Squamous Cell Carcinoma

  • Eileen Larkin Axibal
  • Mariah Ruth BrownEmail author


Cutaneous squamous cell carcinoma is an exceedingly common neoplasm with a rising incidence. It frequently affects individuals who are fair-skinned with high cumulative ultraviolet radiation exposure, are immunosuppressed, or have a genetic predisposition. Squamous cell carcinoma can be suspected clinically by an erythematous, hyperkeratotic, tender, infiltrated, or ulcerated papule or plaque. Biopsy with histopathologic examination is the gold standard diagnostic modality, but several noninvasive techniques for diagnosis are being developed. Features affecting tumor risk include location, clinical size, depth of extension, histologic subtype, degree of histologic differentiation, recurrence, and immunosuppressed status of patient. Aggressive, high-risk lesions have the potential to invade surrounding tissue, metastasize, and recur, resulting in significant morbidity and even death. Mohs micrographic surgery is the preferred treatment for high-risk tumors, as it affords the highest cure rates, preservation of normal tissue, and cosmetic outcome. The standard of treatment for low-risk tumors is conventional surgical excision. Other treatment options include electrodesiccation and curettage, cryosurgery, radiotherapy, photodynamic therapy, and topical agents. Due to the risk of tumor recurrence and additional skin cancers, patients with a history of SCC should undergo regular clinical follow-up with a frequency guided by risk assessment.


Squamous cell carcinoma SCC Non-melanoma skin cancer Epidemiology Risk factors Prevention High-risk Treatment Mohs micrographic surgery Recurrence 


  1. 1.
    Alam M, Ratner D. Cutaneous squamous-cell carcinoma. N Engl J Med. 2001;344(13):975–83.CrossRefPubMedGoogle Scholar
  2. 2.
    Karia PS, Han J, Schmults CD. Cutaneous squamous cell carcinoma: estimated incidence of disease, nodal metastasis, and deaths from disease in the United States, 2012. J Am Acad Dermatol. 2013;68(6):957–66.CrossRefPubMedGoogle Scholar
  3. 3.
    Muzic JG, Schmitt AR, Wright AC, Alniemi DT, Zubair AS, Olazagasti Lourido JM, et al. Incidence and trends of basal cell carcinoma and cutaneous squamous cell carcinoma: a population-based study in Olmsted County, Minnesota, 2000 to 2010. Mayo Clin Proc. 2017;92(6):890–8.PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Lomas A, Leonardi-Bee J, Bath-Hextall F. A systematic review of worldwide incidence of nonmelanoma skin cancer. Br J Dermatol. 2012;166(5):1069–80.PubMedCrossRefGoogle Scholar
  5. 5.
    Agbai ON, Buster K, Sanchez M, Hernandez C, Kundu RV, Chiu M, et al. Skin cancer and photoprotection in people of color: a review and recommendations for physicians and the public. J Am Acad Dermatol. 2014;70(4):748–62.PubMedCrossRefGoogle Scholar
  6. 6.
    Xiang F, Lucas R, Hales S, Neale R. Incidence of nonmelanoma skin cancer in relation to ambient UV radiation in white populations, 1978–2012: empirical relationships. JAMA Dermatol. 2014;150(10):1063–71.PubMedCrossRefGoogle Scholar
  7. 7.
    Miller DL, Weinstock MA. Nonmelanoma skin cancer in the United States: incidence. J Am Acad Dermatol. 1994;30(5 Pt 1):774–8.CrossRefPubMedGoogle Scholar
  8. 8.
    Kauvar AN, Arpey CJ, Hruza G, Olbricht SM, Bennett R, Mahmoud BH. Consensus for nonmelanoma skin cancer treatment, part II: squamous cell carcinoma, including a cost analysis of treatment methods. Dermatol Surg. 2015;41(11):1214–40.CrossRefPubMedGoogle Scholar
  9. 9.
    Donaldson MR, Coldiron BM. No end in sight: the skin cancer epidemic continues. Semin Cutan Med Surg. 2011;30(1):3–5.PubMedCrossRefGoogle Scholar
  10. 10.
    Lewis KG, Weinstock MA. Nonmelanoma skin cancer mortality (1988–2000): the Rhode Island follow-back study. Arch Dermatol. 2004;140(7):837–42.PubMedCrossRefGoogle Scholar
  11. 11.
    Armstrong BK, Kricker A. The epidemiology of UV induced skin cancer. J Photochem Photobiol B. 2001;63(1–3):8–18.PubMedCrossRefGoogle Scholar
  12. 12.
    O’Sullivan NA, Tait CP. Tanning bed and nail lamp use and the risk of cutaneous malignancy: a review of the literature. Australas J Dermatol. 2014;55(2):99–106.PubMedCrossRefGoogle Scholar
  13. 13.
    D’Orazio J, Jarrett S, Amaro-Ortiz A, Scott T. UV radiation and the skin. Int J Mol Sci. 2013;14(6):12222–48.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Green AC, Olsen CM. Cutaneous squamous cell carcinoma: an epidemiological review. Br J Dermatol. 2017;177(2):373–81.PubMedCrossRefGoogle Scholar
  15. 15.
    Brash DE, Rudolph JA, Simon JA, Lin A, McKenna GJ, Baden HP, et al. A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma. Proc Natl Acad Sci U S A. 1991;88(22):10124–8.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Wehner MR, Chren MM, Nameth D, Choudhry A, Gaskins M, Nead KT, et al. International prevalence of indoor tanning: a systematic review and meta-analysis. JAMA Dermatol. 2014;150(4):390–400.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Stern RS, Study PF-U. The risk of squamous cell and basal cell cancer associated with psoralen and ultraviolet A therapy: a 30-year prospective study. J Am Acad Dermatol. 2012;66(4):553–62.CrossRefPubMedGoogle Scholar
  18. 18.
    Euvrard S, Kanitakis J, Claudy A. Skin cancers after organ transplantation. N Engl J Med. 2003;348(17):1681–91.PubMedCrossRefGoogle Scholar
  19. 19.
    Zwald FO, Brown M. Skin cancer in solid organ transplant recipients: advances in therapy and management: part I. Epidemiology of skin cancer in solid organ transplant recipients. J Am Acad Dermatol. 2011;65(2):253–61. quiz 62PubMedCrossRefGoogle Scholar
  20. 20.
    Kallini JR, Hamed N, Khachemoune A. Squamous cell carcinoma of the skin: epidemiology, classification, management, and novel trends. Int J Dermatol. 2015;54(2):130–40.PubMedCrossRefGoogle Scholar
  21. 21.
    Otley CC, Cherikh WS, Salasche SJ, McBride MA, Christenson LJ, Kauffman HM. Skin cancer in organ transplant recipients: effect of pretransplant end-organ disease. J Am Acad Dermatol. 2005;53(5):783–90.PubMedCrossRefGoogle Scholar
  22. 22.
    Garrett GL, Blanc PD, Boscardin J, Lloyd AA, Ahmed RL, Anthony T, et al. Incidence of and risk factors for skin cancer in organ transplant recipients in the United States. JAMA Dermatol. 2017;153(3):296–303.CrossRefPubMedGoogle Scholar
  23. 23.
    Chockalingam R, Downing C, Tyring SK. Cutaneous squamous cell carcinomas in organ transplant recipients. J Clin Med. 2015;4(6):1229–39.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Perrett CM, Walker SL, O’Donovan P, Warwick J, Harwood CA, Karran P, et al. Azathioprine treatment photosensitizes human skin to ultraviolet A radiation. Br J Dermatol. 2008;159(1):198–204.PubMedCrossRefGoogle Scholar
  25. 25.
    Norman KG, Canter JA, Shi M, Milne GL, Morrow JD, Sligh JE. Cyclosporine A suppresses keratinocyte cell death through MPTP inhibition in a model for skin cancer in organ transplant recipients. Mitochondrion. 2010;10(2):94–101.PubMedCrossRefGoogle Scholar
  26. 26.
    Kauffman HM, Cherikh WS, Cheng Y, Hanto DW, Kahan BD. Maintenance immunosuppression with target-of-rapamycin inhibitors is associated with a reduced incidence of de novo malignancies. Transplantation. 2005;80(7):883–9.CrossRefPubMedGoogle Scholar
  27. 27.
    Ducroux E, Martin C, Bouwes Bavinck JN, Decullier E, Brocard A, Westhuis-van Elsacker ME, et al. Risk of aggressive skin cancers after kidney retransplantation in patients with previous posttransplant cutaneous squamous cell carcinomas: a retrospective study of 53 cases. Transplantation. 2017;101(4):e133–e41.PubMedCrossRefGoogle Scholar
  28. 28.
    Brewer JD, Shanafelt TD, Khezri F, Sosa Seda IM, Zubair AS, Baum CL, et al. Increased incidence and recurrence rates of nonmelanoma skin cancer in patients with non-Hodgkin lymphoma: a Rochester Epidemiology Project population-based study in Minnesota. J Am Acad Dermatol. 2015;72(2):302–9.PubMedCrossRefGoogle Scholar
  29. 29.
    Zhao H, Shu G, Wang S. The risk of non-melanoma skin cancer in HIV-infected patients: new data and meta-analysis. Int J STD AIDS. 2016;27(7):568–75.CrossRefPubMedGoogle Scholar
  30. 30.
    Hock BD, McIntosh ND, McKenzie JL, Pearson JF, Simcock JW, MacPherson SA. Incidence of cutaneous squamous cell carcinoma in a New Zealand population of chronic lymphocytic leukaemia patients. Intern Med J. 2016;46(12):1414–21.PubMedCrossRefGoogle Scholar
  31. 31.
    Amari W, Zeringue AL, McDonald JR, Caplan L, Eisen SA, Ranganathan P. Risk of non-melanoma skin cancer in a national cohort of veterans with rheumatoid arthritis. Rheumatology (Oxford). 2011;50(8):1431–9.CrossRefGoogle Scholar
  32. 32.
    Singh H, Nugent Z, Demers AA, Bernstein CN. Increased risk of nonmelanoma skin cancers among individuals with inflammatory bowel disease. Gastroenterology. 2011;141(5):1612–20.PubMedCrossRefGoogle Scholar
  33. 33.
    Karagas MR, Cushing GL, Greenberg ER, Mott LA, Spencer SK, Nierenberg DW. Non-melanoma skin cancers and glucocorticoid therapy. Br J Cancer. 2001;85(5):683–6.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Baibergenova AT, Weinstock MA, Group VT. Oral prednisone use and risk of keratinocyte carcinoma in non-transplant population. The VATTC trial. J Eur Acad Dermatol Venereol. 2012;26(9):1109–15.PubMedCrossRefGoogle Scholar
  35. 35.
    Veness MJ, Quinn DI, Ong CS, Keogh AM, Macdonald PS, Cooper SG, et al. Aggressive cutaneous malignancies following cardiothoracic transplantation: the Australian experience. Cancer. 1999;85(8):1758–64.PubMedCrossRefGoogle Scholar
  36. 36.
    Jaju PD, Ransohoff KJ, Tang JY, Sarin KY. Familial skin cancer syndromes: increased risk of nonmelanotic skin cancers and extracutaneous tumors. J Am Acad Dermatol. 2016;74(3):437–51. quiz 52-4PubMedCrossRefGoogle Scholar
  37. 37.
    Perry PK, Silverberg NB. Cutaneous malignancy in albinism. Cutis. 2001;67(5):427–30.PubMedGoogle Scholar
  38. 38.
    Burger B, Itin PH. Epidermodysplasia verruciformis. Curr Probl Dermatol. 2014;45:123–31.CrossRefPubMedGoogle Scholar
  39. 39.
    Ramoz N, Rueda LA, Bouadjar B, Montoya LS, Orth G, Favre M. Mutations in two adjacent novel genes are associated with epidermodysplasia verruciformis. Nat Genet. 2002;32(4):579–81.PubMedCrossRefGoogle Scholar
  40. 40.
    Dubina M, Goldenberg G. Viral-associated nonmelanoma skin cancers: a review. Am J Dermatopathol. 2009;31(6):561–73.PubMedCrossRefGoogle Scholar
  41. 41.
    Mellerio JE, Robertson SJ, Bernardis C, Diem A, Fine JD, George R, et al. Management of cutaneous squamous cell carcinoma in patients with epidermolysis bullosa: best clinical practice guidelines. Br J Dermatol. 2016;174(1):56–67.PubMedCrossRefGoogle Scholar
  42. 42.
    Fine JD, Johnson LB, Weiner M, Li KP, Suchindran C. Epidermolysis bullosa and the risk of life-threatening cancers: the National EB Registry experience, 1986–2006. J Am Acad Dermatol. 2009;60(2):203–11.PubMedCrossRefGoogle Scholar
  43. 43.
    Johnson TM, Rowe DE, Nelson BR, Swanson NA. Squamous cell carcinoma of the skin (excluding lip and oral mucosa). J Am Acad Dermatol. 1992;26(3 Pt 2):467–84.PubMedCrossRefGoogle Scholar
  44. 44.
    Kerr-Valentic MA, Samimi K, Rohlen BH, Agarwal JP, Rockwell WB. Marjolin’s ulcer: modern analysis of an ancient problem. Plast Reconstr Surg. 2009;123(1):184–91.PubMedCrossRefGoogle Scholar
  45. 45.
    Wang J, Aldabagh B, Yu J, Arron ST. Role of human papillomavirus in cutaneous squamous cell carcinoma: a meta-analysis. J Am Acad Dermatol. 2014;70(4):621–9.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Arron ST, Ruby JG, Dybbro E, Ganem D, Derisi JL. Transcriptome sequencing demonstrates that human papillomavirus is not active in cutaneous squamous cell carcinoma. J Invest Dermatol. 2011;131(8):1745–53.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Arron ST, Jennings L, Nindl I, Rosl F, Bouwes Bavinck JN, Seçkin D, et al. Viral oncogenesis and its role in nonmelanoma skin cancer. Br J Dermatol. 2011;164(6):1201–13.PubMedCrossRefGoogle Scholar
  48. 48.
    Lichter MD, Karagas MR, Mott LA, Spencer SK, Stukel TA, Greenberg ER. Therapeutic ionizing radiation and the incidence of basal cell carcinoma and squamous cell carcinoma. The New Hampshire Skin Cancer Study Group. Arch Dermatol. 2000;136(8):1007–11.CrossRefPubMedGoogle Scholar
  49. 49.
    Davis MM, Hanke CW, Zollinger TW, Montebello JF, Hornback NB, Norins AL. Skin cancer in patients with chronic radiation dermatitis. J Am Acad Dermatol. 1989;20(4):608–16.PubMedCrossRefGoogle Scholar
  50. 50.
    Su F, Viros A, Milagre C, Trunzer K, Bollag G, Spleiss O, et al. RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N Engl J Med. 2012;366(3):207–15.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Williams K, Mansh M, Chin-Hong P, Singer J, Arron ST. Voriconazole-associated cutaneous malignancy: a literature review on photocarcinogenesis in organ transplant recipients. Clin Infect Dis. 2014;58(7):997–1002.PubMedCrossRefGoogle Scholar
  52. 52.
    Yu HS, Liao WT, Chai CY. Arsenic carcinogenesis in the skin. J Biomed Sci. 2006;13(5):657–66.PubMedCrossRefGoogle Scholar
  53. 53.
    Gallagher RP, Bajdik CD, Fincham S, Hill GB, Keefe AR, Coldman A, et al. Chemical exposures, medical history, and risk of squamous and basal cell carcinoma of the skin. Cancer Epidemiol Biomarkers Prev. 1996;5(6):419–24.PubMedGoogle Scholar
  54. 54.
    Gawkrodger DJ. Occupational skin cancers. Occup Med (Lond). 2004;54(7):458–63.CrossRefGoogle Scholar
  55. 55.
    Sorahan T, Cooke MA, Wilson S. Incidence of cancer of the scrotum, 1971–84. Br J Ind Med. 1989;46(6):430–1.PubMedPubMedCentralGoogle Scholar
  56. 56.
    Karagas MR. Occurrence of cutaneous basal cell and squamous cell malignancies among those with a prior history of skin cancer. The Skin Cancer Prevention Study Group. J Invest Dermatol. 1994;102(6):10S–3S.PubMedCrossRefGoogle Scholar
  57. 57.
    Dzubow LM, Rigel DS, Robins P. Risk factors for local recurrence of primary cutaneous squamous cell carcinomas. Treatment by microscopically controlled excision. Arch Dermatol. 1982;118(11):900–2.PubMedCrossRefGoogle Scholar
  58. 58.
    Marcil I, Stern RS. Risk of developing a subsequent nonmelanoma skin cancer in patients with a history of nonmelanoma skin cancer: a critical review of the literature and meta-analysis. Arch Dermatol. 2000;136(12):1524–30.CrossRefPubMedGoogle Scholar
  59. 59.
    van der Pols JC, Williams GM, Pandeya N, Logan V, Green AC. Prolonged prevention of squamous cell carcinoma of the skin by regular sunscreen use. Cancer Epidemiol Biomarkers Prev. 2006;15(12):2546–8.PubMedCrossRefGoogle Scholar
  60. 60.
    Olsen CM, Wilson LF, Green AC, Bain CJ, Fritschi L, Neale RE, et al. Cancers in Australia attributable to exposure to solar ultraviolet radiation and prevented by regular sunscreen use. Aust N Z J Public Health. 2015;39(5):471–6.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Darlington S, Williams G, Neale R, Frost C, Green A. A randomized controlled trial to assess sunscreen application and beta carotene supplementation in the prevention of solar keratoses. Arch Dermatol. 2003;139(4):451–5.PubMedCrossRefGoogle Scholar
  62. 62.
    Damian DL. Nicotinamide for skin cancer chemoprevention. Australas J Dermatol. 2017;58(3):174–80.PubMedCrossRefGoogle Scholar
  63. 63.
    Chen AC, Martin AJ, Choy B, Fernández-Peñas P, Dalziell RA, McKenzie CA, et al. A phase 3 randomized trial of nicotinamide for skin-cancer chemoprevention. N Engl J Med. 2015;373(17):1618–26.CrossRefPubMedGoogle Scholar
  64. 64.
    Kreul SM, Havighurst T, Kim K, Mendonça EA, Wood GS, Snow S, et al. A phase III skin cancer chemoprevention study of DFMO: long-term follow-up of skin cancer events and toxicity. Cancer Prev Res (Phila). 2012;5(12):1368–74.CrossRefGoogle Scholar
  65. 65.
    Wu PA, Stern RS. Topical tretinoin, another failure in the pursuit of practical chemoprevention for non-melanoma skin cancer. J Invest Dermatol. 2012;132(6):1532–5.PubMedCrossRefGoogle Scholar
  66. 66.
    Weinstock MA, Bingham SF, Digiovanna JJ, Rizzo AE, Marcolivio K, Hall R, et al. Tretinoin and the prevention of keratinocyte carcinoma (Basal and squamous cell carcinoma of the skin): a veterans affairs randomized chemoprevention trial. J Invest Dermatol. 2012;132(6):1583–90.CrossRefPubMedGoogle Scholar
  67. 67.
    Harwood CA, Leedham-Green M, Leigh IM, Proby CM. Low-dose retinoids in the prevention of cutaneous squamous cell carcinomas in organ transplant recipients: a 16-year retrospective study. Arch Dermatol. 2005;141(4):456–64.CrossRefPubMedGoogle Scholar
  68. 68.
    George R, Weightman W, Russ GR, Bannister KM, Mathew TH. Acitretin for chemoprevention of non-melanoma skin cancers in renal transplant recipients. Australas J Dermatol. 2002;43(4):269–73.CrossRefPubMedGoogle Scholar
  69. 69.
    Prieto-Granada C, Rodriguez-Waitkus P. Cutaneous squamous cell carcinoma and related entities: epidemiology, clinical and histological features, and basic science overview. Curr Probl Cancer. 2015;39(4):206–15.PubMedCrossRefGoogle Scholar
  70. 70.
    Werner RN, Sammain A, Erdmann R, Hartmann V, Stockfleth E, Nast A. The natural history of actinic keratosis: a systematic review. Br J Dermatol. 2013;169(3):502–18.PubMedCrossRefGoogle Scholar
  71. 71.
    Marks R, Rennie G, Selwood TS. Malignant transformation of solar keratoses to squamous cell carcinoma. Lancet. 1988;1(8589):795–7.PubMedCrossRefGoogle Scholar
  72. 72.
    Callen JP, Bickers DR, Moy RL. Actinic Keratoses. J Am Acad Dermatol. 1997 Apr; 36(4):650–3.PubMedCrossRefGoogle Scholar
  73. 73.
    Plasmeijer EI, Neale RE, de Koning MN, Quint WG, McBride P, Feltkamp MC, et al. Persistence of betapapillomavirus infections as a risk factor for actinic keratoses, precursor to cutaneous squamous cell carcinoma. Cancer Res. 2009;69(23):8926–31.PubMedCrossRefGoogle Scholar
  74. 74.
    Stratigos A, Garbe C, Lebbe C, Malvehy J, del Marmol V, Pehamberger H, et al. Diagnosis and treatment of invasive squamous cell carcinoma of the skin: European consensus-based interdisciplinary guideline. Eur J Cancer. 2015;51(14):1989–2007.PubMedCrossRefGoogle Scholar
  75. 75.
    Kwiek B, Schwartz RA. Keratoacanthoma (KA): an update and review. J Am Acad Dermatol. 2016;74(6):1220–33.PubMedCrossRefGoogle Scholar
  76. 76.
    Klima M, Kurtis B, Jordan PH. Verrucous carcinoma of skin. J Cutan Pathol. 1980;7(2):88–98.PubMedCrossRefGoogle Scholar
  77. 77.
    Compton LA, Murphy GF, Lian CG. Diagnostic immunohistochemistry in cutaneous neoplasia: an update. Dermatopathology (Basel). 2015;2(1):15–42.CrossRefGoogle Scholar
  78. 78.
    Warszawik-Hendzel O, Olszewska M, Maj M, Rakowska A, Czuwara J, Rudnicka L. Non-invasive diagnostic techniques in the diagnosis of squamous cell carcinoma. J Dermatol Case Rep. 2015;9(4):89–97.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Ulrich M, Lange-Asschenfeldt S. In vivo confocal microscopy in dermatology: from research to clinical application. J Biomed Opt. 2013;18(6):061212.PubMedCrossRefGoogle Scholar
  80. 80.
    Rishpon A, Kim N, Scope A, Porges L, Oliviero MC, Braun RP, et al. Reflectance confocal microscopy criteria for squamous cell carcinomas and actinic keratoses. Arch Dermatol. 2009;145(7):766–72.PubMedCrossRefGoogle Scholar
  81. 81.
    Wortsman X, Wortsman J. Clinical usefulness of variable-frequency ultrasound in localized lesions of the skin. J Am Acad Dermatol. 2010;62(2):247–56.PubMedCrossRefGoogle Scholar
  82. 82.
    Boone MA, Suppa M, Marneffe A, Miyamoto M, Jemec GB, Del Marmol V. A new algorithm for the discrimination of actinic keratosis from normal skin and squamous cell carcinoma based on in vivo analysis of optical properties by high-definition optical coherence tomography. J Eur Acad Dermatol Venereol. 2016;30(10):1714–25.PubMedCrossRefGoogle Scholar
  83. 83.
    Schmults CD, Karia PS, Carter JB, Han J, Qureshi AA. Factors predictive of recurrence and death from cutaneous squamous cell carcinoma: a 10-year, single-institution cohort study. JAMA Dermatol. 2013;149(5):541–7.PubMedCrossRefGoogle Scholar
  84. 84.
    Mourouzis C, Boynton A, Grant J, Umar T, Wilson A, Macpheson D, et al. Cutaneous head and neck SCCs and risk of nodal metastasis – UK experience. J Craniomaxillofac Surg. 2009;37(8):443–7.PubMedCrossRefGoogle Scholar
  85. 85.
    Brougham ND, Dennett ER, Cameron R, Tan ST. The incidence of metastasis from cutaneous squamous cell carcinoma and the impact of its risk factors. J Surg Oncol. 2012;106(7):811–5.PubMedCrossRefGoogle Scholar
  86. 86.
    Miller SJ. The National Comprehensive Cancer Network (NCCN) guidelines of care for nonmelanoma skin cancers. Dermatol Surg. 2000;26(3):289–92.PubMedCrossRefGoogle Scholar
  87. 87.
    Rowe DE, Carroll RJ, Day CL. Prognostic factors for local recurrence, metastasis, and survival rates in squamous cell carcinoma of the skin, ear, and lip. Implications for treatment modality selection. J Am Acad Dermatol. 1992;26(6):976–90.CrossRefPubMedGoogle Scholar
  88. 88.
    Thompson AK, Kelley BF, Prokop LJ, Murad MH, Baum CL. Risk factors for cutaneous squamous cell carcinoma recurrence, metastasis, and disease-specific death: a systematic review and meta-analysis. JAMA Dermatol. 2016;152(4):419–28.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Jambusaria-Pahlajani A, Kanetsky PA, Karia PS, Hwang WT, Gelfand JM, Whalen FM, et al. Evaluation of AJCC tumor staging for cutaneous squamous cell carcinoma and a proposed alternative tumor staging system. JAMA Dermatol. 2013;149(4):402–10.CrossRefPubMedGoogle Scholar
  90. 90.
    Edge S, Byrd D, Comptom C, Fritz A, Greene F, Trotti A. AJCC cancer staging manual. 7th ed. New York: Springer; 2010.Google Scholar
  91. 91.
    Sobin L, Gospodarowicz M, Wittekind C. TNM classification of malignant tumours. 7th ed. Chichester: Wiley-Blackwell; 2010.Google Scholar
  92. 92.
    Gonzalez JL, Cunningham K, Silverman R, Madan E, Nguyen BM. Comparison of the American Joint Committee on Cancer Seventh Edition and Brigham and Women’s Hospital cutaneous squamous cell carcinoma tumor staging in immunosuppressed patients. Dermatol Surg. 2017;43(6):784–91.PubMedCrossRefGoogle Scholar
  93. 93.
    Stevenson ML, Kim R, Meehan SA, Pavlick AC, Carucci JA. Metastatic cutaneous squamous cell carcinoma: the importance of T2 stratification and hematologic malignancy in prognostication. Dermatol Surg. 2016;42(8):932–5.CrossRefPubMedGoogle Scholar
  94. 94.
    Navarrete-Dechent C, Veness MJ, Droppelmann N, Uribe P. High-risk cutaneous squamous cell carcinoma and the emerging role of sentinel lymph node biopsy: a literature review. J Am Acad Dermatol. 2015;73(1):127–37.PubMedCrossRefGoogle Scholar
  95. 95.
    Kelder W, Ebrahimi A, Forest VI, Gao K, Murali R, Clark JR. Cutaneous head and neck squamous cell carcinoma with regional metastases: the prognostic importance of soft tissue metastases and extranodal spread. Ann Surg Oncol. 2012;19(1):274–9.PubMedCrossRefGoogle Scholar
  96. 96.
    Ross AS, Schmults CD. Sentinel lymph node biopsy in cutaneous squamous cell carcinoma: a systematic review of the English literature. Dermatol Surg. 2006;32(11):1309–21.PubMedGoogle Scholar
  97. 97.
    Jank S, Robatscher P, Emshoff R, Strobl H, Gojer G, Norer B. The diagnostic value of ultrasonography to detect occult lymph node involvement at different levels in patients with squamous cell carcinoma in the maxillofacial region. Int J Oral Maxillofac Surg. 2003;32(1):39–42.PubMedCrossRefGoogle Scholar
  98. 98.
    Griffith JF, Chan AC, Ahuja AT, Leung SF, Chow LT, Chung SC, et al. Neck ultrasound in staging squamous oesophageal carcinoma – a high yield technique. Clin Radiol. 2000;55(9):696–701.PubMedCrossRefGoogle Scholar
  99. 99.
