American Journal of Clinical Dermatology

, Volume 12, Issue 2, pp 77–86 | Cite as

Malignant Melanoma

From Cell Kinetics to Micrometastases
Leading Article Malignant Melanoma


Malignant melanoma (MM) micrometastases are basically seen in three locations inside the peritumoral dermis. They are localized (i) inside the interstitial sector of the dermal stroma; (ii) abutted to the external surface of the microvasculature; and (iii) more rarely present inside vascular channels. Single-cell and paucicellular micrometastases may be disclosed using immunohistochemistry even in the absence of larger microsatellites, which represent micronodular nests of metastatic cells. The presence of microsatellites is frequently tied to markers of MM aggressiveness including thickness and the Ki-67 index. Micrometastases may be present in the same conditions, but even as early as thin MM showing a small growth fraction. Microsatellites as well as micrometastases appear to predict locoregional extension and decreased relapse-free interval, but not distant metastasis and overall survival. These considerations have implications for patient care since patients with microsatellites and micrometastases are now included in the clinical stage III category of the disease. Their implication as a prognostic factor is not fully dependent on or linked to other markers of MM aggressiveness.



This work was supported by a grant from the ‘Fonds d’Investissement de la Recherche Scientifique’ of the University Hospital of Liège, Liège, Belgium. No other sources of funding were used to prepare this review. The authors have no conflicts of interest that are directly relevant to the content of this review. The authors appreciate the excellent secretarial assistance of Mrs Ida Leclercq and Marie Pugliese.


  1. 1.
    Helmbach H, Sinha P, Schadendorf D. Human melanoma: drug resistance. Recent results. Cancer Res 2003; 161: 93–110Google Scholar
  2. 2.
    Chin L, Garraway LA, Fisher DE. Malignant melanoma: genetics and therapeutics in the genomic era. Genet Dev 2006; 20: 2149–82CrossRefGoogle Scholar
  3. 3.
    Beddingfield FC. Themelanoma epidemic: res ipsa loquitur. Oncologist 2003; 8: 459–65PubMedCrossRefGoogle Scholar
  4. 4.
    Thompson JF, Scolyer RA, Kefford RF. Cutaneous melanoma. Lancet 2005; 365: 687–701PubMedGoogle Scholar
  5. 5.
    Jemal A, Devesa SS, Hartge P, et al. Recent trends in cutaneous melanoma incidence among Whites in the United States. J Natl Cancer Inst 2001; 93: 678–83PubMedCrossRefGoogle Scholar
  6. 6.
    Balch CM, Soong SJ, Gerschenwald JE, et al. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol 2001; 15: 3622–34Google Scholar
  7. 7.
    Dean M, Fojo T, Bates S. Tumour stem cells and drug resistance. Nat Rev Cancer 2005; 5: 275–84PubMedCrossRefGoogle Scholar
  8. 8.
    Fang D, Nguyen TK, Leishear K, et al. A tumorigenic subpopulation with stem cell properties in melanomas. Cancer Res 2005; 65: 9328–37PubMedCrossRefGoogle Scholar
  9. 9.
    Grichnik JM. Genomic instability and tumor stem cells. J Invest Dermatol 2006; 126: 1214–6PubMedCrossRefGoogle Scholar
  10. 10.
    Topczewska JM, Postovit LM, Margaryan NV, et al. Embryonic and tumorigenic pathways converge via nodal signalling: role in melanoma aggressiveness. Nat Med 2006; 12: 925–32PubMedCrossRefGoogle Scholar
  11. 11.
    Wang E, Voiculescu S, Le Poole IC, et al. Clonal persistence and evolution during a decade of recurrent melanoma. J Invest Dermatol 2006; 126: 1372–7PubMedCrossRefGoogle Scholar
  12. 12.
    Monzani E, Facchetti F, Galmozzi E, et al. Melanoma contains CD133 and ABCG2 positive cells with enhanced tumorigenic potential. Eur J Cancer 2007; 43: 935–46PubMedCrossRefGoogle Scholar
  13. 13.
    Reya T, Morrison SJ, Clarke MF, et al. Stem cells, cancer, and cancer stem cells. Nature 2001; 414: 105–11PubMedCrossRefGoogle Scholar
  14. 14.
    Schatton T, Frank MH. Cancer stem cells and human malignant melanoma. Pigm Cell Mel Res 2008; 21: 39–55CrossRefGoogle Scholar
  15. 15.
    Schatton T, Murphy GF, Frank NY, et al. Identification of cells initiating human melanomas. Nature 2008; 451: 345–9PubMedCrossRefGoogle Scholar
  16. 16.
    Wong CE, Paratore C, Dours-Zimmermann MT, et al. Neural crest derived cells with stem cell features can be traced back to multiple lineages in the adult skin. J Cell Biol 2006; 175: 1005–15PubMedCrossRefGoogle Scholar
  17. 17.
    Yu H, Fang D, Kumar SM, et al. Isolation of a novel population of multipotent adult stem cells from human hair follicles. Am J Pathol 2006; 168: 1879–88PubMedCrossRefGoogle Scholar
  18. 18.
    Buac K, Pavan WJ. Stem cells of the melanocyte lineage. Cancer Biomark 2007; 3: 203–9PubMedGoogle Scholar
  19. 19.
    Grichnik JM, Burch JA, Schulteis RD, et al. Melanoma, a tumor based on a mutant stem cell? J Invest Dermatol 2006; 126: 142–53PubMedCrossRefGoogle Scholar
  20. 20.
    Klein WM, Wu BP, Zhao S, et al. Increased expression of stem cell markers in malignant melanoma. Modern Pathol 2007; 20: 102–7CrossRefGoogle Scholar
  21. 21.
    Toma JG, Akhavan M, Fernandes KJ, et al. Isolation of multipotent adult stem cells from the dermis of mammalian skin. Nat Cell Biol 2001; 3: 778–84PubMedCrossRefGoogle Scholar
  22. 22.
    Hendrix MJ, Seftor EA, Hess AR, et al. Vasculogenic mimicry and tumourcell plasticity: lessons from melanoma. Nat Rev Cancer 2003; 3: 411–21PubMedCrossRefGoogle Scholar
  23. 23.
    Alonso SR, Ortiz P, Pollan M, et al. Progression in cutaneous malignant melanoma is associated with distinct expression profiles: a tissuemicroarraybased study. Am J Pathol 2004; 164: 193–203PubMedCrossRefGoogle Scholar
  24. 24.
    Curtin JA, Fridlyand J, Kageshita T, et al. Distinct sets of genetic alterations in melanoma. N Engl J Med 2005; 353: 2135–47PubMedCrossRefGoogle Scholar
  25. 25.
    Hoek KS. DNA microarray analyses of melanoma gene expression: a decade in the mines. Pigment Cell Res 2007; 20: 466–84PubMedCrossRefGoogle Scholar
  26. 26.
    Jönsson G, Dahl C, Staaf J, et al. Genomic profiling of malignant melanoma using tiling-resolution array CGH. Oncogene 2007; 26: 4738–48PubMedCrossRefGoogle Scholar
  27. 27.
    Plaza JA, Suster D, Perez-Montiel D. Expression of immunohistochemical markers in primary and metastatic malignant melanoma, a comparative study in 70 patients using a tissue microarray technique. Appl Immunohistochem Mol Morph 2007; 15: 421–5CrossRefGoogle Scholar
  28. 28.
    Rothhammer T, Bosserhoff AK. Epigenetic events in malignant melanoma. Pigment Cell Res 2007; 20: 92–111PubMedCrossRefGoogle Scholar
  29. 29.
    Stark M, Hayward N. Genome-wide loss of heterozygosity and copy number analysis in melanoma using high-density single-nucleotide polymorphism arrays. Cancer Res 2007; 67: 2632–42PubMedCrossRefGoogle Scholar
  30. 30.
    Simpson AJ, Caballero OL, Jungbluth A, et al. Cancer/testis antigens, gametogenesis and cancer. Nat Rev Cancer 2005; 5: 615–25PubMedCrossRefGoogle Scholar
  31. 31.
    Rothhammer T, Bataille F, Spruss T, et al. Functional implication of BMP4 expression on angiogenesis in malignantmelanoma. Oncogene 2007; 26: 4158–70PubMedCrossRefGoogle Scholar
  32. 32.
    Reya T, Clevers H. Wnt signalling in stem cells and cancer. Nature 2005; 434: 843–50PubMedCrossRefGoogle Scholar
  33. 33.
    Rappa G, Fodstad O, Lorico A. The stem cell-associated antigen CD133 (Prominin-1) is a molecular therapeutic target for metastatic melanoma. Stem Cells 2008; 26: 2008–3017CrossRefGoogle Scholar
  34. 34.
    Quatresooz P, Piérard GE, Piérard-Franchimont C, et al. Molecular pathways supporting the proliferation staging of malignant melanoma. Int J Molec Med 2009; 24: 295–301PubMedGoogle Scholar
  35. 35.
    Piérard-Franchimont C, Henry F, Heymans O, et al. Vascular retardation in dormant growth-stuntedmalignantmelanomas. Int J Mol Med 1999; 4: 403–6PubMedGoogle Scholar
  36. 36.
    Barnhill RL. The biology of melanoma micrometastases. In: Reinhold U, Tilgen W, editors. Minimal residual disease in melanoma: biology, detection and clinical relevance. Berlin: Springer, 2001: 3–13CrossRefGoogle Scholar
  37. 37.
    Ralph SJ. An update on malignant melanoma vaccine research: insight into mechanisms for improving the design and potency of melanoma therapeutic vaccines. Am J Clin Dermatol 2007; 8: 123–41PubMedCrossRefGoogle Scholar
  38. 38.
    Terando AM, Faries MB, Morton DL. Vaccine therapy for melanoma: current status and future directions. Vaccine 2007; 25: 4–16CrossRefGoogle Scholar
  39. 39.
    Lorigan P, Eisen T, Hauschild A. Systemic therapy for metastatic malignant melanoma: from deeply disappointing to bright future? Exp Dermatol 2008; 17: 383–94PubMedCrossRefGoogle Scholar
  40. 40.
    Boni R, Doguoglu A, Burg G, et al. MIB-1 immunoreactivity correlates with metastatic dissemination in primary thick cutaneous melanoma. J Am Acad Dermatol 1996; 35: 416–8PubMedCrossRefGoogle Scholar
  41. 41.
    Sparrow LE, English DR, Taran JM, et al. Prognostic significance of MIB-1 proliferative activity in thinmelanomas and immunohistochemical analysis of MIB-1 proliferative activity in melanocytic tumors. Am J Dermatopathol 1998; 20: 12–6PubMedCrossRefGoogle Scholar
  42. 42.
    Niezabitowski A, Czajecki K, Rys J, et al. Prognostic evaluation of cutaneous malignant melanoma: a clinicopathologic and immunohistochemical study. J Surg Oncol 1999; 70: 150–60PubMedCrossRefGoogle Scholar
  43. 43.
    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: 1845–53PubMedGoogle Scholar
  44. 44.
    Frahm SO, Schubert C, Parwaresch R, et al. High proliferative activity may predict early metastasis of thin melanomas. Hum Pathol 2001; 32: 1376–81PubMedCrossRefGoogle Scholar
  45. 45.
    Quatresooz P, Arrese JE, Piérard-Franchimont C, et al. Immunohistochemical aid at risk stratification of melanocytic neoplasms. Int J Oncol 2004; 24: 211–6PubMedGoogle Scholar
  46. 46.
    Smoller BR. Histologic criteria for diagnosing primary cutaneous malignant melanoma. Modern Pathol 2006; 19: 34–40CrossRefGoogle Scholar
  47. 47.
    Ohsie SJ, Sarantopoulos GP, Cochran AJ, et al. Immunohistochemical characteristics of melanoma. J Cutan Pathol 2008; 35: 433–44PubMedCrossRefGoogle Scholar
  48. 48.
    Quatresooz P, Piérard-Franchimont C, Piérard GE. Highlighting the immunohistochemical profile of melanocytomas. Oncol Rep 2008; 19: 1367–72PubMedGoogle Scholar
  49. 49.
    Quatresooz P, Piérard-Franchimont C, Paquet P, et al. Angiogenic fast-growing melanomas and their micrometastases. Eur J Dermatol 2010; 20: 302–7PubMedGoogle Scholar
  50. 50.
    Quatresooz P, Piérard-Franchimont C, Piérard GE, et al. Molecular histology on the diagnostic cutting edge between malignantmelanomas and cutaneous melanocytomas. Oncol Rep 2009; 22: 1263–7PubMedGoogle Scholar
  51. 51.
    Piérard GE, Piérard-Franchimont C, Henry C, et al. The proliferative activity of cells of malignant melanomas. Am J Dermatopathol 1984; 6: S317–24PubMedGoogle Scholar
  52. 52.
    Claessens N, Piérard GE, Piérard-Franchimont C, et al. Immunohistochemical detection of incipient melanoma micrometastases: relationship with sentinel lymph node involvement. Melanoma Res 2005; 15: 107–10PubMedCrossRefGoogle Scholar
  53. 53.
    Lipsker D. Growth rate, early detection and prevention of melanoma: melanoma epidemiology revisited and future challenges. Arch Dermatol 2006; 142: 1638–40PubMedCrossRefGoogle Scholar
  54. 54.
    Liu W, Dowling JP, Murray WK, et al. Rate of growth in melanomas: characteristics and associations of rapidly growing melanoma. Arch Dermatol 2006; 142: 1551–8PubMedCrossRefGoogle Scholar
  55. 55.
    Lipsker D, Engel F, Cribier B, et al. Trends in melanoma epidemiology suggest three different types of melanoma. Br J Dermatol 2007; 157: 328–43CrossRefGoogle Scholar
  56. 56.
    Zalaudek I, Marghoob AA, Scope A, et al. Three roots of melanoma. Arch Dermatol 2008; 144: 1375–9PubMedCrossRefGoogle Scholar
  57. 57.
    Piérard GE, Pirard-Franchimont C. Stochastic relationship between the growth fraction and vascularity of thin malignant melanomas. Eur J Cancer 1997; 33: 1888–92PubMedCrossRefGoogle Scholar
  58. 58.
    Gebhardt C, Averbeck M, Veirtel A, et al. Ultraviolet-B irradiation enhances melanoma cell motility via induction of autocrine interleukin 8 secretion. Exp Dermatol 2007; 16: 636–43PubMedCrossRefGoogle Scholar
  59. 59.
    Quatresooz P, Piérard-Franchimont C, Piérard GE. Diagnostic challenge of desmoplastic melanoma. Trends Cancer Res 2007; 3: 27–34Google Scholar
  60. 60.
    Shea CP, Kline MA, Lugo J, et al. Angiotropic metastatic malignant melanoma. Am J Dermatopathol 1995; 17: 58–62PubMedCrossRefGoogle Scholar
  61. 61.
    Engbring JA, Kelinman HK. The basement membrane matrix in malignancy. J Pathol 2003; 200: 465–70PubMedCrossRefGoogle Scholar
  62. 62.
    Wernert N. The multiple roles of tumour stroma. Virchows Arch 1997; 430: 433–43PubMedCrossRefGoogle Scholar
  63. 63.
    Danen EHJ, Sonnenberg A. Integrins in regulation of tissue development and function. J Pathol 2003; 200: 471–80PubMedCrossRefGoogle Scholar
  64. 64.
    Wehrle-Haller B, Imhof BA. Integrin-dependent pathologies. J Pathol 2003; 200: 481–7PubMedCrossRefGoogle Scholar
  65. 65.
    Friedl P, Wolf K. Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer 2003; 3: 362–74PubMedCrossRefGoogle Scholar
  66. 66.
    Piérard GE, Quatresooz P, Rorive A, et al. Malignant melanoma: conceptual and therapeutic innovations based on translational research. Rev Med Liège 2008; 63: 579–84PubMedGoogle Scholar
  67. 67.
    Fecher LA, Cummings SD, Keefe MJ, et al. Toward a molecular classification of melanoma. J Clin Oncol 2007; 25: 1606–20PubMedCrossRefGoogle Scholar
  68. 68.
    Bennet DC. How to make a melanoma: what do we know of the primary clonal events? Pigment Cell Melanoma Res 2008; 21: 27–38CrossRefGoogle Scholar
  69. 69.
    Hoek KS, Schlegel NC, Brafford P, et al. Metastatic potential of melanomas defined by specific gene expression profiles with no BRAF signature. Pigment Cell Res 2006; 19: 290–302PubMedCrossRefGoogle Scholar
  70. 70.
    Liu W, Kelly JW, Trivett M, et al. Distinct clinical and pathological features are associated with BRAF mutation in primary melanoma. J Invest Dermatol 2007; 127: 900–5PubMedCrossRefGoogle Scholar
  71. 71.
    Yap AS, Brieher WM, Gumbiner BM. Molecular and functional analysis of cadherin-based adherens junctions. Annu Rev Cell Dev Biol 1997; 13: 119–46PubMedCrossRefGoogle Scholar
  72. 72.
    Tang A, Eller MS, Hara M, et al. E-cadherin is the major mediator of human melanocyte adhesion to keratinocytes in vitro. J Cell Sci 1994; 107: 983–92PubMedGoogle Scholar
  73. 73.
    Haass NK, Smalley KS, Herlyn M. The role of altered cell-cell communication in melanoma progression. J Mol Histol 2004; 35: 309–18PubMedCrossRefGoogle Scholar
  74. 74.
    Li G, Satyamoorthy K, Herlyn M. N-cadherin-mediated intercellular interactions promote survival and migration of melanoma cells. Cancer Res 2001; 61: 3819–25PubMedGoogle Scholar
  75. 75.
    Hsu MY, Meier FE, Nesbit M, et al. E-cadherin expression in melanoma cells restores keratinocyte-mediated growth control and down-regulates expression of invasion-related adhesion receptors. Am J Pathol 2000; 156: 1515–25PubMedCrossRefGoogle Scholar
  76. 76.
    Hendrix M, Maniotics A, Folberg R. Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. Am J Pathol 1999; 155: 739–52PubMedCrossRefGoogle Scholar
  77. 77.
    Pellegrini A. Regressed primary malignant melanoma with regional metastasis. Arch Dermatol 1980; 116: 585–6PubMedCrossRefGoogle Scholar
  78. 78.
    Anbari KK, Schuchter LM, Bucky LM, et al. Melanoma of unknown primary site: presentation, treatment and prognosis. A single institution study. Cancer 1997; 79: 1816–21PubMedCrossRefGoogle Scholar
  79. 79.
    Vijuk G, Coates AS. Survival of patients with visceral metastatic melanoma from an occult primary lesion: a retrospective matched cohort study. Ann Oncol 1998; 9: 419–22PubMedCrossRefGoogle Scholar
  80. 80.
    Henry F, Piérard-Franchimont C, Arrese JE, et al. How I explore y an orphan metastasis from melanoma. Rev Med Liège 2002; 57: 405–7PubMedGoogle Scholar
  81. 81.
    Day Jr CL, Harrist TJ, Gorstein F, et al. Malignant melanoma: prognostic significance of “microscopic satellites” in the reticular dermis and subcutaneous fat. Ann Surg 1981; 194: 108–12PubMedCrossRefGoogle Scholar
  82. 82.
    Shaikh L, Sagebiel RW, Ferreira CM, et al. The role of microsatellites as a pronostic factor in primary malignant melanoma. Arch Dermatol 2008; 14: 739–42Google Scholar
  83. 83.
    Harrist JT, Rigel DS, Day Jr CL, et al. “Microscopic satellites” are more highly associated with regional lymph node metastases than is primary melanoma thickness. Cancer 1984; 53: 2183–7PubMedCrossRefGoogle Scholar
  84. 84.
    Leon P, Daly JM, Synnestved M, et al. The prognostic implications of microscopic satellites in patients with clinical stage I melanoma. Arch Surg 1991; 126: 1461–8PubMedCrossRefGoogle Scholar
  85. 85.
    Balch CM, Buzaid AC, Soong SJ, et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 2001; 19: 3635–48PubMedGoogle Scholar
  86. 86.
    Crowley N, Seigler H. Relationship between disease-free interval and survival in patients with recurrent melanoma. Arch Surg 1992; 127: 1303–8PubMedCrossRefGoogle Scholar
  87. 87.
    Holmgren L, O’Reilly MS, Folkman J. Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat Med 1995; 1: 149–53PubMedCrossRefGoogle Scholar
  88. 88.
    Piepkorn M, Barnhill RL. A factual, not arbitrary, basis for choice of resection margins in melanoma. Arch Dermatol 1996; 132: 811–4PubMedCrossRefGoogle Scholar
  89. 89.
    Piepkorn M, Weinstock MA, Barnhill RL. Theoretical and empirical arguments in relation to elective lymph node dissection for melanoma. Arch Dermatol 1997; 133: 995–1007PubMedCrossRefGoogle Scholar
  90. 90.
    Piérard-Franchimont C, Piérard GE. The wide and deep excision of primary malignant melanoma: a dogma on the decline. Acta Clin Belgica 1998; 53: 98–9Google Scholar
  91. 91.
    Piérard GE, Henry C, Franchimont C, et al. Immunotherapy by dinitrochloro-benzene of melanomas of the skin: II. Histology of the cytotoxic effect. In: Ackerman AB, editor. Pathology of malignant melanoma. New York: Masson, 1981: 373–85Google Scholar
  92. 92.
    Fildler IJ. The biology of melanoma metastasis. In: Balch CM, Houghton AN, Milton GW, et al., editors. Cut melanoma. 2nd ed. Philadelphia (PA): JB Lippincott, 1992: 112–29Google Scholar
  93. 93.
    Reinhold U, Lüdtke-Handjery HC, Schnautz S, et al. The analysis of tyrosinase-specific mRNA in blood samples of melanoma patients by RT-PCR is not a useful test for metastatic tumor progression. J Invest Dermatol 1997; 108: 166–9PubMedCrossRefGoogle Scholar
  94. 94.
    Schittek B, Blaheta HJ, Ellwanger U, et al. Polymerase chain reaction in the detection of circulating tumour cells in peripheral blood of melanoma patients. In: Reinhold U, Tilgen W, editors. Minimal residual disease in melanoma: biology, detection and clinical relevance. Berlin: Springer, 2001: 93–104CrossRefGoogle Scholar
  95. 95.
    Seiter S, Rappl G, Tilgen W, et al. Facts in pitfalls in the detection of tyrosinase mRNA in the blood of melanoma patients by RT-PCR. In: Reinhold U, Tilgen W, editors. Minimal residual disease in melanoma: biology, detection and clinical relevance. Berlin: Springer, 2001: 105–12CrossRefGoogle Scholar
  96. 96.
    Benez A, Schiebel U, Fierlbeck G. Morphologically intact melanoma cells may be detected in peripheral blood of melanoma patients. In: Reinhold U, Tilgen W, editors. Minimal residual disease in melanoma: biology, detection and clinical relevance. Berlin: Springer, 2001: 113–7CrossRefGoogle Scholar
  97. 97.
    Waldmann V, Wacker J, Deichmann M, et al. Prognosis of metastatic melanoma: no correlation of tyrosinase mRNA in bone marrow and survival time. In: Reinhold U, Tilgen W, editors. Minimal residual disease in melanoma: biology, detection and clinical relevance. Berlin: Springer, 2001: 118–25CrossRefGoogle Scholar
  98. 98.
    Von Knebel Doeberitz M, Weitz J, Koch M, et al. Molecular tools in the detection of micrometastatic cancer cells: technical aspects and clinical relevance. In: Reinhold U, Tilgen W, editors. Minimal residual disease in melanoma: biology, detection and clinical relevance. Berlin: Springer, 2001: 181–6CrossRefGoogle Scholar
  99. 99.
    Palmieri G, Pirastu M, Strazzullo M, et al. Clinical significance of PCRpositive mRNA markers in peripheral blood and regional nodes of malignant melanoma patients. In: Reinhold U, Tilgen W, editors. Minimal residual disease in melanoma: biology, detection and clinical relevance. Berlin: Springer, 2001: 200–3CrossRefGoogle Scholar
  100. 100.
    Taback B, Morton DL, O’Day SJ, et al. The clinical utility of multimarker RT-PCR in the detection of occult metastasis in patients with melanoma. In: Reinhold U, Tilgen W, editors. Minimal residual disease in melanoma: biology, detection and clinical relevance. Berlin: Springer, 2001: 78–92CrossRefGoogle Scholar
  101. 101.
    Pantel K, Otte M. Disseminated tumor cells: diagnosis, prognostic relevance, and phenotyping. In: Reinhold U, Tilgen W, editors. Minimal residual disease in melanoma: biology, detection and clinical relevance. Berlin: Springer, 2001: 14–24CrossRefGoogle Scholar
  102. 102.
    Moreno A, Espanol I, Romagosa V. Angiotropic malignant melanoma: report of two cases. J Cutan Pathol 1992; 19: 325–9PubMedCrossRefGoogle Scholar
  103. 103.
    Saluja A, Money N, Zivony DI, et al. Angiotropic malignant melanoma: a rare pattern of local metastases. J Am Acad Dermatol 2001; 44: 829–32PubMedCrossRefGoogle Scholar
  104. 104.
    Siegel DM, McClain SA. Angiotropic malignant melanoma: more common than we think? J Am Acad Dermatol 2001; 44: 870–1PubMedCrossRefGoogle Scholar
  105. 105.
    Barnhill RL, Dy K, Lugassy C. Angiotropism in cutaneous melanoma: a prognostic factor strongly predicting risk formetastasis. J Invest Dermatol 2002; 119: 705–6PubMedCrossRefGoogle Scholar
  106. 106.
    Lugassy C, Barnhill RL. Angiotropicmalignant melanoma and extravascular migratory metastasis: description of 26 cases with emphasis on a new mechanism of tumor spread. Pathology 2004; 36: 485–90PubMedCrossRefGoogle Scholar
  107. 107.
    Lugassy C, Barnhill RL. Angiotropic melanoma and extravascular migratory metastasis: a review. Adv Anat Pathol 2007; 14: 195–201PubMedCrossRefGoogle Scholar

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© Adis Data Information BV 2011

Authors and Affiliations

  1. 1.Department of DermatopathologyUniversity Hospital of LiègeLiègeBelgium

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