Development and Validation of a Diagnostic 35-Gene Expression Profile Test for Ambiguous or Difficult-to-Diagnose Suspicious Pigmented Skin Lesions

Main Article Content

Sarah Estrada
Jeffrey Shackelton
Nathan Cleaver
Natalie Depcik-Smith
Clay Cockerell
Stephen Lencioni
Howard Martin
Jeffrey Wilkinson
Lauren Meldi Sholl
Michael Berg
Brooke Russell
Olga Zolochevska
Kyle Covington
Aaron Farberg
Matthew Goldberg
Pedram Gerami
Gregory Hosler

Keywords

35-GEP, diagnostic test, validation, melanoma, benign nevi

Abstract

Purpose: A clinical hurdle for dermatopathology is the accurate diagnosis of melanocytic neoplasms. While histopathologic assessment is frequently sufficient, high rates of diagnostic discordance are reported. The development and validation of a 35-gene expression profile (35-GEP) test that accurately differentiates benign and malignant pigmented lesions is described.


Methods: Lesion samples were reviewed by at least three independent dermatopathologists and included in the study if 2/3 or 3/3 diagnoses were concordant. Diagnostic utility of 76 genes was assessed with quantitative RT-PCR; neural network modeling and cross-validation were utilized for diagnostic gene selection using 200 benign nevi and 216 melanomas for training. To reflect the complex biology of melanocytic neoplasia, the 35-GEP test was developed to include an intermediate-risk zone.


Results: Validation of the 35-GEP was performed in an independent set of 273 benign and 230 malignant lesions. The test demonstrated 99.1% sensitivity, 94.3% specificity, 93.6% positive predictive value and 99.2% negative predictive value. 96.4% of cases received a differential result and 3.6% had intermediate-risk.


Conclusions: The 35-GEP test was developed to refine diagnoses of melanocytic neoplasms by providing clinicians with an objective tool. A test with these accuracy metrics could alleviate uncertainty in difficult-to-diagnose lesions leading to decreased unnecessary procedures while appropriately identifying at-risk patients.

References

1. National Cancer Institute, National Institutes of Health. Melanoma of the Skin - Cancer Stat Facts. SEER. Published 2020. Accessed October 24, 2019. https://seer.cancer.gov/statfacts/html/melan.html

2. Wang DM, Morgan FC, Besaw RJ, Schmults CD. An ecological study of skin biopsies and skin cancer treatment procedures in the United States Medicare population, 2000 to 2015. J Am Acad Dermatol. 2018;78(1):47-53. doi:10.1016/j.jaad.2017.09.031

3. Cartee TV, Kini SP, Chen SC. Melanoma reporting to central cancer registries by US dermatologists: An analysis of the persistent knowledge and practice gap. J Am Acad Dermatol. 2011;65(5):S124.e1-S124.e9. doi:10.1016/j.jaad.2011.05.032

4. Cockburn M, Swetter SM, Peng D, Keegan THM, Deapen D, Clarke CA. Melanoma underreporting: Why does it happen, how big is the problem, and how do we fix it? J Am Acad Dermatol. 2008;59(6):1081-1085. doi:10.1016/j.jaad.2008.08.007

5. Heuring E, Chen SC. Melanoma underreporting among US dermatopathologists: A pilot study. J Cutan Pathol. 2018;45(7):550-551. doi:10.1111/cup.13149

6. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7-30. doi:10.3322/caac.21590

7. 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

8. 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

9. Farmer ER, Gonin R, Hanna MP. Discordance in the histopathologic diagnosis of melanoma and melanocytic nevi between expert pathologists. Hum Pathol. 1996;27(6):528-531. doi:10.1016/s0046-8177(96)90157-4

10. Patrawala S, Maley A, Greskovich C, et al. Discordance of histopathologic parameters in cutaneous melanoma: Clinical implications. J Am Acad Dermatol. 2016;74(1):75-80. doi:10.1016/j.jaad.2015.09.008

11. Warycha MA, Christos PJ, Mazumdar M, et al. Changes in the Presentation of Nodular and Superficial Spreading Melanomas Over 35 Years. Cancer. 2008;113(12):3341-3348. doi:10.1002/cncr.23955

