Pathways involved in sunburn cell formation: deregulation in skin cancer.
Journal: Photochem Photobiol Sci. 2006 Feb;5(2):199-207. Epub 2005 Sep 5. Claerhout S et al
The incidence of squamous cell carcinoma of the skin is rising worldwide for decades. Chronic exposure to sunlight is the most important environmental risk factor for this type of skin cancer. This is predominantly due to the DNA damaging effect of ultraviolet-B (UVB) in sunlight. UVB induces also sunburn cells, i.e. apoptotic keratinocytes, which is a crucial protective mechanism against the carcinogenic effects of UVB irradiation. This process is regulated by a wide range of molecular determinants involved in the balance between pro- and anti-apoptotic pathways. Growing evidence suggests that the deregulation of this balance by chronic UVB irradiation, contributes to the development of skin cancer. This review gives a brief summary of major known pathways involved in the regulation of keratinocyte survival and cell death upon UVB damage and discusses the contribution of the deregulation of these cascades to photocarcinogenesis.
Systemic strategies for chemoprevention of skin cancers in transplant recipients.
Journal: Clin Transplant. 2005 Dec;19(6):726-34.
Kovach BT et al
BACKGROUND: Solid organ transplant recipients (OTRs) are a growing population at high risk for cutaneous neoplasms, resulting in significant post-transplant morbidity and mortality. Management of malignant and pre-malignant cutaneous lesions in transplant recipients is challenging, making prevention of such neoplasms paramount. The objectives of the present study are to review and analyze systemic strategies for chemoprevention of malignant and pre-malignant cutaneous neoplasms in OTRs. METHODS: MEDLINE and PubMed searches were performed to identify studies with original data quantifying the effects of systemic agents on the development of malignant cutaneous neoplasms in patients with solid organ transplants. RESULTS: We identified nine studies describing 111 transplant recipients that quantified the effects of oral retinoids on cutaneous neoplasms. A majority of the studies found a decrease in the number of malignant and pre-malignant cutaneous lesions in patients treated with systemic retinoids, with several studies noting increased benefit in those patients with multiple previous skin cancers. Multiple studies described a rebound effect, with increased numbers of neoplasms occurring following discontinuation of retinoids. Side effects often limited dosing, but required discontinuation of retinoids in a minority of patients. No studies were identified that adequately quantified the effects of other systemic agents on skin cancer incidence in this population. CONCLUSIONS: Although systemic retinoids are frequently used for chemoprevention of cutaneous malignancies in OTRs, the data supporting their use are composed largely of small uncontrolled case reports and case series. However, the available data suggest that retinoids have chemopreventative effects in this population. Although optimal dosing and indications for initiation of systemic retinoid therapy are not conclusive from the data, it suggests that retinoids are most effective in patients with multiple previous non-melanoma skin cancers. Side effects and beneficial effects were noted across a wide range of doses, suggesting that retinoids should be initiated at a low dose and increased as tolerated to a minimally effective dose. Further investigation through randomized controlled trials is needed to further clarify the tolerability and efficacy of multiple dosing regimens on the incidence of pre-malignant and malignant lesions in transplant recipients. The therapeutic role of other systemic agents in the transplant population has not been established.
Basosquamous carcinoma-an under-recognized, high-risk cutaneous neoplasm: Case study and review of the literature.
Journal: Br J Plast Surg. 2005 Nov 22; [Epub ahead of print]
Costantino D et al
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.
Solar keratosis: from precancerous lesion to pre-invasive squamous cell carcinoma--therapeutic approach with a bioinductive method
Journal: J Dtsch Dermatol Ges. 2003 Oct;1(10):790-6.
Oster-Schmidt C et al
BACKGROUND: Solar keratoses are precancerous lesions in chronically UV-damaged skin with histological features consistent with pre-invasive squamous cell carcinoma. They require therapeutic intervention in order to prevent progression towards invasive carcinoma. Treatment options include topical medications and destructive methods. We report on a new approach--topical bioinductive therapy with imiquimod 5% cream. PATIENTS AND METHODS: In a prospective case series, 7 patients with solar keratoses have been treated with topical imiquimod 5%. The cream was applied 5 days/week over 2 weeks. After end of treatment, the outcome was assessed at regular control visits and, in some cases, histologically confirmed. One patient was followed up as untreated control. RESULTS: In 6 of the 7 treated patients, the lesions cleared completely; one patient did not respond. The patients did not show new solar keratoses during a follow-up period of about 2 years. The untreated patient showed spontaneous clearance of his keratoses. Local skin reactions during treatment included erythema, oedema and erosions in varying degrees, all of which completely resolved. CONCLUSIONS: Bioinductive therapy with imiquimod 5% cream represents a promising therapeutic approach for cutaneous precancerous lesions such as solar keratoses.
The pitfalls of treating all actinic keratoses as squamous cell carcinomas.
Journal: Semin Cutan Med Surg. 2005 Sep;24(3):152-4.
The greatest difficulties in managing a patient with numerous actinic keratoses is deciding the order in which to treat the specific lesions and what modality to use. The patient with a small number of lesions is probably most conveniently and cost effectively treated using destructive techniques like cryosurgery, electrodesiccation or photodynamic therapy with lasers. However, patients with large numbers of lesions are probably best managed using a topical chemotherapy agent, like 5-florouracil or imiquimod. If the patient's health insurance company limits coverage for the treatment of a specific number AK's per visit, it may be most prudent and logical to begin treatment of the largest or most rapidly growing AK's first and continue treatment of remaining lesions at subsequent visits until all lesions have been eradicated.
Treatment recommendations in patients diagnosed with high-risk cutaneous squamous cell carcinoma.
Journal: Australas Radiol. 2005 Oct;49(5):365-76.
Non-melanoma cutaneous cancers occur at an epidemic rate in Australia . With an ageing population, more Australians will develop these cancers and at an increasing rate. In the majority of cases local treatment is highly curative. However, a subset of the population will be diagnosed with a high-risk cutaneous squamous cell carcinoma. These can be defined as patients at risk of having subclinical metastases to regional lymph nodes based on unfavourable primary lesion features (including inadequately excised and recurrent lesions), patients with metastatic squamous cell carcinoma to regional lymph nodes, and squamous cell carcinoma in immunosuppressed patients. The mortality and morbidity associated with high-risk cutaneous squamous cell carcinoma is usually as a consequence of uncontrolled metastatic nodal disease and, to a lesser extent, distant metastases. Radiotherapy has an essential role in treating these patients and in many cases the addition of adjuvant radiotherapy may be life saving. It is therefore important that all clinicians treating skin cancers have an understanding and awareness of the optimal approach to these patients. The aim of this article is to present treatment recommendations based on an overview of the current published literature.
Radiation therapy for Bowen's disease of the skin.
Journal: Int J Radiat Oncol Biol Phys. 2005 Oct 1;63(2):505-10.
Lukas VanderSpek LA et al
PURPOSE: To assess the clinical outcome in the radiation therapy (RT) of squamous carcinoma in situ of the skin (Bowen's disease). We focused on the local control rate and the toxicity according to the biologically effective dose (BED). METHODS AND MATERIALS: A retrospective review was performed on 44 patients with Bowen's disease treated at Princess Margaret Hospital from April 1985 to November 2000. RT was the primary treatment for 32 patients, whereas 12 received RT for residual disease after local ablative therapy. Lesions were located as follows: scalp, 9 patients (20%); face, 12 (27%); trunk, 6 (14%), extremity, 12 (27%), perianal, 3 (7%), and penis, 2 (5%). Orthovoltage X-rays were used in the majority (39 of 44, 89%). There was no standard fractionation regimen: some physicians prescribed high doses, as for invasive skin cancer, whereas others prescribed lower doses because of the noninvasive nature of the disease, a sensitive anatomic location (e.g., extremity), or large treatment area. Because of the variations in fractionation regimens, BED was used as a common metric for biologic effect in the comparison of different regimens and analyzed for correlation with recurrence and toxicity. Local control was defined as the lack of persistent or recurrent disease at the treated site for the follow-up period. Grade 4 toxicity was defined as necrosis (cartilage/bone damage) and/or ulceration for a duration of >3 months. RESULTS: The mean patient age was 67.7 years, and the male/female ratio was 29:15. The median pretreatment lesion size was 2.65 cm(2) (range, 0.07-34.56 cm(2)). Complete remission was achieved in 42 patients, with follow-up unavailable for the remaining 2 patients. Subsequently, 3 patients experienced recurrences at 0.2, 1.1, and 1-1.5 years after complete remission. One recurrence was Bowen's disease (local); the others were squamous cell carcinoma (one local, one marginal). Four patients experienced a new squamous lesion at a distant cutaneous site. As of last follow-up, 32 patients (73%) were known to be alive. Median follow-up was 2.6 years (range, 0-11.8 years). All but 3 patients were disease-free at last follow-up, 1 of whom died with distant, but not local disease. The 5-year overall survival rate was 68%. Biologically effective dose was not associated with recurrence. The crude local control rate was 93%. There was a trend toward higher radiation doses for smaller pretreatment tumor and field sizes. The BED did not correlate with Grade 4 toxicity; however, the three cases of Grade 4 toxicity occurred in patients treated with hypofractionated regimens (dose per fraction >4 Gy) for extremity lesions. CONCLUSIONS: Radiation therapy is an effective treatment option for Bowen's disease of the skin. Local recurrences seem to be equally low in patients treated with high- and low-dose regimens. Avoiding hypofractionated regimens (dose per fraction >4 Gy) in extremity locations might reduce the risk of Grade 4 toxicity.
Occupational nonsolar risk factors of squamous cell carcinoma of the skin: a population-based case-controlled study.
Journal: Dermatol Online J. 2005 Aug 1;11(2):5.
Mitropoulos P and Norman R
The purpose of this study was to investigate associations between occupation, nonsolar environmental exposures, and risk of squamous cell carcinoma (SCC) of the skin. Data from the Southeastern Arizona Health Study-2 were used. This was a population-based case-controlled study [n = 795) conducted during 1992-1996 in southeastern Arizona to primarily assess the risk of skin SCC in relation to sun exposure. Multivariate logistic regression was used to calculate odd ratios as the estimate of effect. High-risk occupations were identified through literature review. There was evidence of a slightly elevated risk of skin SCC for subjects reporting a history of construction work (OR = 1.38, 95 % CI = 0.61-3.14), and automobile and machine work (OR = 1.21, 95 % CI = 0.48-3.06) Furthermore, there were no statistically significant associations between risk of skin SCC and history of exposure to specific chemical and other nonsolar environmental agents. A slight indication of increased risk for skin SCC was noted for exposure to nonsolar light (OR = 1.33, 95 % CI = 0.92-2.26), construction/machinery materials (OR = 1.12, 95 % CI = 0.76-1.84), fluorescent light (OR = 1.56, 95 % CI = 0.92-2.61), gypsum (OR = 1.84, 95 % CI = 0.68-5.0), coal tar and dandruff shampoos (OR = 1.28, 95 % CI = 0.85-1.9), and cement dust (OR = 1.81, 95 % CI = 0.90-3.62). A large although statistically insignificant risk was seen for exposure to arsenic (OR = 4.21, 95 % CI = 0.40-43.9) and ethylene glycol (OR = 8.46, 95 % CI = 0.77-92.9). Several of the results of this analysis are consistent with literature and conclusions from previous epidemiological studies. However, lack of power and small sample size deem these results as inconclusive until more research and larger studies are conducted.
Surgical margins in the treatment of nonmelanoma skin cancer and mohs micrographic surgery.
Journal: Curr Surg. 2005 Sep-Oct;62(5):518-26.
Lane JE and Kent DE
Traditional surgical treatment of nonmelanoma skin cancer includes excision with subsequent evaluation of surgical margins, either via frozen sections intraoperatively or after excision and closure. Accurate communication between surgeon and pathologist regarding the meaning of surgical margins should be confirmed. Recurrences of tumor growth may in part be attributed to asymmetrical tumor growth patterns with extension of tumor in an unanticipated direction. Mohs micrographic surgery is an outpatient procedure that maximizes surgical margin evaluation while minimizing the amount of tissue that must be excised. This article will discuss the concept of surgical margins in excisions of nonmelanoma skin cancer and the role of Mohs micrographic surgery.
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.
The diagnostic concordance of actinic keratosis and squamous cell carcinoma.
Journal: J Cutan Pathol. 2005 Sep;32(8):546-51.
Davis DA et al
Diagnostic concordance of intraepithelial malignancy is generally only fair. Because the diagnosis of actinic keratosis (AK) and squamous cell carcinoma (SCC) is not uniform and because such terms are not consonant with the nomenclature of other human epithelial malignancies, nomenclature revisions have been attempted. One hundred dermatopathologists were solicited to review 15 tissue sections representing a spectrum of varying thickness epidermal malignancy and to choose either AK or SCC as the diagnosis. Among the 77 participating dermatopathologists, intraclass correlation was high for what was perceived as AK, SCC, and their differentiation. Development of a two-tiered diagnostic system that retains our present diagnostic capabilities, but better fits the pathobiology of superficial epidermal malignancy is suggested. Davis DA, Donahue JP, Bost JE, Horn TD. The diagnostic concordance of actinic keratosis and squamous cell carcinoma.
Managing skin cancer--23 golden rules.
Journal: Aust Fam Physician. 2005 Aug;34(8):669-71.
Dixon AJ and Hall RS
From their collective experience in Australia and the USA , dermasurgeons Anthony Dixon and Scott Hall have compiled a list of "golden rules" for general practitioners to help reduce errors and problems with skin cancer management. It is anticipated that these tips will provide a brief yet informative reference when faced with skin cancer management concerns in general practice.
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. Copyright 2005 S. Karger AG, Basel
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 al
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.
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.
Cutaneous effects of smoking.
Journal: J Cutan Med Surg. 2004 Nov-Dec;8(6):415-23.
Freiman A et al
BACKGROUND: Cigarette smoking is the single biggest preventable cause of death and disability in developed countries and is a significant public health concern. While known to be strongly associated with a number of cardiovascular and pulmonary diseases and cancers, smoking also leads to a variety of cutaneous manifestations. OBJECTIVE: This article reviews the effects of cigarette smoking on the skin and its appendages. METHODS: A literature review was based on a MEDLINE search (1966-2004) for English-language articles using the MeSH terms cutaneous, dermatology, tobacco, skin, and smoking. An additional search was subsequently undertaken for articles related to smoking and associated mucocutanous diseases, with the focus on pathogenesis and epidemiologic data. Articles presenting the highest level of evidence and latest reports were preferentially selected. RESULTS: Smoking is strongly associated with numerous dermatologic conditions including poor wound healing, wrinkling and premature skin aging, squamous cell carcinoma, psoriasis, hidradenitis suppurativa, hair loss, oral cancers, and other oral conditions. In addition, it has an impact on the skin lesions observed in diabetes, lupus, and AIDS. The evidence linking smoking and melanoma, eczema, and acne is inconclusive. Anecdotal data exist on the possible protective effects of smoking in oral/genital aphthosis of Behcet's disease, herpes labialis, pyoderma gangrenosum, acral melanoma, and Kaposi's sarcoma in AIDS patients. CONCLUSIONS: An appreciation of the adverse cutaneous consequences of smoking is important. Dermatologists can play an integral role in promoting smoking cessation by providing expert opinion and educating the public on the deleterious effects of smoking on the skin.
Actinic keratosis and development of cutaneous squamous cell carcinoma
Journal: Tidsskr Nor Laegeforen. 2005 Jun 16;125(12):1653-4.
BACKGROUND: Actinic keratosis is a common sun-induced skin disease. For many years there has been a great deal of discussion of the term used for the disease and of its classification. Recent molecular studies indicate an association between actinic keratosis and squamous cell carcinoma. MATERIAL AND METHODS: Review of recent reports on histological, molecular, biochemical and clinical findings in actinic keratosis and cutaneous squamous cell carcinoma. RESULTS AND INTERPRETATION: The morphology of atypical cells in both actinic keratosis and squamous cell carcinoma is identical. The risk of progression to squamous cell carcinoma is minimal, but up to 60% of squamous cell carcinoma cases begin as actinic keratosis. Regression of actinic keratosis occurs when sun exposure is decreased. Examination of possible chromosome aberrations and gene mutations in both actinic keratosis and squamous cell carcinoma reveals similar patterns, including the same mutation in the tumour suppressor gene TP53. Recent studies indicate that actinic keratosis is the earliest manifestation of a potentially malignant disease similar to carcinoma in situ in cervix uteri. Thus, actinic keratosis requires careful diagnosis and follow up.
UV-induced skin cancer: similarities--variations.
Journal: J Dtsch Dermatol Ges. 2005 Jul;3(7):493-503.
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.
Non-melanoma skin cancer: what drives tumor development and progression?
Journal: Carcinogenesis. 2005 Oct;26(10):1657-67. Epub 2005 May 19.
Non-melanoma skin cancer, i.e. basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most frequent tumors and their number is still increasing worldwide. Furthermore, immunosuppression in organ transplant patients strongly contributes to the increase in skin cancer incidence--being 65-250 times more frequent than in the general population. Often these patients suffer from a second and third lesion and the severity of these tumors is linked to their number. SCCs in transplant recipients also appear to be more aggressive. They tend to grow rapidly, show a higher rate of local recurrences and metastasize in 5-8% of the patients (all reviewed in Ref. 2). This largely differs from BCCs which are more frequent in the general population--at a ratio of 4:1 as compared with SCCs--but the number is only increased by a factor of 10 in transplant recipients. This may suggest that 'dormant' SCC precursor cells/lesions are present at a high frequency in the population but they are well controlled by the immune system. BCC, on the other hand, may be less dependent on immune surveillance thereby underlining its different etiology. While for BCC development the genetic hallmark is abrogation of the ptch-sonic hedgehog pathway, little is known about the causal alterations of SCCs. However, the complexity of the genetic alterations (numerical and structural aberration profiles) in SCCs argues for several levels of genomic instability involved in the generation and progression of skin cancer.
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.
Skin cancer in the elderly.
Journal: In Vivo. 2005 May-Jun;19(3):643-52.
Syrigos KN et al
With the significant increase in the average life-span in the industrial world, skin cancer has become a great health concern. There are various epidemiological, biological and molecular data suggesting that skin cancer is predominantly a disease of the elderly, since approximately 53% of skin cancer-related deaths occur in persons more than 65 years old. With regard to the management of elderly patients with skin cancer, this should be individualized depending upon the clinical performance status, and age alone should not constitute an obstruction for the administration of the optimal treatment. Since elderly patients with melanoma have a worse prognosis, emphasis should be given to primary and secondary prevention. Physicians treating elderly patients should be trained in an individualized approach to these patients and encouraged to participate in programs for the early detection of suspicious skin lesions.
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.
Cytogenetic alterations in nonmelanoma skin cancer: a review.
Journal: Genes Chromosomes Cancer. 2005 Jul;43(3):239-48.
Ashton KJ et al
Since the advent of cytogenetic analysis, knowledge about fundamental aspects of cancer biology has increased, allowing the processes of cancer development and progression to be more fully understood and appreciated. Classical cytogenetic analysis of solid tumors had been considered difficult, but new advances in culturing techniques and the addition of new cytogenetic technologies have enabled a more comprehensive analysis of chromosomal aberrations associated with solid tumors. Our purpose in this review is to discuss the cytogenetic findings on a number of nonmelanoma skin cancers, including squamous- and basal cell carcinomas, keratoacanthoma, squamous cell carcinoma in situ (Bowen's disease), and solar keratosis. Through classical cytogenetic techniques, as well as fluorescence-based techniques such as fluorescence in situ hybridization and comparative genomic hybridization, numerous chromosomal alterations have been identified. These aberrations may aid in further defining the stages and classifications of nonmelanoma skin cancer and also may implicate chromosomal regions involved in progression and metastatic potential. This information, along with the development of newer technologies (including laser capture microdissection and comparative genomic hybridization arrays) that allow for more refined analysis, will continue to increase our knowledge about the role of chromosomal events at all stages of cancer development and progression and, more specifically, about how they are associated with nonmelanoma skin cancer. (c) 2005 Wiley-Liss, Inc.
Premalignant and early squamous cell carcinoma.
Journal: Clin Plast Surg. 2005 Apr;32(2):223-35.
Butani A et al
Actinic keratosis (AK) is a common sun-induced precancerous neoplasm confined to the epidermis. The AK is the initial manifestation of a continuum of clinical and histologic abnormalities that progresses to invasive squamous cell carcinoma (SCC). Bowen's disease, also known as squamous cell carcinoma in situ, represents early SCC confined to the epidermis. More than half of all SCCs contain p53 tumor suppressor gene mutations. Like SCCs, the vast majority of AKs and Bowen's disease lesions are asymptomatic. Each AK and suspicious lesion should be treated before it progresses to invasive SCC. Destructive modalities, such as cryosurgery using liquid nitrogen and electrodesiccation and curettage, usually performed by a dermatologist, are the mainstays of therapy.
Ultraviolet radiation and skin cancer: molecular mechanisms.
Journal: J Cutan Pathol. 2005 Mar;32(3):191-205.
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.
Optimum treatment strategies for actinic keratosis (intraepidermal squamous cell carcinoma.
Journal: Am J Clin Dermatol. 2004;5(6):395-401.
Lober BA and Fenske NA
Actinic keratoses are superficial squamous cell carcinomas. Treatment of these lesions is indicated to prevent the cells from invading the dermis and possibly metastasizing. If a lesion exhibits evidence of possible dermal invasion, such as marked erythema, ulceration, tenderness, bleeding, and especially induration, the physician should always consider performing a biopsy. Cryosurgical destruction, the most common treatment employed, has been shown to be 98.8% effective in eliminating the lesions. Adverse reactions such as scarring, textural changes, infection, and pigmentation alteration rarely occur. Physical destruction using electrodesiccation and curettage is particularly effective when the patient has hyperkeratotic lesions. When a patient has a multitude of actinic keratoses, the use of other treatments including fluorouracil, nonsteroidal anti-inflammatory preparations, immune response modifiers, and photodynamic therapy should be considered. However, none of these treatments has proven to be as effective overall as cryosurgical destruction. If a lesion does not respond to treatment, obtaining a biopsy of the lesion should be considered to be certain that the lesion is not an invasive squamous cell carcinoma.
Squamous cell carcinoma of the skin and coal tar creosote exposure in a railroad worker.
Journal: Environ Health Perspect. 2005 Jan;113(1):96-7.
A 50-year-old male railroad worker presented to his primary care physician with an erythematous, tender skin lesion on the right knee; a biopsy of this lesion revealed squamous cell carcinoma in situ. The site of the lesion was sun-protected but had been associated with 30 years of creosote-soaked clothing. In this article, we review dermal and other malignancies associated with creosote, along with creosote occupational exposures and exposure limits. This is a unique case, given the lack of other, potentially confounding, polyaromatic hydrocarbons and the sun-protected location of the lesion.
Surgical margins of excision for basal cell carcinoma and squamous cell carcinoma.
Journal: Semin Cutan Med Surg. 2004 Sep;23(3):167-73.
Huang CC and Boyce SM
In excising basal and squamous cell carcinomata, the surgical margin that is wide enough to completely remove the tumor an acceptable percentage of the time and narrow enough to minimize removal of excessive normal tissue must be selected. This task can be reliably accomplished with comprehensive knowledge of factors that affect subclinical tumor extension such as tumor appearance, diameter, histology, location, treatment status, and, in the case of squamous cell carcinoma, vertical invasion depth and involvement of subcutaneous fat. Information regarding these factors along with specific recommendations about excisional margins for basal cell and squamous cell carcinomata is presented.
Vitamin D and skin cancer.
Journal: J Nutr. 2004 Dec;134(12 Suppl):3472S-3478S.
Skin cancer is the most common cancer afflicting humans. These cancers include melanomas and 2 types of malignant keratinocytes: basal-cell carcinomas (BCC) and squamous-cell carcinomas (SCC). UV light exposure is linked to the incidence of these cancers. On the other hand, the skin is the major source of vitamin D-3 (cholecalciferol) and UV light is critical for its formation. Keratinocytes can convert vitamin D-3 to its hormonal form, 1,25 dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] (calcitriol). 1,25(OH)(2)D(3) in turn stimulates the differentiation of keratinocytes, raising the hope that 1,25(OH)(2)D(3) may prevent the development of malignancies in these cells. We identified a number of mechanisms by which 1,25(OH)(2)D(3) regulates the differentiation of keratinocytes and explored where this regulation breaks down in SCCs. 1,25(OH)(2)D(3) regulates gene expression by activating the vitamin D receptor (VDR). When activated, the VDR binds to one of two coactivator complexes: DRIP or p160/SRC. Binding to DRIP occurs in the undifferentiated keratinocyte, but, as the cell differentiates, DRIP(205) levels fall and p160/SRC binding takes over as SRC3 expression increases. SCCs fail to respond to the prodifferentiating actions of 1,25(OH)(2)D(3). These cells have normal levels of VDR and normal binding of VDR to vitamin D response elements. However, they overexpress DRIP(205) such that the p160/SRC complex is blocked from binding to VDR. We hypothesize that failure of 1,25(OH)(2)D(3) to induce differentiation in SCCs lies at least in part with its failure to induce the replacement of the DRIP complex with the SRC complex in the promoters of genes required for differentiation.
Squamous cell carcinoma of the skin.
Journal: Plast Reconstr Surg. 2004 Nov;114(6):82e-94e.
Rudolph R and Zelac DE
LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Identify the subtypes of squamous cell carcinoma of the skin. 2. Identify factors that affect recurrence and/or metastasis. 3. Develop a surgical management plan for treating high-risk squamous cell carcinoma of the skin.In treating squamous cell carcinoma of the skin, a key concept in proper management is understanding why certain tumors are more prone to both recurrence and metastasis. When developing a surgical management plan, an understanding of "high risk" is essential. This article concentrates on identifying those tumor subtypes and factors that may serve as predictors of high-risk status as well as on providing management suggestions.
Occupational skin cancers.
Journal: Occup Med (Lond). 2004 Oct;54(7):458-63.
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.
The genetics of skin cancer.
Journal: Am J Med Genet C Semin Med Genet. 2004 Nov 15;131C(1):82-92.
Tsai KY and Tsao H.
Recent advances in molecular genetics have led to a better understanding of the biological underpinnings of skin cancer formation. As with most cancers, the RB, p53, and RAS pathways appear to play prominent roles in the pathogenesis of several skin cancer types. Although various components of these pathways may be differentially altered in squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and cutaneous melanoma, the final biochemical expression of these defects may be the same. With the unraveling of these genetic mechanisms, a more targeted approach to diagnosis and treatment may be possible in the near future. (c) 2004 Wiley-Liss, Inc.
Quantifying actinic keratosis: assessing the evidence.
Journal: Am J Clin Dermatol. 2004;5(3):141-4.
Actinic keratoses are pre-malignant lesions, and it is standard practice to destroy them. Optimal management of actinic keratoses requires data on the efficacy of the numerous techniques employed in their treatment. Evaluating treatment efficacy requires before and after treatment quantification of actinic keratoses. Studies on the therapy and natural history of actinic keratoses have quantified these lesions by counting them. Counting actinic keratoses is unreliable because this technique lacks interobserver reproducibility. Consequently, studies based on counting actinic keratoses are fatally flawed and their conclusions of doubtful accuracy. Counting actinic keratoses should be abandoned as a technique for evaluating the therapy of actinic keratoses and the issue of spontaneous regression of actinic keratoses. A technique for reliably quantifying actinic keratoses is sorely needed.
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.
Histopathology of cutaneous squamous cell carcinoma and its variants.
37: Semin Journal: Cutan Med Surg. 2004 Mar;23(1):54-61.
Kane CL, et al
Squamous cell carcinoma is the second most common type of skin cancer, causing approximately 2,500 deaths in the United States each year. The principle risk factor for its development is ultraviolet light exposure. Conventional clinical and pathologic attributes of this neoplasm include an ulcerating papule located in a sun-exposed site with histologic sections showing an infiltrating neoplasm comprised of keratinizing epithelioid cells. Several histologic variants of squamous cell carcinoma with distinctive clinical and pathologic attributes including Bowen's disease, keratoacanthoma, acantholytic, spindle cell, desmoplastic, and verrucous and pigmented types have been described and are the topic of discussion in this article.
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.
Actinic keratosis: the key event in the evolution from photoaged skin to squamous cell carcinoma. Therapy based on pathogenetic and clinical aspects.
Journal: Skin Pharmacol Physiol. 2004 Mar-Apr;17(2):67-76.
Oppel T and Korting HC
Skin aging is the result of intrinsic and extrinsic factors. Extrinsic aging, also called photoaging, is mainly caused by ultraviolet radiation from the sun and leads to a state which has been termed dermatoheliosis. The aim of this article is to provide an overview of photoaged skin addressing actinic keratoses (AKs) in particular. This review will describe the clinical features of photoaged skin and briefly summarize the underlying histological, photobiochemical and molecular mechanisms responsible for photoaging. The concept of the disease continuum from AK to squamous cell carcinoma will also be presented. A special focus will be on established and new therapeutic approaches to undo photoinduced skin damage. Copyright 2004 S. Karger AG, Basel
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.
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.
Targets for molecular therapy of skin cancer.
Journal: Semin Cancer Biol. 2004 Feb;14(1):63-9.
Green CL and Khavari PA
Cancers of the skin encompass the first and second most common neoplasms in the United States , epidermal basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), respectively, as well as the melanocytic malignancy, malignant melanoma (MM). Recently identified alterations in the function of specific genes in these cancers provide new potential therapeutic targets. These alterations affect conserved regulators of cellular proliferation and viability, including the Sonic Hedgehog, Ras/Raf, ARF/p53, p16(INK4A)/CDK4/Rb and NF-kappaB pathways. New modalities designed to target these specific proteins may represent promising approaches to therapy of human skin cancers.
Squamous cell carcinoma of the nail unit with evidence of bony involvement: a multidisciplinary approach to resection and reconstruction.
Journal: Dermatol Surg. 2004 Feb;30(2 Pt 1):218-21.
Peterson SR et al
BACKGROUND: Squamous cell carcinoma (SCC) of the nail bed is a rare disorder that is often misdiagnosed for years before definitive diagnosis with biopsy. Proper evaluation of this carcinoma includes radiographic evaluation for bony involvement of the phalanges of the affected digit. If bony involvement is evident by x-ray, amputation of the distal phalanx or the affected digit is warranted. Mohs micrographic surgery of the affected nail unit is advantageous in preserving vital tissue for reconstruction after phalangeal amputation by a hand surgeon, thus maximizing preservation of the densely innervated tissue from the volar finger pulp. This approach may maximize functional capacity of the reconstructed digit. OBJECTIVE: To describe a multidisciplinary approach to resection, amputation, and reconstruction of digits with SCC of the nail bed. METHODS: This is a description of three cases and a review of the pertinent medical literature. RESULTS: Three SCCs of the nail bed were excised with Mohs micrographic surgery, preserving the volar pulp and skin of the distal finger. The patients were then referred for distal phalanx amputation and reconstruction by a hand surgeon. All patients remained disease free with acceptable function of the reconstructed digits at 15, 17, and 38 months of follow-up. CONCLUSION: Although uncommon, SCC of the nail bed must be considered in all nails with chronic disease. Preoperative evaluation should include hand radiographs in search of bony involvement. Tissue-sparing excision combined with distal amputation of the affected phalanx and reconstruction of the digit using spared tissue may maximize hand and digit function.
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.
Topical and light-based treatments for actinic keratoses.
Journal: Semin Cutan Med Surg. 2003 Sep;22(3):162-70.
Silapunt S et al
Actinic keratosis is currently believed to be an early stage in the evolution of squamous cell carcinoma. Active and intensive treatment of actinic keratosis may prevent the formation of invasive squamous cell carcinoma and potential metastases. While destructive methods of treatment of actinic keratosis remain the gold standard for the eradication of visible and palpable actinic keratoses, new medical therapies may accomplish this goal more comfortably and reliably for the patient. Newer topical medications, light therapy and photodynamic therapy are generating promising results that presage more widespread use in the future. These novel therapies for the early treatment of actinic keratosis may be administered in combination or serially, with the locus of treatment at any given time possibly restricted to a region of affected skin. Treatment of incipient or subclinical lesions may mitigate the risk of future squamous cell carcinomas lesions. Widespread actinic keratosis constitutes a persistent medical problem that requires long-term management. The role of traditional and novel treatments in the routine treatment of actinic keratosis will be determined by the efficacy, limitations and the practicality of each of these methods in individual patients. As the first stage of squamous cell carcinoma, actinic keratosis is worthy of prompt evaluation and active treatment.
New and emerging topical approaches for actinic keratoses.
Journal: Cutis. 2003 Oct;72(4):273-6, 279.
Del Rosso JQ
Actinic keratoses (AKs) are intraepidermal foci of malignancy and represent the earliest clinical stage in the continuum of squamous cell carcinoma (SCC). A variety of topical, physical, and surgical modalities are available for treatment. Until recently, topical 5-fluorouracil was the only topical agent approved by the US Food and Drug Administration (FDA) for the treatment of AK. Topical diclofenac 3% gel, an inhibitor of arachidonic acid, is the second topical approved for the treatment of AK. Although not currently approved in the United States , multiple studies have substantiated the efficacy of topical imiquimod for AKs. This article reviews the efficacy and safety of topical diclofenac and topical imiquimod for the treatment of AKs.
Treatment of nonmelanoma skin cancer in organ transplant recipients: review of responses to a survey.
Journal: J Am Acad Dermatol. 2003 Sep;49(3):413-6.
Clayton AS and tasko T.
There are approximately 100,000 US organ transplant recipients, many with nonmelanoma skin cancers. To better understand how clinicians treat them, we e-mailed a survey to the International Transplant-Skin Cancer Collaborative and the Association of Academic Dermatologic Surgeons. Twenty-five physicians responded. The majority use topical 5-fluorouracil, cryosurgery, electrodesiccation and curettage, and surgery. We review when these modalities are used.
Journal: Hautarzt. 2003 Jun;54(6):551-60; quiz 561-2.
Babilas P et al
Actinic keratoses are defined as proliferation of cytologically atypical keratinocytes in the zone of epidermal-dermal junction in photodamaged skin. In the northern hemisphere the prevalence of actinic keratoses ranges depending on different epidemiological studies from 11% to 25% for people aged 40 or older. The main cause of actinic keratoses is exposure to UVB radiation in sunlight UVB radiation induces mutations in the telomerase gene and in the tumor suppressor gene P53, which can also be detected in invasive squamous cell carcinoma. The only histological parameter to distinguish between actinic keratoses and SCC is the level of invasiveness. The risk for actinic keratoses to develop into SCC is about 16% over lo years. For this reason and because of the high prevalence of actinic keratoses, it has been suggested to replace the term,, actinic keratosis K with intraepidermal squamous cell carcinoma' to better characterize the lesion. In the following review recent aspects of pathogenesis and therapy of actinic keratoses are discussed.
Skin cancer: recognition and management.
Journal: Clin Cornerstone. 2001;4(1):23-32.
Skin cancer is the most common malignancy in humans and accounts for one third of newly diagnosed cancers--it will be diagnosed in approximately 1 in 5 Americans in their lifetime and > 1 million cases are diagnosed each year. Skin cancer can cause local tissue destruction, disfigurement, and even death if left untreated; therefore, timely recognition, treatment, and appropriate referral are critical to reducing morbidity. As the incidence of skin cancer rises each year, the primary care physician needs to be familiar with the clinical presentation, treatment options, and means of prevention of the most common skin cancers: basal cell carcinoma, squamous cell carcinoma, and malignant melanoma. 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 and 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.
Squamous cell carcinoma in solid-organ transplantation.
Journal: Dermatol Online J. 2002 Oct;8(2):4.
Wu JJ and Orengo IF
Multiple advances in the field of transplantation over the last several decades have resulted in a significant increase in the number of surgeries performed and in years of life extended. However, with the success of transplant comes the dilemma of potential complications of lifelong immunosuppressive therapy. An enormous increase in skin cancer, especially highly-aggressive squamous cell carcinoma, may affect this special population of patients. This review article discusses the main etiologic theories of squamous cell carcinoma, characteristics of skin cancer in the immunosuppressed patient, differences in skin cancer amongst three types of solid-organ transplantation (kidney, heart, and liver), and established and new treatments.
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.
Sentinel lymph node biopsy in head and neck squamous cell carcinoma.
Journal: Laryngoscope. 2002 Dec;112(12):2101-13.
Pitman KT et al
OBJECTIVES/HYPOTHESIS: Sentinel lymph node biopsy is a minimally invasive method to stage the regional lymphatics that has revolutionized the management of patients with intermediate-thickness cutaneous melanoma. Head and neck surgeons have been encouraged by the accuracy of sentinel lymph node biopsy in cutaneous melanoma and have applied the technique to patients with head and neck squamous cell carcinoma (HNSCC). The objectives of the study were 1) to study the feasibility and accuracy of sentinel lymph node biopsy as a method to stage the regional lymphatics in HNSCC and 2) to determine whether there are qualitative differences between the cutaneous and mucosal lymphatics that would affect the technique used in HNSCC. STUDY DESIGN: Two methods of investigation were employed: a prospective laboratory study using a feline model for sentinel lymph node biopsy and a retrospective review of patients who received lymphoscintigraphy before neck dissection and intraoperative identification of the sentinel lymph node. METHODS: Lymphoscintigraphy and a gamma probe were used in four felines to study the kinetics of technetium-labeled sulfa colloid (Tc-SC) in the mucosal lymphatics. In the second part of the feline study, eight subjects were studied intraoperatively. Tc-SC and isosulfan blue dye were used to study the injection technique for the mucosal lymphatics and to determine the time course of the dye and Tc-SC to the sentinel lymph node. In Part II of the present study, a retrospective review of 33 patients with HNSCC was conducted. Twenty patients (stage N0) whose treatment included elective neck dissection were studied with preoperative lymphoscintigraphy and underwent intraoperative identification of the sentinel lymph node to determine the accuracy and feasibility of sentinel lymph node biopsy. Eight patients with palpable neck disease and five patients with recurrent or second primary disease whose previous treatment included neck dissection were also studied with lymphoscintigraphy before neck dissection. RESULTS: In the feline study, both Tc-SC and isosulfan blue dye traversed the lymphatics rapidly, appearing in the sentinel lymph node in less than 5 minutes. Modification of the injection technique used for cutaneous melanoma was required to depict the sentinel lymph node of the base of tongue. In the human study, the sentinel lymph node was accurately identified in 19 of 20 (95%) N0 patients. On average, 2.9 sentinel lymph nodes (range, 1-5) were identified in 2.2 (range, 1-4) levels of the neck. Sentinel lymph nodes were bilateral in 4 of 19 patients. When the sentinel lymph node was identified, it accurately predicted the pathological nodal status of the regional lymphatics. Three of 20 patients had cervical metastases, and the sentinel lymph node was identified in 2 of 3 patients with pathologic nodes (pN+). Focal areas of radiotracer uptake were identified in seven of eight patients with palpable disease. These areas corresponded to the level with palpable disease in four patients. The lymphatics delineated by lymphoscintigraphy in the five patients with previous neck dissection were outside the levels that had been dissected. Lymphoscintigraphy depicted collateral patterns of lymphatic drainage. CONCLUSIONS: Sentinel lymph node biopsy is technically feasible and is a promising, minimally invasive method for staging the regional lymphatics in patients with stage N0 HNSCC. Lymphoscintigraphy alone may determine the levels that require treatment in patients with disrupted or previously operated cervical lymphatics.
Skin colour and skin cancer - MC1R, the genetic link.
Journal: Melanoma Res. 2002 Oct;12(5):405-16.
Pigmentary traits such as red hair, fair skin, lack of tanning ability and propensity to freckle (the RHC phenotype) have been identified as genetic risk factors for both melanoma and non-melanocytic skin cancers when combined with the environmental risk factor of high ultraviolet light exposure. The human melanocortin-1 receptor (MC1R) is a key determinant of the pigmentation process and can account in large part for the diverse range of variation in human pigmentation phenotypes and skin phototypes. The coding sequence is highly polymorphic in human populations, with several of these variant forms of the receptor now known to be associated with the RHC phenotype. We have examined variant allele frequencies in the general population and in a collection of adolescent dizygotic and monozygotic twins with defined pigmentation characteristics. Variant allele frequencies have also been determined in several case-control studies of sporadic melanoma, basal cell carcinoma and squamous cell carcinoma, and in familial melanoma kindreds collected within Australia . These studies have shown that three RHC alleles - Arg151Cys, Arg160Trp and Asp294His - were associated with increased risk in all forms of skin cancer and with penetrance and age of onset in familial melanoma in mutation carriers. There is a significant RHC allele heterozygote carrier effect on skin phototype and skin cancer risk, which indicates that variant alleles do not behave in a strictly recessive manner. Ultimately, the genetic and chemical assessment of melanin synthesis rather than skin colour will be the best indicator for skin cancer risk, and such genetic association studies combined with functional analysis of variant alleles should provide the link to understanding skin phototypes.
Molecular carcinogenesis of squamous cell carcinomas of the skin.
Journal: J Med Invest. 2002 Aug;49(3-4):111-7.
Kubo Y et al
Squamous cell carcinomas (SCCs) of the skin were suggested to develop through a multistep process that involves activation of proto-oncogenes and/or inactivation of tumor suppressor genes in the human skin keratinocytes. Exposure to ultra-violet (UV), especially UV-B, radiation is the most common cause for these genetic abnormalities in cells. We review causation of SCCs and genetic abnormalities in human SCCs with the current work. To elucidate the multistep process, we developed a method for examining the combinatorial function in vivo of plural genes in human keratinocytes. Using high efficiency retroviral transductions, we could express plural genes serially in normal human primary keratinocytes and use these cells to regenerate human skin on SCID mice. A combinatorial transduction of H-RasV12 and cyclin dependent kinase 4 (CDK4) produced human epidermal neoplasia resembling SCC. These findings were consistent with our previous results of mutation analysis in SCCs, one of which had both mutations of H-Ras gene and the INK4a locus. Therefore, it is suggested that a combination of these genetic abnormalities might be crucial to the carcinogenesis at least in a subset of SCCs.
Squamous cell carcinoma of the eyelids.
Journal: Br J Ophthalmol. 2002 Oct;86(10):1161-5.
Donaldson MJ et al
AIM: To review the clinical features, management, and outcomes of surgical treatment of eyelid squamous cell carcinoma (SCC). METHODS: A retrospective review of all eyelid SCCs treated between 1992 and 2001. RESULTS: 51 cases were identified in 50 patients. Patient ages ranged from 26 to 93 years, with a mean age of 65 years. 33 patients were male and 17 were female. The lesion was found on the lower lid in 31 cases, upper lid in five cases, lateral canthus in six cases, and medial canthus in nine cases. Perineural invasion was found in four patients, and orbital invasion in three patients. Recurrence occurred in one patient. Treatment was by complete excision with histological confirmation of clear margins. Exenteration was required in three patients. No patients developed lymph node or distant metastases. One patient, who declined treatment, died as a result of the tumour. Mean follow up was 31.1 months. CONCLUSIONS: Eyelid SCC is a relatively uncommon, but potentially fatal disease. However, if detected early and treated adequately, the prognosis is generally excellent. Treatment by complete excision with histological confirmation of tumour clearance is recommended. Perineural spread is an adverse prognostic sign, which may require postoperative radiotherapy. Orbital invasion is a rare complication but, if recognised early, can be treated effectively with exenteration. Because presentation varies and histological examination is required for accurate diagnosis, any suspicious lesion occurring on the eyelids should be excised or biopsied. All patients with eyelid SCC should be advised of the risk of recurrent or new tumours and encouraged to attend lifelong follow up. Prevention remains of prime importance in minimising the morbidity and mortality of these lesions.
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%).
UV protection and skin cancer.
Journal: Recent Results Cancer Res. 2002;160:7-12.
Dummer R and Maier T.
In discussions amongst the public and the scientific community, doubts are repeatedly raised concerning the efficacy of sunscreens in preventing cutaneous malignancy. This article summarizes the most reliable references on UV protection and epithelial skin cancer and discusses the role of UV protection in melanoma prevention. We conclude that there is substantial evidence that UV protection is able to reduce the risk of actinic keratosis, squamous cell carcinoma and probably also the risk of melanoma.
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.
Managing solar keratoses.
Journal: Drug Ther Bull. 2002 May;40(5):33-5.
Solar keratoses (actinic keratoses) are common, often multiple, epidermal lesions found mainly on the sun-exposed skin of fair-skinned middle-aged and older people. They may transform into non-melanoma skin cancers, particularly squamous cell carcinoma. Here, we review the prevention and treatment of solar keratoses.
The epidemiology of skin cancer.
Journal: Br J Dermatol. 2002 Apr;146 Suppl 61:1-6.
Diepgen TL, 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.
Human papillomaviruses and non-melanoma skin cancer.
Journal: Curr Opin Infect Dis. 2002 Apr;15(2):101-14.
Harwood CA , Proby CM
Epidemiological and experimental studies have overwhelmingly confirmed human papillomaviruses as important causal agents in anogenital carcinogenesis. A role for human papillomaviruses has also been proposed in a diverse range of other malignancies, and particular interest has focused on non-melanoma skin cancer, the commonest malignancy in fair-skinned populations worldwide. Although the evidence for this is considerably less convincing than for anogenital cancer, important epidemiological and functional data have emerged over the past year that have furthered our understanding of the possible contribution of human papillomaviruses to skin cancer. Epidemiological human papillomavirus DNA detection studies have shown associations with non-melanoma skin cancer, but have also emphasized the ubiquity of epidermodysplasia verruciformis human papillomavirus types in normal skin, hair follicles and benign hyperproliferative disorders, as have seroepidemiological approaches. Functional investigations have demonstrated mechanistically relevant interactions between the virus and ultraviolet radiation, host cytokines and cellular proteins including p53 and the pro-apoptotic protein Bak. Taken together, these data have advanced our understanding of the contribution of human papillomaviruses to malignant transformation in cutaneous keratinocytes, but further research is required before a causal association between human papillomaviruses and skin cancer is reliably confirmed.
Squamous cell carcinoma of the head and neck in solid organ transplant recipients.
Journal: Head Neck. 2002 Apr;24(4):319-25.
Preciado DA et al
BACKGROUND: The increased incidence of cancer after solid organ transplantation is well established in the literature, yet outcome studies in this population are rare. Excluding skin cancers, squamous cell carcinomas make up most head and neck cancers in transplant recipients. METHODS: At our institution, of 5300 solid organ transplant recipients, 34 have had head and neck cancer develop. We reviewed the records of the 23 recipients whose cancer was treated here. RESULTS: Only 6 of the 23 recipients were alive at the time of our chart review. Of these, three had already survived 5 years. The 10 recipients diagnosed early (stage I or II) had significantly longer survival after cancer diagnosis than the 13 diagnosed at an advanced stage (stage III or IV) (96.0 mo vs 9.0 mo, p <.001). In all, 14 (60.8%) of the 23 recipients died of cancer within 2 years after diagnosis, 12 (50.2%) within 12 months. The sum of the daily doses of immunosuppressive drugs at cancer diagnosis was significantly greater for recipients who died within 2 years (p =.02). Furthermore, the difference in average doses of both prednisone (p =.001) and azathioprine (p =.028) was also significantly greater for those who died within 2 years. The average dose of cyclosporine was also greater, but this difference did not reach statistical significance (p =.18). The average dose of prednisone was significantly lower for recipients diagnosed early (p =.001). This correlation between high immunosuppressive drug doses and worse outcome has not been shown previously. CONCLUSIONS: Solid organ transplant recipients who are diagnosed with advanced head and neck cancer while receiving high doses of immunosuppressive drugs fare extremely poorly. High doses of immunosuppressive drugs, most notably prednisone, correlate significantly with advanced diagnosis of head and neck cancer and earlier death. Copyright 2002 Wiley Periodicals, Inc.
Human papillomavirus infection and skin cancer risk in organ transplant recipients.
Journal: J Investig Dermatol Symp Proc. 2001 Dec;6(3):207-11.
Bouwes Bavinck JN et al
Warts and squamous cell carcinomas are important cutaneous complications in organ transplant recipients. The role of infection with human papillomaviruses (HPV) in the development of cutaneous squamous cell carcinoma is still unclear. An extremely diverse group of HPV types, mainly consisting of epidermodysplasia-verruciformis (EV)-associated HPV types, can be detected in benign, premalignant, and malignant skin lesions of organ transplant recipients. Frequently, there are multiple HPV types present in single skin biopsies. Typically, the prevalence of viral warts rises steadily after transplantation and a strong association exists between the number of HPV-induced warts and the development of skin cancer. The interval between the transplantation to the development of warts is clearly shorter than the interval from transplantation to the diagnosis of the first skin cancer. A comparison of transplant recipients with and without skin cancer, however, showed an equally high prevalence of EV-HPV DNA in keratotic skin lesions in both groups of patients and the detection rate and spectrum of HPV infection in hyperkeratotic papillomas, actinic keratoses, and squamous cell carcinomas was also similar. HPV DNA can frequently be detected in patients with hyperproliferative disorders like psoriasis and antibodies against HPV in patients with regenerating skin (e.g., after extensive second degree burns). Latent infection with EV-HPV seems to be widespread. The hair follicle region might be the reservoir of EV-HPV. The E6 protein from a range of cutaneous HPV types effectively inhibits apoptosis in response to UV-light induced damage. It is therefore conceivable that individuals who are infected by EV-HPV are at an increased risk of developing actinic keratoses and squamous cell carcinomas, possibly by chronically preventing UV-light induced apoptosis.
The sun's damaging effects.
Journal: Dermatol Nurs. 2001 Aug;13(4):279-86.
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.
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.
Genetics of nonmelanoma skin cancer.
Journal: Arch Dermatol. 2001 Nov;137(11):1486-92.
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.
Actinic keratosis. Current treatment options.
Journal: Am J Clin Dermatol. 2000 May-Jun;1(3):167-79.
Jeffes EW 3 rd and Tang EH
Actinic keratoses are hyperkeratotic skin lesions that represent focal abnormal proliferation of epidermal keratinocytes. Some actinic keratoses evolve into squamous cell carcinoma of the skin, while others resolve spontaneously. The conversion rate of actinic keratosis to squamous cell carcinoma is not accurately known, but appears to be in the range of 0.25 to 1% per year. Although there is a low rate of conversion of actinic keratoses to squamous cell carcinoma, 60% of squamous cell carcinomas of the skin probably arise from actinic keratoses. The main cause of actinic keratoses in otherwise healthy Caucasians appears to be the sun. Therapy for actinic keratoses begins with prevention which starts with sun avoidance and physical protection. Sunprotection with sunscreens actually slows the return of actinic keratoses in patients already getting actinic keratoses. Interestingly, a few studies are available that demonstrate that a high fat diet is associated with the production of more actinic keratoses than is a low fat diet. One of the mainstays of therapy has been local destruction of the actinic keratoses with cryotherapy, and curettage and electrodesiccation. A new addition to this group of therapies to treat individual actinic keratoses is photodynamic therapy with topical aminolevulinic acid and light. In patients who have numerous actinic keratoses in an area of severely sun damaged skin, therapies which are applied to the whole actinic keratosis area are used. The goal of treating such an area of skin is to treat all of the early as well as the numerous clinically evident actinic keratoses at the same time. The classical approaches for treating areas of photodamaged skin without treating actinic keratoses individually include: the use of topically applied fluorouracil cream, dermabrasion, and cutaneous peels with various agents like trichloroacetic acid. Both topically as well as orally administered retinoids have been used to treat actinic keratoses but retinoids alone are probably not an optimal monotherapy. Photodynamic therapy with topical aminolevulinic acid and light is a new therapy for actinic keratoses. Aminolevulinic acid is a precursor of protoporphyrin IX (PpIX) which is synthesized in the actinic keratosis when it is treated with aminolevulinic acid, and the PpIX photosensitizes the actinic keratosis so that light exposure can lead to its destruction. Photodynamic therapy with topical aminolevulinic acid is approved in the US to treat multiple individual actinic keratoses on the face and scalp and has similar cure rates to those reported for cryotherapy and fluorouracil therapy.
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.
Prevention of non-melanoma skin cancer.
Journal: Curr Oncol Rep. 2001 Jul;3(4):295-300.
Basal cell and squamous cell carcinomas comprise the majority of non-melanoma skin cancers. Whereas the incidence of skin cancer is equivalent to that of all other cancers combined, non-melanoma skin cancer receives a disproportionate share of attention because mortality is relatively low. However, the impact on public health is striking. This review is intended to update readers on the current findings in research on the prevention of these diseases. Topics covered include preventive strategies targeting high-risk populations, chemoprevention (including treatment of intraepithelial neoplasia), and an overview of recent and ongoing clinical and preclinical studies involving new chemopreventive agents.
Radiation-induced skin cancer in humans.
Journal: Med Pediatr Oncol. 2001 May;36(5):549-54.
The principal epidemiologic studies of ionizing radiation and skin cancer have all shown that radiation causes basal cell carcinoma but have not found dose-related excesses of squamous cell carcinoma or malignant melanoma. The Japanese atomic bomb study indicates that doses of radiation under about 1 Gy confer less risk per unit dose than higher doses do. All available studies show that skin cancer risk is greater from radiation exposure at young ages than at older ages. Finding few excess skin cancers among irradiated African-Americans as compared to Caucasians with a comparable dose indicates that skin susceptibility to ultraviolet exposure modifies the excess risk from ionizing radiation. Available evidence indicates that the excess risk of skin cancer lasts for 45 years or more following irradiation. Several studies indicate a risk of nonmelanoma skin cancer (NMSC) following cancer therapy; however, most of the studies reporting on NMSC have not distinguished between patients who received radiotherapy versus chemotherapy. Some, but not all, follow-up studies of cancer patients have reported excesses of malignant melanoma as second malignant neoplasms. It is not clear from the studies how much, if any, of the excess melanoma risk is attributable to radiotherapy. Copyright 2001 Wiley-Liss, Inc.
Screening for skin cancer.
Journal: Am J Prev Med. 2001 Apr;20(3 Suppl):47-58.
Helfand M et al
CONTEXT: Malignant melanoma is often lethal, and its incidence in the United States has increased rapidly over the past 2 decades. Nonmelanoma skin cancer is seldom lethal, but, if advanced, can cause severe disfigurement and morbidity. Early detection and treatment of melanoma might reduce mortality, while early detection and treatment of nonmelanoma skin cancer might prevent major disfigurement and to a lesser extent prevent mortality. Current recommendations from professional societies regarding screening for skin cancer vary. OBJECTIVE: To examine published data on the effectiveness of routine screening for skin cancer by a primary care provider, as part of an assessment for the U.S. Preventive Services Task Force. DATA SOURCES: We searched the MEDLINE database for papers published between 1994 and June 1999, using search terms for screening, physical examination, morbidity, and skin neoplasms. For information on accuracy of screening tests, we used the search terms sensitivity and specificity. We identified the most important studies from before 1994 from the Guide to Clinical Preventive Services, second edition, and from high-quality reviews. We used reference lists and expert recommendations to locate additional articles. STUDY SELECTION: Two reviewers independently reviewed a subset of 500 abstracts. Once consistency was established, the remainder were reviewed by one reviewer. We included studies if they contained data on yield of screening, screening tests, risk factors, risk assessment, effectiveness of early detection, or cost effectiveness. DATA EXTRACTION: We abstracted the following descriptive information from full-text published studies of screening and recorded it in an electronic database: type of screening study, study design, setting, population, patient recruitment, screening test description, examiner, advertising targeted at high-risk groups or not targeted, reported risk factors of participants, and procedure for referrals. We also abstracted the yield of screening data including probabilities and numbers of referrals, types of suspected skin cancers, biopsies, confirmed skin cancers, and stages and thickness of skin cancers. For studies that reported test performance, we recorded the definition of a suspicious lesion, the "gold-standard" determination of disease, and the number of true positive, false positive, true negative, and false negative test results. When possible, positive predictive values, likelihood ratios, sensitivity, and specificity were recorded. DATA SYNTHESIS: No randomized or case-control studies have been done that demonstrate that routine screening for melanoma by primary care providers reduces morbidity or mortality. Basal cell carcinoma and squamous cell carcinoma are very common, but detection and treatment in the absence of formal screening are almost always curative. No controlled studies have shown that formal screening programs will improve this already high cure rate. While the efficacy of screening has not been established, the screening procedures themselves are noninvasive, and the follow-up test, skin biopsy, has low morbidity. Five studies from mass screening programs reported the accuracy of skin examination as a screening test. One of these, a prospective study, tracked patients with negative results to determine the number of patients with false-negative results. In this study, the sensitivity of screening for skin cancer was 94% and specificity was 98%. Several recent case-control studies confirm earlier evidence that risk of melanoma rises with the presence of atypical moles and/or many common moles. One well-done prospective study demonstrated that risk assessment by limited physical exam identified a relatively small (<10%) group of primary care patients for more thorough evaluation. CONCLUSIONS: The quality of the evidence addressing the accuracy of routine screening by primary care providers for early detection of melanoma or nonmelanoma skin cancer ranged from poor to fair. We found no studies that assessed the effectiveness of periodic skin examination by a clinician in reducing melanoma mortality. Both self-assessment of risk factors or clinician examination can classify a small proportion of patients as at highest risk for melanoma. Skin cancer screening, perhaps using a risk-assessment technique to identify high-risk patients who are seeing a physician for other reasons, merits additional study as a strategy to address the excess burden of disease in older adults.
Solar keratoses and their relationship to non-melanoma skin cancers.
Journal: Australas J Dermatol. 1997 Jun;38 Suppl 1:S30.
Solar keratoses belong to the list of clinically invisible dermatoses, as the loss of their horny layer may create the illusion that they have disappeared, and numerous subclinical lesions can be highlighted by 5-fluorouracil therapy. Solar keratoses are recognized as potential precursors for squamous cell carcinoma. However, basal cell carcinoma (BCC) may develop in a soft type of solar keratoses as a consequence of migration of pluripotential adnexal epithelial cells in reparative response to trauma, particularly in areas rich in adnexal structures, such as the face. These intraepithelial resident adnexal cells may result in the development of BCC following chronic solar exposure and damage.
Sun exposure and skin cancer.
75: Australas J Dermatol. 1997 Jun;38 Suppl 1:S1-6.
Armstrong BK et al
By 1927 for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), and by 1955 for melanoma, the broad grounds for relating sun exposure to skin cancer had been established: that these are more frequent in residents of areas of high ambient solar irradiance, are more frequent in sun-sensitive people, occur mainly on sun-exposed body sites, are more frequent in people with high sun exposure, and are more frequent in people with benign sun-related skin conditions. The past 40 years have added both quantity and quality to the epidemiological evidence and, most recently, provided direct evidence that sun exposure is the cause of mutations in critical tumour suppressor genes in BCC, SCC and melanoma. Complete or more convincing answers are still needed to many questions of detail. They include whether the pattern of sun exposure is really important in, and acts independently of amount of sun exposure in, affecting the risk of melanoma and BCC; what the shape of the relationship between the amount of sun exposure and risk of BCC and melanoma is when the pattern of exposure is held constant; whether there really is a plateau in risk of BCC and melanoma beyond some level of the amount of exposure; whether this exposure-response relationship depends on cutaneous sensitivity to the sun and in what way; whether sunburn makes a specific contribution to the risk of skin cancer independent of the amount of sun exposure; whether sun exposure close to the time of diagnosis of skin cancer contributes anything to the development of the cancer; what the solar radiation action spectrum is for each kind of skin cancer; and whether sunscreens are effective in protecting against skin cancer.
Early detection and treatment of skin cancer.
Journal: Am Fam Physician. 2000 Jul 15;62(2):357-68, 375-6, 381-2.
Jerant AF et al
The incidence of skin cancer is increasing by epidemic proportions. Basal cell cancer remains the most common skin neoplasm, and simple excision is generally curative. Squamous cell cancers may be preceded by actinic keratoses-premalignant lesions that are treated with cryotherapy, excision, curettage or topical 5-fluorouracil. While squamous cell carcinoma is usually easily cured with local excision, it may invade deeper structures and metastasize. Aggressive local growth and metastasis are common features of malignant melanoma, which accounts for 75 percent of all deaths associated with skin cancer. Early detection greatly improves the prognosis of patients with malignant melanoma. The differential diagnosis of pigmented lesions is challenging, although the ABCD and seven-point checklists are helpful in determining which pigmented lesions require excision. Sun exposure remains the most important risk factor for all skin neoplasms. Thus, patients should be taught basic "safe sun" measures: sun avoidance during peak ultraviolet-B hours; proper use of sunscreen and protective clothing; and avoidance of suntanning.
Actinic keratosis is squamous cell carcinoma.
Journal: South Med J. 2000 Jul;93(7):650-5.
Lober BA and Lober CW
BACKGROUND: The prevalence of nonmelanoma skin cancer in the United States is alarming. It can be most appropriately treated if the earliest manifestation of cutaneous squamous cell carcinoma is recognized. METHODS: Clinical, histologic, and molecular biology, considerations were reviewed to determine whether actinic keratosis is the earliest clinical manifestation of cutaneous squamous cell carcinoma. RESULTS: The clinical, histologic, and molecular parameters of actinic keratosis are those of squamous cell carcinoma. CONCLUSION: Actinic keratosis does not transform, convert, or progress into cutaneous squamous cell carcinoma but is the earliest clinically recognizable manifestation of this malignancy.
Skin cancer in liver transplant recipients.
Journal: Liver Transpl. 2000 May;6(3):253-62.
Otley CC and Pittelkow MR
Skin cancer is the most common malignancy arising in the posttransplantation setting. Multiple factors contribute to the high risk for cutaneous carcinoma in immunosuppressed organ-transplant recipients. We review the phenomenon of skin cancer in solid-organ transplant recipients and further delineate the problem in the context of liver transplantation. Skin cancer is a significant medical and surgical problem for organ-transplant recipients. With prolonged allograft function and patient survival, the majority of solid-organ transplant recipients will eventually develop skin cancer. Although squamous cell carcinoma is the most common cutaneous malignancy in this population, basal cell carcinoma, melanoma, and Kaposi's sarcoma, as well as uncommon skin malignancies, may occur. Highly susceptible patients may develop hundreds of squamous cell carcinomas, which may be life threatening. Management strategies focus on regular full-skin and nodal examination, aggressive treatment of established malignancies, and prophylactic measures to reduce the risk for additional photodamage and malignant transformation. Skin cancer is a substantial cause of morbidity and even mortality among solid-organ transplant recipients. As a byproduct of immunosuppression, liver transplant recipients experience a high incidence of skin cancer and should be educated and managed accordingly.