Melanoma pp 193-212 | Cite as

The Pathology of Melanoma

  • Jane L. MessinaEmail author
  • Rahel A. John


Recent advances in techniques for pathologic evaluation of tumor tissue, updates in staging, and improvements in prognostication have brought pathologists to the forefront of the care of the melanoma patient. Specimen procurement, handling, and evaluation are all key to the production of a pathology report that guides the clinician to the proper treatment of the patient. This chapter summarizes the recent, relevant changes in the pathologic analysis of melanoma, highlighting the AJCC 8th edition guidelines, definitions of micrometastases, and staging of melanoma with an unknown primary. A discussion of the biomarkers often analyzed for prediction of response to targeted therapy is included, as well as a brief review of recently developed, commercially available molecular diagnostic techniques for evaluation of diagnostically challenging melanocytic lesions.


Melanoma pathology Immunohistochemistry Fluorescence in situ hybridization Sentinel node pathology Histologic subtype 


  1. 1.
    Ng PC, Barzilai DA, Ismail SA, Averitte RL Jr, Gilliam AC. Evaluating invasive cutaneous melanoma: is the initial biopsy representative of the final depth? J Am Acad Dermatol. 2003;48(3):420–4.PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Riker AI, Glass F, Perez I, Cruse CW, Messina J, Sondak VK. Cutaneous melanoma: methods of biopsy and definitive surgical excision. Dermatol Ther. 2005;18(5):387–93.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR, Buzaid AC, Cochran AJ, Coit DG, Ding S, Eggermont AM, Flaherty KT, Gimotty PA, Kirkwood JM, McMasters KM, Mihm MC Jr, Morton DL, Ross MI, Sober AJ, Sondak VK. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol. 2009;27(36):6199–206.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Ng JC, Swain S, Dowling JP, Wolfe R, Simpson P, Kelly JW. The impact of partial biopsy on histopathologic diagnosis of cutaneous melanoma: experience of an Australian tertiary referral service. Arch Dermatol. 2010;146(3):234–9.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Chen SC, Bravata DM, Weil E, Olkin I. A comparison of dermatologists’ and primary care physicians’ accuracy in diagnosing melanoma: a systematic review. Arch Dermatol. 2001;137(12):1627–34.PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Lederman JS, Sober AJ. Does wide excision as the initial diagnostic procedure improve prognosis in patients with cutaneous melanoma? J Dermatol Surg Oncol. 1986;12(7):697–9.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Lorusso GD, Sarma DP, Sarwar SF. Punch biopsies of melanoma: a diagnostic peril. Dermatol Online J. 2005;11(1):7.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Karimipour DJ, Schwartz JL, Wang TS, Bichakjian CK, Orringer JS, King AL, Huang CC, Johnson TM. Microstaging accuracy after subtotal incisional biopsy of cutaneous melanoma. J Am Acad Dermatol. 2005;52(5):798–802.PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Roses DF, Ackerman AB, Harris MN, Weinhouse GR, Gumport SL. Assessment of biopsy techniques and histopathologic interpretations of primary cutaneous malignant melanoma. Ann Surg. 1979;189(3):294–7.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Criscione VD, Weinstock MA. Melanoma thickness trends in the United States, 1988–2006. J Invest Dermatol. 2010;130(3):793–7.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Network, N. C. C. NCCN clinical practice guidelines in oncology for melanoma (Version I.2017); 2016.Google Scholar
  12. 12.
    Zager JS, Hochwald SN, Marzban SS, Francois R, Law KM, Davis AH, Messina JL, Vincek V, Mitchell C, Church A, Copeland EM, Sondak VK, Grobmyer SR. Shave biopsy is a safe and accurate method for the initial evaluation of melanoma. J Am Coll Surg. 2011;212(4):454–60. discussion 460-452PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Fallowfield ME, Cook MG. Re-excisions of scar in primary cutaneous melanoma: a histopathological study. Br J Dermatol. 1992;126(1):47–51.PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Martin HM, Birkin AJ, Theaker JM. Malignant melanoma re-excision specimens--how many blocks? Histopathology. 1998;32(4):362–7.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Walters RF, Groben PA, Busam K, Millikan RC, Rabinovitz H, Cognetta A, Mihm MC Jr, Prieto VG, Googe PB, King R, Moore DT, Woosley J, Thomas NE. Consumption of the epidermis: a criterion in the differential diagnosis of melanoma and dysplastic nevi that is associated with increasing breslow depth and ulceration. Am J Dermatopathol. 2007;29(6):527–33.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Petronic-Rosic V, Shea CR, Krausz T. Pagetoid melanocytosis: when is it significant? Pathology. 2004;36(5):435–44.PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Huwait H, Hijazi N, Martinka M, Crawford RI. The significance of Melan-A-positive pagetoid melanocytosis in dysplastic nevi. Am J Dermatopathol. 2014;36(4):340–3.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Gerami P, Busam K, Cochran A, Cook MG, Duncan LM, Elder DE, Fullen DR, Guitart J, LeBoit PE, Mihm MC Jr, Prieto VG, Rabkin MS, Scolyer RA, Xu X, Yun SJ, Obregon R, Yazdan P, Cooper C, Weitner BB, Rademaker A, Barnhill RL. Histomorphologic assessment and interobserver diagnostic reproducibility of atypical spitzoid melanocytic neoplasms with long-term follow-up. Am J Surg Pathol. 2014;38(7):934–40.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Magro CM, Crowson AN, Mihm MC. Unusual variants of malignant melanoma. Mod Pathol. 2006;19(Suppl 2):S41–70.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Kamino H, Tam S, Tapia B, Toussaint S. The use of elastin immunostain improves the evaluation of melanomas associated with nevi. J Cutan Pathol. 2009;36(8):845–52.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    El Shabrawi-Caelen L, Kerl H, Cerroni L. Melan-A: not a helpful marker in distinction between melanoma in situ on sun-damaged skin and pigmented actinic keratosis. Am J Dermatopathol. 2004;26(5):364–6.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Theunis A, Richert B, Sass U, Lateur N, Sales F, Andre J. Immunohistochemical study of 40 cases of longitudinal melanonychia. Am J Dermatopathol. 2011;33(1):27–34.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Leleux TM, Prieto VG, Diwan AH. Aberrant expression of HMB-45 in traumatized melanocytic nevi. J Am Acad Dermatol. 2012;67(3):446–50.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Uguen A, Talagas M, Costa S, Duigou S, Bouvier S, De Braekeleer M, Marcorelles P. A p16-Ki-67-HMB45 immunohistochemistry scoring system as an ancillary diagnostic tool in the diagnosis of melanoma. Diagn Pathol. 2015;10:195.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Li LX, Crotty KA, McCarthy SW, Palmer AA, Kril JJ. A zonal comparison of MIB1-Ki67 immunoreactivity in benign and malignant melanocytic lesions. Am J Dermatopathol. 2000;22(6):489–95.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Nasr MR, El-Zammar O. Comparison of pHH3, Ki-67, and survivin immunoreactivity in benign and malignant melanocytic lesions. Am J Dermatopathol. 2008;30(2):117–22.PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Puri PK, Valdes CL, Burchette JL, Grichnik JM, Turner JW, Selim MA. Accurate identification of proliferative index in melanocytic neoplasms with Melan-A/Ki-67 double stain. J Cutan Pathol. 2010;37(9):1010–2.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Tetzlaff MT, Curry JL, Ivan D, Wang WL, Torres-Cabala CA, Bassett RL, Valencia KM, McLemore MS, Ross MI, Prieto VG. Immunodetection of phosphohistone H3 as a surrogate of mitotic figure count and clinical outcome in cutaneous melanoma. Mod Pathol. 2013;26(9):1153–60.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Ottmann K, Tronnier M, Mitteldorf C. Detection of mitotic figures in thin melanomas—immunohistochemistry does not replace the careful search for mitotic figures in hematoxylin-eosin stain. J Am Acad Dermatol. 2015;73(4):637–44.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Ohta M, Berd D, Shimizu M, Nagai H, Cotticelli MG, Mastrangelo M, Shields JA, Shields CL, Croce CM, Huebner K. Deletion mapping of chromosome region 9p21-p22 surrounding the CDKN2 locus in melanoma. Int J Cancer. 1996;65(6):762–7.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Harms PW, Hocker TL, Zhao L, Chan MP, Andea AA, Wang M, Harms KL, Wang ML, Carskadon S, Palanisamy N, Fullen DR. Loss of p16 expression and copy number changes of CDKN2A in a spectrum of spitzoid melanocytic lesions. Hum Pathol. 2016;58:152–60.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Clark WH Jr, Elder DE, Van Horn M. The biologic forms of malignant melanoma. Hum Pathol. 1986;17(5):443–50.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Curtin JA, Fridlyand J, Kageshita T, Patel HN, Busam KJ, Kutzner H, Cho KH, Aiba S, Brocker EB, LeBoit PE, Pinkel D, Bastian BC. Distinct sets of genetic alterations in melanoma. N Engl J Med. 2005;353(20):2135–47.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Bastian BC. The molecular pathology of melanoma: an integrated taxonomy of melanocytic neoplasia. Annu Rev Pathol. 2014;9:239–71.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Flotte TJ, Mihm MC Jr. Lentigo maligna and malignant melanoma in situ, lentigo maligna type. Hum Pathol. 1999;30(5):533–6.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Penneys NS. Microinvasive lentigo maligna melanoma. J Am Acad Dermatol. 1987;17(4):675–80.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Horenstein MG, Norton CL, Evans TN. Displacement of dermal solar elastosis in malignant melanoma. J Cutan Pathol. 2007;34(5):376–80.PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Price NM, Rywlin AM, Ackerman AB. Histologic criteria for the diagnosis of superficial spreading malignant melanoma: formulated on the basis of proven metastatic lesions. Cancer. 1976;38(6):2434–41.PubMedCrossRefGoogle Scholar
  39. 39.
    Hantschke M, Bastian BC, LeBoit PE. Consumption of the epidermis: a diagnostic criterion for the differential diagnosis of melanoma and Spitz nevus. Am J Surg Pathol. 2004;28(12):1621–5.PubMedCrossRefGoogle Scholar
  40. 40.
    Elder DE, Jucovy PM, Tuthill RJ, Clark WH Jr. The classification of malignant melanoma. Am J Dermatopathol. 1980;2(4):315–20.PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Wanebo HJ, Fortner JG, Woodruff J, MacLean B, Binkowski E. Selection of the optimum surgical treatment of stage I melanoma by depth of microinvasion: use of the combined microstage technique (Clark-Breslow). Ann Surg. 1975;182(3):302–15.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Balch CM, Wilkerson JA, Murad TM, Soong SJ, Ingalls AL, Maddox WA. The prognostic significance of ulceration of cutaneous melanoma. Cancer. 1980;45(12):3012–7.PubMedCrossRefGoogle Scholar
  43. 43.
    Chamberlain AJ, Fritschi L, Giles GG, Dowling JP, Kelly JW. Nodular type and older age as the most significant associations of thick melanoma in Victoria, Australia. Arch Dermatol. 2002;138(5):609–14.PubMedCrossRefGoogle Scholar
  44. 44.
    Cascinelli N, Zurrida S, Galimberti V, Bartoli C, Bufalino R, Del Prato I, Mascheroni L, Testori A, Clemente C. Acral lentiginous melanoma. A histological type without prognostic significance. J Dermatol Surg Oncol. 1994;20(12):817–22.PubMedCrossRefGoogle Scholar
  45. 45.
    Phan A, Touzet S, Dalle S, Ronger-Savle S, Balme B, Thomas L. Acral lentiginous melanoma: histopathological prognostic features of 121 cases. Br J Dermatol. 2007;157(2):311–8.PubMedCrossRefGoogle Scholar
  46. 46.
    Lucas DR, Tazelaar HD, Unni KK, Wold LE, Okada K, Dimarzio DJ Jr, Rolfe B. Osteogenic melanoma. A rare variant of malignant melanoma. Am J Surg Pathol. 1993;17(4):400–9.PubMedCrossRefGoogle Scholar
  47. 47.
    de Almeida LS, Requena L, Rutten A, Kutzner H, Garbe C, Pestana D, Gomes MM. Desmoplastic malignant melanoma: a clinicopathologic analysis of 113 cases. Am J Dermatopathol. 2008;30(3):207–15.PubMedCrossRefGoogle Scholar
  48. 48.
