[Skip to Content]
[Skip to Content Landing]

Early Detection and Prognostic Assessment of Cutaneous MelanomaConsensus on Optimal Practice and the Role of Gene Expression Profile Testing

To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  What are the recommended methods for early detection and prognostic assessment of cutaneous melanoma?

Findings  In this consensus statement, via a modified Delphi method, melanoma experts supported a risk-stratified approach to various aspects of melanoma screening as well as the use of visual and dermoscopic examination, the interpretation of reflectance confocal microscopy, and some uses of epidermal tape stripping. They did not, based on available evidence, reach consensus on the role for gene expression profile testing in clinical decision-making.

Meaning  The study results suggest that a risk-stratified approach to melanoma screening may be most appropriate; the role of molecular-based diagnostic and prognostic tests in cutaneous melanoma is evolving.


Importance  Therapy for advanced melanoma has transformed during the past decade, but early detection and prognostic assessment of cutaneous melanoma (CM) remain paramount goals. Best practices for screening and use of pigmented lesion evaluation tools and gene expression profile (GEP) testing in CM remain to be defined.

Objective  To provide consensus recommendations on optimal screening practices and prebiopsy diagnostic, postbiopsy diagnostic, and prognostic assessment of CM.

Evidence Review  Case scenarios were interrogated using a modified Delphi consensus method. Melanoma panelists (n = 60) were invited to vote on hypothetical scenarios via an emailed survey (n = 42), which was followed by a consensus conference (n = 51) that reviewed the literature and the rationale for survey answers. Panelists participated in a follow-up survey for final recommendations on the scenarios (n = 45).

Findings  The panelists reached consensus (≥70% agreement) in supporting a risk-stratified approach to melanoma screening in clinical settings and public screening events, screening personnel recommendations (self/partner, primary care provider, general dermatologist, and pigmented lesion expert), screening intervals, and acceptable appointment wait times. Participants also reached consensus that visual and dermoscopic examination are sufficient for evaluation and follow-up of melanocytic skin lesions deemed innocuous. The panelists reached consensus on interpreting reflectance confocal microscopy and some but not all results from epidermal tape stripping, but they did not reach consensus on use of certain pigmented lesion evaluation tools, such as electrical impedance spectroscopy. Regarding GEP scores, the panelists reached consensus that a low-risk prognostic GEP score should not outweigh concerning histologic features when selecting patients to undergo sentinel lymph node biopsy but did not reach consensus on imaging recommendations in the setting of a high-risk prognostic GEP score and low-risk histology and/or negative nodal status.

Conclusions and Relevance  For this consensus statement, panelists reached consensus on aspects of a risk-stratified approach to melanoma screening and follow-up as well as use of visual examination and dermoscopy. These findings support a practical approach to diagnosing and evaluating CM. Panelists did not reach consensus on a clearly defined role for GEP testing in clinical decision-making, citing the need for additional studies to establish the clinical use of existing GEP assays.

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 Credit(s)™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Accepted for Publication: January 16, 2023.

Published Online: March 15, 2023. doi:10.1001/jamadermatol.2023.0127

Corresponding Author: John M. Kirkwood, MD, University of Pittsburgh, School of Medicine, Melanoma & Skin Cancer Disease Program, UPMC Hillman Cancer Center, UPMC Hillman Cancer Center, 5117 Centre Ave, Ste 1.32, Pittsburgh, PA 15213 (kirkwoodjm@upmc.edu).

Author Contributions: Dr Kirkwood had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Kashani-Sabet, Leachman, and Stein contributed equally to the writing of the manuscript.

Concept and design: Kirkwood, Kashani-Sabet, Leachman, Stein, Arbiser, Grant-Kels, Nelson, Tsao, Karapetyan, Savory, Sondak.

Acquisition, analysis, or interpretation of data: Kirkwood, Kashani-Sabet, Leachman, Stein, Berry, Celebi, Curiel-Lewandrowski, MD, Ferris, Grant-Kels, Grossman, Kulkarni, Marchetti, Polsky, Seiverling, Swetter, Tsao, Verdieck-Devlaeminck, Wei, Bar, Bartlett, Bolognia, Bowles, Cha, Chu, Hartman, Hawryluk, Jampel, Kheterpal, Lawson, Leming, Liebman, Ming, Sahni, Shaikh, Sober, Sondak, Spaccarelli, Usatine, Venna.

Drafting of the manuscript: Kirkwood, Kashani-Sabet, Leachman, Stein, Arbiser, Seiverling, Tsao, Verdieck-Devlaeminck, Karapetyan, Sahni.

Critical revision of the manuscript for important intellectual content: Kirkwood, Kashani-Sabet, Leachman, Stein, Arbiser, Berry, Celebi, Curiel-Lewandrowski, MD, Ferris, Grant-Kels, Grossman, Kulkarni, Marchetti, Nelson, Polsky, Seiverling, Swetter, Tsao, Wei, Bar, Bartlett, Bolognia, Bowles, Cha, Chu, Hartman, Hawryluk, Jampel, Karapetyan, Kheterpal, Lawson, Leming, Liebman, Ming, Sahni, Savory, Shaikh, Sober, Sondak, Spaccarelli, Usatine, Venna.

Obtained funding: Kirkwood.

Administrative, technical, or material support: Kirkwood, Leachman, Arbiser, Curiel-Lewandrowski, MD, Grant-Kels, Nelson, Bolognia, Bowles, Lawson, Sahni, Shaikh.

Supervision: Kirkwood, Kashani-Sabet, Leachman, Arbiser, Grant-Kels, Tsao, Kheterpal.

Other - participated in creating the data: Sober.

Conflict of Interest Disclosures: Dr Kirkwood reported grants from DermTech Inc outside the submitted work. Dr Kashani-Sabet reported stock in Melanoma Diagnostics, ownership interest in DNARX LLC, a patent issued for molecular classification of melanoma, and advisory board service for Bristol-Myers Squibb outside the submitted work. Dr Leachman reported honorarium from the Melanoma Research Foundation during the conduct of the study and research support from Castle Biosciences, Sklip Inc, Orlucent Inc, MAB, and VeriSkin Inc outside the submitted work. Dr Stein reported financial support from MoleSafe USA during the conduct of the study. Dr Berry reported personal fees from Melanoma Research Alliance during the conduct of the study as well as personal fees from Bristol Myers Squibb and Barco Inc outside the submitted work. Dr Celebi reported personal fees from NYU Grossman School of Medicine during the conduct of the study. Dr Curiel-Lewandrowski reports grants from Amgen outside the submitted work. Dr Ferris reported personal fees and grants from Derm Tech and grants from Castle Biosciences outside the submitted work. Dr Grossman reported research support from Derm Tech, Orlucent Inc, and Skin Analytics and personal fees from Orlucent Inc outside the submitted work. Dr Seiverling reported personal fees from DermaSensor Consultant for image quality review outside the submitted work. Dr Wei reported personal fees from Merck outside the submitted work. Dr Bar reported research support from Castle and personal fees from Regeneron during the conduct of the study and outside the submitted work. Dr Bartlett reported grants from SkylineDx and personal fees from Excite International LLC outside the submitted work. Dr Bolognia reported royalties from Elsevier outside the submitted work. Dr Bowles reported research support from Genentech, Amgen, Replimune, and Natera outside the submitted work. Dr Hartman reported grants from DermaSensor outside the submitted work. Dr Hawryluk reported being an author and reviewer for UpToDate outside the submitted work. Dr Savory reported being a board member for the Texas Dermatological Society. Dr Sondak reported personal fees from AMLo Biosciences, Alkermes, Bristol Myers Squibb, Genesis Drug Discovery & Development, Iovance, Merck, Novartis, Regeneron, and Ultimovacs; grants from Neogene Therapeutics and Turnstone; and nonfinancial support from SkylineDX outside the submitted work. No other disclosures were reported.

Funding/Support: The funding for the administration and facilitation of the consensus development conference and the development of thismanuscript was provided by Dermtech Inc in an unrestricted award that was administratively overseen by the Melanoma Research Foundation and managed and executed at UPMC by the principal investigato (Dr Kirkwood). DermTech was not involved in the preparation or editing of the manuscript.

Role of the Funder/Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Aitken  JF , Youlden  DR , Baade  PD , Soyer  HP , Green  AC , Smithers  BM .  Generational shift in melanoma incidence and mortality in Queensland, Australia, 1995-2014.   Int J Cancer. 2018;142(8):1528-1535. doi:10.1002/ijc.31141 PubMedGoogle ScholarCrossref
Whiteman  DC , Olsen  CM , MacGregor  S ,  et al; QSkin Study.  The effect of screening on melanoma incidence and biopsy rates.   Br J Dermatol. 2022;187(4):515-522. doi:10.1111/bjd.21649 PubMedGoogle ScholarCrossref
Johnson  MM , Leachman  SA , Aspinwall  LG ,  et al.  Skin cancer screening: recommendations for data-driven screening guidelines and a review of the US Preventive Services Task Force controversy.   Melanoma Manag. 2017;4(1):13-37. doi:10.2217/mmt-2016-0022 PubMedGoogle ScholarCrossref
Hartman  RI , Xue  Y , Singer  S , Markossian  TW , Joyce  C , Mostaghimi  A .  Modelling the value of risk-stratified skin cancer screening of asymptomatic patients by dermatologists.   Br J Dermatol. 2020;183(3):509-515. doi:10.1111/bjd.18816 PubMedGoogle ScholarCrossref
Shoo  BA , Sagebiel  RW , Kashani-Sabet  M .  Discordance in the histopathologic diagnosis of melanoma at a melanoma referral center.   J Am Acad Dermatol. 2010;62(5):751-756. doi:10.1016/j.jaad.2009.09.043 PubMedGoogle ScholarCrossref
Schadendorf  D , Flaherty  KT , Duncan  LM , Kashani-Sabet  M , Ugurel  S . Biomarkers for melanoma. In: Balch  C , ed.  Cutaneous Melanoma. 6th ed. Springer Nature Switzerland; 2019. doi:10.1007/978-3-319-46029-1_45-1
Elmore  JG , Barnhill  RL , Elder  DE ,  et al.  Pathologists’ diagnosis of invasive melanoma and melanocytic proliferations: observer accuracy and reproducibility study.   BMJ. 2017;357:j2813. doi:10.1136/bmj.j2813 PubMedGoogle ScholarCrossref
Ankeny  JS , Labadie  B , Luke  J , Hsueh  E , Messina  J , Zager  JS .  Review of diagnostic, prognostic, and predictive biomarkers in melanoma.   Clin Exp Metastasis. 2018;35(5-6):487-493. doi:10.1007/s10585-018-9892-z PubMedGoogle ScholarCrossref
Lezcano  C , Jungbluth  AA , Busam  KJ .  Comparison of immunohistochemistry for PRAME with cytogenetic test results in the evaluation of challenging melanocytic tumors.   Am J Surg Pathol. 2020;44(7):893-900. doi:10.1097/PAS.0000000000001492 PubMedGoogle ScholarCrossref
Grossman  D , Okwundu  N , Bartlett  EK ,  et al.  Prognostic gene expression profiling in cutaneous melanoma: identifying the knowledge gaps and assessing the clinical benefit.   JAMA Dermatol. 2020;156(9):1004-1011. doi:10.1001/jamadermatol.2020.1729 PubMedGoogle ScholarCrossref
Hamdan  D , Nguyen  TT , Leboeuf  C , Meles  S , Janin  A , Bousquet  G .  Genomics applied to the treatment of breast cancer.   Oncotarget. 2019;10(46):4786-4801. doi:10.18632/oncotarget.27102 PubMedGoogle ScholarCrossref
Ferris  LK , Jansen  B , Ho  J ,  et al.  Utility of a noninvasive 2-gene molecular assay for cutaneous melanoma and effect on the decision to biopsy.   JAMA Dermatol. 2017;153(7):675-680. doi:10.1001/jamadermatol.2017.0473 PubMedGoogle ScholarCrossref
Castillo  SA , Pham  AK , Dagrosa  AT ,  et al.  Concordance analysis of the 23-gene expression signature (myPath Melanoma) with fluorescence in situ hybridization assay and single nucleotide polymorphism array in the analysis of challenging melanocytic lesions: results from an academic medical center.   Am J Dermatopathol. 2020;42(12):939-947. doi:10.1097/DAD.0000000000001713 PubMedGoogle ScholarCrossref
Hsu  C-C , Sandford  BA . The Delphi technique: making sense of consensus. Accessed February 10, 2023. https://scholarworks.umass.edu/cgi/viewcontent.cgi?article=1177&context=pare
Vogel  C , Zwolinsky  S , Griffiths  C , Hobbs  M , Henderson  E , Wilkins  E .  A Delphi study to build consensus on the definition and use of big data in obesity research.   Int J Obes (Lond). 2019;43(12):2573-2586. doi:10.1038/s41366-018-0313-9 PubMedGoogle ScholarCrossref
Gandini  S , Sera  F , Cattaruzza  MS ,  et al.  Meta-analysis of risk factors for cutaneous melanoma: III. Family history, actinic damage and phenotypic factors.   Eur J Cancer. 2005;41(14):2040-2059. doi:10.1016/j.ejca.2005.03.034 PubMedGoogle ScholarCrossref
Caini  S , Gandini  S , Sera  F ,  et al.  Meta-analysis of risk factors for cutaneous melanoma according to anatomical site and clinico-pathological variant.   Eur J Cancer. 2009;45(17):3054-3063. doi:10.1016/j.ejca.2009.05.009 PubMedGoogle ScholarCrossref
International Agency for Research on Cancer Working Group on Artificial Ultraviolet Light and Skin Cancer.  The association of use of sunbeds with cutaneous malignant melanoma and other skin cancers: a systematic review.   Int J Cancer. 2007;120(5):1116-1122. PubMedGoogle Scholar
Lazovich  D , Isaksson Vogel  R , Weinstock  MA , Nelson  HH , Ahmed  RL , Berwick  M .  Association between indoor tanning and melanoma in younger men and women.   JAMA Dermatol. 2016;152(3):268-275. doi:10.1001/jamadermatol.2015.2938 PubMedGoogle ScholarCrossref
Bradford  PT , Freedman  DM , Goldstein  AM , Tucker  MA .  Increased risk of second primary cancers after a diagnosis of melanoma.   Arch Dermatol. 2010;146(3):265-272. doi:10.1001/archdermatol.2010.2 PubMedGoogle ScholarCrossref
Collins  L , Quinn  A , Stasko  T .  Skin cancer and immunosuppression.   Dermatol Clin. 2019;37(1):83-94. doi:10.1016/j.det.2018.07.009 PubMedGoogle ScholarCrossref
Robbins  HA , Clarke  CA , Arron  ST ,  et al.  Melanoma risk and survival among organ transplant recipients.   J Invest Dermatol. 2015;135(11):2657-2665. doi:10.1038/jid.2015.312 PubMedGoogle ScholarCrossref
Leachman  SA , Lucero  OM , Sampson  JE ,  et al.  Identification, genetic testing, and management of hereditary melanoma.   Cancer Metastasis Rev. 2017;36(1):77-90. doi:10.1007/s10555-017-9661-5 PubMedGoogle ScholarCrossref
Kefford  RF , Newton Bishop  JA , Bergman  W , Tucker  MA .  Counseling and DNA testing for individuals perceived to be genetically predisposed to melanoma: a consensus statement of the Melanoma Genetics Consortium.   J Clin Oncol. 1999;17(10):3245-3251. doi:10.1200/JCO.1999.17.10.3245 PubMedGoogle ScholarCrossref
Gandini  S , Sera  F , Cattaruzza  MS ,  et al.  Meta-analysis of risk factors for cutaneous melanoma: I: common and atypical naevi.   Eur J Cancer. 2005;41(1):28-44. doi:10.1016/j.ejca.2004.10.015 PubMedGoogle ScholarCrossref
Begg  CB , Orlow  I , Hummer  AJ ,  et al; Genes Environment and Melanoma Study Group.  Lifetime risk of melanoma in CDKN2A mutation carriers in a population-based sample.   J Natl Cancer Inst. 2005;97(20):1507-1515. doi:10.1093/jnci/dji312 PubMedGoogle ScholarCrossref
Gonzalez  JL , Cunningham  K , Silverman  R , Madan  E , Nguyen  BM .  Case-control study of tumor stage-dependent outcomes for cutaneous squamous cell carcinoma in immunosuppressed and immunocompetent patients.   Dermatol Surg. 2019;45(12):1467-1476. doi:10.1097/DSS.0000000000001930 PubMedGoogle ScholarCrossref
Rigel  DS , Friedman  RJ , Kopf  AW ,  et al.  Importance of complete cutaneous examination for the detection of malignant melanoma.   J Am Acad Dermatol. 1986;14(5 Pt 1):857-860. doi:10.1016/S0190-9622(86)70100-X PubMedGoogle ScholarCrossref
Elder  DE , Bastian  BC , Cree  IA , Massi  D , Scolyer  RA .  The 2018 World Health Organization classification of cutaneous, mucosal, and uveal Melanoma: detailed analysis of 9 distinct subtypes defined by their evolutionary pathway.   Arch Pathol Lab Med. 2020;144(4):500-522. doi:10.5858/arpa.2019-0561-RA PubMedGoogle ScholarCrossref
Greenhaw  BN , Covington  KR , Kurley  SJ ,  et al.  Molecular risk prediction in cutaneous melanoma: a meta-analysis of the 31-gene expression profile prognostic test in 1,479 patients.   J Am Acad Dermatol. 2020;83(3):745-753. doi:10.1016/j.jaad.2020.03.053 PubMedGoogle ScholarCrossref
Swetter  SM , Thompson  JA , Albertini  MR ,  et al.  NCCN guidelines insights: melanoma: cutaneous, version 2.2021.   J Natl Compr Canc Netw. 2021;19(4):364-376. doi:10.6004/jnccn.2021.0018 PubMedGoogle ScholarCrossref
Shaikh  SS , Yang  X , Fortman  DD ,  et al.  A retrospective analysis of the impact of the COVID-19 pandemic on staging at presentation of patients with invasive melanoma.   J Am Acad Dermatol. 2022;87(4):906-908, 22, 00798-8. doi:10.1016/j.jaad.2022.05.008 PubMedGoogle ScholarCrossref
Marchetti  MA , Dusza  SW , Bartlett  EK .  Utility of a model for predicting the risk of sentinel lymph node metastasis in patients with cutaneous melanoma.   JAMA Dermatol. 2022;158(6):680-683. doi:10.1001/jamadermatol.2022.0970 PubMedGoogle ScholarCrossref
Johansson  I , Tempel  D , Dwarkasing  JT ,  et al.  Validation of a clinicopathological and gene expression profile model to identify patients with cutaneous melanoma where sentinel lymph node biopsy is unnecessary.   Eur J Surg Oncol. 2022;48(2):320-325. doi:10.1016/j.ejso.2021.11.010 PubMedGoogle ScholarCrossref
AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right

Name Your Search

Save Search
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience

Lookup An Activity


My Saved Searches

You currently have no searches saved.


My Saved Courses

You currently have no courses saved.