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Research Abstract & News (updated monthly)
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Tanning and skin cancer.
Journal: Pediatr Dermatol. 2005 Nov-Dec;22(6):501-12.
Abdulla FR et al
Skin cancer is a large and growing problem in the United States . Sun and other ultraviolet (UV) light exposures play a key role in the development of skin cancer. Pediatricians can play an important role in counseling patients and are in a position to help educate children and their families about skin cancer. The purpose of this review is to familiarize pediatricians with the magnitude of the skin cancer problem and the evidence that ultraviolet light exposure, particularly indoor tanning, contributes to this problem. We reviewed the literature on ultraviolet light and skin cancer (based on a MEDLINE search of articles using the headings "ultraviolet light" and "skin cancer") and found that skin cancer is the most rapidly growing cause of cancer deaths in the United State. There is strong epidemiologic evidence for the relationship between UV exposure and nonmelanoma skin cancer and growing evidence for the relationship between indoor tanning and melanoma. We recommend that pediatricians counsel children and their parents about UV protection. Measures such as use of sunscreen and hats for outdoor play, both at home and in school, should be encouraged.
Role of dietary factors in the development of basal cell cancer and squamous cell cancer of the skin.
Journal: Cancer Epidemiol Biomarkers Prev. 2005 Jul;14(7):1596-607.
McNaughton SA et al
The role of dietary factors in the development of skin cancer has been investigated for many years; however, the results of epidemiologic studies have not been systematically reviewed. This article reviews human studies of basal cell cancer (BCC) and squamous cell cancer (SCC) and includes all studies identified in the published scientific literature investigating dietary exposure to fats, retinol, carotenoids, vitamin E, vitamin C, and selenium. A total of 26 studies were critically reviewed according to study design and quality of the epidemiologic evidence. Overall, the evidence suggests a positive relationship between fat intake and BCC and SCC, an inconsistent association for retinol, and little relation between beta-carotene and BCC or SCC development. There is insufficient evidence on which to make a judgment about an association of other carotenoids with skin cancer. The evidence for associations between vitamin E, vitamin C, and selenium and both BCC and SCC is weak. Many of the existing studies contain limitations, however, and further well-designed and implemented studies are required to clarify the role of diet in skin cancer. Additionally, the role of other dietary factors, such as flavonoids and other polyphenols, which have been implicated in skin cancer development in animal models, needs to be investigated.
Sunscreens - which and what for?
Journal: Skin Pharmacol Physiol. 2005 Nov-Dec;18(6):253-62. Epub 2005 Aug 19 .
Maier T and Korting HC
It is well established that sun exposure is the main cause for the development of skin cancer. Chronic continuous UV radiation is believed to induce malignant melanoma, whereas intermittent high-dose UV exposure contributes to the occurrence of actinic keratosis as precursor lesions of squamous cell carcinoma as well as basal cell carcinoma. Not only photocarcinogenesis but also the mechanisms of photoaging have recently become apparent. In this respect the use of sunscreens seemed to prove to be more and more important and popular within the last decades. However, there is still inconsistency about the usefulness of sunscreens. Several studies show that inadequate use and incomplete UV spectrum efficacy may compromise protection more than previously expected. The sunscreen market is crowded by numerous products. Inorganic sunscreens such as zinc oxide and titanium oxide have a wide spectral range of activity compared to most of the organic sunscreen products. It is not uncommon for organic sunscreens to cause photocontact allergy, but their cosmetic acceptability is still superior to the one given by inorganic sunscreens. Recently, modern galenic approaches such as micronization and encapsulation allow the development of high-quality inorganic sunscreens. The potential systemic toxicity of organic sunscreens has lately primarily been discussed controversially in public, and several studies show contradictory results. Although a matter of debate, at present the sun protection factor (SPF) is the most reliable information for the consumer as a measure of sunscreen filter efficacy. In this context additional tests have been introduced for the evaluation of not only the protective effect against erythema but also protection against UV-induced immunological and mutational effects. Recently, combinations of UV filters with agents active in DNA repair have been introduced in order to improve photoprotection. This article reviews the efficacy of sunscreens in the prevention of epithelial and nonepithelial skin cancer, the effect on immunosuppression and the value of the SPF as well as new developments on the sunscreen market.
Occupational skin cancers.
Journal: Occup Med (Lond). 2004 Oct;54(7):458-63.
Gawkrodger DJ
Skin cancer due to occupation is more common than is generally recognized, although it is difficult to obtain an accurate estimate of its prevalence. Over the past two centuries, occupational skin cancers have particularly been due to industrial exposure of men (it seems more so than women) to chemical carcinogens such as polycyclic hydrocarbons (e.g. from coal tar products) or to arsenic. Industrial processes have improved in most Western countries to limit this type of exposure, but those with outdoor occupations are still exposed to solar ultraviolet irradiation without this being widely recognized as an industrial hazard. Ionizing radiation such as X-rays can also cause skin cancer. Occupational skin cancers often resemble skin tumours found in non-occupational subjects, e.g. basal cell carcinoma, squamous cell carcinoma and malignant melanoma, but some pre-malignant lesions can be more specific and point to an occupational origin, e.g. tar keratoses or arsenical keratoses. An uncommon but well-recognized cause of occupational skin cancer is that which results from scar formation following an industrial burn. In the future it will be necessary to focus on preventative measures, e.g. for outdoor workers, the need to cover up in the sun and use sun protective creams and a campaign for earlier recognition of skin cancers, which are usually curable if treated in their early stages.
Basal cell carcinoma: biology, morphology and clinical implications.
Journal: Mod Pathol. 2006 Feb;19 Suppl 2:S127-47.
Crowson AN
Basal cell carcinoma (BCC) is the most common malignant neoplasm of humans. Rising dramatically in incidence in North America , as likely reflects changing habits of the population and a move from more northerly climes to the sunbelt of the Southern and Southwestern United States , the incidence is surely to rise even higher in the future. The last decade has seen significant advances in our understanding of BCC biology and novel approaches to therapy, which hinge upon accurate diagnosis and subclassification by pathologists. The purpose of this review article is to summate the research advances in our understanding of BCC biology and to acquaint pathologists and clinicians to the practical issues in BCC diagnosis and subclassification which flow there from.Modern Pathology (2006) 19, S127-S147. doi:10.1038/modpathol.3800512.
Photodynamic therapy and imiquimod immunotherapy for basal cell carcinomas.
Journal: Acta Clin Belg. 2005 Sep-Oct;60(5):227-34.
Nikkels AF et al
Photodynamic therapy (PDT) and topical imiquimod immunotherapy (TII) are two recently introduced treatment modalities for certain types of basal cell carcinomas (BCC). We present a review of the relevant literature and report our own findings regarding the efficacy and tolerance of PDT and TII in the treatment of BCCs. According to published studies, the cure rates range from 75-95% for PDT and 42-100% for TII, depending on treatment modalities and BCC type. In our observations, 13 patients with nodular or superficial BCCs were treated by PDT using two courses of 3-hour topical application of methyl aminolevulinate, followed by 8 minutes illumination (lambda = 634 nm, e = 37J/cm2). Biopsies were taken before and one month after PDT. Side effects including pain and crusting were assessed. Eight patients with superficial BCC were treated by TII using 3 monthly courses each consisting of 3 weekly applications for 3 weeks followed by one week out of treatment. Biopsies were taken before and after 3 months of TII. Adverse reactions including erythema, oozing, ulceration, and crusting were recorded. Clinico-histological cure was obtained in 12/13 PDT cases as assessed after 1 month, and in 6/8 TII cases after 3 months. Minimal pain during illumination and crust formation were observed in 7/13 and 3/13 PDT cases, respectively. Variable erythema, oozing, ulceration, and crusting were observed in all TII-treated lesions. It is concluded that PDT represents an active and well tolerated alternative treatment for both nodular and superficial BCCs. TII also shows activity, although the tolerance may be poor and cure needs a longer time to be obtained. The final cosmetic appearance was fine following both PDT and TII procedures. Both PDT and TII may leave intact neoplastic aggregates inside the skin. They cannot be clinically perceived, leading to unexpected recurrences. It is stressed that the currently available efficacy information about PDT and TII deals with short term follow-up periods. A 5-year follow-up must be awaited before drawing firm conclusions.
Metastatic basal cell carcinoma: four case reports, review of literature, and immunohistochemical evaluation.
Journal: Arch Pathol Lab Med. 2006 Jan;130(1):45-51.
Ionescu DN et al
CONTEXT: Metastatic basal cell carcinoma (BCC) is relatively rare and is seldom considered a complication in the routine treatment and follow-up of patients with BCC. Although multiple studies have tried to distinguish aggressive from nonaggressive BCCs, to our knowledge, no consistent clinical, histopathologic, or immunohistochemical features have yet been reported. OBJECTIVE: To report 4 cases of metastatic BCCs and to evaluate these in addition to known nonmetastatic BCCs with specific immunostains in an attempt to find distinct morphologic or immunohistochemical patterns that could be helpful in identifying aggressive BCCs. DESIGN: We reviewed 4 cases of metastatic BCCs and recorded the clinical and morphologic findings. We then searched our archives for 14 cases of BCC that followed the usual nonaggressive course. We evaluated these 18 cases with immunohistochemical stains for Ki-67, p53, and bcl-2. RESULTS: In metastasizing BCC, Ki-67 staining was slightly higher in metastatic sites than in primary sites (average 63% and 51%, respectively). p53 was expressed in 3 of 4 primary sites and 2 of 4 metastatic sites. Bcl-2 was positive in both primary and metastatic sites in 3 of 4 cases. In the 14 cases of nonaggressive BCC, staining for Ki-67 averaged 38%, p53 was positive in 11 cases, and Bcl-2 staining was noted in 13 cases. CONCLUSIONS: Overall, in the small sample that we evaluated, the immunohistochemical markers for Ki-67, p53, and Bcl-2 did not distinguish between metastatic and nonaggressive BCCs.
