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Basal Cell Carcinoma
Basal Cell Carcinoma Laura Hansen Creighton University School of Medicine, Omaha, USA ã 2007 Elsevier Inc. All rights reserved.
Introduction Basal cell carcinoma is a common malignant, but not metastatic, tumor of the skin. Exposure to ultraviolet light, usually in the form of sunlight, is the major cause of this condition.
Definition Basal cell carcinoma is a slow-growing, locally invasive malignant tumor that arises from the cells of the epidermis. Basal cell carcinomas are not metastatic.
Classification Basal cell carcinoma is a slow-growing, locally invasive malignant, but not metastatic, tumor that arises from the epithelial cells of the skin.
Consequences As basal carcinomas are slow growing and not metastatic, the cure rate is very high, more than 95% in most studies Albright (1982), Silverman et al (1991a), Silverman et al (1991b). However, if left untreated, these cancers can grow to a large size and result in extensive tissue damage.
Associated Disorders Basal cell nevus syndrome (Gorlin’s Syndrome) is an autosomal dominant inherited form of this disease characterized by epidermal cysts, palmar and plantar pits, keratocysts of the jaw, calcified dural folds, skeletal anomalies, cleft lip and palate, and basal cell carcinomas Gorlin (1995).
Etiology The major cause of basal cell carcinoma is believed to be exposure to ultraviolet radiation, usually in the form of sunlight. Risk factors for basal cell carcinoma include intense intermittent exposure to sunlight, childhood sunlight exposure, light pigmentation, increasing age, residence in geographic regions with high solar intensity, inorganic trivalent arsenic exposure, ionizing radiation exposure, and immunosuppression Fitzpatrick (2000), Weedon (1998). Basal cell nevus syndrome (Gorlin’s Syndrome) is an inherited form of this disorder Gorlin (1995). 1
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Basal Cell Carcinoma
Epidemiology Basal cell carcinoma is the most common type of cancer. A high incidence of basal cell carcinoma is associated with light pigmentation, geographically sunny regions, intermittent and intense exposure to sunlight, exposure to inorganic trivalent arsenic, ionizing radiation exposure, and immunosuppression Fitzpatrick (2000).
Pathophysiology Histologically, basal cell carcinomas appear as nests of undifferentiated basaloid cells with a characteristic palisading appearance near the edges Fitzpatrick (2000), Weedon (1998). Protrusions of tumor cells invade the dermis and characteristically retract away from the adjacent stroma Fitzpatrick (2000), Weedon (1998). Inactivation of the tumor suppressor genes patched and p53 are common in basal cell carcinomas Moles et al (1993), Shea et al (1992), Unden et al (1997). Ultraviolet radiation exposure is frequently the cause of mutations in p53 Brash et al (1991).
Signs and Symptoms Basal cell carcinomas appear as papules that are pink or red and often with a shiny quality. Basal cell carcinomas are usually asymptomatic unless they ulcerate with resultant bleeding Fitzpatrick (2000).
Standard Therapies Removal of the lesion, through surgical excision, Mohs surgery, cryosurgery, or electrosurgery is the usual treatment for basal cell carcinoma. Ionizing radiation may be used for basal cell carcinomas located in delicate regions of the face or for patients for whom surgery in contraindicated Fitzpatrick (2000). Agent Name
Discussion
5-Fluorouracil
5-Fluorouricil is used in patients with small tumors for whom surgery is contraindicated. Topical treatment with 5-fluorouracil, a pyrimidine antagonist, may be employed Fitzpatrick (2000).
Experimental Therapies Agent Name
Discussion
Photodynamic therapy
Lasers and photosensitising agents appear to be effective for the treatment of some basal cell carcinomas, with superior cosmetic results as compared to conventional surgery Morton (2002).
Basal Cell Carcinoma
Animal Models Transgenic mice with skin-targeted overexpression of Smoothened, Sonic hedgehog, or Gli-1 spontaneously develop lesions much like human basal cell carcinomas Oro et al (1997), Xie et al (1998), Nilsson et al (2000). Expression of activated mutant forms of Smoothened, a seven-span transmembrane protein that is the target of Patched signaling, results in basal cell carcinoma Xie et al (1998). Overexpression of Sonic hedgehog, the ligand for Patched, results in perinatal lethality and features of basal cell nevus syndrome, including basal cell carcinomas Oro et al (1997). Expression of the transcription factor Gli-1, which is downstream from the tumor suppressor Patched, to the skin results in the spontaneous development of basal cell carcinomas and trichoepitheliomas, as well as shortened survival Nilsson et al (2000).