12. Damsky WE, Bosenberg M. Melanocytic nevi and melanoma: unraveling a complex relationship. Oncogene. 2017;36(42):5771-5792. doi:10.1038/onc.2017.189

13. Diwan AH, Lazar AJ. Nevoid Melanoma. Clin Lab Med. 2011;31(2):243-253. doi:10.1016/j.cll.2011.03.002

14. DeWane ME, Kelsey A, Oliviero M, Rabinovitz H, Grant-Kels JM. Melanoma on chronically sun-damaged skin: Lentigo maligna and desmoplastic melanoma. J Am Acad Dermatol. 2019;81(3):823-833. doi:10.1016/j.jaad.2019.03.066

15. King R. Lentiginous Melanoma. Arch Pathol Lab Med. 2011;135(3):337-341. doi:10.1043/2009-0538-RA.1

16. Harms KL, Lowe L, Fullen DR, Harms PW. Atypical Spitz Tumors: A Diagnostic Challenge. Arch Pathol Lab Med. 2015;139(10):1263-1270. doi:10.5858/arpa.2015-0207-RA

17. Yang GB. Risk and Survival of Cutaneous Melanoma Diagnosed Subsequent to a Previous Cancer. Arch Dermatol. 2011;147(12):1395. doi:10.1001/archdermatol.2011.1133

18. Magro CM, Crowson AN, Mihm MC. Unusual variants of malignant melanoma. Mod Pathol. 2006;19(2):S41-S70. doi:10.1038/modpathol.3800516

19. Troxel DB. Pitfalls in the Diagnosis of Malignant Melanoma: Findings of a Risk Management Panel Study. Am J Surg Pathol. 2003;27(9):1278–1283.

20. High WA. Malpractice in Dermatopathology—Principles, Risk Mitigation, and Opportunities for Improved Care for the Histologic Diagnosis of Melanoma and Pigmented Lesions. Clin Lab Med. 2008;28(2):261-284. doi:10.1016/j.cll.2007.12.006

21. Fryback DG, Thornbury JR. The Efficacy of Diagnostic Imaging. Med Decis Making. 1991;11(2):88-94. doi:10.1177/0272989X9101100203

22. Miedema J, Andea AA. Through the looking glass and what you find there: making sense of comparative genomic hybridization and fluorescence in situ hybridization for melanoma diagnosis. Mod Pathol. Published online February 17, 2020. doi:10.1038/s41379-020-0490-7

23. Ohsie SJ, Sarantopoulos GP, Cochran AJ, Binder SW. Immunohistochemical characteristics of melanoma. J Cutan Pathol. 2008;35(5):433-444. doi:10.1111/j.1600-0560.2007.00891.x

24. Lezcano C, Jungbluth AA, Nehal KS, Hollmann TJ, Busam KJ. PRAME Expression in Melanocytic Tumors: Am J Surg Pathol. 2018;42(11):1456-1465. doi:10.1097/PAS.0000000000001134

25. Berk DR, LaBuz E, Dadras SS, Johnson DL, Swetter SM. Melanoma and Melanocytic Tumors of Uncertain Malignant Potential in Children, Adolescents and Young Adults-The Stanford Experience 1995-2008: Melanoma and Melanocytic Tumors of Uncertain Malignant Potential. Pediatr Dermatol. 2010;27(3):244-254. doi:10.1111/j.1525-1470.2009.01078.x

26. Cockerell CJ. Commentary on Atypical Melanocytic Proliferations: Dermatol Surg. 2018;44(2):175-176. doi:10.1097/DSS.0000000000001365

27. Elder DE, Xu X. The approach to the patient with a difficult melanocytic lesion. Pathology (Phila). 2004;36(5):428-434. doi:10.1080/00313020412331283905

28. Ensslin CJ, Hibler BP, Lee EH, Nehal KS, Busam KJ, Rossi AM. Atypical Melanocytic Proliferations: A Review of the Literature. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2018;44(2):159-174. doi:10.1097/DSS.0000000000001367

29. Hillen LM, Van den Oord J, Geybels MS, Becker JC, zur Hausen A, Winnepenninckx V. Genomic Landscape of Spitzoid Neoplasms Impacting Patient Management. Front Med. 2018;5. doi:10.3389/fmed.2018.00344

