Squamous Cell Carcinoma In Situ

  • E. StockflethEmail author

Core Messages

  • Actinic keratosis (AK) and Bowen's disease are defined as carcinoma in situ of the skin. AK are very common and the most important risk factor is chronic UV-exposure. AK present as erythematous rough macules or plaques and occur multiple in sun-exposed ares, which has been referred to as actinic field canceriza-tion. In this regard, novel topical agents have been developed which allow treatment of the complete actinically damaged fields.

  • Bowen's disease (BD) clinically present as solitary, well-demarcated erythematous plaques. Treatment includes among others surgical excision, cryotherapy, photodynamic therapy or immune response modifiers.


Hyaluronic Acid Human Papilloma Virus Actinic Keratosis Invasive Squamous Cell Carcinoma Field Cancerization 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Ackerman AB (2003) Solar keratosis is squamous cell carcinoma. Arch Dermatol 139:1216–1217PubMedCrossRefGoogle Scholar
  2. 2.
    Heaphy MR Jr, Ackerman AB (2000) The nature of solar keratosis: a critical review in historical perspective. J Am Acad Dermatol 43:138–150PubMedCrossRefGoogle Scholar
  3. 3.
    Memon AA, Tomenson JA, Bothwell J, Friedmann PS (2000) Prevalence of solar damage and actinic keratosis in a Merseyside population. Br J Dermatol 142:1154–1159PubMedCrossRefGoogle Scholar
  4. 4.
    Salasche SJ (2000) Epidemiology of actinic keratoses and squamous cell carcinoma. J Am Acad Dermatol 42:4–7PubMedCrossRefGoogle Scholar
  5. 5.
    Frost C, Williams G, Green A (2000) High incidence and regression rates of solar keratoses in a queensland community. J Invest Dermatol 115:273–277PubMedCrossRefGoogle Scholar
  6. 6.
    Stockfleth E, Ulrich C, Meyer T, Christophers E (2002a) Epithelial malignancies in organ transplant patients: clinical presentation and new methods of treatment. Recent Results Cancer Res 160:251–258PubMedCrossRefGoogle Scholar
  7. 7.
    Ulrich C, Christophers E, Sterry W, Meyer T, Stockfleth E (2002) Skin diseases in organ transplant patients. Hautarzt 53:524–533PubMedCrossRefGoogle Scholar
  8. 8.
    Brash DE, Ziegler A, Jonason AS, Simon JA, Kunala S, Leffell DJ (1996) Sunlight and sunburn in human skin cancer: p53, apoptosis, and tumor protection. J Invest Dermatol Symp Proc 1:136–142Google Scholar
  9. 9.
    Chuang TY, Heinrich LA, Schultz MD, Reizner GT, Kumm RC, Cripps DJ (1992) PUVA and skin cancer. A historical cohort study on 492 patients. J Am Acad Dermatol 26(2 Pt 1):173–177PubMedCrossRefGoogle Scholar
  10. 10.
    Jackson S, Storey A (2000) E6 proteins from diverse cutaneous HPV types inhibit apoptosis in response to UV damage. Oncogene 19:592–598PubMedCrossRefGoogle Scholar
  11. 11.
    Jackson S, Harwood C, Thomas M, Banks L, Storey A (2000) Role of Bak in UV-induced apoptosis in skin cancer and abrogation by HPV E6 proteins. Genes Dev 14:3065–3073PubMedCrossRefGoogle Scholar
  12. 12.
    Hazard K, Karlsson A, Andersson K, Ekberg H, Dillner J, Forslund O (2007) Cutaneous human papillomaviruses persist on healthy skin. J Invest Dermatol 127(1):116–119PubMedCrossRefGoogle Scholar
  13. 13.
    Nindl I, Gottschling M, Stockfleth E (2007) Human papil-lomaviruses and non-melanoma skin cancer: basic virology and clinical manifestations. Dis Markers 23(4):247–259PubMedGoogle Scholar
  14. 14.
    Braakhuis BJM, Tabor MP, Kummer JA, Leemans CR, Brakenhoff RH (2003) A genetic explanation of Slaughter 's concept of field cancerization. Evidence and clinical implications. Cancer Res 63:1727–1730PubMedGoogle Scholar
  15. 15.
    Berhane T, Halliday GM, Cooke B, Barnetson RSC (2002) Inflammation is associated with progression of actinic kera-toses to squamous cell carcinomas in humans. Br J Dermatol 146:810–815PubMedCrossRefGoogle Scholar
  16. 16.