Other Information – Web Sites http://www.sidnet.org is the website for the Society of Investigative Dermatology. http://www.cancer.org is the website for the American Cancer Society. http://www.skincancer.org/aboutus/research_grants.html is the website for The Skin Cancer Foundation, which funds research related to skin cancer. http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowSection&rid=cmed is an online version of Cancer Medicine.
Journal Citations Morton, C.A., 2002. The emerging role of 5-ALA-PDT in dermatology: is PDT superior to standard treatments? Journal of Dermatological Treatment, 13, 25–29. Moles, J.-P., Moyret, C., Guillot, B., Jeantour, P., Guilhou, J.J., Theillet, C., Basset-Seguin, N., 1993. P53 gene mutations in human epithelial skin cancers. Oncogene, 8, 583–588. Shea, C.R., McNutt, N.S., Volkenandt, M., Lugo, J., Prioleau, P.G., Albino, A.P., 1992. Overexpression of p53 protein in basal cell carcinomas of human skin. American Journal of Pathology, 141, 25–29. Unden, A.B., Zaphiropoulos, P.G., Bruce, K., Toftgard, R., Stahle-Backgard, M., 1997. Human patched (PTCH) mRNA is overexpressed consistently in tumor cells of both familial and sporadic basal cell carcinoma. Cancer Research, 57, 2336–2340. Brash, D.E., Rudolph, J.A., Simon, J.A., Lin, A., McKenna, G.J., Baden, H.P., Halperin, A.J., Ponten, J., 1991. A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma. Proceedings of the National Academy of, 88, 10124–10128. Albright, S.D. III, 1982. Treatment of skin cancer using multiple modalities. Journal of the American Academy of Dermatology, 7, 143–171. Gorlin, R.J., 1995. Nevoid basal cell carcinoma syndrome. Dermatology Clinic, 13(1), 113–125. Silverman, M.K., Kopf, A.W., Grin, C.M., Bart, R.S., Levenstein, M.J., 1991a. Recurrence rates for treated basal cell carcinomas. Part 2: curettage-electrodesiccation. Journal of Dermatological Surgery, 17, 720–726. Silverman, M.K., Kopf, A.W., Grin, C.M., Bart, R.S., Levenstein, M.J., 1991b. Recurrence rates for treated basal cell carcinomas. Part 1: overview. Journal of Dermatological Surgery and Oncology, 17, 713–718. Oro, A.E., Higgins, K.M., Hu, Z., Bonifas, J.M., Epstein, E.H. Jr, Scott, M.P., 1997. Basal cell carcinomas in mice overexpressing sonic hedgehog. Science, 276, 817–821. Xie, J., Murone, M., Luoh, S.M., Ryan, A., Gu, Q., Zhang, C., Bonifas, J.M., Lam, C.W., Hynes, M., Goddard, A., Rosenthal, A., Epstein, E.H. Jr, de Sauvage, F.J., 1998. Activating smoothened mutations in sporadic basal cell carcinoma. Nature, 391, 90–92. Nilsson, M., Unden, A.B., Krause, D., Malmqwist, U., Raza, K., Zaphiropoulos, P.G., Toftgard, R., 2000. Induction of basal cell carcinomas and trichoepitheliomas in mice overexpressing GLI-1. Proceedings of the National Academy of Sciences USA, 97(7), 3438–3443.
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Basal Cell Carcinoma
Book Citations Fitzpatrick, T.B., 2000. Neoplasms of the skin. Bast, R.C. Jr, Kufe, D.W., Pollock, R.E., Weichselbaum, R.R., Holland, J.F., Frei, E. III, Gansler, T.S. (Ed.), Cancer Medicine, Edition 5. , B. C. Decker, Inc., Hamilton, Ontario. Weedon, 1998. Tumors of the epidermis. Skin pathology, pp. 635–671, Churchill Livingstone, Edinburgh, Scotland.
