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Melanoma pp 629-650 | Cite as

Molecular Diagnostics in Melanocytic Neoplasia

  • Jeffrey P. NorthEmail author
Reference work entry

Abstract

Ancillary molecular tests have been developed to assist in the diagnosis of histopathologically ambiguous tumors and as prognostic tools in melanoma. These include DNA-based assays such as comparative genomic hybridization (CGH), fluorescent in situ hybridization (FISH), and next generation sequencing, as well as RNA-based tests including gene expression profiling and microRNA analysis. Protein-based techniques such as immunohistochemistry and mass spectrometry are also available, with immunohistochemistry representing the mostly widely available and highly utilized modality in melanoma diagnostic testing. Each type of test has strengths and limitations. Many of them are expensive (>$1000) and require proper resources and expertise to perform. Familiarity with the available testing options combined with knowledge of genetic and histopathologic features of the various types of melanocytic tumors allows for judicious use of molecular testing to increase diagnostic accuracy and provide valuable prognostic information. Molecular tests can also be used to guide treatment decisions in the expanding era of precision medicine where treatment is based on individual tumor characteristics rather than summary clinical trial data.

Keywords

Comparative genomic hybridization CGH Fluorescent in situ hybridization FISH DNA sequencing Gene expression analysis Immunohistochemistry MicroRNA Mass spectrometry 

References

  1. (2015) Genomic classification of cutaneous melanoma. Cell 161(7):1681–1696.  https://doi.org/10.1016/j.cell.2015.05.044CrossRefGoogle Scholar
  2. Ablain J, Xu M, Rothschild H, Jordan RC, Mito JK, Daniels BH, Bell CF et al (2018) Human tumor genomics and zebrafish modeling identify SPRED1 loss as a driver of mucosal melanoma. Science (New York, NY) 362(6418):1055–1060.  https://doi.org/10.1126/science.aau6509CrossRefGoogle Scholar
  3. Alomari AK, Klump V, Neumeister V, Ariyan S, Narayan D, Lazova R (2015) Comparison of the expression of vimentin and actin in Spitz nevi and Spitzoid malignant melanomas. Am J Dermatopathol 37(1):46–51.  https://doi.org/10.1097/DAD.0000000000000147PubMedCrossRefGoogle Scholar
  4. Al-Rohil RN, Curry JL, Torres-Cabala CA, Nagarajan P, Ivan D, Aung PP, Lyons GF, Bassett RL, Prieto VG, Tetzlaff MT (2016) Proliferation indices correlate with diagnosis and metastasis in diagnostically challenging melanocytic tumors. Hum Pathol 53:73–81.  https://doi.org/10.1016/j.humpath.2016.02.019PubMedCrossRefGoogle Scholar
  5. Anwar MAF, Murad F, Dawson E, Abd Elmageed ZY, Tsumagari K, Kandil E (2016) Immunohistochemistry as a reliable method for detection of BRAF-V600E mutation in melanoma: a systematic review and meta-analysis of current published literature. J Surg Res 203(2):407–415.  https://doi.org/10.1016/j.jss.2016.04.029PubMedCrossRefGoogle Scholar
  6. Babapoor S, Wu R, Kozubek J, Auidi D, Grant-Kels JM, Dadras SS (2017) Identification of MicroRNAs associated with invasive and aggressive phenotype in cutaneous melanoma by next-generation sequencing. Lab Investig J Techn Methods Pathol 97(6):636–648.  https://doi.org/10.1038/labinvest.2017.5CrossRefGoogle Scholar
  7. Bastian BC, LeBoit PE, Hamm H, Bröcker E-B, Pinkel D (1998) Chromosomal gains and losses in primary cutaneous melanomas detected by comparative genomic hybridization. Cancer Res 58(10):2170–2175PubMedPubMedCentralGoogle Scholar
