Abstract
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.
Similar content being viewed by others
References
Diepgen T, Mahler V: The epidemiology of skin cancer. Br J Dermatol 146, S61: 1–6 S, 2002
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, 1990
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, 1990
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, 1991
Ko C, Walton S, Keczkes K, Bury HPR, Nicholson C: The emerging epidemic of skin cancer. Brit J Dermatol 130: 269–272, 1994
Miller D, Weinstock MA: Nonmelanoma skin cancer in the United States: Incidence. J Am Acad Dermatol 30: 774–778, 1994
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, 2000
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, 1995
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, 1998
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, 1999
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, 1984
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, 1973
Blewitt R: Why does basal cell carcinoma metastasize so rarely? J Dermatol 19: 146–148, 1980
Randle H: Basal cell carcinoma: Identification and treatment of the high risk patient. Dermatol Surg 22: 255–261, 1996
Batra RaKL: Predictors of extensive subclinical spread in nonmelanoma skin cancer treated with Mohs micrographic surgery. Arch Dermatol138: 1043–1051, 2002
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, 1986
Mora R, Robins, P: Basal cell carcinomas in the center of the face: Special diagnostic, prognostic, and therapeutic considerations. J Dermatol Surg 4: 315, 1978
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, 1995
Wallberg P, Kaaman T, Lindberg M: Multiple basal cell carcinoma: A clinical evaluation of risk factors. Acta Derm Venereol (Stockh) 78: 127–129, 1998
Leffell D, Headington JT, Wong DS, Swanson NA: Aggressive-growth basal cell carcinoma in young adults. Arch Dermatol 127(11): 1663–1667, 1991
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, 1999
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, 2002
Richmond J, Devie RM: The significance of incomplete excision in patients with basal cell carcinoma. Brit J Plast Surg 40: 63–67, 1987
Griffiths R: Audit of histologically incompletely excized basal cell carcinomas: Recommendations for management by re-excision. Brit J Plast Surg 52: 24–28, 1999
Lever W, Schaumburg-Lever G: Histopathology of the skin. Philadelphia, Lippincott, 622–634, 1990
Sexton M, Jones DB, Maloney ME: Histologic pattern analysis of basal cell carcinoma. J Am Acad Dermatol 23: 1118–1126, 1990
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, 1991
Preston D, Stern RS: Nonmelanoma cancers of the skin. New England J Med 327: 1649–1662, 1992
Siegle R, Macmillan J, Pollack SV: Infiltrative basal cell carcinoma: A nonsclerosing subtype. J Dermatol Surg Oncol 12: 830–836, 1986
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, 1985
Hendrix JJ, Parlette HL: Micronodular basal cell carcinoma. A deceptive histologic subtype with frequent clinically undetected tumor extension. Arch Dermatol 132: 295–298, 1996
Richman TaPN: Analysis of morpheaform basal cell carcinoma. J Cutan Path 15: 359–362, 1988
Brown C, Perry AE: Incidence of perineural invasion in histologically aggressive types of basal cell carcinoma. Am J Dermatopath 22: 123–125, 2000
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, 1996
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, 1995
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, 1997
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, 1998
Salasche S, Amontette RA: Morpheaform basal-cell epitheliomas. J Dermatol Surg Oncol 7: 387–394, 1981
Tromovitch T, Stegman SJ: Microscopic-controled excision of cutaneous tumors. Cancer 41(2): 653–658, 1978
Levine H, Bailin PL: Basal cell carcinoma of the head and neck: Identification of the high-risk patient. Laryngoscope 90: 955–961, 1980
Jacobs G, Rippley JJ, Altini M: Prediction of aggressive behavior in basal cell carcinoma. Cancer 49: 533–537, 1982
Lang P, Maize JC: Histologic evolution of recurrent basal cell carcinoma and treatment implication. J Am Acad Dermatol 14: 186–196, 1986
Sloane J: The value of typing basal cell carcinomas in predicting recurrence after surgical excision. Brit J Dermatol 96: 127–132, 1977
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, 1996
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, 1998
Borel D: Cutaneous basosquamous carcinoma: Review of the literature and report of 35 cases. Arch Path 95: 293, 1973
Farmer E, Helwig EB: Metastatic basal cell carcinoma. Cancer 46: 748–757, 1980
Tavin E, Persky MS, Jacobs, J: Metastatic basal cell carcinoma of the head and neck. Laryng 105: 814–817, 1995
Martin RN, Edwards MJ, Cawte TG, Sewell CL, McMasters KM: Basosquamous carcinoma: Analysis of prognostic factors influencing recurrence. Cancer 88: 1365–1369, 2000
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, 1997
Miller P, Roenigk RK, Brodland DG, Randle HW: Cutaneous micrographic surgery: Moh's procedure. Mayo Clinic Proceedings 67: 971–980, 1992
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, 1993
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, 1997
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, 1994
Ratner D, Lowe L, Johnson TM, Fader DJ. Perineural spread of basal cell carcinomas treated with Mohs micrographic surgery. Cancer 88: 1605–1613, 2000
Niazi ZB LB: Perineural infiltration in basal cell carcinomas. Br J Plast Surg 46(156-157), 1993
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, 1994
Boothman D, Fukunaga N, Wang M: Down-regulation of topoisomerase I in mammalian cells following ionizing radiation. Cancer Res 54: 4618–4626, 1994
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, 1996
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, 2001
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, 1999
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, 2000
Johansson N, Ahonen M, Kahari VM: Matrix metalloproteinases in tumor invasion. Cell Mol Life Sci 57: 5–15, 2000
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, 1997
Cribier B, Noacco G, Peltre B, Grosshans E: Expression of stromelysin 3 in basal cell carcinomas. European J Dermatol 11: 530–533, 2001
Majmudar G, Nelson BR, Jensen TC, Johnson TM: Increased expression of stromelysin-3 in basal cell carcinomas. Mol Carcino 9(1): 29–33, 1994
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, 1997
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, 2000
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, 2001
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, 2002
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, 1979
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, 1989
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, 1992
Robinson J, Fisher SG: Recurrent basal cell carcinoma after incomplete resection. Arch Dermatol 136: 1318–1324, 2000
Robinson J: Risk of developing another basal cell carcinoma: A 5-year prospective study. Cancer 60: 118–120, 1987
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, 1998
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, 1985
Henke A, Wiemerslage SJ, Cohen MB: Cytology of metastatic cutaneous basal cell carcinoma. Diagn Cytopathol 19: 113–115, 1998
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, 1984
Lopes de Faria J, Nunes PH: Basosquamous cell carcinoma of the skin with metastases. Histopath 12(1): 85–94, 1988
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, 1991
Frizelle F, Massey R, Pettigrew RA: Metastatic basal cell carcinoma: Case report. Euro J Surg 161: 369–372, 1995
Berti J, Sharata HH: Metastatic basal cell carcinoma to the lung. Cutis 63: 165–166, 1999
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, 1995
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, 1997
Baker P, Berggren R: Metastatic basal cell carcinoma: Review and report of a case. Ann Plast Surg 11(5): 428–430, 1983
Fasika O, Shokunbi MT: Metastatic basal cell carcinoma of the spine. Cen Afri J Med 42(3): 76–77, 1996
Lam D, Ragoowansi R, Powell BW: Basal cell carcinoma of the scalp with spinal metastasis. J R Soc Med 91: 539–540, 1998
Gall C, Buttner A, Bise K, Steiger H-J: Primary intracranial metatypical basal cell carcinoma: Case report. Neurosurgery 41(1): 279–282, 1997
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, 1988
Sitz K, Kappen M, Johnson, D: Metastatic basal cell carcinoma in acquired immunodeficiency syndromerelated complex. J Am Med Assoc 257: 340–343, 1987
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, 1998
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, 1994
Rasezewski R, Guyuron B: Long-term survival following nodal metastases from basal cell carcinoma. Ann Plastic Surgery 24: 170–175, 1990
Grossman D, Leffell DJ: The molecular basis of nonmelanoma skin cancer: New understanding. Arch Dermatol 133: 1263–1270, 1997
LaCour J: Carcinogenesis of basal cell carcinomas: Genetics and molecular mechanisms. Br J Dermatol 146(S61): 17–19, 2002
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, 1996
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, 1996
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, 1990
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, 1994
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, 2001
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, 1990
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, 1992
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, 1994
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, 1999
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, 2002
Soehnge H, Ouhit A, Anathaswamy HN: Mechanisms of induction of skin cancer by UV radiation. Front Biosci 2: 538–551, 1997
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, 1993
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, 1996
Auepemkiate S, Boonyaphiphat P, Thongsuksai P: p53 expression related to the aggressive infiltrative histopathologic feature of basal cell carcinoma. Histopathol 40: 568–573, 2002
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, 2000
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, 2000
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, 2001
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, 1998
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, 1999
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, 1999
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, 1998
Thissen M, Neumann MHA, Schouten LJ: A systematic review of treatment modalities for primary basal cell carcinomas. Arch Dermatol 135: 1177–1183, 1999
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, 1998
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, 2000
Khandekar J: Complete response of metastatic basal cell carcinoma to cisplatin chemotherapy: A report on two patients. Arch Dermatol 126(12): 1660, 1990
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, 1996
Denic S: Preoperative treatment of advanced skin carcinoma with cisplatin and bleomycin. Am J Clin Oncol-Cancer Clin Trials 22: 32–34, 1999
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, 2002
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, 1991
McGillis S, Whellan RG, Sebben JE: Current issues in the performance of Mohs micrographic surgery. J Dermatol Surg & Oncol 9: 777–788, 1991
Woerle B, Heckmann M, Konz B: Micrographic surgery of basal cell carcinomas of the head. Recent Results Cancer Res 160: 219–224, 2002
Telfer N: Mohs micrographic surgery for nonmelanoma skin cancer. Clin Dermatol 13: 593–600, 1995
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, 1989
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, 1996
Jaramillo-Ayerbe F: Cryosurgery in difficult to treat basal cell carcinoma. Int J Dermatol 39: 223–229, 2000
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, 2000
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, 2002
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, 1997
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, 1990
Koplin L, Zarem HA: Recurrent basal cell carcinoma. Plastic Reconstr Surg 65: 656, 1980
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, 2002
DiGiovanna J: Retinoid chemoprevention in patients at high risk for skin cancer. Med Pediatr Oncol 36: 564–567, 2001
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, 2002
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Walling, H.W., Fosko, S.W., Geraminejad, P.A. et al. Aggressive basal cell carcinoma: Presentation, pathogenesis, and management. Cancer Metastasis Rev 23, 389–402 (2004). https://doi.org/10.1023/B:CANC.0000031775.04618.30
Issue Date:
DOI: https://doi.org/10.1023/B:CANC.0000031775.04618.30