Basosquamous carcinoma-an under-recognized, high-risk cutaneous neoplasm: Case study and review of the literature.
Journal: Br J Plast Surg. 2005 Nov 22
Costantino D et al
Division of Plastic Surgery, Department of Surgery, University of Michigan Medical School , Ann Arbor , MI , USA . Basosquamous carcinoma of the skin is a relatively rare cutaneous neoplasm that has been shown to have significant metastatic potential. Histopathologists debate whether these lesions arise de novo or differentiate from pre-existing basal cell carcinomas. We present a case in which a longstanding lesion initially diagnosed as basal cell carcinoma was later found to have basosquamous histology and regional metastases. Review of the literature reveals a metastatic rate greater than that of basal cell and squamous cell carcinoma, and identifies several important characteristics that impact prognosis after surgical resection. For physicians treating carcinomas of the skin, it is important to understand the natural history and proper treatment of this aggressive neoplasm.
Imiquimod as an antiangiogenic agent.
Journal: J Drugs Dermatol. 2005 Nov-Dec;4(6):708-17.
Li VW et al
Imiquimod (imidazoquinoline 5%) is a topical immune response modifier agent that inhibits angiogenesis, the growth of new blood vessels. In addition to its stimulation of cell-mediated immunity, imiquimod's antiangiogenic activity contributes to its clinical efficacy by interfering with pathological neovascularization that promotes disease progression. The antiangiogenic mechanisms of imiquimod are due to its: 1) induction of cytokines that themselves inhibit angiogenesis (interferons, IL-10, IL-12); 2) local up-regulation of endogenous angiogenesis inhibitors (TIMP, TSP-1); 3) local down-regulation of pro-angiogenic factors (bFGF, MMP-9); and 4) promotion of endothelial cell apoptosis. This report discusses these mechanisms and the rationale for imiquimod's use as an antiangiogenic agent. Key principles of antiangiogenic therapy are presented to describe how imiquimod may be applied in a well-tolerated fashion to treat a broad range of angiogenesis-dependent dermatological conditions, including actinic keratosis (AK), basal cell carcinoma (BCC), squamous cell carcinoma (SCC), lentigo maligna, hemangiomas, Kaposi's sarcoma, pyogenic granuloma, and external genital warts.
Photodynamic therapy in dermatology: current concepts in the treatment of skin cancer.
Journal: Expert Rev Anticancer Ther. 2005 Oct;5(5):791-800.
Garcia-Zuazaga J et al
Photodynamic therapy is a treatment modality that is developing rapidly and increasing in utilization within various medical specialties, including dermatology. This technique requires the presence of a photosensitizer, light energy and molecular oxygen to selectively destroy pathologic cells. A thorough understanding of photobiology and tissue optics is necessary to correctly and effectively utilize photodynamic therapy in dermatology. Photodynamic therapy has been approved by the US Food and Drug Administration to treat actinic keratoses. In Europe , photodynamic therapy is currently being used in the treatment of actinic keratoses and basal cell carcinoma. Other off-label uses of photodynamic therapy have included cutaneous lesions of Bowen's disease, psoriasis, cutaneous T-cell lymphoma and acne. Most recently, photodynamic therapy has been employed in photorejuvenation. The advantages of photodynamic therapy include the capacity for noninvasive targeted therapy via topical application of the drug and local irradiation of involved areas, as well as the ability to generate excellent cosmetic results with minimal discomfort. This review summarizes the fundamentals of photodynamic therapy and its role in the treatment of cutaneous disorders, particularly skin malignancies.
Metastatic basal cell carcinoma: report of two cases and literature review.
Journal: J Cutan Med Surg. 2005 Jan;9(1):10-5.
Ting PT et al
BACKGROUND: Metastatic basal cell carcinoma (MBCC) is defined as primary cutaneous basal cell carcinoma (BCC) that spreads to distant sites as histologically similar metastatic deposits of BCC. There are less than 300 reported cases of MBCC in the literature. METHODS: This article examines two cases of MBCC and provides a literature review of risk factors inherent in epidemiology, patient demographics, and the clinicohistopathological characteristics of primary and metastatic BCC lesions. RESULTS: MBCC is a rare complication of BCC with high morbidity and mortality rates. Patients with MBCC often begin with long-standing primary BCC lesions that are either large or recurrent after treatment. Cases of MBCC have a higher incidence of the more aggressive histologic patterns (morpheic, infiltrating, metatypical, and basosquamous). Perineural space invasion may be an indicator of aggressive disease. Metastases often involve regional lymph nodes, lungs, bone, and skin. CONCLUSION: These case reports and review provide important diagnostic and management considerations for primary BCC and MBCC. Early intervention with aggressive treatment measures may improve the prognosis and survival of MBCC patients.
UV-induced skin cancers
Journal: J Dtsch Dermatol Ges. 2005 Sep;3 Suppl 2:S26-31.
Honigsmann H and Diepgen TL
In this review the epidemiology and pathogenetic aspects of UV-induced malignant skin tumours (basal cell carcinoma, squamous cell carcinoma and melanoma) are discussed with regard to current literature. Whereas present knowledge, in particular, gained from experimental data, permits substantial conclusions about the development of squamous cell carcinoma, the situation for basal cell carcinoma and melanoma does not appear to be unequivocally clear. One reason for this can be explained by the fact that there exist no adequate animal models for these tumours that could exactly reflect the biological behaviour in man. Although there is no doubt about a causal role of sun exposure, this relationship is based on mere epidemiological facts.
Cutaneous carcinoma with mixed histology: a potential etiology for skin cancer recurrence and an indication for Mohs microscopically controlled surgical excision.
Journal: South Med J. 2005 Jul;98(7):740-7.
Cohen PR et al
Cutaneous carcinomas with mixed histology describe nonmelanoma skin cancers which have more than one histologic subtype. These include basal cell carcinomas with concurrent aggressive growth patterns (such as sclerosing, infiltrating, micronodular, keratinizing, and tumors with perineural involvement) and nonaggressive growth patterns (such as superficial, nodular, and follicular) and squamous cell carcinomas with concurrent poorly differentiated and well-differentiated components. One mechanism of recurrence of nonmelanoma skin cancer may very well result from the inadequate initial treatment of cutaneous tumors with mixed histology. If the aggressive histologic subtype of the original tumor is initially not suspected based upon the pathology observed from a superficial biopsy specimen, the clinician may initiate therapy that would be appropriate for the less aggressive variant that was diagnosed. Subsequently, the more aggressive tumor may persist and eventually manifest as a clinical recurrence of the cancer. This is particularly important when there is perineural tumor involvement. We describe two patients whose skin cancers had more than one histologic subtype to demonstrate the histologic features of cutaneous malignancies with more than one pathologic pattern and to emphasize how inaccurate a single diagnostic biopsy can be. We also suggest that clinicians consider Mohs surgical excision of nonmelanoma skin cancers since this technique incorporates microscopically controlled removal of the tumor with complete pathologic evaluation of all surgical margins for any residual cancer.
Incidence of basal cell and squamous cell carcinomas in a population younger than 40 years.
Journal: JAMA. 2005 Aug 10;294(6):681-90.
Christenson LJ et a.
CONTEXT: The incidence of nonmelanoma skin cancer is increasing rapidly among elderly persons, but little is known about its incidence in the population younger than 40 years. OBJECTIVES: To estimate the sex- and age-specific incidences of basal cell carcinoma and squamous cell carcinoma in persons younger than 40 years in Olmsted County , Minnesota , and to evaluate change in incidence over time; to describe the clinical presentation, rate of recurrence and metastasis, and histologic characteristics of these tumors in this population-based sample. DESIGN: Population-based retrospective incidence case review. SETTING: Residents of Olmsted County , Minnesota , a population with comprehensive medical records captured through the Rochester Epidemiology Project. PARTICIPANTS: Patients younger than 40 years with basal cell carcinoma or squamous cell carcinoma diagnosed between 1976 and 2003. MAIN OUTCOME MEASURES: Incident basal cell carcinomas and squamous cell carcinomas and change in incidence of these tumors over time. RESULTS: During the study period, 451 incident basal cell carcinomas were diagnosed in 417 patients and 70 incident squamous cell carcinomas were diagnosed in 68 patients. Of these tumors, 328 were histologically confirmed basal cell carcinomas and 51 were histologically confirmed squamous cell carcinomas. Overall, the age-adjusted incidence of basal cell carcinoma per 100,000 persons was 25.9 (95% confidence interval [CI], 22.6-29.2) for women and 20.9 (95% CI, 17.8-23.9) for men. The incidence of basal cell carcinoma increased significantly during the study period among women (P<.001) but not men (P = .19). Nodular basal cell carcinoma was the most common histologic subtype; 43.0% of tumors were solely nodular basal cell carcinoma and 11.0% had a mixed composition, including the nodular subtype. The incidence of squamous cell carcinoma was similar in men and women, with an average age- and sex-adjusted incidence per 100 000 persons of 3.9 (95% CI, 3.0-4.8); the incidence of squamous cell carcinoma increased significantly over the study period among both women (P = .01) and men (P = .04). CONCLUSIONS: This population-based study demonstrated an increase in the incidence of nonmelanoma skin cancer among young women and men residing in Olmsted County , Minnesota . There was a disproportionate increase in basal cell carcinoma in young women. This increase may lead to an exponential increase in the overall occurrence of nonmelanoma skin cancers over time as this population ages, which emphasizes the need to focus on skin cancer prevention in young adults.
