Skip to main content

Advertisement

Log in

Natural history of cutaneous malignant melanoma

  • Published:
World Journal of Surgery Aims and scope Submit manuscript

Abstract

The rising incidence of cutaneous malignant melanoma with the consequent increase in mortality from melanoma has intensified efforts to understand the factors that initiate the malignant transformation of melanocytes and to define those tumor-host interactions that play a relevant role in the clinical course of this disease. Increased exposure to solar radiation has been proposed as an explanation for the rising incidence of melanoma observed in light-skinned races. Because of the low incidence of melanoma in darkly pigmented races and its tendency in these individuals to develop in relatively nonpigmented areas, such as the sole of the foot, it is postulated that melanin, in addition to its well-known photoprotective effects, may protect against certain intrinsic carcinogenic agents. Developing cutaneous malignant melanomas progress through several cell types that have varying potentials for invasion and metastasis. This developmental process can be appreciated by examination of the various histologic types of melanomas. Early superficial spreading melanoma and lentigo maligna melanoma are characterized by cells that exhibit a prolonged intraepidermal growth phase, and most of these lesions can be diagnosed while they are still curable by simple surgical therapy. Subpopulations of more aggressive cells eventually develop, however. These cells also may characterize the initial stages of nodular melanoma in which the intraepidermal growth phase is absent and early invasion is common. Prognosis for survival depends on the depth of invasion of the primary tumor. Microstaging of the depth of invasion together with information as to mitotic index, sex, site, age, and histologic type will usually predict the natural history of the disease. With present-day management, the overall long-term, disease-free survival rate of patients with cutaneous melanoma is 60–70% and compares favorably with that of the more common cancers.

Résumé

La fréquence croissante des mélanomes malins et l'augmentation de la mortalité ont stimulé les recherches qui étudient les facteurs de transformation maligne des mélanocytes et les interactions hôtetumeur qui jouent un rôle important dans l'évolution de cette maladie. On a suggéré que l'exposition aux rayons solaires expliquait l'augmentation de fréquence du mélanome dans les races à peau claire. Comme le mélanome est rare dans les races à peau foncée et qu'il apparait, chez ces individus, de préférence dans les zones non pigmentées, telles que la plante du pied, on pense que la mélanine, outre ses effets photoprotecteurs, pourrait également protéger contre certains agents carcinogènes intrinsèques. Au cours de leur développement, les mélanomes malins cutanés passent par divers types cellulaires dont les potentialités invasives et métastatiques varient. Ce mode de développement peut être démontré par l'étude des divers types histologiques de mélanomes. Le mélanome à extension superficielle au stade précoce et le mélanome malin à aspect de lentigine sont caractérisés par des cellules qui ont une longue phase de croissance intra-épidermique: la plupart de ces lésions peuvent être diagnostiquées à un stade où elles sont encore curables par la seule chirurgie. Plus tard peuvent se développer des sous-populations de cellules plus agressives. Ces cellules peuvent être également caractéristiques des stades initiaux du mélanome nodulaire, pour lequel la phase de croissance intra-épidermique est absente et l'invasion souvent précoce. Le pronostic dépend de la profondeur de l'envahissement par la tumeur primitive. L'histoire naturelle de la maladie peut en général être prédite par la définition microscopique du degré d'envahissement et de l'index mitotique, ainsi que par le sexe, l'âge et la localisation. Avec les possibilités thérapeutiques actuelles, la survie à long terme sans récidive est de 60–70%; elle est donc comparable à celle d'autres cancers plus fréquents.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Rawles, M.E.: Origin of melanophores and their role in development of color patterns in vertebrates. Physiol. Rev.28:383, 1948

    Google Scholar 

  2. Szabo, G.: The regional anatomy of the human integument with special reference to the distribution of hair follicles, sweat glands, and melanocytes. Phil. Trans. R. Soc. Lond.252B:447, 1967

    Google Scholar 

  3. DeLa Pava, S., Nigogosyar, G., Pickren, J.W., Cabrera, A.: Melanosis of the esophagus. Cancer16:48, 1963

    Google Scholar 

  4. Nigogosyan, G., DeLa Pava, S., Pickren, J.W.: Melanoblasts in vaginal mucosa. Cancer17:912, 1964

    Google Scholar 

  5. Harkins, J.C., Reed, R.J.: Tumors of the peripheral nervous system. In Atlas of Tumor Pathology, Second Series, Fascicle 3. Washington, D.C., Armed Forces Institute of Pathology, 1968, pp. 1–166

    Google Scholar 

  6. Garcia, R.I., Mitchell, R.E., Bloom J., Szabo, G.: Number of epidermal melanocytes, hair follicles, and sweat ducts in skin of Solomon Islanders. Am. J. Phys. Anthropol.47:427, 1977

    Google Scholar 

  7. Quevedo, W.C., Jr., Szabo, G., Virks, J., Sinesi, J.: Melanocyte population in UV-irradiated human skin. J. Invest. Dermatol.45:295, 1965

    Google Scholar 

  8. Szabo, G.: Quantitative histological investigations on the melanocyte system of the human epidermis. In Pigment Cell Biology, Gordon, M., editor. New York, Academic Press, Inc., 1959, pp. 99–125

    Google Scholar 

  9. Jimbow, L., Pathak, M.S., Szabo, G., Fitzpatrick, T.B.: Ultrastructural changes in human melanocyte after ultraviolet radiation. In Sunlight and Man, Pathak, M.A., Harber, L.C., Seiji, M., Kukita, A., editors. Tokyo, University of Tokyo Press, 1974, pp. 195–216

    Google Scholar 

  10. Rosdahl, I.K., Szabo, G.: Thymidine labelling of epidermal melanocyte in UV irradiated skin. Acta Derm. Venerol. (Stockh.)56:159, 1976

    Google Scholar 

  11. Billingham, R.: Dendritic cells. J. Anat.82:93, 1948

    Google Scholar 

  12. Lerner, A.B., McGuire, J.S.: Effect of alpha and beta melanocyte-stimulating hormone on the skin color of man. Nature189:176, 1961

    Google Scholar 

  13. Halaban, R., Lerner, A.B.: The dual effect of melanocyte-stimulating hormone on the growth of cultured mouse melanoma cell. Exp. Cell Res.108:111, 1977

    Google Scholar 

  14. Szabo, G.: The effect of carcinogens on melanocytes. Ann. N.Y. Acad. Sci.100:264, 1963

    Google Scholar 

  15. Snell, R.S.: Hormonal control of pigmentation in man and other mammals. In Advances in Biology of the Skin, Vol. VIII. The Pigmentary System. Montagna, W., Hu, F., editors. New York, Pergamon Press, 1967

    Google Scholar 

  16. Kew, M.C., Mzamane, D., Smith, A.G., Shuster, S.: Melanocyte-stimulating hormone levels in Doxorubicin-induced hyperpigmentation. Lancet1:811, 1977

    Google Scholar 

  17. Quevedo, W.C., Fitzpatrick, T.B., Pathak, M.A., Jimbow, K.: Light and skin color. In Sunlight and Man, Pathak, M.A., Harbor, L.C., Seiji, M., Kukita, A., editors. Tokyo, University of Tokyo Press, 1974, pp. 165–194

    Google Scholar 

  18. MacDonald, E.J.: Incidence and epidemiology of melanoma in Texas. In Neoplasms of the Skin and Malignant Melanoma. Chicago, Year Book Medical Publishers, 1976, pp. 277–292

    Google Scholar 

  19. MacDonald, E.J.: Epidemiology of skin cancer. In Neoplasms of the Skin and Malignant Melanoma. Chicago, Year Book Medical Publishers, 1976, pp. 277–292

    Google Scholar 

  20. Fleming, I.D., Barnawell, J.R., Burlison, P.E., Ronkin, J.S.: Skin cancer in black patients. Cancer35:600, 1975

    Google Scholar 

  21. MacDonald, E.J.: Malignant melanoma among Negroes and Latin Americans in Texas. In Pigment Cell Biology. New York, Academic Press, 1959, pp. 171–181

    Google Scholar 

  22. Lewis, M.G.: Malignant melanoma in Uganda. Br. J. Cancer21:483, 1967

    Google Scholar 

  23. Sompat, M.B., Sirsat, M.V.: Malignant melanoma of the skin and mucous membrane in Indians. Indian J. Cancer3:228, 1966

    Google Scholar 

  24. Mori, W.: Geographic pathology of malignant melanoma in Japan. In Pigment Cell Mechanisms in Pigmentation. McGovern, V.J., Russell, P., editors. Basel, Karger, 1973, pp. 246–254

    Google Scholar 

  25. Pathak, M.A., Fitzpatrick, T.B.: The role of natural photoprotective agents in human skin. In Sunlight and Man, Pathak, M.A., Harber, L.C., Seiji, M., Kukita, A., editors. Tokyo, University of Tokyo Press, 1974, pp. 725–750

    Google Scholar 

  26. Howard-Flanders, P.: DNA repair and recombination. Br. Med. Bull.29:226, 1973

    Google Scholar 

  27. Pathak, M.A., Stratten, K.: Effects of ultraviolet and visible radiation and the production of free radicals in the skin. In The Biologic Effects of Ultraviolet Radiation With Emphasis on the Skin. Urbach, F., editor. New York, Pergamon Press, 1969, pp. 207–222

    Google Scholar 

  28. McGinness, J., Proctor, P.: The importance of the fact that melanin is black. J. Theor. Biol.34:677, 1973

    Google Scholar 

  29. Hirsch, H.M.: Inhibition of melanogenesis by tissues and the control of intracellular autooxidations. In Pigment Cell Biology. New York, Academic Press, 1959, pp. 327–358

    Google Scholar 

  30. Giannelli, F.: Xeroderma pigmentosum. In Scientific Foundations of Oncology, Symington, T., Carter, R.L., editors. London, William Heinemann Medical Books, Lt., 1976, pp. 476–489

    Google Scholar 

  31. Lynch, H.T.: Skin Heredity and Cancer: Cancer Genetics. Springfield, Ill., Charles C Thomas, 1976, pp. 424–470

    Google Scholar 

  32. Cleaver, J.E.: Defective repair replication of DNA in xeroderma pigmentosum. Nature218:652, 1968

    Google Scholar 

  33. McNeer, G., Das Gupta, T.K.: Prognosis in malignant melanoma. Surgery56:512, 1964

    Google Scholar 

  34. McGovern, V.J.: Aetiology of melanoma; classification and histologic reports. Spontaneous regression: frozen section diagnosis. In Malignant Melanoma of the Skin and Mucous Membrane. Milton, G.W., editor. Edinburgh, Churchill Livingstone, 1977, pp. 1–25

    Google Scholar 

  35. Clark, W.H., Mastrangelo, M.J., Ainsworth, A.M., Berd, D., Bellet, R.E., Bernardino, E.A.: Current concepts of the biology of human cutaneous malignant melanoma. Adv. Cancer Res.24:267, 1977

    Google Scholar 

  36. Nicholls, E.M.: Development and elimination of pigmented moles and the anatomical distribution of primary malignant melanoma. Cancer32:191, 1973

    Google Scholar 

  37. Mark, G.J., Mihm, M.C., Liteplo, M.G., Reed, R.J., Clark, W.H.: Congenital melanocytic nevi of the small and garment type. Hum. Pathol.4:395, 1973

    Google Scholar 

  38. Reimer, R.R., Clark, W.H., Greene, M.H., Ainsworth, A.M., Fraumeni, J.F.: Precursor lesions in familial melanoma. A new genetic pre-neoplastic syndrome. J.A.M.A.239:744, 1978

    Google Scholar 

  39. Beardmore, G.L.: The epidemiology of malignant melanoma in Australia. In Melanoma and Skin Cancer. Sydney, Government Printers, 1972, pp. 39–81

    Google Scholar 

  40. Lee, J.A.H.: The current rapid increase in incidence and mortality from malignant melanoma in developed societies. In Pigment Cell, Vol. 2. Basel, Karger, 1976, pp. 414–420

    Google Scholar 

  41. Magnus, K.: Incidence of malignant melanoma of the skin in the five Nordic countries: significance of solar radiation. Int. J. Cancer20:477, 1977

    Google Scholar 

  42. Elwood, J.M., Lee, J.A.H.: Recent data on the epidemiology of malignant melanoma. Semin. Oncol.2:149, 1975

    Google Scholar 

  43. Lane-Brown, M.M., Melia, D.F.: “Celticity” and cutaneous malignant melanoma in Massachusetts. In Pigment Cell, Vol. 1. Basel, Karger, 1973, pp. 229–235

    Google Scholar 

  44. Irving, C.C.: Interaction of chemical carcinogens with DNA methods. Cancer Res.7:189, 1973

    Google Scholar 

  45. Pack, G.T.: The pigment mole and the malignant melanoma. CA12:11, 1962

    Google Scholar 

  46. Gellin, G.A., Kopf, A.W., Garfinkel, L.: Malignant melanoma: a controlled study of possibly associated factors. Arch. Dermatol.99:43, 1969

    Google Scholar 

  47. Clark, W.H., Jr., From, L., Bernardino, E.A., Mihm, M.C.: The histogenesis and biologic behavior of primary human malignant melanomas of the skin. Cancer Res.29:705, 1969

    Google Scholar 

  48. Clark, W.H., Ainsworth, A.M., Bernardino, E.A., Yang, C.H., Mihm, M.C., Reed, R.J.: The developmental biology of primary human malignant melanoma. Semin. Oncol.2:83, 1975

    Google Scholar 

  49. Mihm, M.C., Clark, W.H., Reed, R.J.: The clinical diagnosis of malignant melanoma. Semin. Oncol.2:105, 1975

    Google Scholar 

  50. Rippey, J.J., Rippey, E.: Malignant melanoma with adjacent Hutchinson's melanotic freckle in black Africans. Pathology9:105, 1977

    Google Scholar 

  51. Wanebo, H.J., Fortner, J.G., 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.182:302, 1975

    Google Scholar 

  52. Breslow, A.: Thickness, cross-sectioned area and depth of invasion in the prognosis of cutaneous melanoma. Ann. Surg.172:902, 1970

    Google Scholar 

  53. Breslow, A.: Tumor thickness, level of invasion and node dissection in stage I cutaneous melanoma. Ann. Surg.182:572, 1975

    Google Scholar 

  54. McGovern, V.J.: The classification of melanoma and its relationship with prognosis. Pathology2:85, 1970

    Google Scholar 

  55. Breslow, A.: Problems in the measurement of tumor thickness and level of invasion in cutaneous melanoma. Hum. Pathol.8:1, 1977

    Google Scholar 

  56. Hansen, M.G., McCarten, A.B.: Tumor thickness and lymphocytic infiltration in malignant melanoma of the head and neck. Am. J. Surg.128:557, 1974

    Google Scholar 

  57. Cochran, A.J.: Histology and prognosis in malignant melanoma. J. Pathol.97:459, 1969

    Google Scholar 

  58. Schmoeckel, C., Braun-Falco, O.: Prognostic index in malignant melanoma. Arch. Dermatol.114:871, 1978

    Google Scholar 

  59. Huvos, A.G., Shah, J.P., Mike, V.: Prognostic factors in cutaneous malignant melanoma. Hum. Pathol.5:347, 1974

    Google Scholar 

  60. Smith, J.L.: Histopathology and biologic behavior of malignant melanoma. In Neoplasms of the Skin and Malignant Melanoma. Chicago, Year Book Medical Publishers, 1976, pp. 293–320

    Google Scholar 

  61. Fortner, J.G., Woodruff, J., Schottenfeld, D., MacLean, B.: Biostatistical basis of elective node dissection for malignant melanoma. Ann. Surg.186:101, 1977

    Google Scholar 

  62. Das Gupta, T.K.: Results of treatment of 269 patients with primary cutaneous melanoma. Ann. Surg.186:201, 1977

    Google Scholar 

  63. Veronesi, U., Adamus, J., Bandiera, D.C., Brennhovd, I.O., Caceres, E., Cascinelli, N., Claudio, F., Ikonopisov, R.L., Javorskj, V.V., Kirov, S., Kulakowski, A., Lacour, J., Lejeune, F., Mechl, Z., Morabito, A., Rode, I., Sergeev, S., van Slooten, E., Szczygiel, K., Trapeznikov, N.N., Wagner, R.I.: Inefficacy of immediate node dissection in stage I melanoma of the limbs. N. Engl. J. Med.297:627, 1977

    Google Scholar 

  64. Cochran, A.J.: Malignant melanoma: a review of 10 years' experience in Glasgow. Cancer23:1190, 1969

    Google Scholar 

  65. Olsen, G.: The malignant melanoma of the skin: new theories based on a study of 500 cases. Acta Chir. Scand.365:1, 1966

    Google Scholar 

  66. Shaw, H.M., McCarthy, W.H., Milton, G.W.: Changing trends in mortality from malignant melanoma. Med. J. Aust.2:77, 1977

    Google Scholar 

  67. Pack, G.T.: In discussion of paper by White, L.P., “The role of natural resistance in the prognosis of human melanoma.” Ann. N.Y. Acad. Sci.100:115, 1963

    Google Scholar 

  68. Goldman, L.I., Clark, W.H., Jr., Bernardino, E.A., Ainsworth, A.M.: The accuracy of predicting lymph node metastasis in malignant melanoma by clinical examination and microstaging. Ann. Surg.184:537, 1976

    Google Scholar 

  69. McBride, C.M., Sugarbaker, E.V., Brown, B.W.: Malignant melanoma of the trunk. In Neoplasms of the Skin and Malignant Melanoma. Chicago, Year Book Medical Publishers, 1976, pp. 363–374

    Google Scholar 

  70. Hersey, P., Morgan, G., Stone, D.E., McCarthy, W.H., Milton, G.W.: Previous pregnancy as a protective factor against death from melanoma. Lancet1:451, 1977

    Google Scholar 

  71. Weiss, N.S., Flannery, J.T.: The relationship of marital status to survival from melanoma. Cancer42:296, 1978

    Google Scholar 

  72. Lewis, M.G.: Immunology and immunotherapy in malignant melanoma. In Malignant Melanoma of the Skin and Mucous Membrane, Milton, G.W., editor. Edinburgh, Churchill Livingstone, 1977, pp. 102–150

    Google Scholar 

  73. Gutterman, J.U., Mavligit, G., Reed, R., Richman, S., McBride, C.E., Hersh, E.M.: Immunology and immunotherapy of human malignant melanoma: historic review and perspectives for the future. Semin. Oncol.2:155, 1975

    Google Scholar 

  74. Nathanson, L.: Spontaneous regression of malignant melanoma: a review of the literature on incidence, clinical features, and possible mechanisms. Conference on Spontaneous Regression of Cancer, 1976. Natl. Cancer Inst. Monograph44:67, 1976

    Google Scholar 

  75. Everson, T.C., Cole, W.H.: Spontaneous regression of malignant melanoma. In Spontaneous Regression of Cancer. Philadelphia, W.B. Saunders, 1966, pp. 164–220

    Google Scholar 

  76. Bulkley, G.B., Cohen, M.H., Banks, P.M., Char, D.H., Ketcham, A.S.: Long-term spontaneous regression of malignant melanoma with visceral metastasis. Cancer36:485, 1975

    Google Scholar 

  77. McGovern, V.J.: Spontaneous regression of melanoma. Pathology7:91, 1975

    Google Scholar 

  78. Das Gupta, T.K., Bowden, L., Berg, J.W.: Malignant melanoma of unknown primary origin. Surg. Gynecol. Obstet.117:341, 1963

    Google Scholar 

  79. Baab, G.H., McBride, C.M.: Malignant melanoma: the patient with an unknown site of primary origin. Arch. Surg.110:896, 1975

    Google Scholar 

  80. Copeman, P.W.M., Lewis, M.G., Phillips, T.M., Elliott, P.G.: Immunological associations of the halo naevus with cutaneous malignant melanoma. Br. J. Dermatol.88:127, 1973

    Google Scholar 

  81. Hertz, K.C., Gazze, L.A., Kirkpatrick, C.H., Katz, S.I.: Autoimmune vitiligo. N. Eng. J. Med.297:634, 1977

    Google Scholar 

  82. Gutterman, J.U., Mathé, G., Hersh, E.M.: Rationale and application of immunotherapy for human cancer. Curr. Probl. Cancer2:1, 1978

    Google Scholar 

  83. Shiu, M.H., Schottenfield, D., Maclean, B., Fortner, J.G.: Adverse effect of pregnancy on melanoma. A reappraisal. Cancer37:181, 1976

    Google Scholar 

  84. Sadoff, L., Winkley, J., Tyson, S.: Is malignant melanoma an endocrine-dependent tumor? Oncology27:244, 1973

    Google Scholar 

  85. Pack, G.T., Lenson, N., Gerber, O.M.: Regional distribution of moles and melanomas. Arch. Surg.65:862, 1952

    Google Scholar 

  86. Wander, J.V., Das Gupta, T.K.: Neurofibromatosis. Curr. Probl. Surg.14:1, 1977

    Google Scholar 

  87. Fisher, R.I., Neifeld, J.P., Lippman, M.D.: Oestrogen receptors in human malignant melanoma. Lancet2:337, 1976

    Google Scholar 

  88. Neifeld, J.P., Lippman, M.E., Fisher, R.I.: Receptor for steroid hormones in human melanoma. Surg. Forum27:108, 1976

    Google Scholar 

  89. McGuire, W.L., Horwitz, K.B., Pearson, O.H., Segaloff, A.: Current status of estrogen and progesterone receptors in breast cancer. Cancer39:29, 1977

    Google Scholar 

  90. Johnson, R.O., Bisel, H., Andrews, N., Wilson, W., Rochlin, D., Degaloff, A., Krementz, E., Aust, J., Ansfield, F.: Phase I clinical study of 6-α-methylpregn-4-ene-3,11,20 trione. (NCS 17256). Cancer Chemother. Rep.50:671, 1966

    Google Scholar 

  91. Fidler, I.J., Kripke, M.L.: Metastasis results from preexisting variant cells within a malignant tumor. Science197:893, 1977

    Google Scholar 

  92. Tao, T.W., Burger, M.M.: Non-metastasising variants selected from metastasing melanoma cells. Nature270:437, 1977

    Google Scholar 

  93. Romsdahl, M.M., Cox, I.S.: Biological aspects of pigment cells and malignant melanoma. Chicago, Year Book Medical Publishers, Inc., 1976, pp. 251–277

    Google Scholar 

  94. Clark, W.H., Heggeler, B., Bretton, R.: Electron microscope observations of human cutaneous melanomas correlated with their biologic behavior. In Melanoma and Skin Cancer, McCarthy, W., editor. Proc. International Cancer Conference, Sydney, Australia. Sydney, Government Printer, 1972, pp. 121–141

    Google Scholar 

  95. Einhorn, L.H., Burgess, M.A., Vallejos, C., Bodey, G.P., Sr., Gutterman, J.: Prognostic correlations and response to treatment in advanced metastatic melanoma. Cancer Res.34:1995, 1974

    Google Scholar 

  96. Rothman, L.A., Cohen, C.J., Astarloa, J.: Placental and fetal involvement by maternal malignancy: a report of rectal carcinoma and a review of the literature. Am. J. Obstet. Gynecol.116:1023, 1973

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Supported by Grant No. CA-17954 of the National Cancer Institute, the Pericles P. Stathas Memorial Fund, and the Carol Thomas Brigham Memorial Fund.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Briele, H.A., Das Gupta, T.K. Natural history of cutaneous malignant melanoma. World J. Surg. 3, 255–267 (1979). https://doi.org/10.1007/BF01556570

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01556570

Keywords

Navigation