Skip to main content
SpringerLink
Log in

Anatomy and Physiology of the Skin

  • Chapter
  • First Online:
Melanoma

Abstract

The human skin is organized into three primary layers: epidermis, dermis, and the subcutaneous fat residing directly beneath them. Most germane to melanoma is the melanocyte, a specialized pigment-producing cell which transfers melanin from cellular cytoplasm to keratinocytes. This pigment is responsible for both skin color and protection from ultraviolet radiation (UVR). Exposure to particular wavelengths of UVR may result in DNA damage through a variety of mechanisms, which, in turn, predisposes to cutaneous malignancies such as melanoma. The development, invasion, and spread of melanoma are largely dependent on the interaction of melanocytes and their surrounding microenvironment. Melanocytes promote their own growth and survival by secreting growth factors. Keratinocytes are the main regulators of melanocytes, while surrounding fibroblasts become associated with melanocytes and promote their proliferation. Integrin proteins in the microenvironment mediate cytoskeleton adhesion to the extracellular matrix, which contributes to melanocyte migration and invasion. Melanoma tumors tend to invade lymphatic vessels and involve regional lymph nodes early in their course. Metastasizing through blood vessels may also be possible, but is less common and leads to an overall worse prognosis. Therefore, there is a great emphasis placed upon the early detection and removal of involved lymph nodes in melanoma management. Melanocytic nevi, nonmalignant nests of melanocytes, are classified as either dysplastic or common. Nevi that appear clinically suspicious for malignancy based on certain criteria are called atypical nevi, while those which bear histopathological resemblance to melanoma are termed dysplastic nevi. Whether dysplastic or common nevi carry greater proportionate risk for malignancy is uncertain.

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

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover 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

Similar content being viewed by others

References

  1. Sen GL. Remembering one’s identity: the epigenetic basis of stem cell fate decisions. FASEB J. 2011;25(7):2123–8.

    Article  CAS  PubMed  Google Scholar 

  2. Gantwerker EA, Hom DB. Skin: histology and physiology of wound healing. Facial Plast Surg Clin North Am. 2011;19(3):441–53.

    Article  PubMed  Google Scholar 

  3. Brody I. The ultrastructure of the tonofibrils in the keratinization process of normal human epidermis. J Ultrastruct Res. 1960;4(3):264–97.

    Article  Google Scholar 

  4. Stingl G, Wolff-Schreiner EC, Pichler W, Gschnait F, Knapp W. Epidermal Langerhans cells bear Fc and C3 receptors. Nature. 1977;268:245–6.

    Article  CAS  PubMed  Google Scholar 

  5. Elias PM. Structure and function of the stratum corneum extracellular matrix. J Investig Dermatol. 2012;132(9):2131–3.

    Article  CAS  PubMed  Google Scholar 

  6. Arda O, Göksügür N, Tüzün Y. Basic histological structure and functions of facial skin. Clin Dermatol. 2014;32(1):3–13.

    Article  PubMed  Google Scholar 

  7. Mescher AL. Junqueira’s basic histology: text and atlas: McGraw-Hill; 2013.

    Google Scholar 

  8. Hwang K, Kim H, Kim DJ. Thickness of skin and subcutaneous tissue of the free flap donor sites: a histologic study. Microsurgery. 2016;36(1):54–8.

    Article  PubMed  Google Scholar 

  9. Menon GK, Cleary GW, Lane ME. The structure and function of the stratum corneum. Int J Pharm. 2012;435(1):3–9.

    Article  CAS  PubMed  Google Scholar 

  10. Kanitakis J. Anatomy, histology and immunohistochemistry of normal human skin. Eur J Dermatol. 2001;12(4):390–9. quiz 400-1

    Google Scholar 

  11. Ross M, Pawlina W. Histology a text and atlas. Baltimore: Lippincott Williams & Wilkins, a Wolters Kluwer Business; 2011.

    Google Scholar 

  12. Driskell RR, Jahoda CA, Chuong CM, Watt FM, Horsley V. Defining dermal adipose tissue. Exp Dermatol. 2014;23(9):629–31.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Schmidt B, Horsley V. Unravelling hair follicle–adipocyte communication. Exp Dermatol. 2012;21(11):827–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Mayor R, Theveneau E. The neural crest. Development. 2013;140(11):2247–51.

    Article  CAS  PubMed  Google Scholar 

  15. Nitzan E, Pfaltzgraff ER, Labosky PA, Kalcheim C. Neural crest and Schwann cell progenitor-derived melanocytes are two spatially segregated populations similarly regulated by Foxd3. Proc Natl Acad Sci. 2013;110(31):12709–14.