    Chan JY, Chan RC, Chow VL, To VS, Wei WI. Efficacy of fine-needle aspiration in diagnosing cervical nodal metastasis from nasopharyngeal carcinoma after radiotherapy. Laryngoscope. 2013;123(1):134–9.PubMedCrossRefGoogle Scholar
  100. 100.
    Allen JE, Stolle LB. Utility of sentinel node biopsy in patients with high-risk cutaneous squamous cell carcinoma. Eur J Surg Oncol. 2015;41(2):197–200.PubMedCrossRefGoogle Scholar
  101. 101.
    Schmitt AR, Brewer JD, Bordeaux JS, Baum CL. Staging for cutaneous squamous cell carcinoma as a predictor of sentinel lymph node biopsy results: meta-analysis of American Joint Committee on Cancer criteria and a proposed alternative system. JAMA Dermatol. 2014;150(1):19–24.PubMedCrossRefGoogle Scholar
  102. 102.
    Ruiz ES, Karia PS, Morgan FC, Schmults CD. The positive impact of radiologic imaging on high-stage cutaneous squamous cell carcinoma management. J Am Acad Dermatol. 2017;76(2):217–25.PubMedCrossRefGoogle Scholar
  103. 103.
    MacFarlane D, Shah K, Wysong A, Wortsman X, Humphreys TR. The role of imaging in the management of patients with nonmelanoma skin cancer: diagnostic modalities and applications. J Am Acad Dermatol. 2017;76(4):579–88.PubMedCrossRefGoogle Scholar
  104. 104.
    Cherpelis BS, Marcusen C, Lang PG. Prognostic factors for metastasis in squamous cell carcinoma of the skin. Dermatol Surg. 2002;28(3):268–73.PubMedGoogle Scholar
  105. 105.
    Brodland DG, Zitelli JA. Surgical margins for excision of primary cutaneous squamous cell carcinoma. J Am Acad Dermatol. 1992;27(2 Pt 1):241–8.CrossRefPubMedGoogle Scholar
  106. 106.
    Alam M, Nanda S, Mittal BB, Kim NA, Yoo S. The use of brachytherapy in the treatment of nonmelanoma skin cancer: a review. J Am Acad Dermatol. 2011;65(2):377–88.PubMedCrossRefGoogle Scholar
  107. 107.
    Delishaj D, Rembielak A, Manfredi B, Ursino S, Pasqualetti F, Laliscia C, et al. Non-melanoma skin cancer treated with high-dose-rate brachytherapy: a review of literature. J Contemp Brachytherapy. 2016;8(6):533–40.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Nguyen TH, Ho DQ. Nonmelanoma skin cancer. Curr Treat Options Oncol. 2002;3(3):193–203.CrossRefPubMedGoogle Scholar
  109. 109.
    Reschly MJ, Shenefelt PD. Controversies in skin surgery: electrodessication and curettage versus excision for low-risk, small, well-differentiated squamous cell carcinomas. J Drugs Dermatol. 2010;9(7):773–6.PubMedGoogle Scholar
  110. 110.
    Brightman L, Warycha M, Anolik R, Geronemus R. Do lasers or topicals really work for nonmelanoma skin cancers? Semin Cutan Med Surg. 2011;30(1):14–25.PubMedCrossRefGoogle Scholar
  111. 111.
    Morton C, Horn M, Leman J, Tack B, Bedane C, Tjioe M, et al. Comparison of topical methyl aminolevulinate photodynamic therapy with cryotherapy or fluorouracil for treatment of squamous cell carcinoma in situ: results of a multicenter randomized trial. Arch Dermatol. 2006;142(6):729–35.PubMedCrossRefGoogle Scholar
  112. 112.
    Calzavara-Pinton PG. Repetitive photodynamic therapy with topical delta-aminolaevulinic acid as an appropriate approach to the routine treatment of superficial non-melanoma skin tumours. J Photochem Photobiol B. 1995;29(1):53–7.PubMedCrossRefGoogle Scholar
  113. 113.
    Willey A, Mehta S, Lee PK. Reduction in the incidence of squamous cell carcinoma in solid organ transplant recipients treated with cyclic photodynamic therapy. Dermatol Surg. 2010;36(5):652–8.PubMedCrossRefGoogle Scholar
  114. 114.
    Salim A, Leman JA, McColl JH, Chapman R, Morton CA. Randomized comparison of photodynamic therapy with topical 5-fluorouracil in Bowen’s disease. Br J Dermatol. 2003;148(3):539–43.PubMedCrossRefGoogle Scholar
  115. 115.
    Patel GK, Goodwin R, Chawla M, Laidler P, Price PE, Finlay AY, et al. Imiquimod 5% cream monotherapy for cutaneous squamous cell carcinoma in situ (Bowen's disease): a randomized, double-blind, placebo-controlled trial. J Am Acad Dermatol. 2006;54(6):1025–32.CrossRefPubMedGoogle Scholar
  116. 116.
