Cancer and Metastasis Reviews

, Volume 23, Issue 3–4, pp 389–402 | Cite as

Aggressive basal cell carcinoma: Presentation, pathogenesis, and management

  • Hobart W. Walling
  • Scott W. Fosko
  • Pedram A. Geraminejad
  • Duane C. Whitaker
  • Christopher J. Arpey


Basal cell carcinoma (BCC) is the most common cutaneous skin malignancy. BCC generally has a clinical course characterized by slow growth, minimal soft tissue invasiveness, and a high cure rate. Occasionally, however, BCC behaves aggressively with deep invasion, recurrence, and potential regional and distant metastasis. Several factors, including tumor size, duration, histology, and perineural spread, have been postulated as markers of the aggressive BCC phenotype. It is undetermined whether intrinsic biological factors within certain subsets of BCC predispose these tumors toward an inherently aggressive behavior, or whether any BCC with inadequate early management may assume this phenotype. Review of the pertinent literature on this topic suggests that both intrinsic biological factors and extrinsic management factors play a role in the development and progression of aggressive BCC.

cryotherapy curettage imiquimod pyrimidine dimer cyclin Bcl-2 


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  1. 1.
    Diepgen T, Mahler V: The epidemiology of skin cancer. Br J Dermatol 146, S61: 1–6 S, 2002Google Scholar
  2. 2.
    Chuang T, Popescu A, Su WP, Chute CG: Basal cell carcinoma: A population-based incidence study in Rochester, Minnesota. J Am Acad Dermatol 22: 413–417, 1990PubMedGoogle Scholar
  3. 3.
    Gallagher R, Ma B, McLean D, Yang CP, Ho V, Carruthers JA, Warshawski LM: Trends in basal cell carcinoma, squamous cell carcinoma, and melanoma of the skin from 1973-1987. J Am Acad Dermatol 23: 413–421, 1990PubMedGoogle Scholar
  4. 4.
    Coebergh J, Neumann HAM, Vrints LW, Van Der Heijden L, Meijer WJ, Verhagen-Teulings MT: Trends in the incidence of non-melanoma skin cancer in the SE Netherlands 1975-1988, a registry-based study. Brit J Dermatol 125: 353–359, 1991Google Scholar
  5. 5.
    Ko C, Walton S, Keczkes K, Bury HPR, Nicholson C: The emerging epidemic of skin cancer. Brit J Dermatol 130: 269–272, 1994Google Scholar
  6. 6.
    Miller D, Weinstock MA: Nonmelanoma skin cancer in the United States: Incidence. J Am Acad Dermatol 30: 774–778, 1994PubMedGoogle Scholar
  7. 7.
    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 136: 1524–1530, 2000PubMedGoogle Scholar
  8. 8.
    Kricker A, Armstrong BK, English DR, Heenan PJ: A dose-response curve for sun exposure and basal cell carcinoma. Int J Canc 60: 482–488, 1995Google Scholar
  9. 9.
    Rosso S, Zanetti R, Pippione M, Sancho-Garnier H: Parallel risk assessment of melanoma and basal cell carcinoma: Skin characteristics and sun exposure. Melanoma Res 8: 573–583, 1998PubMedGoogle Scholar
  10. 10.
    Lock-Andersen J, Drzewiecki KT, Wulf HC: Eye and hair color, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma: A Danish case-control study. Acta Derm Venereol 79: 74–80, 1999PubMedGoogle Scholar
  11. 11.
    von Domarus H, Stevens PJ: Metastatic basal cell carcinoma: Report of five cases and review of 170 cases in the literature. J Am Acad Dermatol 10: 1043–1060, 1984PubMedGoogle Scholar
  12. 12.
    Jackson R, Adams RH: Horrifying basal cell carcinoma: A study of 33 cases and a comparison with 435 nonhorror and a report on 4 metastatic cases. J Surgical Oncology 5: 431–463, 1973Google Scholar
  13. 13.
    Blewitt R: Why does basal cell carcinoma metastasize so rarely? J Dermatol 19: 146–148, 1980Google Scholar
  14. 14.
    Randle H: Basal cell carcinoma: Identification and treatment of the high risk patient. Dermatol Surg 22: 255–261, 1996PubMedGoogle Scholar
  15. 15.
    Batra RaKL: Predictors of extensive subclinical spread in nonmelanoma skin cancer treated with Mohs micrographic surgery. Arch Dermatol138: 1043–1051, 2002PubMedGoogle Scholar
  16. 16.
    Roenigk R, Ratz LJ, Bailin PL, Wheeland RG: Trends in the presentation and treatment of basal cell carcinomas. J Dermatol Surg & Oncol 12(8): 860–865, 1986Google Scholar
  17. 17.
    Mora R, Robins, P: Basal cell carcinomas in the center of the face: Special diagnostic, prognostic, and therapeutic considerations. J Dermatol Surg 4: 315, 1978Google Scholar
  18. 18.
    Vico P, Fourez T, Nemec E, Andry G, Deraemaecker R: Aggressive basal cell carcinoma of the head and neck areas. Euro J Surg Oncol 21(5): 490–497, 1995Google Scholar
  19. 19.
    Wallberg P, Kaaman T, Lindberg M: Multiple basal cell carcinoma: A clinical evaluation of risk factors. Acta Derm Venereol (Stockh) 78: 127–129, 1998Google Scholar
  20. 20.
    Leffell D, Headington JT, Wong DS, Swanson NA: Aggressive-growth basal cell carcinoma in young adults. Arch Dermatol 127(11): 1663–1667, 1991PubMedGoogle Scholar
  21. 21.
    Roudier-Pujol C, Auperin A, Nguyen T, Duvillard P, Benhamou E, Avril M: Basal cell carcinoma in young adults: Not more aggressive than in older patients. Dermatol 199: 119–123, 1999Google Scholar
  22. 22.
    Scrivener Y, Grosshans E, Cribier B: Variations of basal cell carcinomas according to gender, age, location, and histopathological subtype. Br J Dermatol 147: 41–47, 2002PubMedGoogle Scholar
  23. 23.
    Richmond J, Devie RM: The significance of incomplete excision in patients with basal cell carcinoma. Brit J Plast Surg 40: 63–67, 1987PubMedGoogle Scholar
  24. 24.
    Griffiths R: Audit of histologically incompletely excized basal cell carcinomas: Recommendations for management by re-excision. Brit J Plast Surg 52: 24–28, 1999PubMedGoogle Scholar
  25. 25.
    Lever W, Schaumburg-Lever G: Histopathology of the skin. Philadelphia, Lippincott, 622–634, 1990Google Scholar
  26. 26.
    Sexton M, Jones DB, Maloney ME: Histologic pattern analysis of basal cell carcinoma. J Am Acad Dermatol 23: 1118–1126, 1990PubMedGoogle Scholar
  27. 27.
    Lo J, Snow SN, Reizner GT, Mohs FE, Larson PO, Hruza GJ: Metastatic basal cell carcinoma: Report of twelve cases with a review of the literature. J Am Acad Dermatol 24(5): 715–719, 1991PubMedGoogle Scholar
  28. 28.
    Preston D, Stern RS: Nonmelanoma cancers of the skin. New England J Med 327: 1649–1662, 1992Google Scholar
  29. 29.
    Siegle R, Macmillan J, Pollack SV: Infiltrative basal cell carcinoma: A nonsclerosing subtype. J Dermatol Surg Oncol 12: 830–836, 1986PubMedGoogle Scholar
  30. 30.
    de Faria J: Basal cell carcinoma of the skin with areas of squamous cell carcinoma: A basosquamous cell carcinoma. J Clin Pathol 38: 1273–1277, 1985PubMedGoogle Scholar
  31. 31.
    Hendrix JJ, Parlette HL: Micronodular basal cell carcinoma. A deceptive histologic subtype with frequent clinically undetected tumor extension. Arch Dermatol 132: 295–298, 1996PubMedGoogle Scholar
  32. 32.
    Richman TaPN: Analysis of morpheaform basal cell carcinoma. J Cutan Path 15: 359–362, 1988PubMedGoogle Scholar
  33. 33.
    Brown C, Perry AE: Incidence of perineural invasion in histologically aggressive types of basal cell carcinoma. Am J Dermatopath 22: 123–125, 2000PubMedGoogle Scholar
  34. 34.
    Wrone D, Swetter SM, Egbert BM, Smoller BR, Khavari PA: Increased proportion of aggressive-growth basal cell carcinoma in the Veteran's Affairs population of Palo Alto, California. J Am Acad Dermatol 35: 907–910, 1996PubMedGoogle Scholar
  35. 35.
    Betti R, Inselvini E, Carducci M, Crosti C: Age and site prevalence of histologic subtypes of basal cell carcinomas. Int J Dermatol 34: 174–176, 1995PubMedGoogle Scholar
  36. 36.
    McCormack C, Kelly JW, Dorevitch AP: Differences in age and body site distribution of the histological subtypes of basal cell carcinoma. Arch Dermatol 133: 593–596, 1997PubMedGoogle Scholar
  37. 37.
    Bastiaens M, Hoefnagel JJ, Bruijn JA, Westendorp RG, Vermeer BJ, Bouwes Bavinck JN: Differences in age, site distribution, and sex between nodular and superficial basal cell carcinoma indicate different types of tumors. J Invest Dermatol 110: 880–884, 1998PubMedGoogle Scholar
  38. 38.
    Salasche S, Amontette RA: Morpheaform basal-cell epitheliomas. J Dermatol Surg Oncol 7: 387–394, 1981PubMedGoogle Scholar
  39. 39.
    Tromovitch T, Stegman SJ: Microscopic-controled excision of cutaneous tumors. Cancer 41(2): 653–658, 1978PubMedGoogle Scholar
  40. 40.
    Levine H, Bailin PL: Basal cell carcinoma of the head and neck: Identification of the high-risk patient. Laryngoscope 90: 955–961, 1980PubMedGoogle Scholar
  41. 41.
    Jacobs G, Rippley JJ, Altini M: Prediction of aggressive behavior in basal cell carcinoma. Cancer 49: 533–537, 1982PubMedGoogle Scholar
  42. 42.
    Lang P, Maize JC: Histologic evolution of recurrent basal cell carcinoma and treatment implication. J Am Acad Dermatol 14: 186–196, 1986PubMedGoogle Scholar
  43. 43.
    Sloane J: The value of typing basal cell carcinomas in predicting recurrence after surgical excision. Brit J Dermatol 96: 127–132, 1977Google Scholar
  44. 44.
    Hendrix JJ, Parlette HL: Duplicitous growth of infiltrative basal cell carcinoma: Analysis of clinically undetected tumor extent in a paired case control study. Dermatol Surg 22: 535–539, 1996PubMedGoogle Scholar
  45. 45.
    Horlock N, Wilson GD, Daley FM, Richman PI, O Grobbelaar A, Sanders R, Foy C: Cellular proliferation characteristics do not account for the behavior of horrifying basal cell carcinoma. A comparison of the growth fraction of horrifying and nonhorrifying tumors. Brit J Plast Surg 51: 59–66, 1998PubMedGoogle Scholar
  46. 46.
    Borel D: Cutaneous basosquamous carcinoma: Review of the literature and report of 35 cases. Arch Path 95: 293, 1973PubMedGoogle Scholar
  47. 47.
    Farmer E, Helwig EB: Metastatic basal cell carcinoma. Cancer 46: 748–757, 1980PubMedGoogle Scholar
  48. 48.
    Tavin E, Persky MS, Jacobs, J: Metastatic basal cell carcinoma of the head and neck. Laryng 105: 814–817, 1995Google Scholar
  49. 49.
    Martin RN, Edwards MJ, Cawte TG, Sewell CL, McMasters KM: Basosquamous carcinoma: Analysis of prognostic factors influencing recurrence. Cancer 88: 1365–1369, 2000PubMedGoogle Scholar
  50. 50.
    Orengo I, Salasche SJ, Fewkes J, Khan J, Thornby J, Rubin F: Correlation of histological subtypes of primary basal cell carcinoma and number of Mohs stages required to achieve a tumor-free plane. J Am Acad Dermatol 37: 395–397, 1997PubMedGoogle Scholar
  51. 51.
    Miller P, Roenigk RK, Brodland DG, Randle HW: Cutaneous micrographic surgery: Moh's procedure. Mayo Clinic Proceedings 67: 971–980, 1992PubMedGoogle Scholar
  52. 52.
    Barrett T, Greenway HT Jr., Massullo V, Carlson C: Treatment of basal cell carcinoma and squamous cell carcinoma with perineural invasion. Adv Dermatol 8: 277–305, 1993PubMedGoogle Scholar
  53. 53.
    Terashi H, Kurata S, Tadokoro T, Ishii Y, Sato H, Kudo Y, Katagiri K, Itami S, Takayasu S: Perineural and neural involvement in skin cancers. Dermatol Surg 22: 259–265, 1997Google Scholar
  54. 54.
    Snow S, Saul WJ, Lo J, Mohs FE, Warner T, Dekkinga JA, Feyzi J: Metastatic basal cell carcinoma: Report of 5 cases. Cancer 73(2): 328–335, 1994PubMedGoogle Scholar
  55. 55.
    Ratner D, Lowe L, Johnson TM, Fader DJ. Perineural spread of basal cell carcinomas treated with Mohs micrographic surgery. Cancer 88: 1605–1613, 2000PubMedGoogle Scholar
  56. 56.
    Niazi ZB LB: Perineural infiltration in basal cell carcinomas. Br J Plast Surg 46(156-157), 1993Google Scholar
  57. 57.
    Boothman D, Lee IW, Sahijdak WM: Isolation of an Xray-responsive element in the promotor region of tissuetype plasminogen activator: Potential uses of X-rayresponsive elements for gene therapy. Radiat Res 138: S68–71, 1994PubMedGoogle Scholar
  58. 58.
    Boothman D, Fukunaga N, Wang M: Down-regulation of topoisomerase I in mammalian cells following ionizing radiation. Cancer Res 54: 4618–4626, 1994PubMedGoogle Scholar
  59. 59.
    Staibano S, Boscaino A, Salvatore G, Orabona P, Palombini L, and DeRosa G: Prognostic significance of tumor angiogenesis in nonaggressive and aggressive basal cell carcinoma of the human skin. Hum Path 27: 695–700, 1996PubMedGoogle Scholar
  60. 60.
    Kerkela E, Ala-aho R, Lohi J, Grenman R, M-Kahari V, Saarialho-Kere U: Differential patterns of stromelysin-2 (MMP-10) and MT1-MMP (MMP-14) expression in epithelial skin cancers. Br J Cancer 84: 659–669, 2001Google Scholar
  61. 61.
    Dumas V, Kanitakis J, Charvat S, Euvrard S, Faure M, Claudy A: Expression of basement membrane antigens and matrix metalloproteinases 2 and 9 in cutaneous and squamous carcinomas. Anticancer Res 19: 2929–2938, 1999PubMedGoogle Scholar
  62. 62.
    Varani J, Hattori Y, Chi Y, Schmidt T, Perone P, Zeigler ME, Fader DJ, Johnson TM: Collagenolytic and gelatinolytic matrix metalloproteinases and their inhibitors in basal cell carcinoma of the skin: Comparison with normal skin. Br J Cancer 82: 657–665, 2000PubMedGoogle Scholar
  63. 63.
    Johansson N, Ahonen M, Kahari VM: Matrix metalloproteinases in tumor invasion. Cell Mol Life Sci 57: 5–15, 2000PubMedGoogle Scholar
  64. 64.
    Tsukifuji R, Sakai Y, Hatamochi A, Shinkai H: Gene expression of matrix metalloproteinase-1 (interstitial collagenase) and matrix metalloproteinase-3 (stromelysin-1) in basal cell carcinoma by in situ hybridization using chondroitin ABC lyase. Histo J 29(5): 401–407, 1997Google Scholar
  65. 65.
    Cribier B, Noacco G, Peltre B, Grosshans E: Expression of stromelysin 3 in basal cell carcinomas. European J Dermatol 11: 530–533, 2001Google Scholar
  66. 66.
    Majmudar G, Nelson BR, Jensen TC, Johnson TM: Increased expression of stromelysin-3 in basal cell carcinomas. Mol Carcino 9(1): 29–33, 1994Google Scholar
  67. 67.
    Basset P, Bellocq JP, Lefebvre O, Noel A, Chenard MP, Wolf C, Angland P, Rio MC: Stromelysin-3: A paradigm for stroma-derived factors implicated in carcinoma progression. Crit Rev Oncol Hematol 26: 43–53, 1997PubMedGoogle Scholar
  68. 68.
    Bayer-Garner I, Dilday B, Sanderson RD, Smoller BR: Syndecan-1 expression is decreased with increasing aggressiveness of basal cell carcinoma. Am J Dermatopathol 22: 119–122, 2000PubMedGoogle Scholar
  69. 69.
    Christian M, Moy RL, Wagner RF, Yen-Moore A: A correlation of alpha-smooth muscle actin and invasion in micronodular basal cell carcinoma. Dermatol Surg 27: 441–445, 2001PubMedGoogle Scholar
  70. 70.
    Takeuchi T, Liang SB, Ohtsuki Y: Downregulation of expression of a novel cadherin molecule, T-cadherin, in basal cell carcinoma of the skin. Mol Carcinog 35: 173–179, 2002PubMedGoogle Scholar
  71. 71.
    Schuller D, Berg JW, Sherman G, Krause CJ: Cutaneous basosquamous carcinoma of the head and neck: a comparative analysis. Otolaryng & Head & Neck Surg 87: 420–427, 1979Google Scholar
  72. 72.
    Rowe D, Carroll RJ, Day CL Jr.: Long-term recurrence rate in previously untreated primary basal cell carcinoma: Implications for patient follow-up. J Dermatol Surg Oncol 15: 315–328, 1989PubMedGoogle Scholar
  73. 73.
    Silverman M, Kopk AW, Bart RS, Grin CM: Recurrence rates of treated basal cell carcinomas. Part 3: Surgical excision. J Dermatol Surg & Oncol 18(6): 471–476, 1992Google Scholar
  74. 74.
    Robinson J, Fisher SG: Recurrent basal cell carcinoma after incomplete resection. Arch Dermatol 136: 1318–1324, 2000PubMedGoogle Scholar
  75. 75.
    Robinson J: Risk of developing another basal cell carcinoma: A 5-year prospective study. Cancer 60: 118–120, 1987PubMedGoogle Scholar
  76. 76.
    Levi F, La Veechia C, Te V-C, Randimbison L, Erler G: Incidence of invasive cancers following basal cell skin cancer. Am J Epid 147(8): 722–726, 1998Google Scholar
  77. 77.
    Conley J, Sachs ME, Romo T, Labay G, Gillooley J: Metastatic basal cell carcinoma of the head and neck. Otolaryng-Head & Neck Surg 93: 78–85, 1985Google Scholar
  78. 78.
    Henke A, Wiemerslage SJ, Cohen MB: Cytology of metastatic cutaneous basal cell carcinoma. Diagn Cytopathol 19: 113–115, 1998PubMedGoogle Scholar
  79. 79.
    Domasus H, Stevens P: Metastatic basal cell carcinoma: Report of five cases and review of 170 cases in the literature. J Am Acad Dermatol 10: 1043–1060, 1984PubMedGoogle Scholar
  80. 80.
    Lopes de Faria J, Nunes PH: Basosquamous cell carcinoma of the skin with metastases. Histopath 12(1): 85–94, 1988Google Scholar
  81. 81.
    Talmi Y, Gal R, Finkelstein Y, Nobel M, Shvilli I, Zohar Y: Squamous and basal cell cancers directly invading major salivary glands. Ann Plast Surg 26(5): 483–487, 1991Google Scholar
  82. 82.
    Frizelle F, Massey R, Pettigrew RA: Metastatic basal cell carcinoma: Case report. Euro J Surg 161: 369–372, 1995Google Scholar
  83. 83.
    Berti J, Sharata HH: Metastatic basal cell carcinoma to the lung. Cutis 63: 165–166, 1999PubMedGoogle Scholar
  84. 84.
    Stanley M, Bardales RH, Farmer CE, Frierson HF Jr., Suhrland M, Powers CN, Rollins SD: Primary and metastatic high-grade carcinomas of the salivary glands: A cytological-histological correlation study of twenty cases. Diagnos Cytopathol 13(1): 37–43, 1995Google Scholar
  85. 85.
    Stanley M, Horwitz CA, Bardales RH, Stern SJ, Korourian S: Basal cell carcinoma metastatic to the salivary glands: Differential diagnosis in fine-needle aspiration cytology. Diagnos Cytopathol 16(3): 247–252, 1997Google Scholar
  86. 86.
    Baker P, Berggren R: Metastatic basal cell carcinoma: Review and report of a case. Ann Plast Surg 11(5): 428–430, 1983PubMedGoogle Scholar
  87. 87.
    Fasika O, Shokunbi MT: Metastatic basal cell carcinoma of the spine. Cen Afri J Med 42(3): 76–77, 1996Google Scholar
  88. 88.
    Lam D, Ragoowansi R, Powell BW: Basal cell carcinoma of the scalp with spinal metastasis. J R Soc Med 91: 539–540, 1998PubMedGoogle Scholar
  89. 89.
    Gall C, Buttner A, Bise K, Steiger H-J: Primary intracranial metatypical basal cell carcinoma: Case report. Neurosurgery 41(1): 279–282, 1997PubMedGoogle Scholar
  90. 90.
    Ambros R, Standiford SB, Sobel HJ, Haim A, Mohit-Tabatabai MA: Rapid development of metastases from basal cell carcinoma presenting as cranial nerve palsies. J Dermatol Surg & Oncol 14(2): 1410–1412, 1988Google Scholar
  91. 91.
    Sitz K, Kappen M, Johnson, D: Metastatic basal cell carcinoma in acquired immunodeficiency syndromerelated complex. J Am Med Assoc 257: 340–343, 1987Google Scholar
  92. 92.
    Franceschi S, Dal Maso L, Arniani S, Crosignani P, Vercelli M, Simonato L, Falcini F, Zanetti R, Barchielli A, Serraino D, Rezza G: Risk of cancer other than Kaposi's sarcoma and non-Hodgkin's lymphoma in persons with AIDS in Italy. Cancer and AIDS Registry Linkage Study. Brit J Canc 78(7): 966–970, 1998Google Scholar
  93. 93.
    Sahl W, Snow SN, Levine NS: Giant basal cell carcinoma: Report of two cases and review of the literature. J Am Acad Dermatol 30: 856–859, 1994PubMedGoogle Scholar
  94. 94.
    Rasezewski R, Guyuron B: Long-term survival following nodal metastases from basal cell carcinoma. Ann Plastic Surgery 24: 170–175, 1990Google Scholar
  95. 95.
    Grossman D, Leffell DJ: The molecular basis of nonmelanoma skin cancer: New understanding. Arch Dermatol 133: 1263–1270, 1997PubMedGoogle Scholar
  96. 96.
    LaCour J: Carcinogenesis of basal cell carcinomas: Genetics and molecular mechanisms. Br J Dermatol 146(S61): 17–19, 2002PubMedGoogle Scholar
  97. 97.
    Yengi L, Inskip A, Gilford J, Alldersea J, Bailey L, Smith A, Lear JT, Heagerty AH, Bowers B, Hand P, Hayes JD, Jones PW, Strange RC, Fryer AA: Polymorphism at the glutathione S-transferase, GSTM3 locus: Interactions with cytochrome P450 and glutathione S-transferase genotypes as risk factors for multiple cutaneous basal cell carcinoma. Cancer Research 56(9): 1974–1977, 1996PubMedGoogle Scholar
  98. 98.
    Heagerty A, Smith A, English J, Lear J, Perkins W, Bowers B, Jones P, Gilford J, Alldersea J, Fryer A, Strange RC: Susceptibility to multiple cutaneous basal cell carcinomas: Significant interactions between glutathione-S-transferase GSTM1 genotypes, skin type, and male gender. Brit J Canc 73(1): 44–48, 1996Google Scholar
  99. 99.
    Van der Schroeff J, Evers LM, Boot AJM, Bos JL: Ras oncogene point mutations in basal cell carcinomas and squamous cell carcinomas of the human skin. J Invest Dermatol 94: 423–425, 1990PubMedGoogle Scholar
  100. 100.
    Urabe A, Nakayama J, Taniguchi S, Kuroki R, Hori Y: Expression of the fos oncogene in basal cell carcinoma. J Dermatol Sci 8: 50–53, 1994PubMedGoogle Scholar
  101. 101.
    Jin Y, Martins C, Salemark L, Persson B, Jin C, Miranda J, Fonseca I, Jonsson N: Nonrandom karyotypic features in basal cell carcinomas of the skin. Cancer Genet Cytogenet 131: 109–119, 2001PubMedGoogle Scholar
  102. 102.
    De Rosa G, Vetrani A, Zeppa P, Zabatta A, Barra E, Gentile R, Fulciniti F, Troncone G, di Benedetto G, Palombini L: Comparative morphometric analysis of aggressive and ordinary basal cell carcinoma of the skin. Cancer 65: 544–549, 1990PubMedGoogle Scholar
  103. 103.
    De Rosa G, Staibano S, Barra E, Zeppa P, Salvatore G, Vetrani A, Palombini L: Nucleolar organizer regions in aggressive and nonaggressive basal cell carcinoma of the skin. Cancer 69: 123–126, 1992PubMedGoogle Scholar
  104. 104.
    De Rosa G, Barra E, Guarino M, Staibano S, Donofrio V, Boscaino A: Fibronectin, laminin, type IV collagen distribution, and myofibroblastic stromal reaction in aggressive and nonaggressive basal cell carcinoma. Am J Dermatopath 16: 258–267, 1994PubMedGoogle Scholar
  105. 105.
    Staibano S, Lo Muzio L, Mezza E, Argenziano G, Tornillo L, Pannone G, De Rosa G: Prognostic value of apoptotic index in cutaneous basal cell carcinomas of the head and neck. Oral Oncol 35: 541–547, 1999PubMedGoogle Scholar
  106. 106.
    Murphy M, Mabruk MJ, Lenane P, Liew A, McCann P, Buckley A, Flatharta CO, Hevey D, Billet P, Robertson W, Javed S, Leader M, Kay E, Murphy GM: Comparison of the expression of p53, p21, Bax, and the induction of apoptosis between patients with basal cell carcinoma and normal controls in response to ultraviolet irradiation. J Clin Pathol 55: 829–833, 2002PubMedGoogle Scholar
  107. 107.
    Soehnge H, Ouhit A, Anathaswamy HN: Mechanisms of induction of skin cancer by UV radiation. Front Biosci 2: 538–551, 1997Google Scholar
  108. 108.
    De Rosa G, Staibano S, Barra E, Donofrio V, Salvatore G, Vessecchia G, Boscaino A: p53 protein in aggressive and nonaggressive basal cell carcinoma. J Cutaneous Pathol 20: 429–434, 1993Google Scholar
  109. 109.
    Crowson A, Magro CM, Kadin ME, Stranc M: Differential expression of the bcl-2 oncogene in human basal cell carcinoma. Human Pathology 27(4): 355–359, 1996PubMedGoogle Scholar
  110. 110.
    Auepemkiate S, Boonyaphiphat P, Thongsuksai P: p53 expression related to the aggressive infiltrative histopathologic feature of basal cell carcinoma. Histopathol 40: 568–573, 2002Google Scholar
  111. 111.
    Boonchai W, Walsh M, Cummings M, Chenevix-Trench G: Expression of p53 in arsenic-related and sporadic basal cell carcinoma. Arch Dermatol 136: 195–198, 2000PubMedGoogle Scholar
  112. 112.
    Ramdial P, Madaree A, Reddy R, Chetty R: bcl-2 protein expression in aggressive and nonaggressive basal cell carcinomas. J Cutaneous Pathol 27: 283–291, 2000Google Scholar
  113. 113.
    Staibano S, Lo Muzio L, Pannone G, Scalvenzi M, Salvatore G, Errico ME, Fanali S, De Rosa G, Piattelli A: Interaction between bcl-2 and p53 in neoplastic progression of basal cell carcinoma of the head and neck. Anticancer Research 21: 3757–3764, 2001PubMedGoogle Scholar
  114. 114.
    Aszterbaum M, Rothman A, Johnson RL, Fisher M, Xie J, Bonifas JM, Zhang X, Scott MP, Epstein EH, Jr.: Identification of mutations in the human patched gene in sporadic basal cell carcinomas and in patients with the basal cell nevus syndrome. J Invest Dermatol 110: 885–888, 1998PubMedGoogle Scholar
  115. 115.
    Bodak N, Queille S, Avril MF, Bouadjar B, Drougard C, Sarasin A, Daya-Grosjean L: High levels of patched gene mutations in basal-cell carcinomas from patients with xeroderma pigmentosa. Proc Natl Acad Sci USA 96: 5117–5122, 1999PubMedGoogle Scholar
  116. 116.
    Smythe I, Narang MA, Evans T, Heimann C, Nakamura Y, Chenevix-Trench G, Pietsch T, Wicking C, Wainwright BJ: Isolation and characterization of human Patched 2 (PTCH2), a putative tumor suppressor gene in basal cell carcinoma and medulloblastoma on chromosome 1p32. Hum Mol Gen 8: 291–297, 1999PubMedGoogle Scholar
  117. 117.
    Xie J, Murone M, Luoh SM, Ryan A, Gu Q, Zhang C, Bonifas JM, Lam CW, Hynes M, Goddard A, Rosenthal A, Epstein EH Jr., deSavage FJ: Activating smoothened mutations in sporadic basal cell carcinomas. Nature 391: 90–92, 1998PubMedGoogle Scholar
  118. 118.
    Thissen M, Neumann MHA, Schouten LJ: A systematic review of treatment modalities for primary basal cell carcinomas. Arch Dermatol 135: 1177–1183, 1999PubMedGoogle Scholar
  119. 119.
    Alecu M, Ursaciuc C, Halalau F, Coma G, Merlevede W, Waelkens E, de Witte P: Photodynamic treatment of basal cell carcinoma and squamous cell carcinoma with hypericin. Anticancer Research 18: 4651–4654, 1998PubMedGoogle Scholar
  120. 120.
    Soler A, Angell-Petersen E, Warloe T, Tausjo J, Steen HB, Moan J, Giercksky KE: Photodynamic therapy of super-ficial basal cell carcinoma with 5-aminolevulinic acid with dimethylsulfoxide and ethylendiaminetetraacetic acid: A comparison of two light sources. Photochem, Photobiol 71: 724–729, 2000Google Scholar
  121. 121.
    Khandekar J: Complete response of metastatic basal cell carcinoma to cisplatin chemotherapy: A report on two patients. Arch Dermatol 126(12): 1660, 1990PubMedGoogle Scholar
  122. 122.
    Moeholt K, Aagaard H, Pfeiffer P, Hansen O: Platinumbased cytotoxic therapy in basal cell carcinoma-a review of the literature. Acta Oncologica 35(6): 677–682, 1996PubMedGoogle Scholar
  123. 123.
    Denic S: Preoperative treatment of advanced skin carcinoma with cisplatin and bleomycin. Am J Clin Oncol-Cancer Clin Trials 22: 32–34, 1999Google Scholar
  124. 124.
    Kuijpers D, Thissen MR, Neumann MH: Basal cell carcinoma: Treatment options and prognosis, a scientific approach to a common malignancy. Am J Clin Dermatol 3: 247–259, 2002PubMedGoogle Scholar
  125. 125.
    Weinstock M, Bogaars HA, Ashley M, Litle V, Bilodeau E, Kimmel S: Non-melanoma skin cancer mortality: A population-based study. Arch Dermatol 127(8): 1194–1197, 1991PubMedGoogle Scholar
  126. 126.
    McGillis S, Whellan RG, Sebben JE: Current issues in the performance of Mohs micrographic surgery. J Dermatol Surg & Oncol 9: 777–788, 1991Google Scholar
  127. 127.
    Woerle B, Heckmann M, Konz B: Micrographic surgery of basal cell carcinomas of the head. Recent Results Cancer Res 160: 219–224, 2002PubMedGoogle Scholar
  128. 128.
    Telfer N: Mohs micrographic surgery for nonmelanoma skin cancer. Clin Dermatol 13: 593–600, 1995PubMedGoogle Scholar
  129. 129.
    Rowe D, Carroll RJ, Day CL Jr.: Mohs surgery is the treatment of choice for recurrent (previously treated) basal cell carcinoma. J Dermatol Surg Oncol 15: 424–431, 1989PubMedGoogle Scholar
  130. 130.
    Mallon E, Dawber R: Cryosurgery in the treatment of basal cell carcinoma. Assessment of one and two freezethaw cycle schedules. Dermatol Surg 22: 854–858, 1996PubMedGoogle Scholar
  131. 131.
    Jaramillo-Ayerbe F: Cryosurgery in difficult to treat basal cell carcinoma. Int J Dermatol 39: 223–229, 2000PubMedGoogle Scholar
  132. 132.
    Thissen M, Nieman FH, Ideler AH, Berretty PJ, Neumann HA: Cosmetic results of cryosurgery versus surgical excision for primary uncomplicated basal cell carcinomas of the head and neck. Dermatol Surg 26: 759–764, 2000PubMedGoogle Scholar
  133. 133.
    Werlinger K, Upton G, Moore AY: Recurrence rates of primary nonmelanoma skin cancers trated by surgical excision compared to electrodesiccation-curettage in a private dermatological practice. Dermatol Surg 28: 1138–1142, 2002PubMedGoogle Scholar
  134. 134.
    Avril M-F, Auperin A, Margulis A, Gerbaulet A, Duvillard P, Benhamou E, Guillaume J-C, Chalon R, Petit J-Y, Sancho-Garnier H, Prade M, Bouzy J, Chassagne D: Basal cell carcinoma of the face: Surgery or radiotherapy? Results of a randomized study. Brit J Canc 76(1): 100–106, 1997Google Scholar
  135. 135.
    Smith S, Foley EH, Grande DJ: Use of Moh's micrographic surgery to establish quantitative proof of heightened tumor spread in basal cell carcinoma recurrent following radiotherapy. Journal Dermatol Surg Oncol 16: 1012–1016, 1990Google Scholar
  136. 136.
    Koplin L, Zarem HA: Recurrent basal cell carcinoma. Plastic Reconstr Surg 65: 656, 1980Google Scholar
  137. 137.
    Geisse J, Rich P, Pandya A, Gross K, Andres K, Ginkel A, Owens M: Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: A double-blind, randomized, vehicle controlled study. J Am Acad Dermatol 47: 390–398, 2002PubMedGoogle Scholar
  138. 138.
    DiGiovanna J: Retinoid chemoprevention in patients at high risk for skin cancer. Med Pediatr Oncol 36: 564–567, 2001PubMedGoogle Scholar
  139. 139.
    Bialy T, Rothe MJ, Grant-Kels JM: Dietary factors in the prevention and treatment of nonmelanoma skin cancer and melanoma. Dermatol Surg 28: 1143–1152, 2002PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Hobart W. Walling
    • 1
  • Scott W. Fosko
    • 1
  • Pedram A. Geraminejad
    • 2
  • Duane C. Whitaker
    • 2
  • Christopher J. Arpey
    • 2
  1. 1.Department of DermatologyUniversity of Iowa Hospitals and ClinicsIowa City
  2. 2.Department of DermatologyUniversity of Iowa Hospitals and ClinicsIowa City

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