Malignant and in situ subtypes of melanoma are associated with basal and squamous cell carcinoma and its precancerous lesions

Background: Patients with cutaneous malignant melanoma (CMM) are at increased risk of non-melanoma skin cancers (NMSCs) and possibly precancerous lesions. Objectives: To analyse the association between CMM and not only NMSCs but also precursor lesions, actinic keratosis (AK) and Bowen disease (BD). Materials & Methods: The Finnish Cancer Registry data was used to calculate the age-standardized incidence ratio during 2000-2013 for basal (BCC) and squamous (SCC) cell carcinoma in patients with CMM. All tissue material collected from 70,420 subjects during 2000-2013 and reposited in the Biobank of Eastern Finland was used to calculate the age-standardized prevalence of BCC, SCC, BD and AK in CMM patients. Results: In both genders, the age-standardized incidence ratio of BCC and SCC was increased in CMM patients. The age-standardized prevalence of NMSCs and precursor lesions was higher in patients with CMM than in those without CMM, and was higher in CMM patients with immunosuppression (IS) than in those without IS. The association of M-Snomed subtypes, lentigo maligna (LM), melanoma in situ (MIS) and malignant melanoma (MM) with AK and/or BD was stronger than with BCC. LM revealed the highest association with the combination of AKBD-SCC. Male subjects showed a higher age-standardized prevalence of CMM, MM and BCC than females, but the opposite was observed for AK. Conclusion: Melanoma increases the risk of NMSCs, and IS may enhance this risk. Both malignant and in situ subtypes of melanoma associate with not only BCC and SCC, but also precancerous lesions.

Laser Treatment for Non-Melanoma Skin Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Surgery is the mainstay of treatment for non-melanoma skin cancer. Lasers are an additional option. OBJECTIVE: The objective of this study was to review the literature on the efficacy and safety of lasers for the treatment of non-melanoma skin cancer. METHODS: A systematic review and meta-analysis of laser treatment for non-melanoma skin cancer was performed. The primary outcome was recurrence rate (RR). RESULTS: The review included 32 studies (six randomized controlled trials and 26 cohort studies): 27 evaluated basal cell carcinomas (BCCs), three squamous cell carcinomas, and two both, for a total of 4755 BCCs and 214 squamous cell carcinoas. Most BCCs were low risk. The Nd:YAG laser (seven studies, 3286 BCCs) had a 3.1% RR (95% confidence interval [CI] 1.4-6.4%) during a mean follow-up of 7.9 years, with a low rate (< 20%) of scarring and dyspigmentation. The CO2 laser (ten studies, 904 BCCs) had a 9.4% RR (95% CI 4.1-20) during a mean follow-up of 2.1 years, with a low rate of side effects. The pulsed dye laser (eight studies, 206 BCCs) had a 38% RR (95% CI 24-55). In two studies, the Nd:YAG laser demonstrated a RR of 10% (95% CI 2-31) for Bowen's disease, and in three studies, the CO2 laser demonstrated a RR of 22% (95% CI 5-61) for squamous cell carcinoma. CONCLUSIONS: Based on cohort studies, the Nd:YAG laser is a safe and efficacious modality for the treatment of low-risk BCC. Based on settings applied in prior studies in the literature, the CO2 laser is less efficacious than the Nd:YAG laser, thus it cannot be recommended for BCC treatment. Insufficient data preclude conclusions regarding laser treatment for squamous cell carcinoma. REGISTRATION: PROSPERO registration number CRD42019129717.

Dermatological Disease in Australian Heart and Lung Transplant Recipients.

BACKGROUND: Research examining skin disease in heart and lung transplant recipients in Australia is limited. This study aims to determine the spectrum of skin diseases encountered in Australian heart and lung transplant recipients, their effect on quality of life, and potential risk factors for skin cancer. METHODS: Ninety-four participants were recruited from an Australian heart and lung transplant centre between March and December 2016. The participants were asked to fill out a questionnaire which included the Dermatology Life Quality Index and were examined for malignant and non-malignant skin disease. The association of study variables with the presence of skin cancer and Dermatology Life Quality Index score were examined using logistic regression analysis. RESULTS: A dermatological diagnosis was made in 82 patients (87%). Actinic keratosis was the most common diagnosis, affecting 50 participants (53%), followed by skin cancer (41; 44%) and warts (14; 15%). Other non-malignant skin diseases were less common. Risk factors associated with skin cancer on multivariate modelling included age at transplantation and a history of ≥5 post-transplant skin cancers. Skin disease had a negative effect on the quality of life of a minority of patients. CONCLUSION: Actinic keratosis and skin cancer are very frequent in Australian heart and lung transplant recipients and more common than non-malignant skin diseases. Routine dermatological surveillance at regular intervals is advised.

Actinic keratoses in subjects from la Mitad del Mundo, Ecuador.

BACKGROUND: Quito, the capital of Ecuador due to its geographical location, has a high skin cancer incidence. Actinic keratoses, as premalignant lesions, are precursors of nonmelanoma skin cancer, and the prevalence of this medical condition in the country is unknown. METHODS: An observational, cross-sectional study was performed to assess the prevalence of actinic keratoses (AKs) in a rural area of Quito. Visual skin exams, dermoscopy and biopsy of suspicious lesions were performed. RESULTS: A total of 254 subjects older than 40 years old (71.3% female) were enrolled. The general AK prevalence was 22.4%; in women, the prevalence was 23.6%, while in men, it was 19.4%. The prevalence rates of basocellular and squamous cell carcinomas and Bowen disease were 1.6, 0.8 and 0.4%, respectively. No statistical associations were found between AKs and the studied variables. CONCLUSIONS: This study was the first reporting the prevalence of premalignant lesions in Ecuador. We could not demonstrate a relationship between the presence of AKs and any of the known risk factors for their development.

Trends in the Incidence of Bowen Disease Based on a Single-Center Study in the Netherlands.

BACKGROUND: Incidence trends of nonmelanoma skin cancer show an increase. Few data have been published about the incidence of Bowen disease (BD). Three previous studies, conducted more than 15 years ago in North America, found large variation in incidence rates in Caucasians, and trends over longer periods have never been studied. OBJECTIVE: To estimate the incidence of BD in a Caucasian population in Northern Europe (Maastricht, the Netherlands) between 2003 and 2013. METHODS: Primary and histologically confirmed BD, diagnosed in Maastricht, the Netherlands, in the years 2003, 2008, and 2013, was retrieved from a pathology database. Age-standardized and sex-specific incidence rates per 100,000 inhabitants were calculated by using the age distribution of the European standard population of 2013. RESULTS: A statistically significant increase in the annual age-standardized incidence rates per 100,000 people was found from 8.1 (95% confidence interval [CI] 3.7-12.5) in 2003 to 68.9 (95% CI 57.2-80.7) in 2013 (p < .001). For women, there was an increase from 7.7/100,000 (95% CI 2.0-13.4) in 2003 to 76.8/100,000 (95% CI 60.2-93.5) in 2013, respectively (p < .001). An increase from 8.8/100,000 (95% CI 1.8-15.9) in 2003 to 59.2/100,000 men (95% CI 42.8-75.6) in 2013 (p < .001) was found. CONCLUSION: These findings suggest an increase in the annual age-standardized incidence rates in BD.

Actinic keratosis area and severity index (AKASI) is associated with the incidence of squamous cell carcinoma.

BACKGROUND: Actinic keratoses (AKs) are commonly diagnosed clinically. Actinic keratosis area and severity index (AKASI) is a new easy-to-use tool to assess the severity of AKs on the head. OBJECTIVES: To determine the association between chronically UV-induced tumours such as basal cell carcinomas (BCC) or squamous cell carcinomas (SCC) and AKASI. METHODS: We performed a retrospective analysis of patients who had undergone oncological surgery due to UV-induced tumours and who were assessed for AKASI and Physician's global assessment (PGA) prior to surgery. Statistical analysis was performed to evaluate correlation between AKASI, PGA and invasive carcinomas. RESULTS: Of the 210 patients included, 26 patients had histologically diagnosed SCCs and presented with a median (range) AKASI of 6.9 (0-13.0) and PGA of 2 (0-4). In contrast, the 82 patients with BCCs showed a median (range) AKASI of 3.3 (0-15.2) and PGA of 1 (0-4). The Mann-Whitney U-test showed significant differences (P = 0.0018) between AKASI of patients with SCC and BCC. In addition, we found a significantly higher AKASI in patients with SCC compared to patients with non-invasive lesions like AK and Bowen disease (BD) (P = 0.0275). Spearman's coefficient of rank correlation between AKASI and PGA indicates that these measures of AK severity were strongly correlated (P < 0.0001; r = 0.90; 95% CI 0.865-0.920). CONCLUSIONS: Patients with SCC show significantly higher AKASI than patients with BCC or patients without invasive tumours. Hence, AKASI may be used to stratify risk for developing invasive SCC.

Cyclin D1 promoter -56 and -54bp CpG un-methylation predicts invasive progression in arsenic-induced Bowen's disease.

BACKGROUND: Patients with arsenic-induced Bowen's disease (As-BD) are at risk of developing invasive cancers in the skin, lung, and urinary bladder. However, a longitudinal follow-up study on the association between As-BD and invasive cancers is still lacking. OBJECTIVES: This study aims to investigate the underlying molecular mechanisms of this malignant progression in the skin and internal organs. METHODS: This is a biopsy-based follow-up study. We tested the DNA histograms, Cyclin D1 (CCND1) protein expression and CCND1 promoter DNA methylation in 40 pathologically confirmed specimens from As-BD patients to correlate with individual's invasive cancer occurrence in the 5-year follow-up. RESULTS: Flow cytometric DNA histogram analysis of skin specimens showed aneuploid (n=15), G2/M arrest (n=22), and normal (n=3) DNA histograms. No patients with normal DNA histograms developed invasive cancers, whereas 13 developed invasive cancers in the aneuploid group and 2 developed invasive cancers in the G2/M arrest group. The aneuploid group showed a high risk of invasive cancer development. In all assessed aneuploid specimens, the CCND1 promoter hypomethylation was observed. Statistically, percentage of un-methylation more than 55.85% among 17 detected CpG sites showed extremely high predictive power in the occurrence of invasive arsenical cancers. Furthermore, the un-methylation at -56 and -54bp CpG sites was statistically significantly associated with invasive arsenical cancer development (p=1.29×10-5). CONCLUSIONS: As-BD lesions showing an aneuploid DNA histogram had a high risk of invasive cancer development. Un-methyaltion at -56 and -54bp CpG in the CCND1 promoter serves as a predictor for invasive progression in As-BD patients.

Prevalence of Skin Cancer and Related Skin Tumors in High-Risk Kidney and Liver Transplant Recipients in Queensland, Australia.

The increased skin cancer incidence in organ transplant recipients is well-known, but the skin cancer burden at any one time is unknown. Our objective was to estimate the period prevalence of untreated skin malignancy and actinic keratoses in high-risk kidney and liver transplant recipients and to assess associated factors. Organ transplant recipients underwent full skin examinations by dermatologically trained physicians. The proportion of examined organ transplant recipients with histopathologically confirmed skin cancer in the 3-month baseline period was estimated. Prevalence ratios with 95% confidence intervals indicated significant associations. Of 495 high-risk organ transplant recipients (average age = 54 years, time immunosuppressed = 8.9 years), 135 (27%) had basal cell carcinoma, squamous cell carcinoma or Bowen's disease (intraepidermal carcinoma) present and confirmed in the baseline period, with respective prevalence proportions of 10%, 11%, and 18% in kidney transplant recipients and 10%, 9%, and 13% in liver transplant recipients. Over 80% had actinic keratosis present, with approximately 30% having 5 or more actinic keratoses. Organ transplant recipients with the highest skin cancer burden were Australian born, were fair skinned (prevalence ratio = 1.61, 95% confidence interval = [1.07, 2.43]), reported past skin cancer (prevalence ratio =3.39, 95% confidence interval = [1.93, 5.95]), and were receiving the most frequent skin checks (prevalence ratio = 1.76, 95% confidence interval = [1.15, 2.70]). In conclusion, high-risk organ transplant recipients carry a substantial measurable skin cancer burden at any given time and require frequent review through easily accessible, specialized services.