    Chen LL, Jaimes N, Barker CA, Busam KJ, Marghoob AA. Desmoplastic melanoma: a review. J Am Acad Dermatol. 2013;68(5):825–33.PubMedCrossRefGoogle Scholar
  49. 49.
    Busam KJ, Mujumdar U, Hummer AJ, Nobrega J, Hawkins WG, Coit DG, Brady MS. Cutaneous desmoplastic melanoma: reappraisal of morphologic heterogeneity and prognostic factors. Am J Surg Pathol. 2004;28(11):1518–25.PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Busam KJ. Desmoplastic melanoma. Clin Lab Med. 2011;31(2):321–30.PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Busam KJ. Desmoplastic Melanoma. Surg Pathol Clin. 2009;2(3):511–20.PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Prieto-Granada CN, Wiesner T, Messina JL, Jungbluth AA, Chi P, Antonescu CR. Loss of H3K27me3 expression is a highly sensitive marker for sporadic and radiation-induced MPNST. Am J Surg Pathol. 2016;40(4):479–89.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Weissinger SE, Keil P, Silvers DN, Klaus BM, Moller P, Horst BA, Lennerz JK. A diagnostic algorithm to distinguish desmoplastic from spindle cell melanoma. Mod Pathol. 2014;27(4):524–34.PubMedCrossRefPubMedCentralGoogle Scholar
  54. 54.
    Mentzel T. Uncommon variants of malignant melanocytic neoplasms. Pathologe. 2007;28(6):445–52.PubMedCrossRefPubMedCentralGoogle Scholar
  55. 55.
    Swetter SM, Ecker PM, Johnson DL, Harvell JD. Primary dermal melanoma: a distinct subtype of melanoma. Arch Dermatol. 2004;140(1):99–103.PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Cassarino DS, Cabral ES, Kartha RV, Swetter SM. Primary dermal melanoma: distinct immunohistochemical findings and clinical outcome compared with nodular and metastatic melanoma. Arch Dermatol. 2008;144(1):49–56.PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    Gershenwald JE, Scolyer RA, Hess KR, Thompson JF, Long GV, Ross MI, Lazar AJ, Atkins MB, Balch CM, Barnhill R, Bilimoria KY, Brierley JD, Buzaid AC, Byrd DR, Chapman PB, Cochran AJ, Coit DG, Eggermont AM, Elder DE, Faries MB, Flaherty KT, Garbe C, Gardner JM, Gimotty PA, Halpern AC, Haydu LE, Johnson T, Kirkwood JM, Lee AWM, McArthur GA, Mihm MC, Prieto VG, Sober AJ, Wahl RL, Wong SL, Sondak VK. Melanoma of the skin. In: AJCC cancer staging manual. 8th ed. Springer: Switzerland; 2017.Google Scholar
  58. 58.
    Barnhill RL, Argenyi ZB, From L, Glass LF, Maize JC, Mihm MC Jr, Rabkin MS, Ronan SG, White WL, Piepkorn M. Atypical Spitz nevi/tumors: lack of consensus for diagnosis, discrimination from melanoma, and prediction of outcome. Hum Pathol. 1999;30(5):513–20.PubMedCrossRefPubMedCentralGoogle Scholar
  59. 59.
    Tom WL, Hsu JW, Eichenfield LF, Friedlander SF. Pediatric “STUMP” lesions: evaluation and management of difficult atypical Spitzoid lesions in children. J Am Acad Dermatol. 64(3):559–72.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Gerami P, Jewell SS, Morrison LE, Blondin B, Schulz J, Ruffalo T, Matushek PT, Legator M, Jacobson K, Dalton SR, Charzan S, Kolaitis NA, Guitart J, Lertsbarapa T, Boone S, LeBoit PE, Bastian BC. Fluorescence in situ hybridization (FISH) as an ancillary diagnostic tool in the diagnosis of melanoma. Am J Surg Pathol. 2009;33(8):1146–56.PubMedCrossRefPubMedCentralGoogle Scholar
  61. 61.
    Scolyer RA, Murali R, McCarthy SW, Thompson JF. Histologically ambiguous (“borderline”) primary cutaneous melanocytic tumors: approaches to patient management including the roles of molecular testing and sentinel lymph node biopsy. Arch Pathol Lab Med. 134(12):1770–7.Google Scholar
  62. 62.