Introduction Basal cell carcinoma is a common malignant, but not metastatic, tumor of the skin. Exposure to ultraviolet light, usually in the form of sunlight, is the major cause of this condition.
Definition Basal cell carcinoma is a slow-growing, locally invasive malignant tumor that arises from the cells of the epidermis. Basal cell carcinomas are not metastatic.
Classification Basal cell carcinoma is a slow-growing, locally invasive malignant, but not metastatic, tumor that arises from the epithelial cells of the skin.
Consequences As basal carcinomas are slow growing and not metastatic, the cure rate is very high, more than 95% in most studies Albright (1982), Silverman et al (1991a), Silverman et al (1991b). However, if left untreated, these cancers can grow to a large size and result in extensive tissue damage.
Associated Disorders Basal cell nevus syndrome (Gorlin’s Syndrome) is an autosomal dominant inherited form of this disease characterized by epidermal cysts, palmar and plantar pits, keratocysts of the jaw, calcified dural folds, skeletal anomalies, cleft lip and palate, and basal cell carcinomas Gorlin (1995).
Etiology The major cause of basal cell carcinoma is believed to be exposure to ultraviolet radiation, usually in the form of sunlight. Risk factors for basal cell carcinoma include intense intermittent exposure to sunlight, childhood sunlight exposure, light pigmentation, increasing age, residence in geographic regions with high solar intensity, inorganic trivalent arsenic exposure, ionizing radiation exposure, and immunosuppression Fitzpatrick (2000), Weedon (1998). Basal cell nevus syndrome (Gorlin’s Syndrome) is an inherited form of this disorder Gorlin (1995). 1
2
Basal Cell Carcinoma
Epidemiology Basal cell carcinoma is the most common type of cancer. A high incidence of basal cell carcinoma is associated with light pigmentation, geographically sunny regions, intermittent and intense exposure to sunlight, exposure to inorganic trivalent arsenic, ionizing radiation exposure, and immunosuppression Fitzpatrick (2000).
Pathophysiology Histologically, basal cell carcinomas appear as nests of undifferentiated basaloid cells with a characteristic palisading appearance near the edges Fitzpatrick (2000), Weedon (1998). Protrusions of tumor cells invade the dermis and characteristically retract away from the adjacent stroma Fitzpatrick (2000), Weedon (1998). Inactivation of the tumor suppressor genes patched and p53 are common in basal cell carcinomas Moles et al (1993), Shea et al (1992), Unden et al (1997). Ultraviolet radiation exposure is frequently the cause of mutations in p53 Brash et al (1991).
Signs and Symptoms Basal cell carcinomas appear as papules that are pink or red and often with a shiny quality. Basal cell carcinomas are usually asymptomatic unless they ulcerate with resultant bleeding Fitzpatrick (2000).
Standard Therapies Removal of the lesion, through surgical excision, Mohs surgery, cryosurgery, or electrosurgery is the usual treatment for basal cell carcinoma. Ionizing radiation may be used for basal cell carcinomas located in delicate regions of the face or for patients for whom surgery in contraindicated Fitzpatrick (2000). Agent Name
Discussion
5-Fluorouracil
5-Fluorouricil is used in patients with small tumors for whom surgery is contraindicated. Topical treatment with 5-fluorouracil, a pyrimidine antagonist, may be employed Fitzpatrick (2000).
Experimental Therapies Agent Name
Discussion
Photodynamic therapy
Lasers and photosensitising agents appear to be effective for the treatment of some basal cell carcinomas, with superior cosmetic results as compared to conventional surgery Morton (2002).
Basal Cell Carcinoma
Animal Models Transgenic mice with skin-targeted overexpression of Smoothened, Sonic hedgehog, or Gli-1 spontaneously develop lesions much like human basal cell carcinomas Oro et al (1997), Xie et al (1998), Nilsson et al (2000). Expression of activated mutant forms of Smoothened, a seven-span transmembrane protein that is the target of Patched signaling, results in basal cell carcinoma Xie et al (1998). Overexpression of Sonic hedgehog, the ligand for Patched, results in perinatal lethality and features of basal cell nevus syndrome, including basal cell carcinomas Oro et al (1997). Expression of the transcription factor Gli-1, which is downstream from the tumor suppressor Patched, to the skin results in the spontaneous development of basal cell carcinomas and trichoepitheliomas, as well as shortened survival Nilsson et al (2000).
Other Information – Web Sites http://www.sidnet.org is the website for the Society of Investigative Dermatology. http://www.cancer.org is the website for the American Cancer Society. http://www.skincancer.org/aboutus/research_grants.html is the website for The Skin Cancer Foundation, which funds research related to skin cancer. http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowSection&rid=cmed is an online version of Cancer Medicine.
Journal Citations Morton, C.A., 2002. The emerging role of 5-ALA-PDT in dermatology: is PDT superior to standard treatments? Journal of Dermatological Treatment, 13, 25–29. Moles, J.-P., Moyret, C., Guillot, B., Jeantour, P., Guilhou, J.J., Theillet, C., Basset-Seguin, N., 1993. P53 gene mutations in human epithelial skin cancers. Oncogene, 8, 583–588. Shea, C.R., McNutt, N.S., Volkenandt, M., Lugo, J., Prioleau, P.G., Albino, A.P., 1992. Overexpression of p53 protein in basal cell carcinomas of human skin. American Journal of Pathology, 141, 25–29. Unden, A.B., Zaphiropoulos, P.G., Bruce, K., Toftgard, R., Stahle-Backgard, M., 1997. Human patched (PTCH) mRNA is overexpressed consistently in tumor cells of both familial and sporadic basal cell carcinoma. Cancer Research, 57, 2336–2340. Brash, D.E., Rudolph, J.A., Simon, J.A., Lin, A., McKenna, G.J., Baden, H.P., Halperin, A.J., Ponten, J., 1991. A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma. Proceedings of the National Academy of, 88, 10124–10128. Albright, S.D. III, 1982. Treatment of skin cancer using multiple modalities. Journal of the American Academy of Dermatology, 7, 143–171. Gorlin, R.J., 1995. Nevoid basal cell carcinoma syndrome. Dermatology Clinic, 13(1), 113–125. Silverman, M.K., Kopf, A.W., Grin, C.M., Bart, R.S., Levenstein, M.J., 1991a. Recurrence rates for treated basal cell carcinomas. Part 2: curettage-electrodesiccation. Journal of Dermatological Surgery, 17, 720–726. Silverman, M.K., Kopf, A.W., Grin, C.M., Bart, R.S., Levenstein, M.J., 1991b. Recurrence rates for treated basal cell carcinomas. Part 1: overview. Journal of Dermatological Surgery and Oncology, 17, 713–718. Oro, A.E., Higgins, K.M., Hu, Z., Bonifas, J.M., Epstein, E.H. Jr, Scott, M.P., 1997. Basal cell carcinomas in mice overexpressing sonic hedgehog. Science, 276, 817–821. Xie, J., Murone, M., Luoh, S.M., Ryan, A., Gu, Q., Zhang, C., Bonifas, J.M., Lam, C.W., Hynes, M., Goddard, A., Rosenthal, A., Epstein, E.H. Jr, de Sauvage, F.J., 1998. Activating smoothened mutations in sporadic basal cell carcinoma. Nature, 391, 90–92. Nilsson, M., Unden, A.B., Krause, D., Malmqwist, U., Raza, K., Zaphiropoulos, P.G., Toftgard, R., 2000. Induction of basal cell carcinomas and trichoepitheliomas in mice overexpressing GLI-1. Proceedings of the National Academy of Sciences USA, 97(7), 3438–3443.
3
4
Basal Cell Carcinoma
Book Citations Fitzpatrick, T.B., 2000. Neoplasms of the skin. Bast, R.C. Jr, Kufe, D.W., Pollock, R.E., Weichselbaum, R.R., Holland, J.F., Frei, E. III, Gansler, T.S. (Ed.), Cancer Medicine, Edition 5. , B. C. Decker, Inc., Hamilton, Ontario. Weedon, 1998. Tumors of the epidermis. Skin pathology, pp. 635–671, Churchill Livingstone, Edinburgh, Scotland.