Imiquimod 5% cream (Aldara).
Journal: Expert Opin Investig Drugs. 1998 Mar;7(3):437-49.
Slade HB et al
Imiquimod is a novel synthetic molecule with potent immune-modifying activities. Formulated in a 5% vanishing cream as Aldara, this self-applied therapy has shown good efficacy and safety in the treatment of external genital and perianal warts caused by human papillomavirus (HPV) infection (Condyloma acuminata). The molecule does not demonstrate direct antiviral activity, but through induction of cytokines results in immune-based resolution of wart tissue and reduction of viral burden. Phase III trials of imiquimod have demonstrated that patients who experience complete clearance of either new or recalcitrant warts tend to remain clear, possibly related to Th1 immune recognition and memory. Self-application, good tolerability and a unique mechanism of action combine to make imiquimod a reasonable first-line therapy for genital warts. The effects of imiquimod on immune function suggest several potential uses. Preclinical studies of infection with herpes simplex virus (HSV), cutaneous leishmaniasis, Rift Valley Fever virus and vesiculostomatitis virus have shown reduced viral persistence, reduced recurrence (HSV) and diminished pathology (Leishmania donovani). In a murine tumour model using the FCB bladder cancer cell line, imiquimod behaves as a potent adjuvant leading to immune-based tumour cell eradication and immunity against subsequent FCB cell challenge. The ability of imiquimod to induce significant production of interferon alpha (IFN-alpha) by monocytes/macrophages suggests that diseases responsive to recombinant interferon therapy, such as basal cell carcinoma, may be reasonable clinical targets. The induction of tumour necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma) and interleukin-12 (IL-12) leads to inhibition of IL-5, with animal models demonstrating immune deviation away from Th2 immune responses. The observation that several patients with hepatitis C infection and eosinophilia showed normalisation of elevated eosinophil counts in association with oral imiquimod therapy encourages further exploration of the immune modifying properties of this novel molecule. This review is focused on the use of imiquimod for the treatment of external genital and perianal warts.
UV-induced skin cancer: similarities--variations.
Journal: J Dtsch Dermatol Ges. 2005 Jul;3(7):493-503.
Boukamp P.
Skin cancer, the most common cancer world wide, encompasses different tumor entities, the keratinocyte-derived basal cell carcinoma (BCC), and squamous cell carcinoma (SCC) as well as the neuroectodermal malignant melanoma (MM) and the neuroendocrine Merkel cell carcinomas (MCC). While knowledge is significantly increasing about genetic changes contributing to BCCs and MMs, our understanding for the development and progression of SCCs and MCCs is still fragmentary. This review, thus, aims, on the one hand to summarize the present knowledge without claiming completeness and, on the other hand, to provide information on the HaCaT in vitro skin carcinogenesis model that is used to evaluate the functional consequence of genetic aberrations believed to play a role in skin cancer development and progression.
Basal cell carcinoma with matrical differentiation in a transplant patient: a case report and review of the literature.
Journal: J Cutan Pathol. 2005 Jul;32(6):445-8.
Ali F et al
BACKGROUND: Shadow cells, characterized by basaloid squamous cells with a distinct well-defined border and a central unstained area as a shadow of lost nuclei, are characteristic of pilomatricoma, a distinct neoplasm of hair matrix differentiation. The presence of shadow cells within tumor islands composed of follicular germinative cells of an otherwise classic basal cell carcinoma (BCC) has been considered as a distinct diagnostic category of BCC with matrical differentiation. We present a case of BCC with matrical differentiation in a transplant patient. To our knowledge, only 10 cases [Aloi et al. Am J Dermatopathol 1988; 10: 509; Ambrojo et al. Am J Dermatopathol 1992; 14: 293; Sagol et al. East J Med 1999; 4: 37; Kwittken J. Cutis 2002; 69: 57; Kim et al. Yonsei Med J 2003; 44: 523] of BCC showing matrical differentiation have been reported. None have been reported arising on the background of immunosuppression. METHODS: A 58-year-old male cardiac transplant patient with a nodule on the dorsum of left hand was studied. It arose and enlarged rapidly within a few months, causing irritation and bleeding. The nodule was surgically excised and submitted for histopathologic evaluation. The sections were prepared by hematoxylin and eosin (H&E) method. RESULTS: The H&E-stained sections of the hand lesion revealed multiple nodular masses of basaloid follicular germinative cells. In some areas, there was peripheral palisading and stromal retraction artifact typical of classic BCC. In these areas, the tumor nodules were connected to the epidermis, whereas in others, it extended deep into the reticular dermis to the subcutaneous fat junction. Elsewhere, the majority of the tumor contained a population of shadow cells, similar to those in pilomatricoma, with basaloid-appearing matrical cells in the periphery. Trichohyaline granules were identified in the cytoplasm of many of the peripheral basaloid cells. These granules are one of the characteristic features of follicular matrix differentiation. Mitoses were rare. Areas of cystic degeneration were present throughout the tumor. There was no evidence of an infiltrating growth pattern, lymphovascular invasion, or sarcomatoid growth pattern. CONCLUSION: BCC with matrical differentiation is a distinct pathologic entity and a rare subtype of BCC featuring shadow and matrical cells, typically seen in pilomatricoma, a benign hair matrix neoplasm. This tumor has not yet been reported in an immunosuppressed transplant patient.
Molecular aetiology and pathogenesis of basal cell carcinoma.
Journal: Br J Dermatol. 2005 Jun;152(6):1108-24.
Tilli CM et al
Recent insights into the cell biology of the epidermis and its appendages are transforming our understanding of the pathogenesis of basal cell carcinoma (BCC). The significant progress that has been made warrants a comprehensive review of the molecular and cellular pathology of BCC. The items addressed include environmental and genetic risk factors, the biology of the putative precursor cell(s), and the contribution of aberrations in processes such as apoptosis, cell proliferation, differentiation and signalling to carcinogenesis. Furthermore, established and novel treatment modalities are discussed with particular attention to future biological approaches.
Imiquimod: in superficial basal cell carcinoma.
Journal: Am J Clin Dermatol. 2005;6(3):195-200; discussion 201-2.
Oldfield V et al
Imiquimod, available as a 5% cream, is a new topical treatment for adults with superficial basal cell carcinoma (BCC). The exact mechanism of action of imiquimod in superficial BCC is unknown. Imiquimod may act as a toll-like receptor-7 agonist, and is thought to exert its anti-tumor effect via modification of the immune response and stimulation of apoptosis in BCC cells. Topical imiquimod 5% cream effectively increased clinical and histologic clearance of single superficial BCC lesions compared with vehicle in patients enrolled in two large, well designed trials. Patients applied imiquimod five or seven times per week or vehicle for 6 weeks, and the composite clearance rates at 12 weeks post-treatment for the corresponding treatment groups were 75%, 73%, and 2%, respectively. In a trial investigating the long-term efficacy of imiquimod 5% cream following application five times per week for 6 weeks, a clinical clearance rate of 90% was reported at the initial 12-week post-treatment examination. The estimated rate of clinical clearance at the 1-year follow-up visit was 84%. Application site and local skin reactions were the most common adverse events reported by imiquimod recipients. The severity of erythema, erosion, and scabbing/crusting correlated positively with the composite and histologic response rates.
Photodynamic therapy in dermatology--an update.
Journal: Photodermatol Photoimmunol Photomed. 2005 Jun;21(3):142-9.
Babilas P et al
Topical photodynamic therapy (PDT) is a well-established treatment modality which has mainly shown to be effective for dermatooncologic conditions like actinic keratoses (AK), Bowen's disease, in situ squamous cell carcinoma and superficial basal cell carcinoma (BCC). However, a therapeutical benefit of PDT is also evident for inflammatory dermatoses like localized scleroderma, acne vulgaris and granuloma annulare. Recent work has been focused on the development and evaluation of topical photosensitizers like the heme precursor 5-aminolevulinic acid (5-ALA) or its methyl ester (methyl aminolevulinate) inducing photosensitizing porphyrins. These drugs do not induce strong generalized cutaneous photosensitization like the systemically applied porphyrins or their derivatives. For dermatological purposes, incoherent lamps or light-emitting diode arrays can be used for light activation. Depending on the applied light dose and the concentration of the photosensitizer either cytotoxic effects resulting in tumor destruction or immunomodulatory effects improving the inflammatory conditions occur. Treating superficial oncologic lesions (tumor thickness <2-3 mm) cure rates achieved by PDT are equal to the cure rates of the respective standard therapeutic procedure. The benefits of PDT are the low level of invasiveness and the excellent cosmetic results after treatment.
Approach to the treatment of cutaneous malignancy in HIV-infected patients.
Journal: Dermatol Ther. 2005 Jan-Feb;18(1):77-86.
Wilkins K et al
Patients infected with human immunodeficiency virus (HIV) have an increased risk of developing skin cancers. These at-risk patients may have atypical presentations and/or altered clinical courses. This article will review and discuss management issues for the following malignancies: lymphomas, malignant melanoma, basal cell carcinoma, squamous cell carcinoma, and Kaposi's sarcoma.
Cutaneous lesions: benign and malignant.
Journal: Facial Plast Surg Clin North Am. 2005 May;13(2):195-202, v.
Padgett JK
This article reviews the clinical characteristics, histology, biologic behavior, and recommended treatment for several benign and malignant lesions that may arise on the head and neck. Nevus sebaceus and congenital melanocytic nevus are two benign lesions that can present at a size of several centimeters. Surgical excision may be considered for cosmetic purposes and to reduce the small risk for the development of malignancy within each lesion. Basal and squamous cell carcinoma, lentigo maligna and lentigo maligna melanoma, dermatofibrosarcoma protuberans, and Merkel cell carcinoma are malignant lesions for which surgical excision is the recommended treatment. Local flap reconstruction may be used to address the surgical defects resulting from excision of these benign and malignant conditions.
Nonmelanoma skin cancer.
Journal: Clin Plast Surg. 2005 Apr;32(2):237-48.
Acarturk TO and Edington H.
Each year, there are as many cases of nonmelanoma skin cancer as all other cancers combined. Although there is relatively low attributable mortality, the morbidity and expense of treatment is significant. Unlike many other malignancies, host and environmental factors relevant to the pathophysiology have been clearly demonstrated. Surgical ablation remains the mainstay of treatment.
Basal cell carcinomas of the eyelids.
Journal: Ophthalmologica. 2005 Mar-Apr;219(2):57-71.
Allali J et al
Basal cell carcinomas (BCC) are the more frequent malignant tumors seen in France as in other western countries. They represent 20% of eyelid tumors and 90% of eyelid malignancies. Due to their local growth, problems may arise when treating BCC, and curative exeresis must be the preferred choice each time it is possible. BCC of the eyelids have a high risk of recurrence. Recurrences are more aggressive, infiltrative and destructive and have a considerably poorer rate of cure than primary tumors. Eyelid reconstructions can entail use of complex methods which should only be carried out by a trained ophthalmologist who is also able to treat any associated age-related ocular pathologies. BCC is the most common cause leading to eyelid reconstructive surgery; a surgery which has a triple objective: tumor removal, functionality and an esthetic outcome. Copyright (c) 2005 S. Karger AG, Basel .
Basal cell nevus syndrome. Presentation of six cases and literature review
Journal: Oral Patol Oral Cir Bucal. 2005 Apr 1;10 Suppl 1:E57-66.
Basal cell nevus syndrome, also known as Gorlin-Goltz syndrome, is an autosomal dominant inherited disorder which is characterised by the presence of multiple maxillary keratocysts and facial basal cell carcinomas, along with other less frequent clinical characteristics such us musculo-skeletal disturbances (costal and vertebrae malformations), characteristic facies, neurological (calcification of the cerebral falx, schizophrenia, learning difficulties), skin (cysts, lipomas, fibromas), sight, hormonal, etc. On occasions it can be associated with aggressive basal cell carcinomas and malignant neoplasias, for which early diagnosis and treatment is essential, as well as family detection and genetic counselling. Currently there are new lines of investigation based on biomolecular studies, which aim at identifying the molecules responsible for these cysts and thus allowing an early diagnosis of these patients. In its clinical management and follow up, the odonto-stomatologist, the maxillofacial surgeon and several other medical specialists are involved. In this paper a review of the literature, and six cases of patients affected by multi-systemic and varied clinical expression of basal cell nevus syndrome, are presented.
Genetic tumor archeology: microdissection and genetic heterogeneity in squamous and basal cell carcinoma.
Backvall H et al. Journal: Mutat Res. 2005 Apr 1;571(1-2):65-79.
Carcinogenesis is a multi-step series of somatic genetic events. The complexity of this multi-hit process makes it difficult to determine each single event and the definitive outcome of such events. To investigate the genetic alterations in cancer-related genes, sensitive and reliable detection methods are of major importance for generating relevant results. Another critical issue is the quality of starting material which largely affects the outcome of the analysis. Microdissection of cells defined under the microscope ensures a selection of representative material for subsequent genetic analysis. Skin cancer provides an advantageous model for studying the development of cancer. Detectable lesions occur early during tumor progression, facilitating molecular analysis of the cell populations from both preneoplastic and neoplastic lesions. Alterations of the p53 tumor suppressor gene are very common in non-melanoma skin cancer, and dysregulation of p53 pathways appear to be an early event in the tumor development. A high frequency of epidermal p53 clones has been detected in chronically sun-exposed skin. The abundance of clones containing p53 mutated keratinocytes adjacent to basal cell (BCC) and squamous cell carcinoma (SCC) suggests a role in human skin carcinogenesis. Studies using p53 mutations as a clonality marker have suggested a direct link between actinic keratosis, SCC in situ and invasive SCC. Microdissection-based studies have also shown that different parts of individual BCC tumors can share a common p53 mutation yet differ with respect to additional alterations within the p53 gene, consistent with subclonal development within tumors. Here, we present examples of using well-defined cell populations, including single cells, from complex tissue in combination with molecular tools to reveal features involved in skin carcinogenesis.
Basal cell nevus syndrome.
Journal: Curr Opin Oncol. 2005 Mar;17(2):160-6.
High A and Zedan W.
PURPOSE OF REVIEW: Basal cell nevus syndrome (BCNS), is a hereditary condition transmitted as an autosomal dominant trait exhibiting high penetrance and variable expressivity. Inherited or spontaneous mutations in the human homologue of the Drosophila patched gene underlie the disorder and in addition to tumor predisposition, are associated with a range of 'patterning' defects. Recent advances, with glimpses of possible therapies are emerging, but because of the wide-ranging nature of phenotypic expression and overlap with other syndromes, there is difficulty. Finally, because of the importance of PTCH and paralogous genes in many species other than humans, reports appear in a correspondingly wide range of journals, which makes 'keeping abreast' difficult. RECENT FINDINGS: Progress has been achieved in understanding the role of Gli-1, 2, & 3 in development of 'sporadic' BCCs and BCNS. Expression of PTCH1 is now known to be regulated by alternative promoters and a single functional Gli-binding site. Expression of FOXE1 as a new transcriptional target of Gli2 has been demonstrated in human epidermis and BCCs. Finally, the discovery of Shh pathway inhibitors such as cyclopamine, a naturally occurring alkaloid and ornithine decarboxylase inhibition suggest possible interventional therapies. SUMMARY: In BCNS, phenotype does not correlate with position of mutations within Patched, suggesting genetic makeup and environment modulate effects of premature protein truncation induced by PTCH mutation. These developmental abnormalities occur as a result of haplo-insufficiency in heterozygotes for the mutated gene, whereas neoplastic complications arise from a classical two-hit tumor suppressor gene model. Attention is therefore turning toward TP53 and PTCH associations.
Ultraviolet radiation and skin cancer: molecular mechanisms.
Journal: J Cutan Pathol. 2005 Mar;32(3):191-205.
Hussein MR. Every living organism on the surface of the earth is exposed to the ultraviolet (UV) fraction of the sunlight. This electromagnetic energy has both life-giving and life-endangering effects. UV radiation can damage DNA and thus mutagenize several genes involved in the development of the skin cancer. The presence of typical signature of UV-induced mutations on these genes indicates that the ultraviolet-B part of sunlight is responsible for the evolution of cutaneous carcinogenesis. During this process, variable alterations of the oncogenic, tumor-suppressive, and cell-cycle control signaling pathways occur. These pathways include (a) mutated PTCH (in the mitogenic Sonic Hedgehog pathway) and mutated p53 tumor-suppressor gene in basal cell carcinomas, (b) an activated mitogenic ras pathway and mutated p53 in squamous cell carcinomas, and (c) an activated ras pathway, inactive p16, and p53 tumor suppressors in melanomas. This review presents background information about the skin optics, UV radiation, and molecular events involved in photocarcinogenesis.
Role of imiquimod in skin cancer treatment.
Journal: Am J Clin Dermatol. 2004;5(6):453-8.
Urosevic M and Dummer R.
Cancer of the skin is by far the most common form of all cancers. Given the increasing incidence of skin cancer worldwide, it seems feasible to reconsider the treatment options available for dealing with this growing problem. Despite the lower costs associated with classical methods such as surgery and radiotherapy, immune response modifiers such as imiquimod appear to be good candidates for the future given their good cosmetic effects, the possibility of treating large areas, and the simpleness of patient-applied treatment with a cream formulation. This article reviews current literature on the use of imiquimod in the treatment of nonmelanoma and melanoma skin cancer.
Treatment of basal cell carcinoma with the pulsed carbon dioxide laser: a retrospective analysis.