30. Raghavan SS, Peternel S, Mully TW, et al. Spitz melanoma is a distinct subset of spitzoid melanoma. Mod Pathol. 2020;33(6):1122-1134. doi:10.1038/s41379-019-0445-z

31. Sepehr A, Tahan SR. “Nevus/Melanocytoma/Melanoma”: That Which We Call a Rose by Any Other Name Would Smell as Sweet. Arch Pathol Lab Med. 2012;136(2):135-135. doi:10.5858/arpa.2011-0148-LE

32. Urso C. Tertium Non Datur ? Legitimacy of a Third Diagnostic Category in Melanocytic Lesions. Arch Pathol Lab Med. 2012;136(10):1181-1183. doi:10.5858/arpa.2012-0071-LE

33. Zembowicz A, Scolyer RA. Nevus/Melanocytoma/Melanoma: An Emerging Paradigm for Classification of Melanocytic Neoplasms? Arch Pathol Lab Med. 2011;135:7.

34. Ferris LK, Moy RL, Gerami P, et al. Noninvasive Analysis of High-Risk Driver Mutations and Gene Expression Profiles in Primary Cutaneous Melanoma. J Invest Dermatol. 2019;139(5):1127-1134. doi:10.1016/j.jid.2018.10.041

35. Ferris LK, Gerami P, Skelsey MK, et al. Real-world performance and utility of a noninvasive gene expression assay to evaluate melanoma risk in pigmented lesions: Melanoma Res. Published online July 2018:1. doi:10.1097/CMR.0000000000000478

36. 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. doi:10.1001/jamadermatol.2017.0473

37. Gerami P, Yao Z, Polsky D, et al. Development and validation of a noninvasive 2-gene molecular assay for cutaneous melanoma. J Am Acad Dermatol. 2017;76(1):114-120.e2. doi:10.1016/j.jaad.2016.07.038

38. Lee JJ, Lian CG. Molecular Testing for Cutaneous Melanoma: An Update and Review. Arch Pathol Lab Med. 2019;143(7):811-820. doi:10.5858/arpa.2018-0038-RA

39. Shah A, Hyngstrom J, Florell SR, Grossman D. Use of the Pigmented Lesion Assay to rapidly screen a patient with numerous clinically atypical pigmented lesions. JAAD Case Rep. 2019;5(12):1048-1050. doi:10.1016/j.jdcr.2019.10.004

40. Clarke LE, Flake DD, Busam K, et al. An independent validation of a gene expression signature to differentiate malignant melanoma from benign melanocytic nevi. Cancer. 2017;123(4):617-628. doi:10.1002/cncr.30385

41. Clarke LE, Warf MB, Flake DD, et al. Clinical validation of a gene expression signature that differentiates benign nevi from malignant melanoma. J Cutan Pathol. 2015;42(4):244-252. doi:10.1111/cup.12475

42. Minca EC, Al-Rohil RN, Wang M, et al. Comparison between melanoma gene expression score and fluorescence in situ hybridization for the classification of melanocytic lesions. Mod Pathol. 2016;29(8):832-843. doi:10.1038/modpathol.2016.84

43. Clarke LE, Pimentel JD, Zalaznick H, Wang L, Busam KJ. Gene expression signature as an ancillary method in the diagnosis of desmoplastic melanoma. Hum Pathol. 2017;70:113-120. doi:10.1016/j.humpath.2017.10.005

44. Ko JS, Matharoo-Ball B, Billings SD, et al. Diagnostic Distinction of Malignant Melanoma and Benign Nevi by a Gene Expression Signature and Correlation to Clinical Outcomes. Cancer Epidemiol Biomarkers Prev. 2017;26(7):1107-1113. doi:10.1158/1055-9965.EPI-16-0958

45. Kabbarah O, Nogueira C, Feng B, et al. Integrative Genome Comparison of Primary and Metastatic Melanomas. PLOS ONE. 2010;5(5):e10770. doi:10.1371/journal.pone.0010770

46. Shain AH, Joseph NM, Yu R, et al. Genomic and Transcriptomic Analysis Reveals Incremental Disruption of Key Signaling Pathways during Melanoma Evolution. Cancer Cell. 2018;34(1):45-55.e4. doi:10.1016/j.ccell.2018.06.005

47. Scatolini M, Grand MM, Grosso E, et al. Altered molecular pathways in melanocytic lesions. Int J Cancer. 2010;126(8):1869-1881. doi:10.1002/ijc.24899

48. Goldberg DE. Genetic Algorithms in Search, Optimization, and Machine Learning. 1st Edition. Addison-Wesley Professional; 1989.

49. Holland JH. Adaptation in Natural and Artificial Systems. The MIT Press; 1975. Accessed September 9, 2020. https://mitpress.mit.edu/books/adaptation-natural-and-artificial-systems

50. Wysong A, Newman JG, Covington KR, et al. Validation of a 40-Gene Expression Profile Test to Predict Metastatic Risk in Localized High-Risk Cutaneous Squamous Cell Carcinoma. J Am Acad Dermatol. Published online April 25, 2020. doi:10.1016/j.jaad.2020.04.088

51. Ripley BD. Pattern Recognition and Neural Networks. Cambridge University Press; 1996. Accessed September 9, 2020. http://www.stats.ox.ac.uk/~ripley/PRbook/

52. Leshno M, Lin VYa, Pinkus A, Schocken S. Multilayer feedforward networks with a nonpolynomial activation function can approximate any function. Neural Netw. 1993;6(6):861-867. doi:10.1016/S0893-6080(05)80131-5

53. Sayed S, Nassef M, Badr A, Farag I. A Nested Genetic Algorithm for feature selection in high-dimensional cancer Microarray datasets. Expert Syst Appl. 2019;121:233-243. doi:10.1016/j.eswa.2018.12.022

54. Ableser MJ, Penuela S, Lee J, Shao Q, Laird DW. Connexin43 Reduces Melanoma Growth within a Keratinocyte Microenvironment and during Tumorigenesis in Vivo. J Biol Chem. 2014;289(3):1592-1603. doi:10.1074/jbc.M113.507228

55. Ancans J, Thody AJ. Activation of melanogenesis by vacuolar type H+-ATPase inhibitors in amelanotic, tyrosinase positive human and mouse melanoma cells. FEBS Lett. 2000;478(1-2):57-60. doi:10.1016/S0014-5793(00)01795-6

56. Brand M, Moggs JG, Oulad-Abdelghani M, et al. UV-damaged DNA-binding protein in the TFTC complex links DNA damage recognition to nucleosome acetylation. EMBO J. 2001;20(12):3187-3196. doi:10.1093/emboj/20.12.3187

57. Bresnick AR, Weber DJ, Zimmer DB. S100 proteins in cancer. Nat Rev Cancer. 2015;15(2):96-109. doi:10.1038/nrc3893

58. Choi WJ, Kim M, Park J-Y, Park TJ, Kang HY. Pleiotrophin inhibits melanogenesis via Erk1/2-MITF signaling in normal human melanocytes. Pigment Cell Melanoma Res. 2015;28(1):51-60. doi:10.1111/pcmr.12309

59. Davis DG, Siddiqui MT, Oprea-Ilies G, et al. GATA-3 and FOXA1 expression is useful to differentiate breast carcinoma from other carcinomas. Hum Pathol. 2016;47(1):26-31. doi:10.1016/j.humpath.2015.09.015

60. De Filippo E, Manga P, Schiedel AC. Identification of Novel G Protein–Coupled Receptor 143 Ligands as Pharmacologic Tools for Investigating X-Linked Ocular Albinism. Invest Ophthalmol Vis Sci. 2017;58(7):3118-3126. doi:10.1167/iovs.16-21128

61. Eckhart L, Schmidt M, Mildner M, et al. Histidase expression in human epidermal keratinocytes: Regulation by differentiation status and all-trans retinoic acid. J Dermatol Sci. 2008;50(3):209-215. doi:10.1016/j.jdermsci.2007.12.009

62. Gou R, Zhu L, Zheng M, et al. Annexin A8 can serve as potential prognostic biomarker and therapeutic target for ovarian cancer: based on the comprehensive analysis of Annexins. J Transl Med. 2019;17(1):275. doi:10.1186/s12967-019-2023-z

63. Guyonneau L, Murisier F, Rossier A, Moulin A, Beermann F. Melanocytes and Pigmentation Are Affected in Dopachrome Tautomerase Knockout Mice. Mol Cell Biol. 2004;24(8):3396-3403. doi:10.1128/MCB.24.8.3396-3403.2004

64. Ho H, Kapadia R, Al-Tahan S, Ahmad S, Ganesan AK. WIPI1 Coordinates Melanogenic Gene Transcription and Melanosome Formation via TORC1 Inhibition. J Biol Chem. 2011;286(14):12509-12523. doi:10.1074/jbc.M110.200543

65. Hu D, Ansari D, Bauden M, Zhou Q, Andersson R. The Emerging Role of Calcium-activated Chloride Channel Regulator 1 in Cancer. Anticancer Res. 2019;39(4):1661-1666. doi:10.21873/anticanres.13271

66. Jacob JT, Coulombe PA, Kwan R, Omary MB. Types I and II Keratin Intermediate Filaments. Cold Spring Harb Perspect Biol. 2018;10(4). doi:10.1101/cshperspect.a018275

67. Murali R, Wiesner T, Scolyer RA. Tumours associated with BAP1 mutations. Pathology (Phila). 2013;45(2):116-126. doi:10.1097/PAT.0b013e32835d0efb

68. Nishimoto SK, Nishimoto M. Matrix Gla Protein Binds to Fibronectin and Enhances Cell Attachment and Spreading on Fibronectin. International Journal of Cell Biology. doi:https://doi.org/10.1155/2014/807013

69. Pelletier J, Thomas G, Volarević S. Ribosome biogenesis in cancer: new players and therapeutic avenues. Nat Rev Cancer. 2018;18(1):51-63. doi:10.1038/nrc.2017.104

70. Qendro V, Lundgren DH, Rezaul K, et al. Large-Scale Proteomic Characterization of Melanoma Expressed Proteins Reveals Nestin and Vimentin as Biomarkers That Can Potentially Distinguish Melanoma Subtypes. J Proteome Res. 2014;13(11):5031-5040. doi:10.1021/pr5006789

71. Schmidt A, Bekeschus S, von Woedtke T, Hasse S. Cell migration and adhesion of a human melanoma cell line is decreased by cold plasma treatment. Clin Plasma Med. 2015;3(1):24-31. doi:10.1016/j.cpme.2015.05.003

72. Schultz J, Ibrahim SM, Vera J, Kunz M. 14-3-3σ gene silencing during melanoma progression and its role in cell cycle control and cellular senescence. Mol Cancer. 2009;8:53. doi:10.1186/1476-4598-8-53

73. Xia T, Lau K-M, Cheng CK, Chan NC, Ng MHL. Abstract 2498: Over-expression of dual-specificity phosphatase 4 (DUSP4) in multiple myeloma. Cancer Res. 2018;78(13 Supplement):2498. doi:10.1158/1538-7445.AM2018-2498

74. Yang X-Y, Ozawa S, Kato Y, et al. C-X-C Motif Chemokine Ligand 14 is a Unique Multifunctional Regulator of Tumor Progression. Int J Mol Sci. 2019;20(8). doi:10.3390/ijms20081872

75. Yang Y, Tetreault M-P, Yermolina YA, Goldstein BG, Katz JP. Krüppel-like Factor 5 Controls Keratinocyte Migration via the Integrin-linked Kinase. J Biol Chem. 2008;283(27):18812-18820. doi:10.1074/jbc.M801384200

76. Zeeuwen PLJM, Cheng T, Schalkwijk J. The Biology of Cystatin M/E and its Cognate Target Proteases. J Invest Dermatol. 2009;129(6):1327-1338. doi:10.1038/jid.2009.40

77. Zhu R, Li W, Xu Y, Wan J, Zhang Z. Upregulation of BTG1 enhances the radiation sensitivity of human breast cancer in vitro and in vivo. Oncol Rep. 2015;34(6):3017-3024. doi:10.3892/or.2015.4311

78. Matin RN, Chikh A, Law Pak Chong S, et al. p63 is an alternative p53 repressor in melanoma that confers chemoresistance and a poor prognosis. J Exp Med. 2013;210(3):581-603. doi:10.1084/jem.20121439

79. Luo S, Sepehr A, Tsao H. Spitz nevi and other Spitzoid lesions: Part II. Natural History and Management. J Am Acad Dermatol. 2011;65(6):1087-1092. doi:10.1016/j.jaad.2011.06.045

80. Jafry M, Peacock S, Radick A, et al. Pathologists’ Agreement on Treatment Suggestions for Melanocytic Skin Lesions. J Am Acad Dermatol. Published online 2019. doi:10.1016/j.jaad.2019.12.020

81. Di Blasio S, van Wigcheren GF, Becker A, et al. The tumour microenvironment shapes dendritic cell plasticity in a human organotypic melanoma culture. Nat Commun. 2020;11(1):2749. doi:10.1038/s41467-020-16583-0

82. Pruessmann W, Rytlewski J, Wilmott J, et al. Molecular analysis of primary melanoma T cells identifies patients at risk for metastatic recurrence. Nat Cancer. 2020;1(2):197-209. doi:10.1038/s43018-019-0019-5

83. Lilyquist J, White KAM, Lee RJ, Philips GK, Hughes CR, Torres SM. Quantitative Analysis of Immunohistochemistry in Melanoma Tumors. Medicine (Baltimore). 2017;96(15). doi:10.1097/MD.0000000000006432

84. Field MG, Decatur CL, Kurtenbach S, et al. PRAME as an independent biomarker for metastasis in uveal melanoma. Clin Cancer Res. 2016;22(5):1234-1242. doi:10.1158/1078-0432.CCR-15-2071

85. Clarke LE, Mabey B, Flake II DD, et al. Clinical validity of a gene expression signature in diagnostically uncertain neoplasms. Pers Med. Published online June 17, 2020:pme-2020-0048. doi:10.2217/pme-2020-0048

86. Bevona C, Goggins W, Quinn T, Fullerton J, Tsao H. Cutaneous Melanomas Associated With Nevi. Arch Dermatol. 2003;139(12):1620-1624. doi:10.1001/archderm.139.12.1620

87. 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. Published online April 2020:1. doi:10.1097/PAS.0000000000001492

88. Reimann JDR, Salim S, Velazquez EF, et al. Comparison of melanoma gene expression score with histopathology, fluorescence in situ hybridization, and SNP array for the classification of melanocytic neoplasms. Mod Pathol Off J U S Can Acad Pathol Inc. 2018;31(11):1733-1743. doi:10.1038/s41379-018-0087-6

89. Gerami P, Cook RW, Russell MC, et al. Gene expression profiling for molecular staging of cutaneous melanoma in patients undergoing sentinel lymph node biopsy. J Am Acad Dermatol. 2015;72(5):780-785.e3. doi:10.1016/j.jaad.2015.01.009

90. Gerami P, Cook RW, Wilkinson J, et al. Development of a prognostic genetic signature to predict the metastatic risk associated with cutaneous melanoma. Clin Cancer Res Off J Am Assoc Cancer Res. 2015;21(1):175-183. doi:10.1158/1078-0432.CCR-13-3316

91. Vetto JT, Monzon FA, Cook RW, Johnson C, Covington KR, Leachman S. Clinical utility of a 31-gene expression profile test to determine eligibility for sentinel lymph node biopsy in melanoma patients >65 years of age. In: ; 2018.

92. Swetter SM, Thompson JA, Coit DG, et al. NCCN Clinical Practice Guidelines in Oncology. Cutaneous Melanoma. Version 3.2020. Published online May 18, 2020.

93. Cockerell C, Tschen J, Billings SD, et al. The influence of a gene-expression signature on the treatment of diagnostically challenging melanocytic lesions. Pers Med. 2017;14(2):123-130. doi:10.2217/pme-2016-0097

94. Cockerell CJ, Tschen J, Evans B, et al. The influence of a gene expression signature on the diagnosis and recommended treatment of melanocytic tumors by dermatopathologists: Medicine (Baltimore). 2016;95(40):e4887. doi:10.1097/MD.0000000000004887

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