    Ulrich M, Maltusch A, Röwert-Huber J, Gonz ález S, Sterry W, Stockfleth E, Astner S (2007) Actinic keratoses: non-invasive diagnosis for field cancerisation. Br J Dermatol 156(Suppl 3):13–17PubMedCrossRefGoogle Scholar
  17. 17.
    Röwert-Huber J, Patel MJ, Forschner T, Ulrich C, Eberle J, Kerl H, Sterry W, Stockfleth E (2007) Actinic keratosis is an early in situ squamous cell carcinoma: a proposal for reclas-sification. Br J Dermatol 156(Suppl 3):8–12PubMedCrossRefGoogle Scholar
  18. 18.
    Emmett AJ, Broadbent GD (1987) Shave excision of super-ficial solar skin lesions. Plast Reconstr Surg 80:47–54PubMedCrossRefGoogle Scholar
  19. 19.
    Dinehart SM (2000) The treatment of actinic keratoses. J Am Acad Dermatol 42:25–28PubMedCrossRefGoogle Scholar
  20. 20.
    Drake LA, Ceiley R, Cornelison RL, Dobes WL, Dorner W, Goltz W, Graham G, Lewis CW, Salasche SJ, Chanco Turner ML, Lewery BJ (1995) Guidelines of care for actinic kera-toses. J Am Acad Dermatol 32:95–98PubMedCrossRefGoogle Scholar
  21. 21.
    Zouboulis ChC (1999) Principles of cutaneous cryosurgery: an update. Dermatology 198:111–117PubMedCrossRefGoogle Scholar
  22. 22.
    Chiarello SE (2000) Cryopeeling (extensive cryosurgery) for treatment of actinic keratoses: An update and comparison. Dermatol Surg 26:728–732PubMedCrossRefGoogle Scholar
  23. 23.
    Szeimies RM, Radakovic S, Calzavara-Pinton PG et al (2000) A prospective, randomized study comparing photo-dynamic therapy with Metvix ® to cryotherapy in actinic keratoses. J Eur Acad Dermatol Venereol 14:235Google Scholar
  24. 24.
    Lubritz RR, Smolewski SA (1982) Cryosurgery cure rate of actinic keratoses. J Am Acad Dermatol 7:631–632PubMedCrossRefGoogle Scholar
  25. 25.
    Witheiler DD, Lawrence N, Cox SE, Cruz C, Cockerell CJ, Freeman RG (1997) Long-term efficacy and safety of Jessner 's solution and 35% trichloroacetic acid vs 5% fluo-rouracil in the treatment of widespread facial actinic kera-toses. Dermatol Surg 23:191–196PubMedCrossRefGoogle Scholar
  26. 26.
    Lawrence N (2000) New and emerging treatments for pho-toaging. Dermatol Clin 18:99–112PubMedCrossRefGoogle Scholar
  27. 27.
    Otley CC, Roenigk RK (1996) Medium-depth chemical peeling. Semin Cutan Med Surg 15:145–154PubMedCrossRefGoogle Scholar
  28. 28.
    Stone PA (1998) The use of modified phenol for chemical face peeling. Clin Plast Surg 25:21–44PubMedGoogle Scholar
  29. 29.
    Iyer S, Friedli A, Bowes L, Kricorian G, Fitzpatrick RE (2004) Full face laser resurfacing: therapy and prophylaxis for actinic keratoses and non-melanoma skin cancer. Lasers Surg Med 34:114–119PubMedCrossRefGoogle Scholar
  30. 30.
    Wollina U, Konrad H, Karamfilov T (2001) Treatment of common warts and actinic keratoses by Er:YAG laser. J Cutan Laser Ther 3:63–66PubMedCrossRefGoogle Scholar
  31. 31.
    Yu TC, Rahman Z, Ross BS (2003) Actinic keratoses –surgical and physical therapeutic modalities. Cutis 71:381–384PubMedGoogle Scholar
  32. 32.
    Fulton JE, Rahimi AD, Helton P, Dahlberg K, Kelly AG (1999) Disappointing results following resurfacing of facial skin with CO2 lasers for prophylaxis of keratoses and cancers. Dermatol Surg 25:729–732PubMedCrossRefGoogle Scholar
  33. 33.
    Szeimies RM, Karrer S, Radakovic-Fijan S, Tanew A, Calzavara-Pinton PG, Zane C, Sidoroff A, Hempel M, Ulrich J, Proebstle T, Meffert H, Mulder M, Salomon D, Dittmar HC, Bauer JW, Kernland K, Braathen L (2002) Photodynamic therapy using topical methyl 5-aminolevulinate compared with cryotherapy for actinic keratosis: a prospective, randomized study. J Am Acad Dermatol 47:258–262PubMedCrossRefGoogle Scholar
  34. 34.