Results of second-stage screening for skin cancers in Oita Prefecture, Japan.

We performed skin cancer screenings for 2 or 3 days annually from 2006 through 2013 in Oita Prefecture, Japan. Screening of approximately 3000 people in total allowed us to identify and treat several skin cancers, including five cases of malignant melanoma, four of squamous cell carcinoma, 16 of basal cell carcinoma, 11 of Bowen's disease, 17 of actinic keratosis, one of extramammary Paget's disease and one of metastatic breast carcinoma. The sensitivity and specificity for the category defined by an identified lesion associated with risk of cancer and requiring further examination (category C) were 92.7% and 95%, respectively. We cannot estimate the outcome of our skin cancer screenings in terms of cancer mortality because of the small number of subjects examined and the brief follow-up period. However, we did estimate the effectiveness of these screenings in terms of stages or sizes of cancerous lesions. The relative numbers of subjects with malignant melanoma at various clinical stages, identified during skin cancer screenings and during a routine visit to our hospital, were significantly different. We also compared, statistically, the sizes of lesions in Bowen's disease that were found during cancer screenings and during a direct visit to our hospital. The former lesions were smaller than the latter. Our data suggest the benefits of our skin cancer screenings and the importance of campaigns and education to encourage people to visit dermatologists for the detection of skin cancers at an early stage.

Occupational skin cancer due to UV-irradiation--Analyses of notified cases as "virtually-certain" occupational disease in Germany between 2005 and 2011.

BACKGROUND: UV-induced skin cancer is not yet included in the German ordinance on occupational diseases and can only be notified and recognized acknowledged as "virtually-certain" occupational disease. The objective of the study was to analyze notified and acknowledged cases of occupational skin cancer due to UV-irradiation in Germany between 2005 and 2011. PATIENTS AND METHODS: All notified cases of occupational skin cancer due to UV-irradiation have been analyzed which have been registered by the German Statutory accident insurance as of May 2012 were analyzed. The data analyze was descriptive stratified annually for presenting time trends.Data analysis was descriptive, stratified by year to defect time trends. RESULTS: Notified cases have increased annually with a total of 548 registered cases of occupational skin cancer induced by UV-irradiation between 2005 and 2011, and 74 recognized acknowledged cases. In 56 cases the procedure was not yet finished. Squamous cell carcinoma (SCC) and in-situ squamous cell carcinoma (actinic keratosis, Bowen's disease) were most frequent and have been the most frequentlyobserved in 333 notified cases. and between 15.6 % and 24.9 % have been recognizedof cases with SCC and actinic keratosis were recognized, respectively. 184 patients with basal cell carcinoma were notified but only 6.5 % recognized acknowledged and only 3 cases with exclusive basal cell carcinoma. Out of 50 notified patients with Mmelanoma only one was recognizedacknowledged. CONCLUSIONS: The results are in good agreement with the proposal of the German Minister of labor to establish UV-induced skin cancer as a new occupational disease.

[Risk factors of non melanoma skin cancers in kidney transplant patients]. / Czynniki ryzyka rozwoju nieczerniakowych raków skóry u chorych po przeszczepieniu nerki.

UNLABELLED: Non melanoma skin cancers (NMSC) represent a major challenge within the ever growing group of different organs recipients. The aim of the study was to evaluate risk factors influencing on frequency appearance of NMSC in patients after kidney transplantation. The clinical dermatological examination was performed in 486 patients after kidney transplantation consisted of 296 man (60.9%) and 190 woman (30.1%) in the mean age 46.1 +/- 13.1 (18-74 years) with median time after transplantation 74.3 +/- 52.1 months. Most of them (80.7%) before transplantation were treated by maintenance hemodialysis. Patients after kidney transplantation were checked by dermatologist for all skin abnormalities based on iniciated skin cancers screening program. All discovered abnormalities were described, their type, size, localization and results of histopathological examination were collected. The obtained results were analyzed based on t-Student's, Mann-Whitney's, chi-square and Fisher tests. Out of 486 studied patients, 53 NMSC were diagnosed in 25 kidney recipients including 39 basal cell carcinoma (BCC), 13 squamous cell carcinoma (SCC) and 1 Bowen's disease. The proportion of BCC to SCC was 2.79. NMSC occurred more often on sun skin exposure area, especially on the face. Almost all (96.2%) of the cancers were diagnosed in patients older than 50 years of age. Patients with NMSC comparing with those without were significantly older (52.8 +/- 7.8 vs. 41.0 +/- 7.8; p < 0.0001), have longer post-transplant period and have more frequent positive anamnesis of this cancer. There was no significant relationship between NMSC appearance and sex, cause of kidney failure, HLA mismatch, blood group as well as Rh factor. CONCLUSIONS: Older age of patients while transplantation, longer time of immunosuppressive therapy and previous NMSC are independent predictors of new skin cancers appearance.

Location of nonmelanoma skin cancers in patients after kidney transplantation.

INTRODUCTION: Long -term use of immunosuppressant therapy makes kidney transplant recipients particularly susceptible to infections and skin cancers. OBJECTIVES: The aim of the study was to evaluate the type and location of nonmelanoma skin cancers (NMSCs) in patients after kidney transplantation. PATIENTS AND METHODS: The study included 486 patients (296 men and 190 women; mean age, 46.1 ±13.1 years) after deceased -donor kidney transplantation, most of whom received triple immunosuppressive therapy. Patients underwent skin examination. All suspicious lesions were thoroughly described in terms of their type, size, and location. Only patients with histologically confirmed malignancy were included in the study. RESULTS: Of all 486 patients, 25 were diagnosed with 53 NMSCs, including 39 basal cell carcinomas, 13 squamous cell carcinomas, and 1 case of Bowen's disease. The lesions were observed on the face (n = 34), upper limb (n = 8), neck (n = 6), and trunk (n = 5). CONCLUSIONS: Most NMSCs were located on the sun -exposed areas, emphasizing the effect of ultraviolet radiation on the pathogenesis of skin cancers. The presence of lesions on the skin that had not been exposed to the sun indicates that a physical examination of the entire skin is necessary.

Ischemic bowel disease and risk of stroke: a one-year follow-up study.

BACKGROUND: Ischemic bowel disease and stroke have been noted to have shared pathomechanisms. However, data regarding the stroke occurrence following ischemic bowel disease are still lacking. AIM: The aim of this study is to explore the risk of stroke in patients with ischemic bowel disease during a one-year follow-up period in Taiwan. METHODS: Data used in this study were retrieved from the 'Longitudinal Health Insurance Database 2000. Five hundred sixty-nine patients hospitalized with ischemic bowel disease were included as the study group, and 3414 subjects, matched by age and gender, were randomly extracted as a comparison group. Cox proportional hazards regression analysis was performed to test the relationship of ischemic bowel disease and subsequent stroke during the one-year follow-up period. RESULTS: The incidence rate of stroke among the sampled subjects during the 30-day, 90-day, and 365-day follow-up period was 1·24, 0·76, and 0·43 per 10 person-years. The adjusted hazard ratio for stroke for those patients with ischemic bowel disease within 30-, 90-, and 365-day follow-up periods was found to be 3·71 (95% confidence interval = 1·89-7·27), 2·11 (95% confidence interval = 1·22-3·66), and 1·70 (95% confidence interval = 1·14-2·52) times that of matched comparisons, respectively. The adjusted hazard ratio of ischemic stroke for patients with ischemic bowel disease was found to be 5·29 during the 30-day follow-up period than comparisons. CONCLUSIONS: We found ischemic bowel disease to be significantly associated with stroke occurrence.

Bowen's disease: epidemiological and clinical study of 9 Tunisian cases.