Journal: Dermatol Surg. 2004 Sep;30(9):1214-8.
Iyer S et al
BACKGROUND AND OBJECTIVE: Treatment options for basal cell carcinoma include surgical excision, cryotherapy, radiation, photodynamic therapy, Moh's micrographic surgery, and topical treatment with 5-fluorouracil and immunomodulators such as imiquimod. Resurfacing and ablation with a CO(2) laser (UltraPulse, Coherent Inc.) may present an attractive and effective treatment option in the management of these cutaneous cancers. We demonstrate the efficacy and safety of the UltraPulse CO(2) in the treatment of basal cell carcinomas of the skin. METHODS: We performed a retrospective chart review of 23 patients treated with the UltraPulse CO(2) laser. A total of 61 biopsy-proven superficial and nodular basal cell carcinomas without prior treatment were included in the study. The patients were followed postoperatively for a period of 15 to 85 months (mean 41.7 months) and assessed for clinical recurrence. RESULTS: Of the 61 tumors treated, clinical recurrence was observed in two cases (3.2%). Adverse effects included significant hypertrophic scarring in one patient and hypopigmentation in one patient. CONCLUSIONS: Destruction of superficial and nodular basal cell carcinomas may be accomplished successfully and safely with the UltraPulse CO(2) laser with a cure rate of 97%.
Use of Ber-EP4 protein in recurrent metastatic basal cell carcinoma: a case report and review of the literature.
Journal: Int J Dermatol. 2004 Aug;43(8):600-3.
Saladi RN et al
The occurrence of metastatic basal cell carcinoma (MBCC) is extremely low, ranging from 0.0028 to 0.5%. We present a rare case report of MBCC in a 57-year-old Caucasian male with a known history of numerous nonmelanoma cutaneous neoplasms. The patient presented with a large ulcerated right axillary mass that recurred 2 months after an initial BCC was resected from the same site. An excisional biopsy of the recurrent mass and regional lymph nodes showed atypical basaloid cells with hyperchromatic nuclei, stromal retraction and rare squamous features in the soft tissue and lymph node. The tumor cells were bcl-2 negative and positive for Ber-EP4. The negative expression of bcl-2 correlates with the aggressive nature of this tumor and Ber-EP4 confirmed the diagnosis of BCC. Topical photodynamic therapy in clinical dermatology. Journal: Br J Dermatol. 2004 Jun;150(6):1061-9. Kormeili T et al. The growing incidence of cutaneous malignancies each year necessitates the development of new and more effective methods for both the diagnosis and the treatment of cancerous lesions, while assuring better cosmetic results and improving patient satisfaction. With that in mind, the use of topical photodynamic therapy (PDT) has been explored in the treatment as well as the diagnosis of various cutaneous malignancies. Using the intrinsic cellular haem biosynthetic pathway and principles of photoillumination, topical PDT carries the goal of selectively targeting abnormal cells, while preserving the normal surrounding structures. This paper will discuss the various applications and data on the use of topical PDT in dermatology.
Aggressive basal cell carcinoma: presentation, pathogenesis, and management.
Journal: Cancer Metastasis Rev. 2004 Aug-Dec;23(3-4):389-402.
Walling HW et al
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.
Ultraviolet carcinogenesis in nonmelanoma skin cancer part II: review and update on epidemiologic correlations.
Journal: Skinmed. 2004 May-Jun;3(3):132-9.
Almahroos M and Kurban AK
The relationship between ultraviolet radiation and nonmelanoma skin cancer (NMSC) is further elucidated by a review of case-control studies relating type of exposure to the development of NMSC. Intermittent sun exposure is important in the pathogenesis of basal cell carcinoma, whereas cumulative exposure is important for both basal cell carcinoma and squamous cell carcinoma. The regional distribution of NMSC is also in areas of sun exposure. Furthermore, there are inherent risk factors for the development of NMSC that include hair and eye colors. Once an individual develops NMSC, he/she has increased risk of developing basal cell carcinoma, squamous cell carcinoma, or melanoma.
Skin cancers following pediatric organ transplantation.
Journal: Dermatol Surg. 2004 Apr;30(4 Pt 2):616-21.
Euvrard S et al
BACKGROUND: Organ transplant recipients taking immunosuppressants are at increased risk of skin cancer. Although several studies have been devoted to adult transplant patients, few data are available on the long-term skin malignancies following pediatric organ transplantation. OBJECTIVE: The objective of this study was to present the current state of knowledge on skin malignancies in patients who received their graft during childhood. METHODS: This study reviews data from the literature and includes our personal experience. RESULTS: Skin cancer is the most frequent malignancy following pediatric renal transplantation and the second most common after pediatric nonrenal transplantation. Skin cancers mainly include squamous and basal cell carcinomas. The occurrence of skin cancer in transplanted children is an extremely rare event during childhood. By contrast, skin carcinomas develop in early adulthood at an average age of 27 years. Other reported skin malignancies include anogenital carcinomas and melanoma. Cutaneous forms of Kaposi's sarcoma are exceptional in children. CONCLUSION: The increased risk of skin cancer following pediatric transplantation justifies prevention and adequate education of children and their parents concerning sun avoidance and protection.
Basal cell carcinoma: an overview of tumor biology and treatment.
Journal: Plast Reconstr Surg. 2004 Apr;113(5):74E-94E.
Netscher DT and Spira M
Learning Objectives: After studying this article, the participant should be able to: 1. Describe the epidemiology and etiology of basal cell carcinomas. 2. Understand the biology, histogenesis, predisposing conditions, and syndromes associated with basal cell carcinomas. 3. Have a clear understanding of tumor types and their clinical behavior. 4. Discuss the importance of diagnostic tumor biopsy and treatment options as they pertain to anatomic site, tumor type, and patient age. 5. Understand the basis for surgical management of basal cell carcinomas, the margins of excision, indications for frozen section, and Mohs micrographic surgery. 6. Discuss the value of patient follow-up after treatment of a primary basal cell carcinoma. 7. Review the most recently published literature on this topic and understand new concepts in tumor biology as they relate to diagnosis and treatment options.Basal cell carcinoma is a malignant epithelial neoplasm of the skin that often arises in areas of chronic sun exposure. This article reviews the epidemiology, etiology, and treatment of basal cell carcinomas. Tumor biology is emphasized to provide a rational basis for specific treatment options. Nevoid basal cell carcinoma syndrome: a review of the literature. Journal: Int J Oral Maxillofac Surg. 2004 Mar;33(2):117-24. Manfredi M et al. The nevoid basal cell carcinoma syndrome (NBCCS) or Gorlin-Goltz Syndrome is an autosomal dominant disorder principally characterized by cutaneous basal cell carcinomas, multiple keratocysts, and skeletal anomalies. The present report reviews current knowledge of this disorder that has profound relevance to specialists in Oral and Maxillo-Facial Surgery, Oral Medicine and Radiology.
Pathways sufficient to induce epidermal carcinogenesis.
Ridky TW and Khavari PA. Journal: Cell Cycle. 2004 May;3(5):621-4. Epub 2004 May 15
Abnormal epidermal proliferation is characteristic of a number of disorders, including the two most common cancers in the United States , basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Both cancers display a disruption in the normal homeostatic balance between cell division and programmed cell death. While abnormal activation of the sonic hedgehog/patched pathway has been established as sufficient to induce hallmark features of BCC in both human and murine epidermis, pathways sufficient to convert normal epidermis into SCC have been less well defined. Building on findings that indicate a potent role for Ras and NF-kappaB in normal epidermal growth regulation, recent work indicates that activation of Ras signaling in concert with inhibition of NF-kappaB function is entirely sufficient to transform normal human epidermis into tumor tissue with all the cardinal features of SCC.
A review of laser and photodynamic therapy for the treatment of nonmelanoma skin cancer.
Journal: Dermatol Surg. 2004 Feb;30(2 Pt 2):264-71.
Marmur ES et al
BACKGROUND: The role of laser and light sources used alone and in conjunction with photodynamic therapy (PDT) for the treatment of nonmelanoma skin cancers (NMSCs) remains unclear. PDT is a newly accepted treatment option for actinic keratoses (AKs) with clearance rates comparable to 5-flourouracil. The purpose of this study was to review literature pertaining to the use of light-emitting technologies and PDT for the treatment of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and AKs. METHODS: A National Library of Medicine PubMed Internet search of English-language journals was performed using the terms laser, PDT, BCC, SCC, and AK. The search encompassed all English-language clinical trials on human subjects from the mid-1960s to the present using laser and light source therapy and/or topical aminolevulinic acid. Articles were excluded if they contained fewer than 10 patients, had a follow-up time of less than 1 month, used intravenous photosensitizers, or were review articles. RESULTS: A total of 20 papers were included for review (10 for BCC, 4 for AK, and 6 for SCC). Follow-up for these patients ranged from 1 to 36 months. Clearance rates were reported up to 100% for superficial BCCs, AKs, and SCC in situ, and lower (8%) for more invasive SCC. Recurrence rates ranged from to 0% to 31% for superficial BCCs, 16% to 31% for AKs, 0% to 52% for SCC in situ, and 82% for invasive SCC. CONCLUSION: Precise PDT and laser clearance and recurrence rates for superficial and nodular BCC and SCC treated with laser and PDT are not yet known. From the available data, it appears that PDT may be capable of achieving clearance rates comparable to radiation therapy for BCC. However, with current technology, PDT treatment of BCC remains inferior to surgical excision and Mohs surgery, for which recurrence rates have been reported to be less than 10%. The reported clearance rates currently limit the usefulness of PDT and laser therapy. However, multiple treatments and the use of penetration enhancers may significantly increase the efficacy of 5-aminolevulinic acid-PDT. With regard to SCCs, the risk of metastatic disease restricts the use of laser and PDT. Studies are currently underway with new light sources, photosensitizers, and various therapeutic regimens. At this time, because the reported recurrence rates are significantly higher than those achieved with standard therapies, laser and PDT should be reserved for only those patients who cannot undergo surgical therapy for BCC and SCC.
Skin cancer and occupational disease
Journal: Hautarzt. 2004 Jan;55(1):22-7. Diepgen TL and Drexler H.
Although it is universally accepted that UV light exposure can cause malignant skin tumors, UV-induced skin cancers are not recognized as an occupational disease in Germany . Exposure to natural or artificial UV light occurs in many work places, so that the induction of occupational skin cancers is certainly plausible. In recent years, a special clause in the occupational disability rules has recognized some cases of UV-induced skin cancers. We discuss the nature of occupational UV exposure, explore preventative measures and review the data regarding occupational UV-induced skin tumors. After evaluating recent publications, we conclude that for squamous cell carcinoma the epidemiological proof of an at least doubled risk (RR >2) due to occupational UV radiation can be given. The clear dose response relationship supports these epidemiological findings. For the individual risk assessment, an attributive UV radiation >40% due to occupational factors must exist. Under those circumstances, squamous cell carcinoma should be recognized and compensated as an occupational disease.
Ultraviolet carcinogenesis in nonmelanoma skin cancer. Part I: incidence rates in relation to geographic locations and in migrant populations.
Journal: Skinmed. 2004 Jan-Feb;3(1):29-35; quiz 35-6.
Almahroos M and Kurban AK
Over the past two decades a worldwide increase in the incidence of skin cancer to near epidemic proportions has led to increased morbidity and appreciating cost. Well known risk factors include UV radiation, x or gamma irradiation, chemical carcinogens, genetic aberrations, and immunosuppression. This article reviews and analyzes the evidence for UV radiations role in the pathogenesis of nonmelanoma skin cancer (NMSC). Observations on the incidence of NMSC among migrants to temperate regions show an increase in both basal cell carcinoma and squamous cell carcinoma. There is also an increase in NMSC in areas with lower latitudes. Irradiation of human skin grafted to animals and animal models that develop NMSC lend further support to the role of UV radiation in the pathogenesis of NMSC. In the forthcoming Part II of this review, epidemiologic evidence will be presented attesting to the relationship between UV radiation and NMSC.
Combined imiquimod and acitretin for non-surgical treatment of basal cell carcinoma.
Journal: Scand J Plast Reconstr Surg Hand Surg. 2003;37(5):293-5.
Ingves C and Jemec GB
We report the successful outcome of treatment of a basal cell carcinoma (BCC) with topical imiquimod and systemic acitretin in a 48-year-old woman. We think that this treatment is a possible option for management of these non-life-threatening tumours. Experimental evidence suggests that combination treatment with retinoids increase the effects of imiquimod and would therefore seem to be possible when treating superficial tumours in areas where the cosmetic outcome is particularly important.
Immunotherapy of basal cell carcinoma: evolving approaches.
Journal: Dermatol Surg. 2003 Oct;29(10):1027-34.
Gaspari AA and Sauder DN
Nonmelanoma skin cancer (NMSC) is one of the most common types of cancer in the world. There is strong evidence that ultraviolet (UV) light plays a central role in the molecular pathogenesis of NMSC development. UV light causes DNA damage and loss of activity of tumor suppressor genes and overexpression of oncogenes and other genes related to enhanced growth and survival as well as tissue invasion. Also, UV light impairs the cutaneous immune response, especially Langerhans cell antigen-presenting function, resulting in immune tolerance to developing tumor cells. Standard treatments for NMSC include surgical excision, curettage and electrodessication, and Moh's micrographic surgery. Immunotherapy of NMSC has been attempted in the form of dinitrobenzene sensitization followed by topical application on the tumor, intralesional interferon injections, or perilesional interleukin-2. These treatments, although showing promise, have not been developed because of lower efficacy compared with surgical approaches, morbidity associated with treatments, as well as the expense of using recombinant cytokine treatments. The topical immune response modifier imiquimod is being developed as a novel local treatment for selected NMSC. Studies of the mechanism of action of imiquimod in NMSC indicate the presence of activated, natural killer cells (innate immunity), T-lymphocytes (adaptive immunity), antigen-presenting cells, and cytokines consistent with a delayed-type hypersensitivity reaction (Th1-lymphocyte cytokine pattern). This agent has been associated with a high response rate for the treatment of superficial basal cell carcinoma, with clearance rates ranging from 70% to 90% in a number of clinical trials. This novel immunotherapy represents a new, nonsurgical treatment option in the care of patients with NMSC.
Role of modern radiotherapy in treating skin cancer.
Journal: Australas J Dermatol. 2003 Aug;44(3):159-66; quiz 167-8.
Veness M and Richards S
Radiotherapy is an important modality in the treatment of non-melanoma skin cancers. While the majority of patients will be adequately treated without the need for radiotherapy, there are factors that may favour a recommendation for radiotherapy. The established roles of modern radiotherapy include the definitive, adjuvant and palliative settings. It is important that clinicians treating skin cancers have an understanding and awareness of these roles. The aim of this article is to present an overview of radiotherapy in the current Australian setting.
Metastatic basal cell carcinoma.
Journal: Dermatol Surg. 2003 Jun;29(6):650-2.
Spates ST et al
BACKGROUND: Basal cell carcinoma is the most common malignancy of humans. Although it is axiomatic that this tumor does not evolve into metastatic disease, such events rarely occur, and this possibility should not be overlooked. OBJECTIVES: The reader should better understand the sequence of events that resulted in metastatic disease and how these events are emblematic of the rare cases of basal cell carcinoma that systemically spread. METHODS: We present a case report of basal cell carcinoma that underwent distant metastasis. A short review of the literature is included. RESULTS: Although basal cell carcinoma is commonly considered a regional tumor with virtually no propensity for distant spread, this case reveals that metastatic disease does occur and with devastating results. CONCLUSION: Metastatic disease in basal cell carcinoma is a very rare but catastrophic consequence of this very common skin malignancy. Basal cell and squamous cell carcinoma. Journal: Semin Oncol Nurs. 2003 Feb;19(1):12-21. Vargo N. OBJECTIVES: To describe the clinical and histologic subtypes, pathophysiology, recognition, and treatment options for basal cell and squamous cell carcinoma, and the molecular biology of sunlight-induced carcinogenesis. DATA SOURCES: Journal and review articles, research studies, textbooks, and clinical practice. CONCLUSIONS: Basal cell and squamous cell carcinoma will occur in more than one million cases annually in the United States , and are highly curable when detected and treated early. During the last decade, significant progress has been made in elucidating the molecular basis of skin carcinogenesis and in identifying newer approaches for the management and treatment of these keratinocyte cancers. IMPLICATIONS FOR NURSING PRACTICE: Nurses can play crucial roles in decreasing the morbidity and mortality from the skin cancer epidemic by identifying and referring patients with lesions suspicious for basal cell and squamous cell carcinomas.
Epidemiology of melanoma and nonmelanoma skin cancer.
Journal: Semin Oncol Nurs. 2003 Feb;19(1):2-11.
Geller AC, Annas GD
OBJECTIVES: To describe the epidemiology of melanoma and nonmelanoma skin cancers. DATA SOURCES: Review and research articles, book chapters, and Surveillance, Epidemiology, and End Results (SEER) data. CONCLUSIONS: In 2002, an estimated 1.3 million Americans were diagnosed with skin cancer. Of these, 53,000 individuals were diagnosed with melanoma, the most common fatal form of skin cancer, and more than 7,000 Americans died of melanoma. Nonmelanoma skin cancer has the highest incidence of all cancers and the rise in the rate of cutaneous melanoma exceeds all other preventable cancers. IMPLICATIONS FOR NURSING PRACTICE: Nurses can act as case-finders and as advocates and educators for prevention of overexposure to ultraviolet radiation. Nurses should ascertain possible inherited risk and monitor patients for additional primary skin cancers.
Basal cell carcinoma: a dermatopathological and molecular biological update.
Journal: Br J Dermatol. 2003 Feb;148(2):195-202.
Saldanha G et al
The ideal classification of basal cell carcinoma (BCC) should be able to identify subtypes which correlate with clinical behaviour and treatment requirements. Unfortunately, however, such a classification has yet to be defined. In the interim, the currently most favoured classification is one based predominantly on histological growth pattern. This classification contributes to the useful concept of low- and high-risk histological subtypes of BCC. The latter are characterized by an increased probability of subclinical extension and/or incomplete excision and/or aggressive local invasive behaviour and/or local recurrence. The Royal College of Pathologists has published a minimum dataset for the histopathological reporting of BCC and this has been written to be compatible with the British Association of Dermatologists' management guidelines. Growth patterns to be reported include nodular, superficial, infiltrative/morphoeic and micronodular types, together with differentiation when of severely atypical or malignant squamous type (basosquamous carcinoma). Deep and peripheral excision margins will be reported to be either involved or clear. The latter will include a comment of a clearance of less than 1 mm for close margins and a measured distance in whole millimetres for other excisions. Clinical assessment and histology remain the 'gold standard' for evaluating BCC and cancers in general. However, in the postgenomic era emphasis is changing from the gathering and archiving of genomic data to its analysis and use in guiding clinical practice. In this context, a current goal is to define cancer phenotype in terms of molecular abnormalities and use this as a new gold standard. One way to assess whether this goal is being achieved for BCC is to determine whether our knowledge of its molecular pathology has any relevance to the minimum dataset for histological reporting. Knowledge of BCC molecular pathology has been fuelled by the recent discovery that deregulation of the Hedgehog (Hh) signalling pathway, a key player in embryonic patterning, appears to be fundamental to tumour growth. But despite accrual of a large amount of data concerning Hh pathway molecular alterations in neoplasia, little is known about the functional consequences of these changes in BCC, how they lead to tumour development, or how they relate to non-Hh pathway alterations such as TP53 mutation. Recent work suggests that the cellular localization of beta-catenin gives a degree of credence to the growth pattern classification of BCC. Furthermore, it is possible that beta-catenin may have a pathogenetic role in the invasive behaviour of BCC. This review draws on current evidence to discuss these issues and assess whether they are relevant to the minimum dataset.
Dietary factors in the prevention and treatment of nonmelanoma skin cancer and melanoma.
Journal: Dermatol Surg. 2002 Dec;28(12):1143-52.
Bialy TL et al
BACKGROUND: The endogenous antioxidant system of the skin scavenges reactive oxygen species and combats ultraviolet induced oxidative skin damage. Supporting this cutaneous defense system with topical or oral antioxidants may provide a successful strategy for the treatment and prevention of skin cancer. OBJECTIVE: Review evidence regarding treatment and prevention of melanoma and nonmelanoma skin cancers through dietary and topical antioxidants, vitamins, and herbal supplements. METHODS: Literature review. RESULTS: Review of the literature demonstrates that the administration of synthetic retinoids has not proved beneficial for otherwise healthy patients with nonmelanoma skin cancer. Selenium supplementation has reduced the incidence of several internal malignancies but not of nonmelanoma skin cancer. Synergistic use of beta-carotene with vitamins C and E has demonstrated prophylaxis against reactive oxygen radicals involved in nonmelanoma skin cancer and reduced sunburn reactions significantly. 1,25-dihydroxyvitamin D3 analog CB1093 has demonstrated promise as a therapeutic agent in the regression of the early stages of melanoma in specific cell lines. CONCLUSION: Delivery of exogenous antioxidants in combination appears to be a more successful strategy for enhancing the cutaneous antioxidant system than the administration of isolated antioxidants alone. Vitamin D analogs may have a role in the medical therapy of melanoma. However, avoiding exposure to ultraviolet light appears to be the only true panacea against the development of melanoma and NMSC. Molecular and cellular biology of basal cell carcinoma. Journal: Australas J Dermatol. 2002 Nov;43(4):241-6. Dicker T et al. The finding of mutations in the PTCH gene in both Gorlin's syndrome and sporadic basal cell carcinomas has significantly advanced our understanding of the molecular defects that lead to the formation of these tumours. Knowledge of the specific molecular and functional changes that have taken place in these tumours will help us devise more defined therapies, as well as give us a better understanding of normal molecular pathways involved in skin development and function. The following is a summary of our current understanding of the molecular and cellular biology of basal cell carcinoma.
Epidemiology of skin cancer.
Journal: Neuro Endocrinol Lett. 2002 Jul;23 Suppl 2:48-51.
Boni R et al
The skin is the most common site of malignancy. Due to several mostly unknown factors, the frequency of skin tumors is increasing. Except for malignant melanoma, reliable statistical data on the frequency of skin tumors are scarce. Discussion on the epidemiology of skin tumors may take different aspects and factors into consideration: (1) histogenetic type; (2) race, (3) sex; (4) age, (5) localization; (6) environment. Moreover, precancerous conditions also may play an important role in this context. Epithelial tumors, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most frequent tumors of the skin. Figures show a wide range between 40 and over 700 or 5 and 250 respectively per 100 000 inhabitants per year depending on the country or area of report. Malignant melanoma is more frequently seen in Caucasians living in sunny regions (40) than in northern countries or in dark skinned races (4-12 per 100 000 per year), representing 4% of all skin tumors, but being responsible for 79% of skin cancer deaths. Other types of skin tumors like cutaneous lymphoma, Kaposi sarcoma, lipomas, adnexal tumors etc. are either not reported regularly and reliable epidemiologic data is not available, or are rare cutaneous tumors (taken all together < 1%).
Novel approaches to the diagnosis of basal cell nevous syndrome.
Journal: Expert Rev Mol Diagn. 2002 Jul;2(4):321-8.
High AS and Robinson PA
In 1960, Robert James Gorlin and William Goltz, both American physicians, defined a new syndrome. Little did they realize that 40 years later, the pathways involved in its development would be provoking serious and sustained interest amongst a plethora of specialists. Fruit-fly biologists, oncologists, geneticists, dermatologists, indeed, hardly a medical or dental specialist gets excluded. To date, there have been some major breakthroughs in identifying abnormal gene sequences. Much has been discovered about this syndrome and its pivotal role in a number of cancer pathways but much more waits to be done or explained. This article sets out to discuss the current position and aims to stimulate further work on this intriguing and puzzling disorder.
New treatment modalities for basal cell carcinoma.
Journal: Recent Results Cancer Res. 2002;160:259-68.
Stockfleth E and Sterry W.
Basal cell carcinoma (BCC) is a subtype of nonmelanoma skin cancer (NMSC), a potentially fatal disease linked to overexposure to the sun during childhood. BCC has been associated with UV-induced mutations of the PTC and p53 tumor suppressor genes, and to polymorphisms in the melanocortin-1 receptor and XPD genes. Mortality rates due to BCC are low, but its increasing incidence and prolonged morbidity means the disease is costly to treat. Early recognition and effective treatment are therefore important, to reduce the incidence of BCC and lighten the economic burden of its management. This paper reviews current treatments for BCC, including excision and curettage, electrodessication, surgery, cryosurgery, radiotherapy, and treatment with 5-fluorouracil and intralesional/perilesional cytokines. It also deals with two new treatment modalities, photodynamic therapy and imiquimod 5% cream, an immune response modifier that effectively resolves BCC lesions.
Photodynamic therapy and fluorescence diagnosis of skin cancers.
Journal: Recent Results Cancer Res. 2002;160:240-5.
Szeimies RM and Landthaler M.
In several countries throughout the world the photosensitizer porfimer-sodium has been approved for systemic photodynamic therapy (PDT) for different oncological indications. However, owing to the prolonged photosensitization entailed, the use of this porphyrin derivative is restricted. Currently, the most promising sensitizers in dermatology that can be applied topically are 5-aminolevulinic acid ( ALA ) or ester derivatives that are precursors of heme biosynthesis. ALA has shown good clinical and excellent cosmetic results in superficial skin cancer and precancerous conditions, e.g. superficial basal cell carcinoma (BCC), or actinic keratoses (AK): phase III studies have demonstrated its efficacy especially in Bowen's disease and AK. ALA-PDT for AK was therefore approved by the FDA in late 1999, and the corresponding registration process is currently in train in Europe . Besides its usefulness in oncological therapy, ALA also has a unique feature that can be exploited for diagnostic purposes: after topical or systemic application protoporphyrin IX is induced rather selectively in epithelial tumors, with a high tumor-to-surrounding tissue ratio, which can be visualized after excitation with light. By using a CCD camera system together with digital imaging, the contrast of the acquired fluorescence images can be significantly enhanced and allows the determination of a threshold, which can be utilized either for a directed biopsy or for preoperative planning when Mohs' surgery is scheduled. At present, the routine employment of such systems is being assessed in prospective studies.
Skin cancer in organ transplant recipients: Epidemiology, pathogenesis, and management.
Journal: J Am Acad Dermatol. 2002 Jul;47(1):1-17; quiz 18-20.
Berg D and Otley CC.
In the United States more than 100,000 people are living with solid organ transplants. The intense immunosuppressive regimens necessary for prolonged survival of allografts significantly increase the rates of both internal and cutaneous malignancies in recipients of solid organ transplants. Skin cancer is the most common cancer in patients after transplantation. Because of the early onset and high tumor burden in transplant recipients, dermatologists have significant challenges in managing the treatment of these patients. This article describes the epidemiology and clinical presentation of skin cancer during posttransplantation immunosuppression, discusses pathogenic cofactors, and reviews the optimal management for mild and severe skin cancer in transplant recipients.
Nonmelanoma skin cancer.
Journal: Curr Treat Options Oncol. 2002 Jun;3(3):193-203.
Nguyen TH and Ho DQ.
Therapy for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) does not end with treatment of the initial lesion because almost 50% of patients with one nonmelanoma skin cancer (NMSC) develop another NMSC in the next 5 years. An integrated program of skin cancer awareness, sun protection, and prophylactic approaches is critical. The risk profile of the tumor influences which therapies and specialties will be involved. Most NMSCs may be treated with outpatient methods. Primary care physicians may treat low-risk tumors, but dermatologists specially trained in cutaneous oncology and a multidisciplinary team should manage high-risk lesions. Superficial BCC and SCC may be treated adequately with superficial modalities such as electrodesiccation and curettage (EDC) and cryotherapy. Topical 5-fluorouracil is effective for small in situ lesions. Invasive but low-risk lesions may be treated with EDC and cryotherapy provided that the tumor is limited to the papillary dermis, is not recurrent, and does not have high-risk features. High-risk tumors are best treated with excision and histologic examination or Mohs micrographic surgery (MMS). MMS is the therapeutic gold standard for all NMSCs in terms of cure rates, margin control, and tissue conservation. Because of its higher cost and specialized process, MMS is best reserved for specific indications.
Treatment of a large superficial basal cell carcinoma with 5% imiquimod: a case report and review of the literature.
Journal: Dermatol Surg. 2002 Apr;28(4):344-6.
Chen TM et al.
BACKGROUND: Large superficial basal cell carcinomas (BCCs) may be difficult to treat surgically due to the potentially large resulting defect after removal. Imiquimod, an immune response modifier, when applied topically, has been demonstrated to be successful in treating superficial BCCs. There is no published experience on the treatment of larger superficial BCCs (greater than 2 cms2) with imiquimod at this time. OBJECTIVE: To assess the clinical and histologic regression, as well as the short- and long-term effects of topical imiquimod on large superficial BCC. METHOD: A 52-year-old white female with a 30 cm2 biopsy proven superficial BCC of 28 years duration on the right dorsal arm was treated with 5% imiquimod three times a week for 12 weeks. Clinical follow-up was conducted 1, 4, 6, and 10 months after treatment, as well as histologic assessment of recurrence at 4 months after treatment. RESULTS: Apparent clinical and histologic clearance was achieved. The treatment was well-tolerated and the patient completed the treatment schedule without a rest period, despite erosion of the lesion in the last week of treatment. CONCLUSION: This report describes the first case of a large superficial BCC (30 cm2) successfully treated with topical imiquimod and with a 10 month follow-up.
The epidemiology of skin cancer.
Journal: Br J Dermatol. 2002 Apr;146 Suppl 61:1-6.
Diepgen TL and Mahler V.
Melanoma and non-melanoma (basal and squamous cell carcinoma) skin cancer (NMSC) are now the most common types of cancer in the white populations and the incidence of skin cancer has reached epidemic proportions. According to recent population-based studies from Australia the incidence rate is over 2% for basal cell carcinoma in males and 1% for squamous cell carcinoma, and there are over 50 new cases of melanoma per 100 000.
The sun's damaging effects.
Journal: Dermatol Nurs. 2001 Aug;13(4):279-86.
Schober-Flores C.
Many people find exposure to the sunlight enjoyable and relaxing. In fact, most people agree that a tan looks great. For years, sunlight has been viewed as beneficial to one's well-being both emotionally and physically ( Ness , Frankel, Gunnell, & Smith, 1999). However, exposure to ultraviolet radiation has its drawbacks. Sunlight is responsible for wrinkling, blotching, drying, and leathering of skin. In fact, 90% of all skin cancers result from long-term exposure to ultraviolet radiation. It is important to be educated about the effects of ultraviolet radiation and learn to balance its beneficial effects with its negative effects.
Basal cell carcinoma follow-up practices by dermatologists: a national survey.
Journal: Br J Dermatol. 2001 Dec;145(6):949-56.
Bower CP et al.
BACKGROUND: After treatment of a basal cell carcinoma (BCC) patients are at risk of recurrence of that BCC; also, patients who have had a primary BCC are those who have an increased risk of developing a subsequent primary BCC. However, long-term hospital-based follow-up of all patients would put large strains on the U.K. health service. OBJECTIVES: To investigate the follow-up intentions of U.K. dermatologists for well-defined facial BCC and to investigate the effect that variations in site and clinical indicators might have on those intentions. METHODS: A self-completion questionnaire relating to BCC follow-up sent to 388 dermatology consultants and associate specialists in the U.K. had a response rate of 68%. The effects of treatment modality, tumour site, histology, multiple lesions and various patient variables that might alter the likelihood of follow-up were examined. General views on the subject of BCC follow-up were sought. RESULTS: Twenty-seven per cent of respondents reported that they would not review further after excision of a 'well-defined' BCC from inside a central 'T' area on the face; 37% reported that they would review on one occasion; and 36% reported that they review more than once. CONCLUSIONS: While it is currently not feasible to follow-up all treated BCCs, a strategy to identify and monitor high-risk patients and a system to gather long-term outcome data prospectively are necessary aspects of a national health service. This study illustrates that the first issue is being addressed to some extent, but at the currently reported level of BCC follow-up in the U.K. there is little scope for collecting comprehensive long-term data on outcomes.
UV damage, DNA repair and skin carcinogenesis.
Journal: Front Biosci. 2002 Apr 1;7:d1024-43.
Cleaver JE and Crowley E.
Skin cancer is unique among human cancers in its etiology, accessibility and the volume of detailed knowledge now assembled concerning its molecular mechanisms of origin. The major carcinogenic agent for most skin cancers is well established as solar ultraviolet light. This is absorbed in DNA with the formation of UV-specific dipyrimidine photoproducts. These can be repaired by nucleotide excision repair or replicated by low fidelity class Y polymerases. Insufficient repair followed by errors in replication produce characteristic mutations in dipyrimidine sequences that may represent initiation events in carcinogenesis. Chronic exposure to UVB results in disruption of the epithelial structure and expansion of pre-malignant clones which undergo further genomic changes leading to full malignancy. Genetic diseases in DNA repair, xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy, show varied elevated symptoms of sun sensitivity involving skin cancers and other symptoms including neurological degeneration and developmental delays. In humans, only xeroderma pigmentosum shows high levels of cancer, but mouse strains, with any of the genes corresponding to these diseases knocked-out, show elevated skin carcinogenesis. The three major skin cancers exhibit characteristic molecular changes defined by certain genes and associated pathways. Squamous cell carcinoma involves mutations in the p53 gene; basal cell carcinoma involves mutations in the PATCHED gene, and melanoma in the p16 gene. The subsequent development of malignant tumors involves many additional genomic changes that have yet to be fully cataloged.
Photodynamic therapy: applications in dermatology.
Journal: Expert Opin Biol Ther. 2002 Jan;2(1):45-53.
Leman JA and Morton CA.
Photodynamic therapy (PDT) offers the potential of an effective new treatment in several areas of medicine. Topical photodynamic therapy is practical and non-invasive and is particularly suited to dermatological indications. A variety of pre-malignant and malignant skin lesions including Bowen's disease, actinic keratoses (AKs) and basal cell carcinoma (BCC) have been treated with success. The role of PDT in inflammatory dermatoses remains to be established. The currently available literature is reviewed.
Genetics of nonmelanoma skin cancer.
Journal: Arch Dermatol. 2001 Nov;137(11):1486-92.
Tsao H.
Cancer is in essence a genetic disease characterized by genomic instability. Unlike classic genetic syndromes in which a single inherited mutation is often sufficient to determine the perturbed phenotype, most cancers, especially solid tumors, develop after an accumulation of multiple genetic lesions. Inherited mutations that predispose individuals to cancer formation are termed germline, while acquired mutations that contribute to tumor development are designated somatic. Bona fide hereditary cancers account for only a small proportion of all documented cancers. Most tumors result from mutations caused by inherent infidelities in DNA replication, carcinogens, or defects in the DNA reparative apparatus. When mutations occur in critical growth regulatory genes, variations in cellular proliferation and survival contribute to the selection of dominant tumor population(s). Furthermore, these mutations may alter the antigenic properties of the cancerous cell and encourage escape from the host response. Thus, cancer is evolution at the microscopic level.
The epidemiology of UV induced skin cancer.
Journal: J Photochem Photobiol B. 2001 Oct;63(1-3):8-18.
Armstrong BK and Kricker A.
There is persuasive evidence that each of the three main types of skin cancer, basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and melanoma, is caused by sun exposure. The incidence rate of each is higher in fairer skinned, sun-sensitive rather than darker skinned, less sun-sensitive people; risk increases with increasing ambient solar radiation; the highest densities are on the most sun exposed parts of the body and the lowest on the least exposed; and they are associated in individuals with total (mainly SCC), occupational (mainly SCC) and non-occupational or recreational sun exposure (mainly melanoma and BCC) and a history of sunburn and presence of benign sun damage in the skin. That UV radiation specifically causes these skin cancers depends on indirect inferences from the action spectrum of solar radiation for skin cancer from studies in animals and the action spectrum for dipyrimidine dimers and evidence that presumed causative mutations for skin cancer arise most commonly at dipyrimidine sites. Sun protection is essential if skin cancer incidence is to be reduced. The epidemiological data suggest that in implementing sun protection an increase in intermittency of exposure should be avoided, that sun protection will have the greatest impact if achieved as early as possible in life and that it will probably have an impact later in life, especially in those who had high childhood exposure to solar radiation.
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