    Morton CA, Brown SB, Collins S Ibbotson S, Jenkinson H, Kurwa H, Langmack K, McKenna K, Moseley H, Pearse AD, Stringer M, Taylor DK, Wong G, Rhodes LE (2002) Guidelines for topical photodynamic therapy: report of a workshop of the British Photodermatology Group. Br J Dermatol 146:552–567PubMedCrossRefGoogle Scholar
  35. 35.
    Pariser DM, Lowe NJ, Stewart DM, Jarrat MT, Lucky AW, Pariser RJ, Yamauchi PS (2003) Photodynamic therapy with topical methyl aminolevulinate for actinic keratosis: results of a prospective randomized multicenter trial. J Am Acad Dermatol 48:227–232PubMedCrossRefGoogle Scholar
  36. 36.
    Freeman M, Vinciullo C, Francis D, Spelman L, Nguyen R, Fergin P, Thai KE, Murrell D, Weightman W, Anderson C, Reid C, Watson A, Foley P (2003) A comparison of photo-dynamic therapy using topical methyl aminolevulinate (Metvix) with single cycle cryotherapy in patients with actinic keratosis: a prospective, randomized study. J Dermatolog Treat 14:99–106PubMedCrossRefGoogle Scholar
  37. 37.
    Hemmi H, Kaisho T, Takeuchi O, Sato S, Sanjo H, Hoshino K, Horiuchi T, Tomizawa H, Takeda K, Akira S (2002) Small antiviral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat Immunol 3:196–200PubMedCrossRefGoogle Scholar
  38. 38.
    Miller RL, Gerster JF, Owens ML, Slade HB, Tomai MA (1999) Imiquimod applied topically: a novel immune response modi-fier and new class of drug. Int J Immunop harmacol 21:1–14CrossRefGoogle Scholar
  39. 39.
    Stockfleth E, Meyer T, Benninghoff B, Salasche S, Papadopoulos L, Ulrich C, Christophers E (2002b) A randomized, double-blind, vehicle-controlled study to assess 5% imiquimod cream for the treatment of multiple actinic keratoses. Arch Dermatol 138:1498–1502PubMedCrossRefGoogle Scholar
  40. 40.
    Stockfleth E, Christophers E, Benninghoff B, Sterry W (2004b) Low incidence of new actinic keratoses after topical 5% imiquimod cream treatment: a long-term follow-up study. Arch Dermatol 140:1542PubMedCrossRefGoogle Scholar
  41. 41.
    Lebwohl M, Dinehart S, Whiting D, Lee PK, Tawfik N, Jorizzo J, Lee JH, Fox TL (2004) Imiquimod 5% cream for the treatment of actinic keratosis: results from two phase III, randomized, double-blind, parallel group, vehicle-controlled trials. J Am Acad Dermatol 50(5):714–721PubMedCrossRefGoogle Scholar
  42. 42.
    Gupta AK (2002) The management of actinic keratoses in the United States with topical fluorouracil: a pharmacoeco-nomic evaluation. Cutis 70:30–36PubMedGoogle Scholar
  43. 43.
    Lawrence N, Cox SE, Cockerell CJ, Freeman RG, Cruz PD Jr (1995) A comparison of the efficacy and safety of Jessner 's solution and 35% trichloroacetic vs 5% fluorouracil in the treatment of widespread facial actinic keratoses. Arch Dermatol 131:176–181PubMedCrossRefGoogle Scholar
  44. 44.
    Levy S, Furst K, Chern W (2001) A comparison of the skin permeation of three topical 0.5% fluorouracil formulations with that of a 5% formulation. Clin Ther 23:901–907PubMedCrossRefGoogle Scholar
  45. 45.
    Jorizzo J, Stewart D, Bucko A, Davis A, Davis SA, Espy P, Hino P, Rodriguez D, Savin R, Stough D, Furst K, Connolly M, Levy S (2002) Randomized trial evaluating a new 0.5% fluorouracil formulation demonstrates efficacy after 1-, 2-, or 4-week treatment in patients with actinic kera-tosis. Cutis 10:335–339Google Scholar
  46. 46.
    Loven K, Stein L, Furst K, Levy S (2002) Evaluation of the efficacy and tolerability of 0.5% fluorouracil cream and 5% fluorouracil cream applied to each side of the face in patients with actinic keratosis. Clin Ther 24:990–1000PubMedCrossRefGoogle Scholar
  47. 47.
    Sachsenberg-Studer EM (1999) Tolerance of topical retinal-dehyde in humans. Dermatology 199:S61–63CrossRefGoogle Scholar
  48. 48.
    Sorg O, Tran C, Saurat JH (2001) Cutaneous vitamins A and E in the context of ultraviolet- or chemically-induced oxida-tive stress. Skin Pharmacol Appl Skin Physiol 14:363–372PubMedCrossRefGoogle Scholar
  49. 49.
    Moriarty M, Dunn J, Darragh A, Lambe R, Brick I (1982) Etretinate in treatment of actinic keratosis. A double-blind crossover study. Lancet 13:364–365CrossRefGoogle Scholar
  50. 50.
    DiGiovanna JJ (2001) Retinoid chemoprevention in patients at high risk for skin cancer. Med Pediatr Oncol 36:564–567PubMedCrossRefGoogle Scholar
  51. 51.
    McNamara IR, Muir J, Galbraith AJ (2002) Acitretin for prophylaxis of cutaneous malignancies after cardiac transplantation. J Heart Lung Transplant 21:1201–1205PubMedCrossRefGoogle Scholar
  52. 52.
    Jung YJ, Isaacs JS, Lee S, Trepel J, Neckers L (2003) IL-1ß-mediated up-regulation of HIF-1α via an NFκB/COX-2 pathway identifies HIF-1 as a critical link between inflam-mation and oncogenesis. FASEB J 17:2115–2117PubMedGoogle Scholar
  53. 53.
    Rivers JK, Arlette J, Shear N, Guenther L, Carey W, Poulin Y (2002) Topical treatment of actinic keratoses with 3.0% diclofenac in 2,5% hyaluronan gel. Br J Dermatol 146:94–100PubMedCrossRefGoogle Scholar
  54. 54.
    Gebauer K, Brown P, Varigos G (2003) Topical diclofenac in hyaluronan gel for the treatment of solar keratoses. Australas J Dermatol 44:40–45PubMedCrossRefGoogle Scholar
  55. 55.
    Wolf JE Jr, Taylor JR, Tschen E, Kang S (2001) Topical 3,0% diclofenac in 2,5% hyaluronan gel in the treatment of actinic keratoses. Int J Dermatol 40:709–713PubMedCrossRefGoogle Scholar
  56. 56.
    Armstrong BK, Kricker A (2001) The epidemiology of UV induced skin cancer. J Photochem Photobiol B 63:8–18PubMedCrossRefGoogle Scholar
  57. 57.
    Thompson SC, Jolley D, Marks R (1993) Reduction of solar keratoses by regular sunscreen use. N Engl J Med 329:1147–1151PubMedCrossRefGoogle Scholar
  58. 58.
    Ulrich C, Jürgensen JS, Degen A, Hackethal M, Ulrich M, Patel MJ, Eberle J, Terhorst D, Sterry W, Stockfleth E (2009) Prevention of non-melanoma skin cancer in organ transplant patients by regular use of a sunscreen: a 24 months, prospective, case-control study.;Br J Dermatol 161(Suppl 3):78–84PubMedCrossRefGoogle Scholar
  59. 59.
    Bowen JT (1912) Precancerous dermatoses: a study of two cases of chronic atypical epithelial proliferation. J Cutan Dis 30:241–255Google Scholar
  60. 60.
    Cox NH, Eedy DJ, Morton CA (1999) Guidelines for management of Bowen 's disease. Br J Dermatol 141:633–641PubMedCrossRefGoogle Scholar
  61. 61.
    Lycka BAS (1989) Bowen 's disease and internal malignancy. A meta analysis. Int J Dermatol 28:531–533PubMedCrossRefGoogle Scholar
  62. 62.
    Thestrup-Pedersen K, Ravnborg L, Reymann F (1988) Morbus Bowen. Acta Derm Venereol (Stockh) 68:236–239Google Scholar
  63. 63.
    Moreno G, Chia ALK, Lim, Shumack S (2007) Therapeutic options for Bowen 's disease. Australas J Dermatol 48:1–10PubMedCrossRefGoogle Scholar
  64. 64.
    Rosen T, Harting M, Gibson M (2007) Treatment of Bowen 's disease with topical 5% imiquimod cream. Retrospective study. Dermatol Surg 33:427–432PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  1. 1.Department of Dermatology, Venerology and AllergologyCharité Universty Hospital Berlin, Skin Cancer Center CharitéBerlinGermany

Personalised recommendations