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Skin Cancer

Understanding the Anatomy

The skin is the largest organ in the body. The three main layers of the skin are the epidermis, dermis and subcutaneous tissue (also called the hypodermis or subcutis).

Within the different layers of the skin are different cell types. Any of these cells can, in theory, turn into cancer. For example, lymphocytes are immune cells found all over the body, including in the skin. Lymphocytes can turn cancerous, and this would be called lymphoma of the skin (or cutaneous lymphoma).

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  • Epidermis: This is the outermost layer of the skin. The epidermis is in turn made up of a number of layers. There is some slight variation in these layers, depending on the location in the body.

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The main cell types in the epidermis are keratinocytes, melanocytes, Merkel cells and Langerhans cells.

    • Keratinocytes: The epidermis is made up mainly of keratinocytes. They form a barrier for the body. Keratinocytes in the deeper layers of the epidermis are called basal cells, and basal cell carcinoma is from cancerous cells in this deepest epidermal layer.
    • Melanocytes: These are cells in the epidermis that make the protein melanin. Melanin is a protein pigment that gives skin a darker color. More melanin means darker skin. Melanin also protects skin cells from ultraviolet damage.
    • Merkel cells: These are “neuroendocrine cells” that resemble nerve cells but also have some features of hormone cells. Their exact function is not known, but they might play some role in sensing light touch.
    • Langerhans cells: These are immune, or infection-fighting, cells found in the epidermis. They are also in the dermis, lymph nodes and other parts of the body.
  • Dermis: This is generally the thickest of the three layers of the skin, which is still just a few millimeters. In this layer are blood vessels, lymphatic vessels, hair follicles, sweat glands, oil glands, nerve endings and fibrous tissue. The dermis is made up of two layers—the papillary dermis and reticular dermis.

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  • Subcutaneous layer (aka hypodermis or subcutis): This is the innermost layer of the skin. Here there are fat cells and collagen cells as well as bigger blood and lymphatic vessels.

Because you might see something called a “Clark Level of Thickness” on a pathology report about your skin cancer, it is worth knowing a little about. This is a way for a pathologist to report what layer of the dermis the skin cancer has grown into, regardless of how thick the tumor actually is. The greater the Clark Level, the deeper the tumor has grown into the dermis skin. This is still used in the staging system; invasion into Clark Level IV for an NMSC is considered an adverse feature and can upstage your cancer; that is, regardless of tumor size, having two or more adverse features puts your tumor into at least Stage II (see Staging of NMSC). The Clark Levels are as follows:

Clark Levels of Invasion of Skin Cancer

  • Level I: The cancer is limited to the epidermis.
  • Level II: The cancer invades partly into the papillary dermis.
  • Level III: The cancer completely fills the papillary dermis but does not extend into the reticular dermis.
  • Level IV: The cancer extends into the reticular dermis.
  • Level V: The cancer extends into the subcutaneous tissue.

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References

1 Miller DL, Weinstock MA. Nonmelanoma skin cancer in the United State: Incidence. J Am Academy of Dermatology. 1994;30:774.

2 American Cancer Society. Cancer Facts & Figures 2012. Atlanta: American Cancer Society; 2012.

3 Albores-Saavedra J, Batich K, Chable-Montero F, Sagy N, Schwartz AM, Henson DE. Merkel cell carcinoma demographics, morphology, and survival based on 3870 cases: a population based study. J Cutan Pathol. 2010:37:20-27.

4 LeBoit PE, Burg G, Weedon D, Sarasain A. (Eds.): World Health Organization. Classification of Tumours. Pathology and Genetics of Skin Tumours. IARC Press: Lyon 2006.

5 Referenced with permission from The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Basal Cell and Squamous Cell Skin Cancers V.1.2014. © National Comprehensive Cancer Network, Inc 2014. All rights reserved. Accessed Jan. 22, 2014. To view the most recent and complete version of the guideline, go online to www.nccn.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc.

6 Referenced with permission from The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Melanoma V.3.2014. © National Comprehensive Cancer Network, Inc 2014. All rights reserved. Accessed Feb 12, 2014. To view the most recent and complete version of the guideline, go online to www.nccn.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc.

7 Referenced with permission from The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Merkel Cell Carcinoma V.1.2014. © National Comprehensive Cancer Network, Inc 2014. All rights reserved. Accessed Jan. 22, 2014. To view the most recent and complete version of the guideline, go online to www.nccn.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc.

8 Referenced with permission from the NCCN Guidelines for Patients®: Melanoma V.1.2013. © National Comprehensive Cancer Network, Inc 2013. All rights reserved. Accessed July 2, 2013. To view the most recent and complete version of the guideline, go online to www.nccn.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc.

9 Rubin AI, Chen EH, Ratner D. Basal Cell Carcinoma. N Engl J Med. 2005;353:2262-2269.

10 Walling HW, Fosko SW, Geraminejad PA, Whitaker DC, Arpey CJ. Aggressive basal cell carcinoma: Presentation, pathogenesis, and management. Cancer and Metastasis Reviews. 2004;23(3-4):389-402.

11 Hollestein LM, de Vries E, Nijsten T. Trends of cutaneous squamous cell carcinoma in the Netherlands: Increased incidence rates, but stable relative survival and mortality 1989-2008. European Journal of Cancer. 2012;48(13):2046-2053.

12 Lardar T, Shea SM, Sharfman W, Liegeois N, Sober AJ. Improvements in the Staging of Cutaneous Squamous-Cell Carcinoma in the 7th Edition of the AJCC Cancer Staging Manual. Annals of Surgical Oncology. 2010;17(8):1979-1980.

13 Cockburn M, Peng D, Key C. Chapter 12: Melanoma. Ries LAG, Young JL, Keel GE, Eisner MP, Lin YD, Horner M-J (editors). SEER Survival Monograph: Cancer Survival Among Adults: U.S. SEER Program, 1988-2001, Patient and Tumor Characteristics. National Cancer Institute, SEER Program, NIH Pub. No. 07-6215, Bethesda, MD, 2007.

14 Edge SB, et al. The AJCC Cancer Staging Manual – Seventh Edition. American Joint Committee on Cancer 2010. Chapter 31: Melanoma of the Skin. P329.

15 Howlader N, Noone AM, Krapcho M, Neyman N, Aminou R, Altekruse SF, Kosary CL, Ruhl J, Tatalovich Z, Cho H, Mariotto A, Eisner MP, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2009 (Vintage 2009 Populations), National Cancer Institute. Bethesda, MD.

16 Agelli M, Clegg LX. Epidemiology of primary Merkel cell carcinoma in the United States. J Am Acad Dermatol. 2003;49:832-41.

17 Engels EA, Frisch M, Goedert JJ, Biggar RJ, Miller RW. Merkel cell carcinoma and HIV infection. The Lancet. 2002;359(9305):497-498.

18 Buell JF, Trofe J, Hanaway MJ, et al. Immunosuppresion and Merkel cell cancer. Transplant Proc. 2002;34(5):1780-1.

19 Penn I, First MR. Merkel cell carcinoma in organ recipients: report of 41 cases. Transplantation. 1999;68(11):1717-21.

20 Young JL, Ward, KC, Ries LAG. Chapter 30: Cancers of Rare Sites. Ries LAG, Young JL, Keel GE, Eisner MP, Lin YD, Horner M-J (editors). SEER Survival Monograph: Cancer Survival Among Adults: U.S. SEER Program, 1988-2001, Patient and Tumor Characteristics. National Cancer Institute, SEER Program, NIH Pub. No. 07-6215, Bethesda, MD, 2007.

21 Albores-Saavedra J, Batich K, Chable-Montero F, Sagy N, Schwartz AM, Henson DE. Merkel cell carcinoma demographics, morphology, and survival based on 3870 cases: a population based study. J Cutan Pathol. 2010:37:20.

22 Wang TS, Byrne PJ, Jacobs LK, Taube JM. Merkel Cell Carcinoma: Update and Review. 2011 Seminars in Cutaneous Medicine and Surgery: 30(1):48-56.