BACKGROUND: Bowen's disease (BD) is a form of in situ SCC, characterized by chronic and progressive course, with low potential for invasive malignancy. AIM: To assess epidemiology and clinical features of BD in a Tunisian cohort. METHODS: A retrospective study of 9 cases of BD managed in a Tunisian dermatology department. RESULTS: There were 7 males (77.8%) and 2 females (22.2%). The mean age of patients was about 68.8 years (46-89). Lesions were solitary in 7 cases and occurred in various sites: face (1 patient), trunk (2 patients), limbs (6 patients). The mean diameter of the tumour was about 3.4 cm. Lesions presented clinically as an enlarging well demarcated erythematous plaque with irregular borders and crusted or scaling surface. Histological examination showed in all cases abnormal keratinocytes with disordered maturation and loss of polarity replacing the epidermis in its whole thickness. The main treatment was surgery (N=5). Only one patient had radiotherapy (case 1). Outcome was mentioned in 2 patients who remained free from recurrence respectively after a follow-up of 1 and 12 years. CONCLUSION: Our series outlines epidemiological and clinical features of BD in Tunisia through a small but representative sample. As in the literature, this condition prevailed mainly over 60 years. In our study, BD occurred predominantly in men and affected nonexposed sites in 8 cases. This profile is uncommon in a sunny country in Tunisia, in the absence of other aetiological agents.

Use of arsenic-induced palmoplantar hyperkeratosis and skin cancers to predict risk of subsequent internal malignancy.

Hyperpigmentation, hyperkeratoses, and Bowen's disease are hallmarks of chronic arsenic exposure. The association between arsenic-induced skin lesions and subsequent internal cancers is examined by using a community-based prospective study. The cohort was enrolled from an arseniasis-endemic area in southwestern Taiwan, where 2,447 residents participated in skin examinations during the late 1980s. The number of participants diagnosed with hyperpigmentation was 673; with hyperkeratosis, 243; and with skin cancer (Bowen's disease or non-melanoma skin cancer), 378. Newly diagnosed internal cancers were ascertained through linkage with National Cancer Registry profiles. Cox regression was performed to estimate hazard ratios with 95% confidence intervals for potential risk predictors. Compared with participants without skin lesions, patients affected with skin cancers had a significantly increased risk of lung cancer (hazard ratio = 4.64, 95% confidence interval: 2.92, 7.38) and urothelial carcinoma (hazard ratio = 2.02, 95% confidence interval: 1.23, 3.30) after adjustment for potential confounders and cumulative arsenic exposure. Hyperkeratosis is significantly associated with an increased lung cancer risk (hazard ratio = 2.76, 95% confidence interval: 1.35, 5.67). A significant interactive effect on lung cancer risk between hyperkeratosis and cigarette smoking was identified, which suggests that patients with hyperkeratosis who have been exposed to arsenic should cease smoking.

Recent trend in the incidence of premalignant and malignant skin lesions in Korea between 1991 and 2006.

We evaluated the recent trend in the incidence of premalignant and malignant skin lesions between 1991 and 2006. Among 571,057 newly registered dermatology out-patients from our 8 affiliated university hospitals, 2,598 were diagnosed with a premalignant (899, 0.16%) or malignant skin lesions (1,699, 0.30%). Of 899 premalignant cases, 71.2% were actinic keratosis (AK), and 24.6% were Bowen's disease. Of 1,699 malignant cases, 46.2% were basal cell carcinoma, followed by squamous cell carcinoma (19.1%) and melanoma (7.1%). This 16-yr survey was divided equally into two time periods to compare the incidence of premalignant and malignant skin lesions at different time settings. Between 1991 and 1998, the incidence of cutaneous premalignancy was 0.10% which doubled during 1999-2006. For cutaneous malignancy, the incidence was 0.25% during 1991-1998 and 0.34% in 1999-2006. Incidence of AK among the new outpatients was 0.07% in 1991-1998 which staggered up to 0.15% in 1999-2006. These findings show an increase of both premalignant and malignant skin lesions, AK in particular in the dermatology outpatient-based incidence.