. This review aims to evaluate the evidence for differences in tumours within Merkel cell carcinoma and to stratify these. A literature search of research pertaining to various characteristics MCC was undertaken from 1972, when Merkel cell carcinoma was first described, to 2018, using PubMed and similar search engines. A total of 41 papers were analysed, including clinical trials, laboratory-based research and reviews. A proportion of MCC has Merkel cell polyomavirus genome integrated (MCPyV+) while others do not (MCPyV-). Both types have a different mutation burden. MCPyV+ tumours are likely true neuroendocrine carcinomas, with a dermal origin, probably from fibroblasts which have been transformed by integration of the viral genome. MCPyV-tumours are likely derived from either keratinocytes or epidermal stem cells, are probably squamous cell carcinomas with neuroendocrine differentiation, and are related to sun damage. Prognostic factors (apart from tumour stage) include the MCPyV status, with MCPyV+ tumours having a better prognosis. P63 expression confers a worse prognosis in most studies. CD8+ lymphocytes play an important role, providing a possible target for PD1/PD-L1 blockade treatment. The incidence of MCC varies from country to country. Countries such as Australia have a high rate and a far greater proportion of MCPyV- tumours than places such as the United Kingdom. MCC doubtlessly encompasses two tumours. The two tumours have demonstrated differences in prognosis and management. One is a neuroendocrine carcinoma related to MCPyV integration likely derived from fibroblasts, and the other is a UV-related squamous cell carcinoma with neuroendocrine differentiation, presumptively derived from either keratinocytes or epidermal stem cells. We propose naming the former Merkel type sarcoma and the latter squamous cell carcinoma, Merkel type.

Journal of the European Academy of Dermatology and VenereologyVolume 34, Issue 10 p. e598-e599 Letter to the Editor Melanoma extravascular migratory metastasis: an important underrecognized phenomenon A. Nirenberg, Corresponding Author A. Nirenberg nirenberg@protonmail.com orcid.org/0000-0001-8645-5388 Australasian College of Cutaneous Oncology, Docklands, Australia Correspondence: A. Nirenberg. E-mail: nirenberg@protonmail.comSearch for more papers by this authorH. Steinman, H. Steinman US Dermatology Partners, Dallas, USA Campbell University of School of Osteopathic Medicine, Lillington, USASearch for more papers by this authorA. Dixon, A. Dixon Australasian College of Cutaneous Oncology, Docklands, Australia American Osteopathic College of Dermatology, Kirksville, USASearch for more papers by this author A. Nirenberg, Corresponding Author A. Nirenberg nirenberg@protonmail.com orcid.org/0000-0001-8645-5388 Australasian College of Cutaneous Oncology, Docklands, Australia Correspondence: A. Nirenberg. E-mail: nirenberg@protonmail.comSearch for more papers by this authorH. Steinman, H. Steinman US Dermatology Partners, Dallas, USA Campbell University of School of Osteopathic Medicine, Lillington, USASearch for more papers by this authorA. Dixon, A. Dixon Australasian College of Cutaneous Oncology, Docklands, Australia American Osteopathic College of Dermatology, Kirksville, USASearch for more papers by this author First published: 16 April 2020 https://doi.org/10.1111/jdv.16479Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume34, Issue10October 2020Pages e598-e599 RelatedInformation

BACKGROUND:Maximising survival for patients with invasive melanoma hinges on early diagnosis of primary melanoma and appropriate management. Despite well-documented guidelines, many patients with melanoma have not been managed ideally. OBJECTIVE:The aim of this paper is to identify suboptimal aspects of melanoma management. DISCUSSION:Delayed or erroneous diagnosis is more likely to occur when a shave or punch biopsy is used to obtain histopathology. Wherever feasible, local excision with a narrow margin is the preferred biopsy choice for a suspected melanoma. The Breslow thickness of the primary melanoma remains the greatest predictor of outcome. Ulceration is associated with a poorer prognosis. Most invasive melanomas are managed with a margin of ≥10 mm of normal tissue. Patients who have developed one primary melanoma are at high risk of a second tumour. Ongoing management includes regular lifelong skin checks. Targeted approaches to improve occupational or lifestyle exposure to ultraviolet radiation are useful. Imaging is largely used when metastases are suspected on the basis of clinical symptoms or signs.

Background Maximising survival for patients with invasive melanoma hinges on early diagnosis of primary melanoma and appropriate management. Despite well-documented guidelines, many patients with melanoma have not been managed ideally. Objective The aim of this paper is to identify suboptimal aspects of melanoma management. Discussion Delayed or erroneous diagnosis is more likely to occur when a shave or punch biopsy is used to obtain histopathology. Wherever feasible, local excision with a narrow margin is the preferred biopsy choice for a suspected melanoma. The Breslow thickness of the primary melanoma remains the greatest predictor of outcome. Ulceration is associated with a poorer prognosis. Most invasive melanomas are managed with a margin of >= 10 mm of normal tissue. Patients who have developed one primary melanoma are at high risk of a second tumour. Ongoing management includes regular lifelong skin checks. Targeted approaches to improve occupational or lifestyle exposure to ultraviolet radiation are useful. Imaging is largely used when metastases are suspected on the basis of clinical symptoms or signs.

BACKGROUND Several new medications have shown improved survival rates in high-risk patients with melanoma. OBJECTIVE The aim of this article is to discuss the new medications and outline their roles, the expected benefit from each and the risk of adverse events. We explain the place of sentinel lymph node biopsy (SLNB) and ultrasonography with fine needle aspiration (US-FNA) in assessing and treating patients with melanoma. DISCUSSION Ipilimumab has limited efficacy and a very concerning complication profile. More than 50% of patients taking ipilimumab have severe or life-threatening adverse events. BRAF inhibitors have greater efficacy and fewer adverse events than ipilimumab. Combining BRAF inhibitors with mitogen-activated protein kinase inhibitors enhances their effect and improves the overall adverse event profile. BRAF inhibitors are only effective when the melanoma has a BRAF gene mutation, something that occurs in only 50% of cases. Programmed cell death protein 1 medications are also more effective and have a much more acceptable adverse event profile than ipilimumab. Both SLNB and US-FNA can detect early node involvement in patients with melanoma, although US-FNA is a safer procedure.