Recurrence rates associated with incompletely excised low-risk nonmelanoma skin cancer

Background: Reported recurrence rates for transected nonmelanoma skin cancer (NMSC) vary widely, and few studies have addressed recurrence of tumors followed clinically or treated with nonsurgical modalities.
Methods: Retrospective review of dermatopathology records from January 1999 to January 2005 was conducted to identify biopsies or excision specimens with histologically transected basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) which were not subsequently excised. Patient and tumor characteristics associated with recurrence were analyzed in a subgroup of patients with predominantly 'low-risk' and/or minimally transected NMSCs. Prospective follow up was performed through March 31, 2008. Data was analyzed with Chi-square and Fishers exact tests and multivariate logistic regression.
Results: Of 376 transected NMSCs, 27 (7.2%) recurred, including 20 (9%) of 223 BCCs and 7 (4.6%) SCCs in situ of 153 SCCs. The overall recurrence rate of the 124 minimally transected NMSCs was even lower (5.6%). Multivariate logistic regression identified three significant predictors of recurrence: tumor location on the head and neck (p = 0.041), tumor size (p = 0.00741) and superficial subtype of BCC (p = .035).
Conclusions: Although surgical excision of NMSC remains the standard of care, observation or nonsurgical treatment may be acceptable in many cases of incompletely excised low-risk or minimally transected NMSCs.     

HLA alleles in renal transplant recipients with nonmelanoma skin cancer in southeastern Brazil

Background: Renal transplant recipients are submitted to immunosuppression to avoid graft rejection, which makes them susceptible to various conditions. Furthermore, these individuals present malignant tumors more frequently than the general population, including nonmelanoma skin cancer. The individual genetic basis that acts in the pathogenesis of cutaneous cancer may present a protection or susceptibility factor for disease development. One of these factors is the HLA complex.Objective: To investigate HLA alleles association to the occurrence of nonmelanoma skin cancer in renal transplant recipients from Sao Paulo State.Methods: A total of 213 patients (93 renal transplant recipients with nonmelanoma skin cancer and 120 renal transplant recipients without nonmelanoma skin cancer) were evaluated by retrospective and cross-sectional study. Epidemiological, clinical and HLA typing data were found in databases. HLA class I (A, B) and class II (DR) alleles were compared to establish their association with nonmelanoma skin cancer.Results: Comparing renal transplant recipients with and without nonmelanoma skin cancer, the HLA-B*13 allele was associated with higher risk of developing nonmelanoma skin cancer while B*45 and B*50 alleles were associated with protection.Study limitations: The HLA A, B and DR alleles identification for the kidney transplantation routine is done by low and medium resolution techniques that do not allow discrimination of specific alleles.Conclusion: The involvement of HLA alleles in nonmelanoma skin cancer in renal transplant recipients was confirmed in this study. Renal transplant recipients with HLA-B*13 showed higher risk for developing a skin cancer (OR= 7.29) and should be monitored for a long period of time after transplantation.     

Incidence of nonmelanoma skin cancer

Nonmelanoma skin cancers are the most common malignant neoplasms of fair-skinned people, in many sunny countries exceeding the total of all other neoplasms. The evidence that the primary causal agent is chronic repeated exposure to solar ultraviolet radiation is overwhelming. The incidence of basal cell carcinoma is always greater than that of squamous cell carcinoma, varying by latitude from 10:1 to 2.5:1. The incidence of nonmelanoma skin cancer has been increasing by 2% to 3% per year, at least in the United States. Most likely, this is caused by greater outdoor exposure for leisure and social reasons.     

Chemoprevention of nonmelanoma skin cancer

Skin cancer is the most common cancer in human beings. The increased incidence of skin cancer has brought much attention to the process by which these tumors develop and how they can be prevented. Efforts have been made to educate the public about the importance of protecting skin from excessive ultraviolet light. Despite this work, the incidence of skin cancer continues to increase. Available compounds may be useful in the chemoprevention of skin cancer. Chemoprevention is defined as oral or topical use of dietary or pharmacologic agents to inhibit or reverse the development of cancer. Potential agents included are the retinoids; difluoromethylornithine; T4 endonuclease V; polyphenolic antioxidants, such as (-)-epigallocatechin gallate, found in green tea and grape seed extract; silymarin; isoflavone genestein; nonsteroidal anti-inflammatory drugs; curcumin; lycopene; vitamin E; beta-carotene; and selenium. Many of these agents are available over the counter as topical or oral preparations. LEARNING OBJECTIVE: At the conclusion of this activity, participants should be familiar with the chemopreventive agents and their efficacy, as well as any significant side effects associated with them.     

Non-melanoma skin cancer risk in the Queensland renal transplant population

BACKGROUND: Non-melanoma skin cancer (NMSC) is an important complication of solid organ transplantation, especially in areas of high ultraviolet light exposure. Registry data may underestimate the scale of the problem. OBJECTIVES: A single-observer study of a Queensland renal transplant population was conducted between July 1999 and April 2000 utilizing both cross-sectional and retrospective data. The aims were to determine accurately the risk of NMSC following renal transplantation and compare this with currently available registry data. PATIENTS AND METHODS: A structured interview and full skin examination was completed by 398 renal transplant recipients. Case notes and histology reports were examined for details of previous skin tumours. Independently collected data on 341 subjects from the Australia and New Zealand Dialysis and Transplantation Registry (ANZDATA) were also examined. RESULTS: One hundred and eighty-seven of 361 (51.8%) transplant recipients of Fitzpatrick skin types I-IV had developed 3979 histologically diagnosed NMSCs since first transplantation. The ratio of SCC/BCC was reversed from 1 : 3.7 before transplantation to 2 : 1 after transplantation. NMSC increased with duration of immunosuppression; 29.1%, 52.2%, 72.4% and 82.1% of those immunosuppressed for < 5, 5-10, 10-20 and > 20 years, respectively, had developed at least one tumour. The ANZDATA registry under-recorded the numbers of patients with NMSC by 28.4% and gave no indication of tumour numbers. CONCLUSIONS: NMSC is a greater clinical problem in renal transplant recipients living in subtropical Queensland, Australia, than is shown by currently available registry data. This has implications for the development of prevention and surveillance strategies.     

Polymorphisms in glutathione S-transferases are associated with altered risk of nonmelanoma skin cancer in renal transplant recipients: a preliminary analysis

Non-melanoma skin cancer (NMSC) represents a significant cause of morbidity and mortality among renal transplant recipients, with tumors behaving more aggressively than those in nontransplant patients. Not all immunosuppressed patients develop NMSC, however, and in those that do, the rate of accrual and numbers of lesions vary considerably. Though ultraviolet light is critical, it is unlikely that this alone explains the observed phenotypic diversity, suggesting the possible involvement of genetic factors. Furthermore, although twin studies in nontransplant patients with NMSC suggest a low genetic component, several genes associated with susceptibility and outcome in these patients have been identified. Thus, having previously shown that polymorphism in members of the glutathione S-transferase (GST) supergene family is associated with altered NMSC risk in nontransplant patients, we examined allelism in GSTM1, GSTP1, GSTM3, and GSTT1 in 183 renal transplant recipients. GSTM1 null was associated with increased squamous cell carcinoma (SCC) risk (p = 0.042, OR = 3.1). This remained significant after correction for age, gender, and ultraviolet light exposure (p = 0.012, OR = 8.4) and was particularly strong in patients with higher ultraviolet light exposure (e.g., sunbathing score > 3, p = 0.003, OR = 11.5) and in smokers (p = 0.021, OR = 4.8). Analysis of the interaction between GSTM1 null and sunbathing score showed that the two factors were synergistic and individuals with both risk parameters demonstrated a shorter time from transplantation to development of the first SCC (p = 0.012, hazard ratio = 7.1). GSTP1*Ile homozygotes developed larger numbers of SCC (p = 0.002, rate ratio = 7.6), particularly those with lower ultraviolet light exposure and cigarette consumption. GSTM3 and GSTT1 also demonstrated significant associations, though some genotype frequencies were low. These preliminary data suggest that genetic factors mediating protection against oxidative stress are important in NMSC development in immunosuppressed patients and may be useful in identifying high-risk individuals.     

Mortality in Danish patients with nonmelanoma skin cancer, 1978-2001

Background  Nonmelanoma skin cancer (NMSC) is a growing public health problem among Caucasians, thus mortality data that may provide insight into the clinical course and foster our understanding of NMSC are important.
Objectives  We examined total and cause-specific mortality among patients with NMSC registered in the Danish Cancer Registry from 1978 to 2001.
Methods  A total of 82 837 patients with basal cell carcinoma (BCC) and 13 453 patients with squamous cell carcinoma (SCC) were followed through the National Death Registry for specific causes of death. Standardized mortality ratios (SMRs) were computed based on mortality rates in the general population.
Results  Among patients with BCC, we found a slightly reduced total mortality [SMR 0·97, 95% confidence interval (CI) 0·96–0·98] with decreased SMRs seen for chronic obstructive pulmonary disease (COPD), cardiovascular disease (CVD) and diabetes mellitus. The SMR for suicide was increased. Among patients with SCC, we found an increased total mortality (SMR 1·30, 95% CI 1·26–1·33) due primarily to excess deaths from cancers, COPD, CVD and infectious diseases.
Conclusions  We found markedly different mortality patterns among patients with BCC and those with SCC, suggesting important differences in the clinical course of these patients.     

Genetics of nonmelanoma skin cancer.

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.     

Measurement of utility in nonmelanoma skin cancer

BACKGROUND: Quality of life is an important variable in assessing the impact of a condition on patients. The current literature shows a minimal effect of nonmelanoma skin cancer (NMSC) on patients' quality of life. This contrasts with our own experience. Given this disparity, we sought to perform an additional study in this area. Past studies have used multiattribute methods to assess quality of life. In contrast, the present study uses health utility methods, which rate a patient's quality of life from 0 to 1, with 1 representing perfect health. METHODS: Forty-one patients were guided through two standardized scenarios using a standard gamble process with a trained interviewer. Health utility scores were determined for both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) using various NMSC treatment modalities. RESULTS: All patients had health utility scores of 0.99 or higher. The standard gamble method showed no statistically significant differences in health utility scores for any treatment scenario for BCC or SCC using raw data comparisons. However, a modified standard gamble approach showed significantly higher health utility scores for both BCC and SCC treated using surgical modalities. CONCLUSION: Using the standard gamble health utility method in patients with BCC or SCC, it appears that these tumors have a minimal impact on the quality of life in the present study group. However, the results may simply reflect the poor sensitivity of the standard gamble health utility method to accurately assess quality of life changes in patients with NMSC. A modification of the standard gamble method did show that patients with NMSC associated surgical treatments with a better health outcome. New outcome measures need to be devised to accurately assess the toll of NMSC on patients.     

Surgical option for nonmelanoma skin cancer

BACKGROUND: Basal cell carcinoma (BCC) is one of the most frequent malignancies in the general population. Its best treatment option is the complete excision of the lesion. Mohs' micrographic surgery has demonstrated to be the surgical method with the highest cure rates, however, it is not available in many countries or institutions. METHODS: We propose, as a treatment option for high-risk BCC, surgical resection of the tumor with transoperatory histological examination with the hematoxilin-eosin technique, delaying closure of the wounds until the margins and surgical bed are tumor-free. RESULTS: We studied 83 patients with BCC; 49 were treated with the transoperatory technique and delay closure.We observed no recurrence in any patient that we followed up and there were no complications resulting from the technique in a 25-month follow up. CONCLUSIONS: We recommend this technique for tumors with high-risk of recurrence if Mohs' micrographic surgery is not available.