    Dalton SR, 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. 34(2):231–7.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Gerami P, Wass A, Mafee M, Fang Y, Pulitzer MP, Busam KJ. Fluorescence in situ hybridization for distinguishing nevoid melanomas from mitotically active nevi. Am J Surg Pathol. 2009;33(12):1783–8.PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Pouryazdanparast P, Newman M, Mafee M, Haghighat Z, Guitart J, Gerami P. Distinguishing epithelioid blue nevus from blue nevus-like cutaneous melanoma metastasis using fluorescence in situ hybridization. Am J Surg Pathol. 2009;33(9):1396–400.PubMedCrossRefPubMedCentralGoogle Scholar
  65. 65.
    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(6):808–17.PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    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(3):413–9.PubMedCrossRefPubMedCentralGoogle Scholar
  67. 67.
    Massi D, Cesinaro AM, Tomasini C, Paglierani M, Bettelli S, Dal Maso L, Simi L, Salvianti F, Pinzani P, Orlando C, De Giorgi V, Lukic S, Maiorana A, Santucci M, Canzonieri V. Atypical Spitzoid melanocytic tumors: a morphological, mutational, and FISH analysis. J Am Acad Dermatol. 2011;64(5):919–35.PubMedCrossRefPubMedCentralGoogle Scholar
  68. 68.
    Vergier B, Prochazkova-Carlotti M, de la Fouchardiere A, Cerroni L, Massi D, De Giorgi V, Bailly C, Wesselmann U, Karlseladze A, Avril MF, Jouary T, Merlio JP. Fluorescence in situ hybridization, a diagnostic aid in ambiguous melanocytic tumors: European study of 113 cases. Mod Pathol. 2011;24(5):613–23.PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    Tetzlaff MT, Wang WL, Milless TL, Curry JL, Torres-Cabala CA, McLemore MS, Ivan D, Bassett RL, Prieto VG. Ambiguous melanocytic tumors in a tertiary referral center: the contribution of fluorescence in situ hybridization (FISH) to conventional histopathologic and immunophenotypic analyses. Am J Surg Pathol. 2013;37(12):1783–96.PubMedCrossRefPubMedCentralGoogle Scholar
  70. 70.
    Clarke LE, Warf MB, Flake DD 2nd, Hartman AR, Tahan S, Shea CR, Gerami P, Messina J, Florell SR, Wenstrup RJ, Rushton K, Roundy KM, Rock C, Roa B, Kolquist KA, Gutin A, Billings S, Leachman S. Clinical validation of a gene expression signature that differentiates benign nevi from malignant melanoma. J Cutan Pathol. 2015;42(4):244–52.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Minca EC, Al-Rohil RN, Wang M, Harms PW, Ko JS, Collie AM, Kovalyshyn I, Prieto VG, Tetzlaff MT, Billings SD, Andea AA. Comparison between melanoma gene expression score and fluorescence in situ hybridization for the classification of melanocytic lesions. Mod Pathol. 2016;29(8):832–43.PubMedCrossRefPubMedCentralGoogle Scholar
  72. 72.
    Bauer J, Bastian BC. Distinguishing melanocytic nevi from melanoma by DNA copy number changes: comparative genomic hybridization as a research and diagnostic tool. Dermatol Ther. 2006;19(1):40–9.PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Bastian BC, LeBoit PE, Hamm H, Brocker EB, Pinkel D. Chromosomal gains and losses in primary cutaneous melanomas detected by comparative genomic hybridization. Cancer Res. 1998;58(10):2170–5.PubMedPubMedCentralGoogle Scholar
  74. 74.
    Ali L, Helm T, Cheney R, Conroy J, Sait S, Guitart J, Gerami P. Correlating array comparative genomic hybridization findings with histology and outcome in spitzoid melanocytic neoplasms. Int J Clin Exp Pathol. 3(6):593–9.Google Scholar
  75. 75.