  8. Bastian BC, Xiong J, Frieden IJ, Williams ML, Chou P, Busam K, Pinkel D, LeBoit PE (2002) Genetic changes in neoplasms arising in congenital melanocytic nevi: differences between nodular proliferations and melanomas. Am J Pathol 161(4):1163–1169.  https://doi.org/10.1016/S0002-9440(10)64393-3PubMedPubMedCentralCrossRefGoogle Scholar
  9. Busam KJ, Fang Y, Jhanwar SC, Pulitzer MP, Marr B, Abramson DH (2010) Distinction of conjunctival melanocytic nevi from melanomas by fluorescence in situ hybridization. J Cutan Pathol 37(2):196–203.  https://doi.org/10.1111/j.1600-0560.2009.01488.xPubMedCrossRefGoogle Scholar
  10. Busam KJ, Kutzner H, Cerroni L, Wiesner T (2014) Clinical and pathologic findings of Spitz nevi and atypical Spitz tumors with ALK fusions. Am J Surg Pathol 38(7):925–933.  https://doi.org/10.1097/PAS.0000000000000187PubMedPubMedCentralCrossRefGoogle Scholar
  11. Carter MD, Durham AB, Miedema JR, Harms PW, Chan MP, Patel RM, Lowe L et al (2018) Molecular testing of borderline cutaneous melanocytic lesions: SNP array is more sensitive and specific than FISH. Hum Pathol.  https://doi.org/10.1016/j.humpath.2018.12.002PubMedCrossRefPubMedCentralGoogle Scholar
  12. Castillo SA, Pham AK, Barton DT, Lefferts JA, Yan S, Bridge JA, Linos K (2018) A diagnostically-challenging case of melanoma ex blue nevus with comprehensive molecular analysis, including the 23-gene expression signature (myPath melanoma). J Cutan Pathol.  https://doi.org/10.1111/cup.13400PubMedCrossRefPubMedCentralGoogle Scholar
  13. Clarke LE, Warf MB, Flake DD, Hartman A-R, Tahan S, Shea CR, Gerami P et al (2015) Clinical validation of a gene expression signature that differentiates benign nevi from malignant melanoma. J Cutan Pathol 42(4):244–252.  https://doi.org/10.1111/cup.12475PubMedCrossRefPubMedCentralGoogle Scholar
  14. Clarke LE, Flake DD, Busam K, Cockerell C, Helm K, McNiff J, Reed J et al (2017a) An independent validation of a gene expression signature to differentiate malignant melanoma from benign melanocytic nevi. Cancer 123(4):617–628.  https://doi.org/10.1002/cncr.30385PubMedCrossRefPubMedCentralGoogle Scholar
  15. Clarke LE, Pimentel JD, Zalaznick H, Wang L, Busam KJ (2017b) Gene expression signature as an ancillary method in the diagnosis of desmoplastic melanoma. Hum Pathol 70:113–120.  https://doi.org/10.1016/j.humpath.2017.10.005PubMedCrossRefPubMedCentralGoogle Scholar
  16. Costa S, Byrne M, Pissaloux D, Haddad V, Paindavoine S, Thomas L, Aubin F et al (2016) Melanomas associated with blue nevi or mimicking cellular blue nevi: clinical, pathologic, and molecular study of 11 cases displaying a high frequency of GNA11 mutations, BAP1 expression loss, and a predilection for the scalp. Am J Surg Pathol 40(3):368–377.  https://doi.org/10.1097/PAS.0000000000000568PubMedCrossRefPubMedCentralGoogle Scholar
  17. Curtin JA, Fridlyand J, Kageshita T, Patel HN, Busam KJ, Kutzner H, Cho K-H et al (2005) Distinct sets of genetic alterations in melanoma. N Engl J Med 353(20):2135–2147.  https://doi.org/10.1056/NEJMoa050092CrossRefGoogle Scholar
  18. Dalton SR, Gerami P, Kolaitis NA, Charzan S, Werling R, LeBoit PE, Bastian BC (2010) Use of fluorescence in situ hybridization (FISH) to distinguish Intranodal nevus from metastatic melanoma. Am J Surg Pathol 34(2):231–237.  https://doi.org/10.1097/PAS.0b013e3181c805c4PubMedPubMedCentralCrossRefGoogle Scholar
  19. Farmer ER, Gonin R, Hanna MP (1996) Discordance in the histopathologic diagnosis of melanoma and melanocytic nevi between expert pathologists. Hum Pathol 27(6):528–531PubMedCrossRefPubMedCentralGoogle Scholar
  20. Ferris LK, Gerami P, Skelsey MK, Peck G, Hren C, Gorman C, Frumento T, Siegel DM (2018) Real-world performance and utility of a noninvasive gene expression assay to evaluate melanoma risk in pigmented lesions. Melanoma Res 28(5):478–482.  https://doi.org/10.1097/CMR.0000000000000478PubMedGoogle Scholar
  21. Gammon B, Beilfuss B, Guitart J, Busam KJ, Gerami P (2011) Fluorescence in situ hybridization for distinguishing cellular blue nevi from blue nevus-like melanoma. J Cutan Pathol 38(4):335–341.  https://doi.org/10.1111/j.1600-0560.2010.01667.xPubMedGoogle Scholar
  22. Gammon B, Beilfuss B, Guitart J, Gerami P (2012) Enhanced detection of Spitzoid melanomas using fluorescence in situ hybridization with 9p21 as an adjunctive probe. Am J Surg Pathol 36(1):81–88.  https://doi.org/10.1097/PAS.0b013e31822d5ff8PubMedCrossRefGoogle Scholar
  23. Gerami P, Jewell SS, Morrison LE, Blondin B, Schulz J, Ruffalo T, Matushek P et al (2009a) Fluorescence in situ hybridization (FISH) as an ancillary diagnostic tool in the diagnosis of melanoma. Am J Surg Pathol 33(8):1146–1156.  https://doi.org/10.1097/PAS.0b013e3181a1ef36PubMedCrossRefGoogle Scholar
  24. Gerami P, Wass A, Mafee M, Fang Y, Pulitzer MP, Busam KJ (2009b) Fluorescence in situ hybridization for distinguishing nevoid melanomas from mitotically active nevi. Am J Surg Pathol 33(12):1783–1788.  https://doi.org/10.1097/PAS.0b013e3181ba6db6PubMedCrossRefGoogle Scholar
  25. Gerami P, Barnhill RL, Beilfuss BA, LeBoit P, Schneider P, Guitart J (2010) Superficial melanocytic neoplasms with pagetoid melanocytosis: a study of interobserver concordance and correlation with FISH. Am J Surg Pathol 34(6):816–821.  https://doi.org/10.1097/PAS.0b013e3181dd1e72PubMedCrossRefGoogle Scholar
  26. Gerami P, Beilfuss B, Haghighat Z, Fang Y, Jhanwar S, Busam KJ (2011a) Fluorescence in situ hybridization as an ancillary method for the distinction of desmoplastic melanomas from sclerosing melanocytic nevi. J Cutan Pathol 38(4):329–334.  https://doi.org/10.1111/j.1600-0560.2010.01666.xPubMedCrossRefGoogle Scholar
  27. Gerami P, Jewell SS, Pouryazdanparast P, Wayne JD, Haghighat Z, Busam KJ, Rademaker A, Morrison L (2011b) Copy number gains in 11q13 and 8q24 [corrected] are highly linked to prognosis in cutaneous malignant melanoma. J Mol Diagn: JMD 13(3):352–358.  https://doi.org/10.1016/j.jmoldx.2011.01.011PubMedCrossRefGoogle Scholar
  28. Gerami P, Li G, Pouryazdanparast P, Blondin B, Beilfuss B, Slenk C, Jing D, Guitart J, Jewell S, Pestova K (2012) A highly specific and discriminatory FISH assay for distinguishing between benign and malignant melanocytic neoplasms. Am J Surg Pathol 36(6):808–817.  https://doi.org/10.1097/PAS.0b013e31824b1efdPubMedCrossRefGoogle Scholar
  29. Gerami P, Scolyer RA, Xiaowei X, Elder DE, Abraham RM, Fullen D, Prieto VG et al (2013) Risk assessment for atypical spitzoid melanocytic neoplasms using FISH to identify chromosomal copy number aberrations. Am J Surg Pathol 37(5):676–684.  https://doi.org/10.1097/PAS.0b013e3182753de6PubMedCrossRefPubMedCentralGoogle Scholar
  30. Gerami P, Cook RW, Russell MC, Wilkinson J, Amaria RN, Gonzalez R, Lyle S et al (2015) Gene expression profiling for molecular staging of cutaneous melanoma in patients undergoing sentinel lymph node biopsy. J Am Acad Dermatol 72(5):780–785.e3.  https://doi.org/10.1016/j.jaad.2015.01.009PubMedCrossRefPubMedCentralGoogle Scholar
  31. Gerami P, Yao Z, Polsky D, Jansen B, Busam K, Ho J, Martini M, Ferris LK (2017) Development and validation of a noninvasive 2-gene molecular assay for cutaneous melanoma. J Am Acad Dermatol 76(1):114–120.e2.  https://doi.org/10.1016/j.jaad.2016.07.038PubMedCrossRefGoogle Scholar
  32. Gill HS, Char DH (2012) Uveal melanoma prognostication: from lesion size and cell type to molecular class. Can J Ophthalmol 47(3):246–253.  https://doi.org/10.1016/j.jcjo.2012.03.038PubMedCrossRefGoogle Scholar
  33. Griewank KG, Murali R, Puig-Butille JA, Schilling B, Livingstone E, Potrony M, Carrera C et al (2014) TERT promoter mutation status as an independent prognostic factor in cutaneous melanoma. J Natl Cancer Inst 106(9).  https://doi.org/10.1093/jnci/dju246
  34. Grignol V, Fairchild ET, Zimmerer JM, Lesinski GB, Walker MJ, Magro CM, Kacher JE et al (2011) MiR-21 and MiR-155 are associated with mitotic activity and lesion depth of borderline melanocytic lesions. Br J Cancer 105(7):1023–1029.  https://doi.org/10.1038/bjc.2011.288PubMedPubMedCentralCrossRefGoogle Scholar
  35. Hamid O, Robert C, Daud A, Stephen Hodi F, Hwu W-J, Kefford R, Wolchok JD et al (2013) Safety and tumor responses with Lambrolizumab (anti-PD-1) in melanoma. N Engl J Med 369(2):134–144.  https://doi.org/10.1056/NEJMoa1305133PubMedPubMedCentralCrossRefGoogle Scholar
  36. Harbour JW, Onken MD, Roberson EDO, Duan S, Cao L, Worley LA, Council ML, Matatall KA, Helms C, Bowcock AM (2010) Frequent mutation of BAP1 in metastasizing uveal melanomas. Science (New York, NY) 330(6009):1410–1413.  https://doi.org/10.1126/science.1194472CrossRefGoogle Scholar
  37. Harbour JW, Roberson EDO, Anbunathan H, Onken MD, Worley LA, Bowcock AM (2013) Recurrent mutations at codon 625 of the splicing factor SF3B1 in uveal melanoma. Nat Genet 45(2):133–135.  https://doi.org/10.1038/ng.2523PubMedPubMedCentralCrossRefGoogle Scholar
  38. Harms PW, Hocker TL, Zhao L, Chan MP, Andea AA, Wang M, Harms KL et al (2016) Loss of P16 expression and copy number changes of CDKN2A in a spectrum of spitzoid melanocytic lesions. Hum Pathol 58:152–160.  https://doi.org/10.1016/j.humpath.2016.07.029PubMedCrossRefGoogle Scholar
  39. Hayward NK, Wilmott JS, Waddell N, Johansson PA, Field MA, Nones K, Patch A-M et al (2017) Whole-genome landscapes of major melanoma subtypes. Nature 545(7653):175–180.  https://doi.org/10.1038/nature22071PubMedCrossRefGoogle Scholar
  40. Hirsch D, Kemmerling R, Davis S, Camps J, Meltzer PS, Ried T, Gaiser T (2012) Chromothripsis and focal copy number alterations determine poor outcome in malignant melanoma. Cancer Res.  https://doi.org/10.1158/0008-5472.CAN-12-0928PubMedPubMedCentralCrossRefGoogle Scholar
  41. Ladstein RG, Bachmann IM, Straume O, Akslen LA (2010) Ki-67 expression is superior to mitotic count and novel proliferation markers PHH3, MCM4 and Mitosin as a prognostic factor in thick cutaneous melanoma. BMC Cancer 10(April):140.  https://doi.org/10.1186/1471-2407-10-140PubMedPubMedCentralCrossRefGoogle Scholar
  42. Latchana N, Martin Del Campo SE, Grignol VP, Clark JR, Albert SP, Zhang J, Wei L et al (2017) Classification of indeterminate melanocytic lesions by microRNA profiling. Ann Surg Oncol 24(2):347–354.  https://doi.org/10.1245/s10434-016-5476-9PubMedCrossRefGoogle Scholar
  43. Lazova R, Seeley EH, Keenan M, Gueorguieva R, Caprioli RM (2012) Imaging mass spectrometry – a new and promising method to differentiate Spitz nevi from Spitzoid malignant melanomas. Am J Dermatopathol 34(1):82–90.  https://doi.org/10.1097/DAD.0b013e31823df1e2PubMedPubMedCentralCrossRefGoogle Scholar
  44. Lazova R, Seeley EH, Kutzner H, Scolyer RA, Scott G, Cerroni L, Fried I et al (2016) Imaging mass spectrometry assists in the classification of diagnostically challenging atypical Spitzoid neoplasms. J Am Acad Dermatol 75(6):1176–1186.e4.  https://doi.org/10.1016/j.jaad.2016.07.007PubMedPubMedCentralCrossRefGoogle Scholar
  45. Lazova R, Yang Z, El Habr C, Lim Y, Choate KA, Seeley EH, Caprioli RM, Yangqun L (2017) Mass spectrometry imaging can distinguish on a proteomic level between proliferative nodules within a benign congenital nevus and malignant melanoma. Am J Dermatopathol 39(9):689–695.  https://doi.org/10.1097/DAD.0000000000000849PubMedPubMedCentralCrossRefGoogle Scholar
  46. Le Guellec S, Macagno N, Velasco V, Lamant L, Lae M, Filleron T, Malissen N et al (2017) Loss of H3K27 Trimethylation is not suitable for distinguishing malignant peripheral nerve sheath tumor from melanoma: a study of 387 cases including mimicking lesions. Mod Pathol Off J U S Can Acad Pathol Inc 30(12):1677–1687.  https://doi.org/10.1038/modpathol.2017.91Google Scholar
  47. Lee S, Barnhill RL, Dummer R, Dalton J, Jianrong W, Pappo A, Bahrami A (2015a) TERT promoter mutations are predictive of aggressive clinical behavior in patients with Spitzoid melanocytic neoplasms. Sci Rep 5(June):11200.  https://doi.org/10.1038/srep11200PubMedPubMedCentralCrossRefGoogle Scholar
  48. Lee JJ, Granter SR, Laga AC, Saavedra AP, Zhan Q, Guo W, Shuyun X, Murphy GF, Lian CG (2015b) 5-Hydroxymethylcytosine expression in metastatic melanoma versus nodal nevus in sentinel lymph node biopsies. Mod Pathol Off J U S Can Acad Pathol Inc 28(2):218–229.  https://doi.org/10.1038/modpathol.2014.99Google Scholar
  49. Lee JJ, Vilain RE, Granter SR, Hu NR, Bresler SC, Xu S, Frank AH et al (2017) 5-Hydroxymethylcytosine is a nuclear biomarker to assess biological potential in histologically ambiguous heavily pigmented melanocytic neoplasms. J Cutan Pathol 44(3):249–255.  https://doi.org/10.1111/cup.12880PubMedCrossRefGoogle Scholar
  50. Leichsenring J, Stögbauer F, Volckmar A-L, Buchhalter I, Oliveira C, Kirchner M, Fröhling S et al (2018) Genetic profiling of melanoma in routine diagnostics: assay performance and molecular characteristics in a consecutive series of 274 cases. Pathology 50(7):703–710.  https://doi.org/10.1016/j.pathol.2018.08.004PubMedCrossRefGoogle Scholar
  51. Lezcano C, Jungbluth AA, Nehal KS, Hollmann TJ, Busam KJ (2018) PRAME expression in melanocytic tumors. Am J Surg Pathol 42(11):1456–1465.  https://doi.org/10.1097/PAS.0000000000001134PubMedPubMedCentralCrossRefGoogle Scholar
  52. Lian CG, Yufei X, Ceol C, Feizhen W, Larson A, Dresser K, Wenqi X et al (2012) Loss of 5-Hydroxymethylcytosine is an epigenetic Hallmark of melanoma. Cell 150(6):1135–1146.  https://doi.org/10.1016/j.cell.2012.07.033PubMedPubMedCentralCrossRefGoogle Scholar
  53. Long GV, Menzies AM, Nagrial AM, Haydu LE, Hamilton AL, Mann GJ, Hughes TM, Thompson JF, Scolyer RA, Kefford RF (2011) Prognostic and Clinicopathologic associations of oncogenic BRAF in metastatic melanoma. J Clin Oncol Off J Am Soc Clin Oncol 29(10):1239–1246.  https://doi.org/10.1200/JCO.2010.32.4327CrossRefGoogle Scholar
  54. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A et al (2005) MicroRNA expression profiles classify human cancers. Nature 435(7043):834–838.  https://doi.org/10.1038/nature03702PubMedCrossRefPubMedCentralGoogle Scholar
  55. Machan S, Molina-Ruiz AM, Fernández-Aceñero MJ, Encabo B, LeBoit P, Bastian BC, Requena L (2015) Metastatic melanoma in association with a Giant congenital melanocytic nevus in an adult: controversial CGH findings. Am J Dermatopathol 37(6):487–494.  https://doi.org/10.1097/DAD.0000000000000152PubMedCrossRefPubMedCentralGoogle Scholar
  56. Maize JCJ, McCalmont TH, Carlson JA, Busam KJ, Kutzner H, Bastian BC (2005) Genomic analysis of blue nevi and related dermal melanocytic proliferations. Am J Surg Pathol 29(9):1214–1220PubMedCrossRefPubMedCentralGoogle Scholar
  57. Marchetti MA, Bartlett EK, Dusza SW, Bichakjian CK (2018) Use of a prognostic gene expression profile test for T1 cutaneous melanoma: will it help or harm patients? J Am Acad Dermatol.  https://doi.org/10.1016/j.jaad.2018.11.063PubMedCrossRefPubMedCentralGoogle Scholar
  58. Martin M, Maßhöfer L, Temming P, Rahmann S, Metz C, Bornfeld N, van de Nes J et al (2013) Exome sequencing identifies recurrent somatic mutations in EIF1AX and SF3B1 in uveal melanoma with Disomy 3. Nat Genet 45(8):933–936.  https://doi.org/10.1038/ng.2674PubMedPubMedCentralCrossRefGoogle Scholar
  59. Massi D, Simi L, Sensi E, Baroni G, Xue G, Scatena C, Caldarella A et al (2015) Immunohistochemistry is highly sensitive and specific for the detection of NRASQ61R mutation in melanoma. Mod Pathol Off J U S Can Acad Pathol Inc 28(4):487–497.  https://doi.org/10.1038/modpathol.2014.137Google Scholar
  60. Minca EC, Al-Rohil RN, Wang M, Harms PW, Ko JS, Collie AM, Kovalyshyn I et al (2016) Comparison between melanoma gene expression score and fluorescence in situ hybridization for the classification of melanocytic lesions. Mod Pathol Off J U S Can Acad Pathol Inc 29(8):832–843.  https://doi.org/10.1038/modpathol.2016.84Google Scholar
  61. Nagore E, Requena C, Traves V, Guillen C, Hayward NK, Whiteman DC, Hacker E (2014) Prognostic value of BRAF mutations in localized cutaneous melanoma. J Am Acad Dermatol 70(5):858–862.e1-2.  https://doi.org/10.1016/j.jaad.2013.10.064PubMedCrossRefGoogle Scholar
  62. Newman MD, Mirzabeigi M, Gerami P (2009) Chromosomal copy number changes supporting the classification of lentiginous junctional melanoma of the elderly as a subtype of melanoma. Mod Pathol Off J U S Can Acad Pathol Inc 22(9):1258–1262.  https://doi.org/10.1038/modpathol.2009.93Google Scholar
  63. Nielsen PS, Riber-Hansen R, Jensen TO, Schmidt H, Steiniche T (2013) Proliferation indices of Phosphohistone H3 and Ki67: strong prognostic markers in a consecutive cohort with stage I/II melanoma. Mod Pathol Off J U S Can Acad Pathol Inc 26(3):404–413.  https://doi.org/10.1038/modpathol.2012.188Google Scholar
  64. North JP, Kageshita T, Pinkel D, LeBoit PE, Bastian BC (2008) Distribution and significance of occult Intraepidermal tumor cells surrounding primary melanoma. J Invest Dermatol 128(8):2024–2030.  https://doi.org/10.1038/jid.2008.41PubMedPubMedCentralCrossRefGoogle Scholar
  65. North JP, Vetto JT, Murali R, White KP, Jr CRW, Bastian BC (2011) Assessment of copy number status of chromosomes 6 and 11 by FISH provides independent prognostic information in primary melanoma. Am J Surg Pathol 35(8):1146–1150.  https://doi.org/10.1097/PAS.0b013e318222a634PubMedPubMedCentralCrossRefGoogle Scholar
  66. North JP, Yeh I, McCalmont TH, Leboit PE (2012) Melanoma ex blue nevus: two cases resembling large plaque-type blue nevus with subcutaneous cellular nodules. J Cutan Pathol 39(12):1094–1099.  https://doi.org/10.1111/cup.12015PubMedCrossRefGoogle Scholar
  67. North JP, Garrido MC, Kolaitis NA, LeBoit PE, McCalmont TH, Bastian BC (2014) Fluorescence in situ hybridization as an ancillary tool in the diagnosis of ambiguous melanocytic neoplasms. Am J Surg Pathol 38:824–831PubMedCrossRefGoogle Scholar
  68. Raskin L, Ludgate M, Iyer RK, Ackley TE, Bradford CR, Johnson TM, Fullen DR (2011) Copy number variations and clinical outcome in atypical Spitz tumors. Am J Surg Pathol 35(2):243–252.  https://doi.org/10.1097/PAS.0b013e31820393eePubMedCrossRefGoogle Scholar
  69. Reimann JDR, Salim S, Velazquez EF, Wang L, Williams KM, Flejter WL, Brooke L, Sunder S, Busam KJ (2018) 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 31(11):1733–1743.  https://doi.org/10.1038/s41379-018-0087-6Google Scholar
  70. Schaefer I-M, Fletcher CD, Hornick JL (2016) Loss of H3K27 Trimethylation distinguishes malignant peripheral nerve sheath tumors from histologic mimics. Mod Pathol Off J U S Can Acad Pathol Inc 29(1):4–13.  https://doi.org/10.1038/modpathol.2015.134Google Scholar
  71. Shain AH, Yeh I, Kovalyshyn I, Sriharan A, Talevich E, Gagnon A, Dummer R et al (2015) The genetic evolution of melanoma from precursor lesions. N Engl J Med 373(20):1926–1936.  https://doi.org/10.1056/NEJMoa1502583CrossRefPubMedPubMedCentralGoogle Scholar
  72. Shen L, Cooper C, Bajaj S, Liu P, Pestova E, Guitart J, Gerami P (2013) Atypical Spitz tumors with 6q23 deletions: a clinical, histological, and molecular study. Am J Dermatopathol 35(8):804–812.  https://doi.org/10.1097/DAD.0b013e31828671bfPubMedCrossRefGoogle Scholar
  73. Shoo BA, Sagebiel RW, Kashani-Sabet M (2010) Discordance in the histopathologic diagnosis of melanoma at a melanoma referral center. J Am Acad Dermatol 62(5):751–756.  https://doi.org/10.1016/j.jaad.2009.09.043PubMedCrossRefGoogle Scholar
  74. Sisley K, Rennie IG, Parsons MA, Jacques R, Hammond DW, Bell SM, Potter AM, Rees RC (1997) Abnormalities of chromosomes 3 and 8 in posterior uveal melanoma correlate with prognosis. Genes Chromosomes Cancer 19(1):22–28PubMedCrossRefGoogle Scholar
  75. Su J, Yu W, Liu J, Zheng J, Huang S, Wang Y, Qi S, Ma X, Chen J, Zhang Y (2017) Fluorescence in situ hybridisation as an ancillary tool in the diagnosis of acral melanoma: a review of 44 cases. Pathology 49(7):740–749.  https://doi.org/10.1016/j.pathol.2017.08.006PubMedCrossRefGoogle Scholar
  76. Sunshine J, Taube JM (2015) PD-1/PD-L1 inhibitors. Curr Opin Pharmacol 23:32–38.  https://doi.org/10.1016/j.coph.2015.05.011PubMedPubMedCentralCrossRefGoogle Scholar
  77. Topalian SL, Stephen Hodi F, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD et al (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 366(26):2443–2454.  https://doi.org/10.1056/NEJMoa1200690PubMedPubMedCentralCrossRefGoogle Scholar
  78. Tumeh PC, Harview CL, Yearley JH, Peter Shintaku I, Taylor EJM, Robert L, Chmielowski B et al (2014) PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 515(7528):568–571.  https://doi.org/10.1038/nature13954PubMedPubMedCentralCrossRefGoogle Scholar
  79. Uchiyama R, Uhara H, Uchiyama A, Ogawa E, Takazawa Y, Ashida A, Koga H, Hayashi K, Kiniwa Y, Okuyama R (2014) 5-Hydroxymethylcytosine as a useful marker to differentiate between malignant melanomas and benign melanocytic nevi. J Dermatol Sci 73(2):161–163.  https://doi.org/10.1016/j.jdermsci.2013.09.008PubMedCrossRefGoogle Scholar
  80. Van Allen EM, Miao D, Schilling B, Shukla SA, Blank C, Zimmer L, Sucker A et al (2015) Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science (New York, NY) 350(6257):207–211.  https://doi.org/10.1126/science.aad0095CrossRefGoogle Scholar
  81. Vergier B, Prochazkova-Carlotti M, de la Fouchardière A, Cerroni L, Massi D, De Giorgi V, Bailly C et al (2011) Fluorescence in situ hybridization, a diagnostic aid in ambiguous melanocytic tumors: European study of 113 cases. Mod Pathol Off J U S Can Acad Pathol Inc 24(5):613–623.  https://doi.org/10.1038/modpathol.2010.228Google Scholar
  82. Wachsman W, Morhenn V, Palmer T, Walls L, Hata T, Zalla J, Scheinberg R et al (2011) Noninvasive genomic detection of melanoma. Br J Dermatol 164(4):797–806.  https://doi.org/10.1111/j.1365-2133.2011.10239.xPubMedPubMedCentralCrossRefGoogle Scholar
  83. Wiedemeyer K, Guadagno A, Davey J, Brenn T (2018) Acral Spitz nevi: a Clinicopathologic study of 50 cases with Immunohistochemical analysis of P16 and P21 expression. Am J Surg Pathol 42(6):821–827.  https://doi.org/10.1097/PAS.0000000000001051PubMedCrossRefGoogle Scholar
  84. Wiesner T, He J, Yelensky R, Esteve-Puig R, Botton T, Yeh I, Lipson D et al (2014) Kinase fusions are frequent in Spitz Tumours and Spitzoid melanomas. Nat Commun 5(3116).  https://doi.org/10.1038/ncomms4116
  85. Wiesner T, Lee W, Obenauf AC, Ran L, Murali R, Zhang QF, Wong EWP et al (2015) Alternative transcription initiation leads to expression of a novel ALK isoform in Cancer. Nature 526(7573):453–457.  https://doi.org/10.1038/nature15258PubMedPubMedCentralCrossRefGoogle Scholar
  86. Yeh I, Jorgenson E, Shen L, Xu M, North JP, Hunter Shain A, Reuss D et al (2019) Targeted genomic profiling of Acral melanoma. J Natl Cancer Inst.  https://doi.org/10.1093/jnci/djz005
  87. Yélamos O, Arva NC, Obregon R, Yazdan P, Wagner A, Guitart J, Gerami P (2015a) A comparative study of proliferative nodules and lethal melanomas in congenital nevi from children. Am J Surg Pathol 39(3):405–415.  https://doi.org/10.1097/PAS.0000000000000351PubMedCrossRefGoogle Scholar
  88. Yélamos O, Busam KJ, Lee C, Meldi Sholl L, Amin SM, Merkel EA, Obregon R, Guitart J, Gerami P (2015b) Morphologic clues and utility of fluorescence in situ hybridization for the diagnosis of nevoid melanoma. J Cutan Pathol 42(11):796–806.  https://doi.org/10.1111/cup.12627PubMedCrossRefGoogle Scholar
  89. Zager JS, Gastman BR, Leachman S, Gonzalez RC, Fleming MD, Ferris LK, Ho J et al (2018) Performance of a prognostic 31-gene expression profile in an independent cohort of 523 cutaneous melanoma patients. BMC Cancer 18(1):130.  https://doi.org/10.1186/s12885-018-4016-3PubMedPubMedCentralCrossRefGoogle Scholar
  90. Zembowicz A, Yang S-E, Kafanas A, Lyle SR (2012) Correlation between histologic assessment and fluorescence in situ hybridization using MelanoSITE in evaluation of histologically ambiguous melanocytic lesions. Arch Pathol Lab Med 136(12):1571–1579.  https://doi.org/10.5858/arpa.2011-0673-OAPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Departments of Dermatology and PathologyUniversity of CaliforniaSan FranciscoUSA

Section editors and affiliations

  • Keith T. Flaherty
    • 1
  • Boris C. Bastian
    • 2
  • Hensin Tsao
    • 3
    • 4
  • F. Stephen Hodi
    • 5
    • 6
  1. 1.Henri and Belinda Termeer Center for Targeted TherapiesMGH Cancer CenterCambridgeUSA
  2. 2.Departments of Dermatology and Pathology, Helen Diller Family Comprehensive Cancer CenterUniversity of California, San FranciscoSan FranciscoUSA
  3. 3.AuburndaleUSA
  4. 4.Harvard-MIT Health Sciences and TechnologyCambridgeUSA
  5. 5.FraminghamUSA
  6. 6.Department of Medicine, Brigham and Women's HospitalDana-Farber Cancer InstituteBostonUSA

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