    Mackenzie-Wood A, Kossard S, de Launey J, Wilkinson B, Owens ML. Imiquimod 5% cream in the treatment of Bowen’s disease. J Am Acad Dermatol. 2001;44(3):462–70.PubMedCrossRefGoogle Scholar
  117. 117.
    Cozzi SJ, Le TT, Ogbourne SM, James C, Suhrbier A. Effective treatment of squamous cell carcinomas with ingenol mebutate gel in immunologically intact SKH1 mice. Arch Dermatol Res. 2013;305(1):79–83.PubMedCrossRefGoogle Scholar
  118. 118.
    Connolly SM, Baker DR, Coldiron BM, Fazio MJ, Storrs PA, Vidimos AT, et al. AAD/ACMS/ASDSA/ASMS 2012 appropriate use criteria for Mohs micrographic surgery: a report of the American Academy of Dermatology, American College of Mohs Surgery, American Society for Dermatologic Surgery Association, and the American Society for Mohs Surgery. Dermatol Surg. 2012;38(10):1582–603.PubMedCrossRefGoogle Scholar
  119. 119.
    Alam M, Kakar R, Nodzenski M, Ibrahim O, Disphanurat W, Bolotin D, et al. Multicenter prospective cohort study of the incidence of adverse events associated with cosmetic dermatologic procedures: lasers, energy devices, and injectable neurotoxins and fillers. JAMA Dermatol. 2015;151(3):271–7.PubMedCrossRefGoogle Scholar
  120. 120.
    Jambusaria-Pahlajani A, Miller CJ, Quon H, Smith N, Klein RQ, Schmults CD. Surgical monotherapy versus surgery plus adjuvant radiotherapy in high-risk cutaneous squamous cell carcinoma: a systematic review of outcomes. Dermatol Surg. 2009;35(4):574–85.CrossRefPubMedGoogle Scholar
  121. 121.
    Galer CE, Corey CL, Wang Z, Younes MN, Gomez-Rivera F, Jasser SA, et al. Dual inhibition of epidermal growth factor receptor and insulin-like growth factor receptor I: reduction of angiogenesis and tumor growth in cutaneous squamous cell carcinoma. Head Neck. 2011;33(2):189–98.PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Bejar C, Maubec E. Therapy of advanced squamous cell carcinoma of the skin. Curr Treat Options Oncol. 2014;15(2):302–20.PubMedCrossRefGoogle Scholar
  123. 123.
    Rudnick EW, Thareja S, Cherpelis B. Oral therapy for nonmelanoma skin cancer in patients with advanced disease and large tumor burden: a review of the literature with focus on a new generation of targeted therapies. Int J Dermatol. 2016;55(3):249–58. quiz 56, 58.PubMedCrossRefGoogle Scholar
  124. 124.
    Trodello C, Pepper JP, Wong M, Wysong A. Cisplatin and cetuximab treatment for metastatic cutaneous squamous cell carcinoma: a systematic review. Dermatol Surg. 2017;43(1):40–9.PubMedCrossRefGoogle Scholar
  125. 125.
    Stevenson ML, Wang CQ, Abikhair M, Roudiani N, Felsen D, Krueger JG, et al. Expression of programmed cell death ligand in cutaneous squamous cell carcinoma and treatment of locally advanced disease with pembrolizumab. JAMA Dermatol. 2017;153(4):299–303.PubMedCrossRefGoogle Scholar
  126. 126.
    Deinlein T, Lax SF, Schwarz T, Giuffrida R, Schmid-Zalaudek K, Zalaudek I. Rapid response of metastatic cutaneous squamous cell carcinoma to pembrolizumab in a patient with xeroderma pigmentosum: case report and review of the literature. Eur J Cancer. 2017;83:99–102.PubMedCrossRefGoogle Scholar
  127. 127.
    Degache E, Crochet J, Simon N, Tardieu M, Trabelsi S, Moncourier M, et al. Major response to pembrolizumab in two patients with locally advanced cutaneous squamous cell carcinoma. J Eur Acad Dermatol Venereol. 2017 May 30. doi: 10.1111/jdv.14371. [Epub ahead of print].Google Scholar
  128. 128.
    Chen J, Ruczinski I, Jorgensen TJ, Yenokyan G, Yao Y, Alani R, et al. Nonmelanoma skin cancer and risk for subsequent malignancy. J Natl Cancer Inst. 2008;100(17):1215–22.PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Wu S, Cho E, Li WQ, Qureshi AA. History of keratinocyte carcinoma and risk of melanoma: a prospective cohort study. J Natl Cancer Inst. 2017 Apr 1;109(4):1–8.Google Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of DermatologyUniversity of Colorado DenverAuroraUSA

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