    Bastian BC, Olshen AB, LeBoit PE, Pinkel D. Classifying melanocytic tumors based on DNA copy number changes. Am J Pathol. 2003;163(5):1765–70.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Horn S, Figl A, Rachakonda PS, Fischer C, Sucker A, Gast A, Kadel S, Moll I, Nagore E, Hemminki K, Schadendorf D, Kumar R. TERT promoter mutations in familial and sporadic melanoma. Science. 2013;339(6122):959–61.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Lu C, Zhang J, Nagahawatte P, Easton J, Lee S, Liu Z, Ding L, Wyczalkowski MA, Valentine M, Navid F, Mulder H, Tatevossian RG, Dalton J, Davenport J, Yin Z, Edmonson M, Rusch M, Wu G, Li Y, Parker M, Hedlund E, Shurtleff S, Raimondi S, Bhavin V, Donald Y, Mardis ER, Wilson RK, Evans WE, Ellison DW, Pounds S, Dyer M, Downing JR, Pappo A, Bahrami A. The genomic landscape of childhood and adolescent melanoma. J Invest Dermatol. 2015;135(3):816–23.PubMedCrossRefPubMedCentralGoogle Scholar
  78. 78.
    Lee S, Barnhill RL, Dummer R, Dalton J, Wu J, Pappo A, Bahrami A. TERT promoter mutations are predictive of aggressive clinical behavior in patients with spitzoid melanocytic neoplasms. Sci Rep. 2015;5:11200.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Breslow A. Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma. Ann Surg. 1970;172(5):902–8.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Scolyer RA, Judge MJ, Evans A, Frishberg DP, Prieto VG, Thompson JF, Trotter MJ, Walsh MY, Walsh NMG, Ellis DW. Data set for pathology reporting of cutaneous invasive melanoma: recommendations from the International Collaboration on Cancer Reporting (ICCR). Am J Surg Pathol. 2013;37(12):1797–814.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    In ’t Hout FE, Haydu LE, Murali R, Bonenkamp JJ, Thompson JF, Scolyer RA. Prognostic importance of the extent of ulceration in patients with clinically localized cutaneous melanoma. Ann Surg. 2012;255(6):1165–70.PubMedCrossRefPubMedCentralGoogle Scholar
  82. 82.
    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(3):705–27.PubMedPubMedCentralGoogle Scholar
  83. 83.
    Buzaid AC, Ross MI, Balch CM, Soong S, McCarthy WH, Tinoco L, Mansfield P, Lee JE, Bedikian A, Eton O, Plager C, Papadopoulos N, Legha SS, Benjamin RS. Critical analysis of the current American Joint Committee on Cancer staging system for cutaneous melanoma and proposal of a new staging system. J Clin Oncol. 1997;15(3):1039–51.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Burton AL, Roach BA, Mays MP, Chen AF, Ginter BA, Vierling AM, Scoggins CR, Martin RC, Stromberg AJ, Hagendoorn L, McMasters KM. Prognostic significance of tumor infiltrating lymphocytes in melanoma. Am Surg. 2011;77(2):188–92.PubMedPubMedCentralGoogle Scholar
  85. 85.
    Azimi F, Scolyer RA, Rumcheva P, Moncrieff M, Murali R, McCarthy SW, Saw RP, Thompson JF. Tumor-infiltrating lymphocyte grade is an independent predictor of sentinel lymph node status and survival in patients with cutaneous melanoma. J Clin Oncol. 2012;30(21):2678–83.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Xu X, Chen L, Guerry D, Dawson PR, Hwang WT, VanBelle P, Elder DE, Zhang PJ, Ming ME, Schuchter L, Gimotty PA. Lymphatic invasion is independently prognostic of metastasis in primary cutaneous melanoma. Clin Cancer Res. 2012;18(1):229–37.CrossRefPubMedGoogle Scholar
  87. 87.
    Yun SJ, Gimotty PA, Hwang WT, Dawson P, Van Belle P, Elder DE, Elenitsas R, Schuchter L, Zhang PJ, Guerry D, Xu X. High lymphatic vessel density and lymphatic invasion underlie the adverse prognostic effect of radial growth phase regression in melanoma. Am J Surg Pathol. 2011;35(2):235–42.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Ribero S, Gualano MR, Osella-Abate S, Scaioli G, Bert F, Sanlorenzo M, Balagna E, Fierro MT, Macripo G, Sapino A, Siliquini R, Quaglino P. Association of Histologic Regression in primary melanoma with sentinel lymph node status: a systematic review and meta-analysis. JAMA Dermatol. 2015;151(12):1301–7.PubMedCrossRefPubMedCentralGoogle Scholar
  89. 89.
    Alkhatib W, Hertzenberg C, Jewell W, Al-Kasspooles MF, Damjanov I, Cohen MS. Utility of frozen-section analysis of sentinel lymph node biopsy specimens for melanoma in surgical decision making. Am J Surg. 2008;196(6):827–32; discussion 832–3PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Gipponi M, Solari N, Lionetto R, Di Somma C, Villa G, Schenone F, Queirolo P, Cafiero F. The prognostic role of the sentinel lymph node in clinically node-negative patients with cutaneous melanoma: experience of the Genoa group. Eur J Surg Oncol. 2005;31(10):1191–7.PubMedCrossRefPubMedCentralGoogle Scholar
  91. 91.
    Scolyer RA, Thompson JF, McCarthy SW, Gershenwald JE, Ross MI, Cochran AJ. Intraoperative frozen-section evaluation can reduce accuracy of pathologic assessment of sentinel nodes in melanoma patients. J Am Coll Surg. 2005;201(5):821–3; author reply 823–4PubMedCrossRefPubMedCentralGoogle Scholar
  92. 92.
    Badgwell BD, Pierce C, Broadwater JR, Westbrook K, Korourian S, Davis D, Hiatt K, Lee J, Cheung WL, Klimberg VS. Intraoperative sentinel lymph node analysis in melanoma. J Surg Oncol. 2011;103(1):1–5.PubMedCrossRefPubMedCentralGoogle Scholar
  93. 93.
    Karimipour DJ, Lowe L, Su L, Hamilton T, Sondak V, Johnson TM, Fullen D. Standard immunostains for melanoma in sentinel lymph node specimens: which ones are most useful? J Am Acad Dermatol. 2004;50(5):759–64.PubMedCrossRefPubMedCentralGoogle Scholar
  94. 94.
    Jennings C, Kim J. Identification of nodal metastases in melanoma using sox-10. Am J Dermatopathol. 2011;33(5):474–82.PubMedCrossRefPubMedCentralGoogle Scholar
  95. 95.
    Abrahamsen HN, Hamilton-Dutoit SJ, Larsen J, Steiniche T. Sentinel lymph nodes in malignant melanoma: extended histopathologic evaluation improves diagnostic precision. Cancer. 2004;100(8):1683–91.PubMedCrossRefPubMedCentralGoogle Scholar
  96. 96.
    Cochran AJ. The pathologist’s role in sentinel lymph node evaluation. Semin Nucl Med. 2000;30(1):11–7.PubMedCrossRefPubMedCentralGoogle Scholar
  97. 97.
    Murray CA, Leong WL, McCready DR, Ghazarian DM. Histopathological patterns of melanoma metastases in sentinel lymph nodes. J Clin Pathol. 2004;57(1):64–7.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Morton DL, Wen DR, Wong JH, Economou JS, Cagle LA, Storm FK, Foshag LJ, Cochran AJ. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg. 1992;127(4):392–9.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Morton DL, Cochran AJ, Thompson JF. Authors’ response to a letter to the editor re: sentinel node biopsy for early-stage melanoma. Ann Surg. 2007;245(5):828–9.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Cook MG, Green MA, Anderson B, Eggermont AM, Ruiter DJ, Spatz A, Kissin MW, Powell BW. The development of optimal pathological assessment of sentinel lymph nodes for melanoma. J Pathol. 2003;200(3):314–9.PubMedCrossRefPubMedCentralGoogle Scholar
  101. 101.
    Spanknebel K, Coit DG, Bieligk SC, Gonen M, Rosai J, Klimstra DS. Characterization of micrometastatic disease in melanoma sentinel lymph nodes by enhanced pathology: recommendations for standardizing pathologic analysis. Am J Surg Pathol. 2005;29(3):305–17.PubMedCrossRefPubMedCentralGoogle Scholar
  102. 102.
    van Akkooi AC, Spatz A, Eggermont AM, Mihm M, Cook MG. Expert opinion in melanoma: the sentinel node; EORTC Melanoma Group recommendations on practical methodology of the measurement of the microanatomic location of metastases and metastatic tumour burden. Eur J Cancer. 2009;45(16):2736–42.PubMedCrossRefPubMedCentralGoogle Scholar
  103. 103.
    van Akkooi AC, Verhoef C, Eggermont AM. Importance of tumor load in the sentinel node in melanoma: clinical dilemmas. Nat Rev Clin Oncol. 2010;7(8):446–54.PubMedCrossRefPubMedCentralGoogle Scholar
  104. 104.
    Starz H, Balda BR, Kramer KU, Buchels H, Wang H. A micromorphometry-based concept for routine classification of sentinel lymph node metastases and its clinical relevance for patients with melanoma. Cancer. 2001;91(11):2110–21.PubMedCrossRefPubMedCentralGoogle Scholar
  105. 105.
    Cochran AJ, Wen DR, Huang RR, Wang HJ, Elashoff R, Morton DL. Prediction of metastatic melanoma in nonsentinel nodes and clinical outcome based on the primary melanoma and the sentinel node. Mod Pathol. 2004;17(7):747–55.PubMedCrossRefPubMedCentralGoogle Scholar
  106. 106.
    Dewar DJ, Newell B, Green MA, Topping AP, Powell BW, Cook MG. The microanatomic location of metastatic melanoma in sentinel lymph nodes predicts nonsentinel lymph node involvement. J Clin Oncol. 2004;22(16):3345–9.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Holtkamp LH, Wang S, Wilmott JS, Madore J, Vilain R, Thompson JF, Nieweg OE, Scolyer RA. Detailed pathological examination of completion node dissection specimens and outcome in melanoma patients with minimal (<0.1 mm) sentinel lymph node metastases. Ann Surg Oncol. 2015;22(9):2972–7.PubMedCrossRefPubMedCentralGoogle Scholar
  108. 108.
    Folpe AL, Mentzel T, Lehr HA, Fisher C, Balzer BL, Weiss SW. Perivascular epithelioid cell neoplasms of soft tissue and gynecologic origin: a clinicopathologic study of 26 cases and review of the literature. Am J Surg Pathol. 2005;29(12):1558–75.PubMedCrossRefPubMedCentralGoogle Scholar
  109. 109.
    Goldblum JR, Folpe AL, Weiss SW. Enzinger and Weiss’s soft tissue tumors. Philadelphia: Saunders; 2013.Google Scholar
  110. 110.
    Kindblom LG, Lodding P, Angervall L. Clear-cell sarcoma of tendons and aponeuroses. An immunohistochemical and electron microscopic analysis indicating neural crest origin. Virchows Arch A Pathol Anat Histopathol. 1983;401(1):109–28.PubMedCrossRefPubMedCentralGoogle Scholar
  111. 111.
    Swanson PE, Wick MR. Clear cell sarcoma. An immunohistochemical analysis of six cases and comparison with other epithelioid neoplasms of soft tissue. Arch Pathol Lab Med. 1989;113(1):55–60.PubMedPubMedCentralGoogle Scholar
  112. 112.
    Langezaal SM, Graadt van Roggen JF, Cleton-Jansen AM, Baelde JJ, Hogendoorn PC. Malignant melanoma is genetically distinct from clear cell sarcoma of tendons and aponeurosis (malignant melanoma of soft parts). Br J Cancer. 2001;84(4):535–8.PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Jeck WR, Parker J, Carson CC, Shields JM, Sambade MJ, Peters EC, Burd CE, Thomas NE, Chiang DY, Liu W, Eberhard DA, Ollila D, Grilley-Olson J, Moschos S, Neil Hayes D, Sharpless NE. Targeted next generation sequencing identifies clinically actionable mutations in patients with melanoma. Pigment Cell Melanoma Res. 2014;27(4):653–63.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    National Cancer Institute, N. C. NCI-MATCH Trial (Molecular Analysis for Therapy Choice). 2017. Accessed 30 Apr 2017.

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Departments of Anatomic Pathology and Cutaneous OncologyMoffitt Cancer CenterTampaUSA
  2. 2.Department of PathologyLutheran General HospitalPark RidgeUSA

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