    Article  PubMed  Google Scholar 

  16. White RM, Zon LI. Melanocytes in development, regeneration, and cancer. Cell Stem Cell. 2008;3(3):242–52.

    Article  CAS  PubMed  Google Scholar 

  17. Shakhova O. Neural crest stem cells in melanoma development. Curr Opin Oncol. 2014;26(2):215–21.

    Article  CAS  PubMed  Google Scholar 

  18. Mort RL, Jackson IJ, Patton EE. The melanocyte lineage in development and disease. Development. 2015;142(4):620–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Fitzpatrick TB, Breathnach A. The epidermal melanin unit system. Dermatol Wochenschr. 1963;147:481–9.

    PubMed  CAS  Google Scholar 

  20. Joly-Tonetti N, Wibawa JI, Bell M, Tobin DJ. Melanin fate in the human epidermis: a re-assessment of how best to detect and analyze histologically. Exp Dermatol. 2016;

    Google Scholar 

  21. Thody AJ, Higgins EM, Wakamatsu K, Ito S, Burchill SA, Marks JM. Pheomelanin as well as eumelanin is present in human epidermis. J Investig Dermatol. 1991;97(2):340–4.

    Article  CAS  PubMed  Google Scholar 

  22. Pathak M, Jimbow K. Fitzpatrick T, editors. Sendai, Japan: Photobiology of pigment cell phenotypic expression in pigment cells. Proceedings of the Xth International Pigment Cell Conference; 1980.

    Google Scholar 

  23. Brenner M, Hearing VJ. The protective role of melanin against UV damage in human skin. Photochem Photobiol. 2008;84(3):539–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kushimoto T, Valencia JC, Costin GE, Toyofuku K, Watabe H, Yasumoto KI, et al. The melanosome: an ideal model to study cellular differentiation. Pigment Cell Res. 2003;16(3):237–44.

    Article  CAS  PubMed  Google Scholar 

  25. Dell’Angelica EC. Melanosome biogenesis: shedding light on the origin of an obscure organelle. Trends Cell Biol. 2003;13(10):503–6.

    Article  CAS  PubMed  Google Scholar 

  26. Wu X, Hammer JA. Melanosome transfer: it is best to give and receive. Curr Opin Cell Biol. 2014;29:1–7.

    Article  CAS  PubMed  Google Scholar 

  27. Gilchrest BA, Eller MS, Geller AC, Yaar M. The pathogenesis of melanoma induced by ultraviolet radiation. N Engl J Med. 1999;340(17):1341–8.

    Article  CAS  PubMed  Google Scholar 

  28. Young AR, Chadwick CA, Harrison GI, Nikaido O, Ramsden J, Potten CS. The similarity of action spectra for thymine dimers in human epidermis and erythema suggests that DNA is the chromophore for erythema. J Investig Dermatol. 1998;111(6):982–8.

    Article  CAS  PubMed  Google Scholar 

  29. Hölzle E, Hönigsmann H. [UV-radiation--sources, wavelength, environment]. Journal der Deutschen Dermatologischen Gesellschaft= Journal of the German Society of Dermatology: JDDG. 2005;3:S3-10.

    Google Scholar 

  30. De Fabo EC. Arctic stratospheric ozone depletion and increased UVB radiation: potential impacts to human health. International journal of circumpolar health. 2005;64(5).

    Google Scholar 

  31. Fisher GJ, Kang S, Varani J, Bata-Csorgo Z, Wan Y, Datta S, et al. Mechanisms of photoaging and chronological skin aging. Arch Dermatol. 2002;138(11):1462–70.

    Article  CAS  PubMed  Google Scholar 

  32. Vink AA, Roza L. Biological consequences of cyclobutane pyrimidine dimers. J Photochem Photobiol B Biol. 2001;65(2):101–4.

    Article  CAS  Google Scholar 

  33. Kvam E, Tyrrell RM. Induction of oxidative DNA base damage in human skin cells by UV and near visible radiation. Carcinogenesis. 1997;18(12):2379–84.

    Article  CAS  PubMed  Google Scholar 

  34. Kaidbey KH, Agin PP, Sayre RM, Kligman AM. Photoprotection by melanin—a comparison of black and Caucasian skin. J Am Acad Dermatol. 1979;1(3):249–60.

    Article  CAS  PubMed  Google Scholar 

  35. Mervic L. Time course and pattern of metastasis of cutaneous melanoma differ between men and women. PLoS One. 2012;7(3):e32955.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Streit M, Detmar M. Angiogenesis, lymphangiogenesis, and melanoma metastasis. Oncogene. 2003;22(20):3172–9.

    Article  CAS  PubMed  Google Scholar 

  37. León P, Daly JM, Synnestvedt M, Schultz DJ, Elder DE, Clark WH. The prognostic implications of microscopic satellites in patients with clinical stage I melanoma. Arch Surg. 1991;126(12):1461–8.

    Article  PubMed  Google Scholar 

  38. Leiter U, Meier F, Schittek B, Garbe C. The natural course of cutaneous melanoma. J Surg Oncol. 2004;86(4):172–8.

    Article  PubMed  Google Scholar 

  39. Meier F, Will S, Ellwanger U, Schlagenhauff B, Schittek B, Rassner G, et al. Metastatic pathways and time courses in the orderly progression of cutaneous melanoma. Br J Dermatol. 2002;147(1):62–70.

    Article  CAS  PubMed  Google Scholar 

  40. Cascinelli N, Morabito A, Santinami M, MacKie R, Belli F. Immediate or delayed dissection of regional nodes in patients with melanoma of the trunk: a randomised trial. Lancet. 1998;351(9105):793–6.

    Article  CAS  PubMed  Google Scholar 

  41. Kretschmer L, Hilgers R, Möhrle M, Balda B, Breuninger H, Konz B, et al. Patients with lymphatic metastasis of cutaneous malignant melanoma benefit from sentinel lymphonodectomy and early excision of their nodal disease. Eur J Cancer. 2004;40(2):212–8.

    Article  CAS  PubMed  Google Scholar 

  42. Sappey M. Anatomy, physiology and pathology of the lymphatic vessels in man and vertebrates. DeLahaye A, Lecrosnier E (trans-eds) Paris, France. 1874.

    Google Scholar 

  43. Sugarbaker E, McBride C. Melanoma of the trunk: the results of surgical excision and anatomic guidelines for predicting nodal metastasis. Surgery. 1976;80(1):22–30.

    PubMed  CAS  Google Scholar 

  44. Norman J, Cruse CW, Espinosa C, Cox C, Berman C, Clark R, et al. Redefinition of cutaneous lymphatic drainage with the use of lymphoscintigraphy for malignant melanoma. Am J Surg. 1991;162(5):432–7.

    Article  CAS  PubMed  Google Scholar 

  45. Reynolds HM, Walker CG, Dunbar P, O’Sullivan MJ, Uren RF, Thompson JF, et al. Functional anatomy of the lymphatics draining the skin: a detailed statistical analysis. J Anat. 2010;216(3):344–55.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Damsky W, Theodosakis N, Bosenberg M. Melanoma metastasis: new concepts and evolving paradigms. Oncogene. 2014;33(19):2413–22.

    Article  CAS  PubMed  Google Scholar 

  47. Salmon M. Arteres de la peau: Etude anatomique et chirurgicale; Travail du Laboratoire d’anatomie de la Fac. de Marseille: Masson; 1936.

    Google Scholar 

  48. Taylor GI, Palmer J. The vascular territories (angiosomes) of the body: experimental study and clinical applications. Br J Plast Surg. 1987;40(2):113–41.

    Article  CAS  PubMed  Google Scholar 

  49. Taylor IG, Pan WR. Angiosomes of the leg: anatomic study and clinical implications. Plast Reconstr Surg. 1998;102(3):599–616.

    Article  CAS  PubMed  Google Scholar 

  50. Ryan T. Cutaneous circulation. Biochemistry and physiology of the skin. 1983;2:817–77.

    Google Scholar 

  51. Braverman IM, editor The cutaneous microcirculation. Journal of Investigative Dermatology Symposium Proceedings; 2000: Elsevier.

    Google Scholar 

  52. Braverman IM, Keh-Yen A. Ultrastructure of the human dermal microcirculation. IV. Valve-containing collecting veins at the dermal–subcutaneous junction. J Investig Dermatol. 1983;81(5):438–42.

    Article  CAS  PubMed  Google Scholar 

  53. Fernandez-Flores A. Prognostic factors for melanoma progression and metastasis: from hematoxylin-eosin to genetics. Romanian J Morphol Embryol. 2012;53(3):449–59.

    CAS  Google Scholar 

  54. Lugassy C, Barnhill RL. Angiotropic melanoma and extravascular migratory metastasis: a review. Adv Anat Pathol. 2007;14(3):195–201.

    Article  PubMed  Google Scholar 

  55. Zbytek B, Carlson JA, Granese J, Ross J, Mihm M, Slominski A. Current concepts of metastasis in melanoma. Expert Rev Dermatol. 2008;3(5):569–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Bayer-Garner IB, Hough AJ Jr, Smoller BR. Vascular endothelial growth factor expression in malignant melanoma: prognostic versus diagnostic usefulness. Modern pathology: an official journal of the United States and Canadian Academy of Pathology, Inc. 1999;12(8):770–4.

    CAS  Google Scholar 

  57. Villanueva J, Herlyn M. Melanoma and the tumor microenvironment. Current oncology reports. 2008;10(5):439-46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Brandner JM, Haass NK. Melanoma’s connections to the tumour microenvironment. Pathology-Journal of the RCPA. 2013;45(5):443–52.

    CAS  Google Scholar 

  59. Tannous ZS, Mihm MC, Sober AJ, Duncan LM. Congenital melanocytic nevi: clinical and histopathologic features, risk of melanoma, and clinical management. J Am Acad Dermatol. 2005;52(2):197–203.

    Article  PubMed  Google Scholar 

  60. Li G, Schaider H, Satyamoorthy K, Hanakawa Y, Hashimoto K, Herlyn M. Downregulation of E-cadherin and Desmoglein 1 by autocrine hepatocyte growth factor during melanoma development. Oncogene. 2001;20(56):8125–35.

    Article  CAS  PubMed  Google Scholar 

  61. Tang A, Eller MS, Hara M, Yaar M, Hirohashi S, Gilchrest BA. E-cadherin is the major mediator of human melanocyte adhesion to keratinocytes in vitro. J Cell Sci. 1994;107(4):983–92.

    PubMed  CAS  Google Scholar 

  62. Van Marck V, Stove C, Van Den Bossche K, Stove V, Paredes J, Vander Haeghen Y, et al. P-cadherin promotes cell-cell adhesion and counteracts invasion in human melanoma. Cancer Res. 2005;65(19):8774–83.

    Article  CAS  PubMed  Google Scholar 

  63. Labrousse AL, Ntayi C, Hornebeck W, Bernard P. Stromal reaction in cutaneous melanoma. Crit Rev Oncol Hematol. 2004;49(3):269–75.

    Article  PubMed  Google Scholar 

  64. Li G, Satyamoorthy K, Meier F, Berking C, Bogenrieder T, Herlyn M. Function and regulation of melanoma–stromal fibroblast interactions: when seeds meet soil. Oncogene. 2003;22(20):3162–71.

    Article  CAS  PubMed  Google Scholar 

  65. Clark WH, Elder DE, Guerry D, Epstein MN, Greene MH, Van Horn M. A study of tumor progression: the precursor lesions of superficial spreading and nodular melanoma. Hum Pathol. 1984;15(12):1147–65.

    Article  PubMed  Google Scholar 

  66. Ackerman AB, Mihara I. Dysplasia, dysplastic melanocytes, dysplastic nevi, the dysplastic nevus syndrome, and the relation between dysplastic nevi and malignant melanomas. Hum Pathol. 1985;16(1):87–91.

    Article  CAS  PubMed  Google Scholar 

  67. Duffy K, Grossman D. The dysplastic nevus: from historical perspective to management in the modern era: part I. Historical, histologic, and clinical aspects. Journal of the American Academy of Dermatology. 2012;67(1):1. e-. e16.

    Article  Google Scholar 

  68. Bergman W, van Voorst VP, Ruiter D. Dysplastic nevi and the risk of melanoma: a guideline for patient care. Nederlandse Melanoom Werkgroep van de Vereniging voor Integrale Kankercentra. Ned Tijdschr Geneeskd. 1997;141(42):2010–4.

    PubMed  CAS  Google Scholar 

  69. Clemente C, Cochran AJ, Elder DE, Levene A, Mackie RM, Mihm MC, et al. Histopathologic diagnosis of dysplastic nevi: concordance among pathologists convened by the World Health Organization melanoma Programme. Hum Pathol. 1991;22(4):313–9.

    Article  CAS  PubMed  Google Scholar 

  70. Lynch HT, Frichot BC, Lynch JF. Familial atypical multiple mole-melanoma syndrome. J Med Genet. 1978;15(5):352–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Elder DE, Goldman LI, Goldman SC, Greene MH, Clark WH. Dysplastic nevus syndrome: a phenotypic association of sporadic cutaneous melanoma. Cancer. 1980;46(8):1787–94.

    Article  CAS  PubMed  Google Scholar 

  72. Clark WH, Reimer RR, Greene M, Ainsworth AM, Mastrangelo MJ. Origin of familial malignant melanomas from heritable melanocytic lesions: the BK mole syndrome. Arch Dermatol. 1978;114(5):732–8.

    Article  PubMed  Google Scholar 

  73. Tucker MA, Fraser MC, Goldstein AM, Struewing JP, King MA, Crawford JT, et al. A natural history of melanomas and dysplastic nevi. Cancer. 2002;94(12):3192–209.

    Article  PubMed  Google Scholar 

  74. Kelly JW, Yeatman JM, Regalia C, Mason G, Henham AP. A high incidence of melanoma found in patients with multiple dysplastic naevi by photographic surveillance. Med J Aust. 1997;167(4):191–4.

    PubMed  CAS  Google Scholar 

  75. Greene MH, Clark WH Jr, Tucker MA, Elder DE, Kraemer KH, Guerry D IV, et al. Acquired precursors of cutaneous malignant melanoma: the familial dysplastic nevus syndrome. N Engl J Med. 1985;312(2):91–7.

    Article  CAS  PubMed  Google Scholar 

  76. Meyer LJ, Piepkorn M, Goldgar DE, Lewis CM, Cannon-Albright LA, Zone JJ, et al. Interobserver concordance in discriminating clinical atypia of melanocytic nevi, and correlations with histologic atypia. J Am Acad Dermatol. 1996;34(4):618–25.

    Article  CAS  PubMed  Google Scholar 

  77. Annessi G, Cattaruzza MS, Abeni D, Baliva G, Laurenza M, Macchini V, et al. Correlation between clinical atypia and histologic dysplasia in acquired melanocytic nevi. J Am Acad Dermatol. 2001;45(1):77–85.

    Article  CAS  PubMed  Google Scholar 

  78. Crucioli V, Stilwell J. The Histogenesis of malignant melanoma in relation to pre-existing pigmented lesions. J Cutan Pathol. 1982;9(6):396–404.

    Article  CAS  PubMed  Google Scholar 

  79. Sagebiel RW. Melanocytic nevi in histologic association with primary cutaneous melanoma of superficial spreading and nodular types: effect of tumor thickness. J Investig Dermatol. 1993;100(3):322–5.

    Article  Google Scholar 

  80. Bevona C, Goggins W, Quinn T, Fullerton J, Tsao H. Cutaneous melanomas associated with nevi. Arch Dermatol. 2003;139(12):1620–4.

    Article  PubMed  Google Scholar 

  81. Barnhill RL, Fleischli M. Histologic features of congenital melanocytic nevi in infants 1 year of age or younger. J Am Acad Dermatol. 1995;33(5):780–5.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Medicine, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

    Amir Dehdashtian M.D., M.P.H.

  2. Ronald O. Perelman Department of Dermatology, NYU School of Medicine, New York, NY, USA

    Thomas P. Stringer M.D., M.S.

  3. Department of Plastic Surgery, UT Southwestern Medical Center, Dallas, TX, USA

    Abby Joan Warren M.D. & Bardia Amirlak M.D., F.A.C.S.

  4. Ronald O. Perelman Department of Dermatology, NYU Langone Medical Center, New York, NY, USA

    Euphemia W. Mu M.D. & Ladan Shahabi M.D., F.A.A.D.

Authors
  1. Amir Dehdashtian M.D., M.P.H.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas P. Stringer M.D., M.S.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Abby Joan Warren M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Euphemia W. Mu M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bardia Amirlak M.D., F.A.C.S.
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ladan Shahabi M.D., F.A.A.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bardia Amirlak M.D., F.A.C.S. .

Editor information

Editors and Affiliations

  1. Louisiana State University, New Orleans, Louisiana, USA

    Adam I. Riker

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Dehdashtian, A., Stringer, T.P., Warren, A.J., Mu, E.W., Amirlak, B., Shahabi, L. (2018). Anatomy and Physiology of the Skin. In: Riker, A. (eds) Melanoma. Springer, Cham. https://doi.org/10.1007/978-3-319-78310-9_2

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-78310-9_2

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-78309-3

  • Online ISBN: 978-3-319-78310-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation