Skip to main content
SpringerLink
Log in

The Laboratory Evaluation of Melanoma

  • Chapter
  • First Online:
Practical Manual for Dermatologic and Surgical Melanoma Management

  • 395 Accesses

Abstract

The laboratory evaluation of cutaneous melanoma is dependent upon the accuracy and complete evaluation of the primary tumor by an experienced histopathologist. The current state of the art for any given melanoma diagnosis always involves examination of formalin fixed paraffin embedded tissue by hematoxylin and eosin (H&E) staining. This chapter will also discuss additional tests which may be helpful in the difficult cases where H&E may not be sufficient. There are several additional laboratory tests in various stages of development and adoption in clinical practice such as immunohistochemistry (IHC) and molecular assays. In the cases of testing for somatic mutations in the tumor, these assays may be performed upon both tissue samples along with peripheral blood for comparison. This additional information provides the treating physicians with additional prognostic data and helps to guide therapeutic options for the patient. By defining each melanoma with a unique histopathologic and molecular profile, the laboratory is at the forefront of bringing the management of melanoma closer to the goal of personalized medicine.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Brenn T. Melanocytic lesions—staying out of trouble. Ann Diagn Pathol. 2018;37:91–102.

    Article  PubMed  Google Scholar 

  2. Plaza JA, Torres-Cabala C, Evans H, Diwan HA, Suster S, Prieto VG. Cutaneous metastases of malignant melanoma: a clinicopathologic study of 192 cases with emphasis on the morphologic spectrum. Am J Dermatopathol. 2010;32:129–36.

    Article  PubMed  Google Scholar 

  3. Elder DE, Piepkorn MW, Barnhill RL, et al. Pathologist characteristics associated with accuracy and reproducibility of melanocytic skin lesion interpretation. J Am Acad Dermatol. 2018;79:52–59.e5.

    Article  PubMed  PubMed Central  Google Scholar 

  4. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Clark WH Jr, From L, Bernardino EA, Mihm MC. The histogenesis and biologic behavior of primary human malignant melanomas of the skin. Cancer Res. 1969;29:705–27.

    PubMed  Google Scholar 

  6. Elmore JG, Elder DE, Barnhill RL, et al. Concordance and reproducibility of melanoma staging according to the 7th vs 8th edition of the AJCC Cancer Staging Manual. JAMA Netw Open. 2018;1:e180083. https://doi.org/10.1001/jamanetworkopen.2018.0083.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Lindsey KG, Ingram C, Bergeron J, Yang J. Cytological diagnosis of metastatic malignant melanoma by fine-needle aspiration biopsy. Semin Diagn Pathol. 2016;33:198–203.

    Article  PubMed  Google Scholar 

  8. Cota C, Saggini A, Lora V, Kutzner H, Rütten A, Sangüeza O, Requena L, Cerroni L. Uncommon histopathological variants of malignant melanoma: part 1. Am J Dermatopathol. 2019;41:243–63.

    Article  PubMed  Google Scholar 

  9. Saggini A, Cota C, Lora V, Kutzner H, Rütten A, Sangüeza O, Requena L, Cerroni L. Uncommon histopathological variants of malignant melanoma. Part 2. Am J Dermatopathol. 2019;41:321–42.

    Article  PubMed  Google Scholar 

  10. Requena C, Botella R, Nagore E, Sanmartín O, Llombart B, Serra-Guillén C, Guillén C, Requena L, Traves V. Characteristics of spitzoid melanoma and clues for differential diagnosis with spitz nevus. Am J Dermatopathol. 2012;34:478–86.

    Article  PubMed  Google Scholar 

  11. Smoller BR. Histologic criteria for diagnosing primary cutaneous malignant melanoma. Mod Pathol. 2006;19(Suppl 2):S34–40.

    Article  PubMed  Google Scholar 

  12. Bsirini C, Smoller BR. Histologic mimics of malignant melanoma. Singapore Med J. 2018;59:602–7.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Cho-Vega JH. A diagnostic algorithm for atypical spitzoid tumors: guidelines for immunohistochemical and molecular assessment. Mod Pathol. 2016;29:656–70.

    Article  PubMed  Google Scholar 

  14. Chung J-Y, Choi J, Sears JD, Ylaya K, Perry C, Choi CH, Hong S-M, Cho H, Brown KM, Hewitt SM. A melanin-bleaching methodology for molecular and histopathological analysis of formalin-fixed paraffin-embedded tissue. Lab Investig. 2016;96:1116–27.

    Article  CAS  PubMed  Google Scholar 

  15. Ohsie SJ, Sarantopoulos GP, Cochran AJ, Binder SW. Immunohistochemical characteristics of melanoma. J Cutan Pathol. 2008;35:433–44.

    Article  PubMed  Google Scholar 

  16. Xiong T-F, Pan F-Q, Li D. Expression and clinical significance of S100 family genes in patients with melanoma. Melanoma Res. 2019;29:23–9.

    Article  CAS  PubMed  Google Scholar 

  17. Coulie PG, Brichard V, Van Pel A, et al. A new gene coding for a differentiation antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. J Exp Med. 1994;180:35–42.

    Article  CAS  PubMed  Google Scholar 

  18. Kawakami Y, Eliyahu S, Delgado CH, Robbins PF, Rivoltini L, Topalian SL, Miki T, Rosenberg SA. Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor. Proc Natl Acad Sci U S A. 1994;91:3515–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Gown AM, Vogel AM, Hoak D, Gough F, McNutt MA. Monoclonal antibodies specific for melanocytic tumors distinguish subpopulations of melanocytes. Am J Pathol. 1986;123:195–203.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Kapur RP, Bigler SA, Skelly M, Gown AM. Anti-melanoma monoclonal antibody HMB45 identifies an oncofetal glycoconjugate associated with immature melanosomes. J Histochem Cytochem. 1992;40:207–12.

    Article  CAS  PubMed  Google Scholar 

  21. Willis BC, Johnson G, Wang J, Cohen C. SOX10: a useful marker for identifying metastatic melanoma in sentinel lymph nodes. Appl Immunohistochem Mol Morphol. 2015;23:109–12.

    Article  CAS  PubMed  Google Scholar 

  22. Mu EW, Quatrano NA, Yagerman SE, Ratner D, Meehan SA. Evaluation of MITF, SOX10, MART-1, and R21 immunostaining for the diagnosis of residual melanoma in situ on chronically sun-damaged skin. Dermatol Surg. 2018;44:933–8.

    Article  CAS  PubMed  Google Scholar 

  23. Kim J, Taube JM, McCalmont TH, Glusac EJ. Quantitative comparison of MiTF, Melan-A, HMB-45 and Mel-5 in solar lentigines and melanoma in situ. J Cutan Pathol. 2011;38:775–9.

    Article  PubMed  Google Scholar 

  24. Plaza JA, Bonneau P, Prieto V, et al. Desmoplastic melanoma: an updated immunohistochemical analysis of 40 cases with a proposal for an additional panel of stains for diagnosis. J Cutan Pathol. 2016;43:313–23.

    Article  PubMed  Google Scholar 

  25. Behrens EL, Boothe W, D’silva N, Walterscheid B, Watkins P, Tarbox M. SOX-10 staining in dermal scars. J Cutan Pathol. 2019;46:579–85. https://doi.org/10.1111/cup.13468.

    Article  PubMed  Google Scholar 

  26. Shidham VB, Qi D, Nagarjun Rao R, Acker SM, Chang C-C, Kampalath B, Dawson G, Machhi JK, Komorowski RA. Improved immunohistochemical evaluation of micrometastases in sentinel lymph nodes of cutaneous melanoma with “MCW Melanoma Cocktail”—a mixture of monoclonal antibodies to MART-1, melan-A, and tyrosinase. BMC Cancer. 2003;3:15. https://doi.org/10.1186/1471-2407-3-15.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Busam KJ, Iversen K, Coplan KC, Jungbluth AA. Analysis of microphthalmia transcription factor expression in normal tissues and tumors, and comparison of its expression with S-100 protein, gp100, and tyrosinase in desmoplastic malignant melanoma. Am J Surg Pathol. 2001;25:197–204.

    Article  CAS  PubMed  Google Scholar 

  28. Hofbauer GF, Kamarashev J, Geertsen R, Böni R, Dummer R. Tyrosinase immunoreactivity in formalin-fixed, paraffin-embedded primary and metastatic melanoma: frequency and distribution. J Cutan Pathol. 1998;25:204–9.

    Article  CAS  PubMed  Google Scholar 

  29. Carbone M, Yang H, Pass HI, Krausz T, Testa JR, Gaudino G. BAP1 and cancer. Nat Rev Cancer. 2013;13:153–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Shah AA, Bourne TD, Murali R. BAP1 protein loss by immunohistochemistry: a potentially useful tool for prognostic prediction in patients with uveal melanoma. Pathology. 2013;45:651–6.

    Article  CAS  PubMed  Google Scholar 

  31. March J, Hand M, Truong A, Grossman D. Practical application of new technologies for melanoma diagnosis: part II. Molecular approaches. J Am Acad Dermatol. 2015;72:943–58; quiz 959–60.

    Article  PubMed  Google Scholar 

  32. Mason A, Wititsuwannakul J, Klump VR, Lott J, Lazova R. Expression of p16 alone does not differentiate between Spitz nevi and Spitzoid melanoma. J Cutan Pathol. 2012;39:1062–74.

    Article  PubMed  Google Scholar 

  33. Wiedemeyer K, Guadagno A, Davey J, Brenn T. Acral Spitz nevi. Am J Surg Pathol. 2018;42:821–7.

    Article  PubMed  Google Scholar 

  34. Koh SS, Roehmholdt BF, Cassarino DS. Immunohistochemistry of p16 in nevi of pregnancy and nevoid melanomas. J Cutan Pathol. 2018;45:891–6.

    Article  PubMed  Google Scholar 

  35. Henrique R, Azevedo R, Bento MJ, Domingues JC, Silva C, Jerónimo C. Prognostic value of Ki-67 expression in localized cutaneous malignant melanoma. J Am Acad Dermatol. 2000;43:991–1000.

    Article  CAS  PubMed  Google Scholar 

  36. Straume O, Sviland L, Akslen LA. Loss of nuclear p16 protein expression correlates with increased tumor cell proliferation (Ki-67) and poor prognosis in patients with vertical growth phase melanoma. Clin Cancer Res. 2000;6:1845–53.

    CAS  PubMed  Google Scholar 

  37. Shtivelman E, Davies MA, Hwu P, Yang J, Lotem M, Oren M, Flaherty KT, Fisher DE. Pathways and therapeutic targets in melanoma. Oncotarget. 2014;5:1701–52. https://doi.org/10.18632/oncotarget.1892.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Lin WM, Fisher DE. Signaling and immune regulation in melanoma development and responses to therapy. Annu Rev Pathol. 2017;12:75–102.

    Article  CAS  PubMed  Google Scholar 

  39. Kitano S, Nakayama T, Yamashita M. Biomarkers for immune checkpoint inhibitors in melanoma. Front Oncol. 2018;8:270. https://doi.org/10.3389/fonc.2018.00270.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Helgadottir H, Rocha Trocoli Drakensjö I, Girnita A. Personalized medicine in malignant melanoma: towards patient tailored treatment. Front Oncol. 2018;8:202.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Mackiewicz J, Mackiewicz A. BRAF and MEK inhibitors in the era of immunotherapy in melanoma patients. Contemp Oncol. 2018;22:68–72.

    Google Scholar 

  42. Spathis A, Katoulis A, Damaskou V, et al. BRAF mutation status in primary, recurrent, and metastatic malignant melanoma and its relation to histopathological parameters. Dermatol Pract Concept. 2019;9:54–62. https://doi.org/10.5826/dpc.0901a13.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Thomas NE. BRAF somatic mutations in malignant melanoma and melanocytic naevi. Melanoma Res. 2006;16:97–103.

    Article  CAS  PubMed  Google Scholar 

  44. Grimaldi AM, Simeone E, Festino L, Vanella V, Strudel M, Ascierto PA. MEK inhibitors in the treatment of metastatic melanoma and solid tumors. Am J Clin Dermatol. 2017;18:745–54.

    Article  PubMed  Google Scholar 

  45. Pasquali S, Hadjinicolaou AV, Chiarion Sileni V, Rossi CR, Mocellin S. Systemic treatments for metastatic cutaneous melanoma. Cochrane Database Syst Rev. 2018;2:CD011123.

    PubMed  Google Scholar 

  46. Long GV, Stroyakovskiy D, Gogas H, et al. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med. 2014;371:1877–88.

    Article  PubMed  CAS  Google Scholar 

  47. Anwar MAF, Murad F, Dawson E, Abd Elmageed ZY, Tsumagari K, Kandil E. 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. 2016;203:407–15.

    Article  CAS  PubMed  Google Scholar 

  48. O’Brien O, Lyons T, Murphy S, Feeley L, Power D, Cynthia CB. BRAF V600 mutation detection in melanoma: a comparison of two laboratory testing methods. J Clin Pathol. 2017;70:935–40.

    Article  PubMed  CAS  Google Scholar 

  49. Zhu M-L, Zhou L, Sadri N. Comparison of targeted next generation sequencing (NGS) versus isolated BRAF V600E analysis in patients with metastatic melanoma. Virchows Arch. 2018;473:371–7.

    Article  CAS  PubMed  Google Scholar 

  50. Kiuru M, Tartar DM, Qi L, Chen D, Yu L, Konia T, McPherson JD, Murphy WJ, Fung MA. Improving classification of melanocytic nevi: association of BRAF V600E expression with distinct histomorphologic features. J Am Acad Dermatol. 2018;79:221–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Ardakani NM. Dysplastic/Clark naevus in the era of molecular pathology. Australas J Dermatol. 2019. https://doi.org/10.1111/ajd.13019

  52. Meng D, Carvajal RD. KIT as an oncogenic driver in melanoma: an update on clinical development. Am J Clin Dermatol. 2019;20:315–23. https://doi.org/10.1007/s40257-018-0414-1.

    Article  PubMed  Google Scholar 

  53. Torres-Cabala CA, Wang W-L, Trent J, et al. Correlation between KIT expression and KIT mutation in melanoma: a study of 173 cases with emphasis on the acral-lentiginous/mucosal type. Mod Pathol. 2009;22:1446–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Syn NL, Teng MWL, Mok TSK, Soo RA. De-novo and acquired resistance to immune checkpoint targeting. Lancet Oncol. 2017;18:e731–41.

    Article  PubMed  Google Scholar 

  55. Buder-Bakhaya K, Hassel JC. Biomarkers for clinical benefit of immune checkpoint inhibitor treatment—a review from the melanoma perspective and beyond. Front Immunol. 2018;9:1474.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Meng X, Huang Z, Teng F, Xing L, Yu J. Predictive biomarkers in PD-1/PD-L1 checkpoint blockade immunotherapy. Cancer Treat Rev. 2015;41:868–76.

    Article  CAS  PubMed  Google Scholar 

  57. Tsao MS, Kerr KM, Kockx M, et al. PD-L1 immunohistochemistry comparability study in real-life clinical samples: results of blueprint phase 2 project. J Thorac Oncol. 2018;13:1302–11.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Conroy JM, Pabla S, Nesline MK, et al. Next generation sequencing of PD-L1 for predicting response to immune checkpoint inhibitors. J Immunother Cancer. 2019;7:18.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Yélamos O, Gerami P. Predicting the outcome of melanoma: can we tell the future of a patient’s melanoma? Melanoma Manag. 2015;2:217–24.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Weiss MM, Hermsen MA, Meijer GA, van Grieken NC, Baak JP, Kuipers EJ, van Diest PJ. Comparative genomic hybridisation. Mol Pathol. 1999;52:243–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Wang L, Rao M, Fang Y, Hameed M, Viale A, Busam K, Jhanwar SC. A genome-wide high-resolution array-CGH analysis of cutaneous melanoma and comparison of array-CGH to FISH in diagnostic evaluation. J Mol Diagn. 2013;15:581–91.

    Article  CAS  PubMed  Google Scholar 

  62. Gaiser T, Kutzner H, Palmedo G, Siegelin MD, Wiesner T, Bruckner T, Hartschuh W, Enk AH, Becker MR. Classifying ambiguous melanocytic lesions with FISH and correlation with clinical long-term follow up. Mod Pathol. 2010;23:413–9.

    Article  CAS  PubMed  Google Scholar 

  63. Lyu G-Y, Yeh Y-H, Yeh Y-C, Wang Y-C. Mutation load estimation model as a predictor of the response to cancer immunotherapy. npj Genomic Med. 2018;3:12. https://doi.org/10.1038/s41525-018-0051-x.

    Article  CAS  Google Scholar 

  64. Gerami P, Li G, Pouryazdanparast P, Blondin B, Beilfuss B, Slenk C, Du J, Guitart J, Jewell S, Pestova K. A highly specific and discriminatory FISH assay for distinguishing between benign and malignant melanocytic neoplasms. Am J Surg Pathol. 2012;36:808–17.

    Article  PubMed  Google Scholar 

  65. Gammon B, Beilfuss B, Guitart J, Gerami P. Enhanced detection of spitzoid melanomas using fluorescence in situ hybridization with 9p21 as an adjunctive probe. Am J Surg Pathol. 2012;36:81–8.

    Article  PubMed  Google Scholar 

  66. Gerami P, Beilfuss B, Haghighat Z, Fang Y, Jhanwar S, Busam KJ. Fluorescence in situ hybridization as an ancillary method for the distinction of desmoplastic melanomas from sclerosing melanocytic nevi. J Cutan Pathol. 2011;38:329–34.

    Article  PubMed  Google Scholar 

  67. Gerami P, Scolyer RA, Xu X, et al. Risk assessment for atypical spitzoid melanocytic neoplasms using FISH to identify chromosomal copy number aberrations. Am J Surg Pathol. 2013;37:676–84.

    Article  PubMed  Google Scholar 

  68. Coit DG, Thompson JA, Albertini MR, et al. Cutaneous melanoma, version 2.2019, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw. 2019;17:367–402.

    Article  Google Scholar 

  69. Verver D, van Klaveren D, van Akkooi ACJ, et al. Risk stratification of sentinel node-positive melanoma patients defines surgical management and adjuvant therapy treatment considerations. Eur J Cancer. 2018;96:25–33.

    Article  PubMed  Google Scholar 

  70. Verver D, Louwman WJ, Koljenović S, Verhoef C, Grünhagen DJ, van Akkooi ACJ. Improved stratification of pT1 melanoma according to the 8th American Joint Committee on Cancer staging edition criteria: a Dutch population-based study. Eur J Cancer. 2018;92:100–7.

    Article  CAS  PubMed  Google Scholar 

  71. Vetto JT, Hsueh EC, Gastman BR, et al. Guidance of sentinel lymph node biopsy decisions in patients with T1–T2 melanoma using gene expression profiling. Future Oncol. 2019;15:1207–17. https://doi.org/10.2217/fon-2018-0912.

    Article  CAS  PubMed  Google Scholar 

  72. Clarke LE, Warf MB, Flake DD 2nd, et al. Clinical validation of a gene expression signature that differentiates benign nevi from malignant melanoma. J Cutan Pathol. 2015;42:244–52.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Clarke LE, Flake DD 2nd, Busam K, et al. An independent validation of a gene expression signature to differentiate malignant melanoma from benign melanocytic nevi. Cancer. 2017;123:617–28.

    Article  CAS  PubMed  Google Scholar 

  74. 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. 2015;21:175–83.

    Article  CAS  PubMed  Google Scholar 

  75. Greenhaw BN, Zitelli JA, Brodland DG. Estimation of prognosis in invasive cutaneous melanoma: an independent study of the accuracy of a gene expression profile test. Dermatol Surg. 2018;44:1494–500.

    Article  CAS  PubMed  Google Scholar 

  76. Hsueh EC, DeBloom JR, Lee J, Sussman JJ, Covington KR, Middlebrook B, Johnson C, Cook RW, Slingluff CL, McMasters KM. Interim analysis of survival in a prospective, multi-center registry cohort of cutaneous melanoma tested with a prognostic 31-gene expression profile test. J Hematol Oncol. 2017;10:152. https://doi.org/10.1186/s13045-017-0520-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Gastman BR, Gerami P, Kurley SJ, Cook RW, Leachman S, Vetto JT. Identification of patients at risk of metastasis using a prognostic 31-gene expression profile in subpopulations of melanoma patients with favorable outcomes by standard criteria. J Am Acad Dermatol. 2019;80:149–157.e4.

    Article  CAS  PubMed  Google Scholar 

  78. Keller J, Schwartz TL, Lizalek JM, Chang E-S, Patel AD, Hurley MY, Hsueh EC. Prospective validation of the prognostic 31-gene expression profiling test in primary cutaneous melanoma. Cancer Med. 2019;8:2205–12. https://doi.org/10.1002/cam4.2128.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Zager JS, Gastman BR, Leachman S, et al. Performance of a prognostic 31-gene expression profile in an independent cohort of 523 cutaneous melanoma patients. BMC Cancer. 2018;18:130. https://doi.org/10.1186/s12885-018-4016-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Gerami P, Yao Z, Polsky D, Jansen B, Busam K, Ho J, Martini M, Ferris LK. Development and validation of a noninvasive 2-gene molecular assay for cutaneous melanoma. J Am Acad Dermatol. 2017;76:114–120.e2.

    Article  CAS  PubMed  Google Scholar 

  81. Reimann JDR, Salim S, Velazquez EF, Wang L, Williams KM, Flejter WL, Brooke L, Sunder S, Busam KJ. Comparison of melanoma gene expression score with histopathology, fluorescence in situ hybridization, and SNP array for the classification of melanocytic neoplasms. Mod Pathol. 2018;31:1733–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. 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;29:832–43.

    Article  CAS  PubMed  Google Scholar 

  83. Swetter SM, Tsao H, Bichakjian CK, et al. Guidelines of care for the management of primary cutaneous melanoma. J Am Acad Dermatol. 2019;80:208–50.

    Article  PubMed  Google Scholar 

  84. Rowe SP, Luber B, Makell M, et al. From validity to clinical utility: the influence of circulating tumor DNA on melanoma patient management in a real-world setting. Mol Oncol. 2018;12:1661–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Gaiser MR, von Bubnoff N, Gebhardt C, Utikal JS. Liquid biopsy to monitor melanoma patients. J Dtsch Dermatol Ges. 2018;16:405–14.

    PubMed  Google Scholar 

  86. Lim SY, Lee JH, Diefenbach RJ, Kefford RF, Rizos H. Liquid biomarkers in melanoma: detection and discovery. Mol Cancer. 2018;17:8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  87. Lim SY, Lee JH, Welsh SJ, et al. Evaluation of two high-throughput proteomic technologies for plasma biomarker discovery in immunotherapy-treated melanoma patients. Biomark Res. 2017;5:32. https://doi.org/10.1186/s40364-017-0112-9.

    Article  PubMed  PubMed Central  Google Scholar 

  88. Cheng F, Su L, Qian C. Circulating tumor DNA: a promising biomarker in the liquid biopsy of cancer. Oncotarget. 2016;7:48832–41.

    PubMed  PubMed Central  Google Scholar 

  89. Pantel K, Speicher MR. The biology of circulating tumor cells. Oncogene. 2016;35:1216–24.

    Article  CAS  PubMed  Google Scholar 

  90. Mumford BS, Robertson GP. Circulating melanoma cells in the diagnosis and monitoring of melanoma: an appraisal of clinical potential. Mol Diagn Ther. 2014;18:175–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Sorber L, Zwaenepoel K, Deschoolmeester V, Roeyen G, Lardon F, Rolfo C, Pauwels P. A comparison of cell-free DNA isolation kits: isolation and quantification of cell-free DNA in plasma. J Mol Diagn. 2017;19:162–8.

    Article  CAS  PubMed  Google Scholar 

  92. Lee JH, Long GV, Boyd S, et al. Circulating tumour DNA predicts response to anti-PD1 antibodies in metastatic melanoma. Ann Oncol. 2017;28:1130–6.

    Article  CAS  PubMed  Google Scholar 

  93. Lee RJ, Gremel G, Marshall A, et al. Circulating tumor DNA predicts survival in patients with resected high-risk stage II/III melanoma. Ann Oncol. 2018;29:490–6.

    Article  CAS  PubMed  Google Scholar 

  94. Lee JH, Saw RP, Thompson JF, et al. Pre-operative ctDNA predicts survival in high-risk stage III cutaneous melanoma patients. Ann Oncol. 2019;30:815–22. https://doi.org/10.1093/annonc/mdz075.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Herbst RS, Soria J-C, Kowanetz M, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014;515:563–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Huang AC, Postow MA, Orlowski RJ, et al. T-cell invigoration to tumour burden ratio associated with anti-PD-1 response. Nature. 2017;545:60–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Weide B, Martens A, Hassel JC, et al. Baseline biomarkers for outcome of melanoma patients treated with Pembrolizumab. Clin Cancer Res. 2016;22:5487–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Shi T, Gao G, Cao Y. Long noncoding RNAs as novel biomarkers have a promising future in Cancer diagnostics. Dis Markers. 2016;2016:9085195.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Fattore L, Costantini S, Malpicci D, Ruggiero CF, Ascierto PA, Croce CM, Mancini R, Ciliberto G. MicroRNAs in melanoma development and resistance to target therapy. Oncotarget. 2017;8:22262–78. https://doi.org/10.18632/oncotarget.14763.

    Article  PubMed  PubMed Central  Google Scholar 

  100. Aftab MN, Dinger ME, Perera RJ. The role of microRNAs and long non-coding RNAs in the pathology, diagnosis, and management of melanoma. Arch Biochem Biophys. 2014;563:60–70.

    Article  CAS  PubMed  Google Scholar 

  101. Yu X, Zheng H, Tse G, Chan MT, Wu WK. Long non-coding RNAs in melanoma. Cell Prolif. 2018;51:e12457.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  102. Tian T, Wang J, Zhou X. A review: microRNA detection methods. Org Biomol Chem. 2015;13:2226–38.

    Article  CAS  PubMed  Google Scholar 

  103. Steuer CE, Ramalingam SS. Tumor mutation burden: leading immunotherapy to the era of precision medicine? J Clin Oncol. 2018;36:631–2.

    Article  CAS  PubMed  Google Scholar 

  104. Stowman AM, Hickman AW, Gru AA, Slingluff CL Jr. Histopathologic review of negative sentinel lymph node biopsies in thin melanomas: an argument for the routine use of immunohistochemistry. Melanoma Res. 2017;27:369–76.

    Article  PubMed  Google Scholar 

  105. Borgognoni L, Bellucci F, Urso C, Manneschi G, Gerlini G, Brandani P, Chiarugi C, Gelli R, Giannotti V, Sestini S. Enhancing the prognostic role of melanoma sentinel lymph nodes through microscopic tumour burden characterization: clinical usefulness in patients who do not undergo complete lymph node dissection. Melanoma Res. 2019;29:163–71.

    Article  PubMed  Google Scholar 

  106. Dalton MSR, Gerami P, Kolaitis NA, Charzan S, Werling R, LeBoit PE, Bastian BC. Use of fluorescence in situ hybridization (FISH) to distinguish intranodal nevus from metastatic melanoma. Am J Surg Pathol. 2010;34:231–7.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Gradilone A, Gazzaniga P, Ribuffo D, Bottoni U, Frati L, Aglian AM, Sorvillo V, Piperno A, Scuderi N, Cigna E. Prognostic significance of tyrosinase expression in sentinel lymph node biopsy for ultra-thin, thin, and thick melanomas. Eur Rev Med Pharmacol Sci. 2012;16:1367–76.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Dermatology, Harbor-UCLA Medical Center, Torrance, CA, USA

    Jenna J. Lullo & Paul K. Shitabata

Authors
  1. Jenna J. Lullo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul K. Shitabata
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Division of Dermatology, Department of Medicine, Harbor-UCLA Medical Center, Torrance, CA, USA

    Delphine J. Lee

  2. Cedars-Sinai Medical Center, The Angeles Clinic and Research Institute, Los Angeles, CA, USA

    Mark B. Faries

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Lullo, J.J., Shitabata, P.K. (2021). The Laboratory Evaluation of Melanoma. In: Lee, D., Faries, M. (eds) Practical Manual for Dermatologic and Surgical Melanoma Management. Springer, Cham. https://doi.org/10.1007/978-3-030-27400-9_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-27400-9_3

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-27399-6

  • Online ISBN: 978-3-030-27400-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation