Second lymphomas and other malignant neoplasms in patients with mycosis fungoides and Sezary syndrome: evidence from population-based and clinical cohorts

OBJECTIVE: To assess risks for developing second malignancies in patients with mycosis fungoides or Sézary syndrome. DESIGN: Retrospective study of 2 cohorts. SETTING: Nine population-based US cancer registries that constitute the Surveillance, Epidemiology, and End Results Program (SEER-9), and Stanford University referral center cohort of patients with cutaneous lymphoma. Patients with mycosis fungoides or Sézary syndrome from the SEER-9 registry diagnosed and followed up from 1984 through 2001 and from the Stanford University cohort diagnosed and followed up from 1973 through 2001. MAIN OUTCOME MEASURES: Relative risk was estimated using the standardized incidence ratio (SIR). The expected cancer incidence for both cohorts was calculated using age-, sex-, race-, and calendar year-specific SEER-9 incidence rates for the general population. Nonmelanoma skin cancers were excluded because these cancers are not routinely reported by the SEER database. RESULTS: In the SEER-9 cohort (n = 1798), there were 197 second instances of cancer (SIR = 1.32; 95% confidence interval [CI], 1.15-1.52) at all sites. Significantly elevated risk (P<.01) was observed for Hodgkin disease (6 cases; SIR = 17.14; 95% CI, 6.25-37.26) and non-Hodgkin lymphoma (27 cases; SIR = 5.08; 95% CI, 3.34-7.38). Elevated risk (P<.05) was also observed for melanoma (10 cases; SIR = 2.60; 95% CI, 1.25-4.79), and urinary cancer (21 cases; SIR = 1.74; 95% CI, 1.08-2.66). In the Stanford University cohort (n = 429), there were 37 second instances of cancer (SIR = 1.04; 95% CI, 0.76-1.44). Elevated risk (P<.01) was observed for Hodgkin disease (3 cases; SIR = 27.27; 95% CI, 5.35-77.54). Elevated risk (P<.05) was also observed for biliary cancer (2 cases; SIR = 11.76; 95% CI, 1.51-42.02). CONCLUSION: Updated SEER (population based) and Stanford (clinic based) data confirm the generalizability of earlier findings of increased risk of lymphoma in patients with mycosis fungoides or Sézary syndrome.     

Bowen disease and risk of subsequent malignant neoplasms: a population-based cohort study of 1147 patients.

OBJECTIVE: To address the long-standing question of whether patients with Bowen disease are at increased risk of internal malignant neoplasms. PATIENTS: A total of 1147 Danish patients diagnosed between 1978 and 1993 as having Bowen disease at nongenital sites were followed up for 6463 person-years for cancer occurrence up to 16 years after the skin lesion. MAIN OUTCOME MEASURE: Standardized incidence ratios (SIRs)--the ratios of observed-to-expected numbers of cancer--served as measures of relative risk. RESULTS: The observed number of noncutaneous cancers occurring in the cohort (n = 115) was close to expected (n = 103.0) (SIR = 1.1; 95% confidence interval, [CI], 0.9-1.3). However, nonmelanoma skin cancer (SIR = 4.3; 95% CI, 3.5-5.4; n = 83), lip cancer (SIR = 8.2; 95% CI, 2.6-19.1; n = 5), and, among men, leukemia (SIR = 3.2; 95% CI, 1.04-7.5; n = 5) occurred in excess. CONCLUSIONS: Patients with Bowen disease do not appear to constitutionally be at any unusually high general cancer risk. The increased risk of invasive skin and lip cancers is likely due to the common risk factor of UV light.     

Cancer risk in a population-based cohort of patients hospitalized for psoriasis in Sweden

Studies of clinical series of psoriasis patients have suggested an increased risk of nonmelanoma skin cancer and melanoma; the risk of other neoplasms has rarely been studied. In order to assess the incidence of cancer in a nationwide series of psoriasis patients from Sweden, we followed up, for the years 1965-89, 9773 patients with a hospital discharge diagnosis of psoriasis made during 1965-83, who were alive and free from malignancy 1 y after first discharge. We compared their incidence of neoplasms with that of the national population by computing standardized incidence ratios (SIR). We observed a total of 789 neoplasms [SIR 1.37, 95% confidence interval (CI) 1.28, 1.47]. There was an increase in the risk of cancers of the oral cavity and pharynx (SIR 2.80, 95% CI 1.96, 3.87), liver (SIR 1.91, 95% CI 1.28, 2.74), pancreas (SIR 1.56, 95% CI 1.02, 2.23), lung (SIR 2.13, 95% CI 1.71, 2.61), skin (squamous cell carcinoma, SIR 2.46, 95% CI 1.82, 3.27), female breast (SIR 1.27, 95% CI 1.00, 1.58), vulva (SIR 3.24, 95% CI 1.18, 7.06), penis (SIR 4.66, 95% CI 1.50, 10.9), bladder (SIR 1.43, 95% CI 1.03, 1.92), and kidney (SIR 1.56, 95% CI 1.04, 2.25). The risk of malignant melanoma was decreased (SIR 0.32, 95% CI 0.10, 0.74). Despite some limitations (possible diagnostic misclassification, lack of data on treatment, relatively short follow-up), our study provides evidence against an increased risk of melanoma among patients hospitalized for psoriasis. In addition to nonmelanoma skin and genital cancers, patients hospitalized for psoriasis were at increased risk of several malignancies, in particular those associated with alcohol drinking and tobacco smoking.     

Incidence of cancer among patients with atopic dermatitis

OBJECTIVE: To assess the risk of skin cancer and other cancers among patients with atopic dermatitis. DESIGN: Register-based retrospective cohort study. SETTING: Sweden.Patients A total of 15 666 hospitalized patients identified in the national Inpatient Register as having discharge diagnoses of atopic dermatitis between January 1, 1965, and December 31, 1999.Interventions The National Swedish Cancer Register coded malignant neoplasms during the entire period of study. Follow-up time was calculated from the date of entry in the cohort until the occurrence of a first cancer diagnosis, emigration, death, or the end of the observation period, whichever occurred first. MAIN OUTCOME MEASURES: Follow-up by means of record linkages to several nationwide registers, among them the National Swedish Cancer Register. Standardized incidence ratios (SIRs) (the ratios of numbers of observed patients with cancer to expected numbers of incident cases of cancer) estimated the risk of developing cancer relative to the risks in the age-, sex-, and calendar year- matched general Swedish population. RESULTS: After excluding the first year of follow-up, the risk of developing any cancer was increased by 13% (95% confidence interval [CI] of SIR, 1.01-1.25, based on 311 observed patients with cancer). Excess risks were observed for cancers of the esophagus (SIR, 3.5; 95% CI, 1.3-7.7; 6 patients), pancreas (SIR, 1.9; 95% CI, 1.0-3.4; 11 patients), brain (SIR, 1.6; 95% CI, 1.1-2.4; 27 patients), and lung (SIR, 2.0; 95% CI, 1.3-2.8; 31 patients) and for lymphoma (SIR, 2.0; 95% CI, 1.4-2.9; 29 patients). There was a nonsignificant 50% excess risk for nonmelanoma skin cancer (SIR, 1.5; 95% CI, 0.8-2.6; 12 patients), seemingly confined to men and to the first 10 years of follow-up. Malignant melanoma did not occur more often than expected. CONCLUSIONS: The observed risk elevations, all of borderline statistical significance, should be interpreted cautiously. We could not control for possible confounding by cases of cancer caused by smoking, and the combination of multiple significance testing and few observed patients may have generated chance findings.     

The risk of developing non‐melanoma skin cancer,lymphoma and melanoma in patients with psoriasis in Taiwan: a 10‐year,population‐based cohort study

Background Hospitalized psoriasis patients are known to have a higher risk of malignancy (e.g., nonmelanoma skin cancer [NMSC], lymphoma, and melanoma) than the general population; currently, it is unclear whether this risk is affected by psoriasis severity. The aim of this study was to compare the cancer risk of patients with mild and severe psoriasis and the general population. Methods Data for this retrospective population‐based cohort study were obtained from the Taiwan National Health Insurance Research Database. This study included 7061 patients with a first‐time diagnosis of psoriasis. All study individuals were followed up until the end of 2007. The crude incidence density ratio and standardized incidence ratio (SIR) of NMSC, melanoma, and lymphoma were determined. Results Among psoriasis patients, the most common cancer was NMSC (density ratio: 7.5); women were at a higher risk of NMSC than men (density ratios: 8.08 vs. 7.0). Psoriasis patients in the south geographic group or in the 50‐ to 59‐year‐old age group were most likely to develop NMSC. The NMSC SIR was higher among patients with severe psoriasis than among patients with mild psoriasis (SIR: 3.72 vs. 7.08). The lymphoma and melanoma SIR among patients with severe psoriasis was also high (lymphoma SIR: 4.85; melanoma: 11.01). Conclusions Psoriasis carries an elevated risk of NMSC and lymphoma. This effect is modified by the severity of psoriasis, age, gender, and geographic location.     

Analysis of 303 Ro/SS‐A antibody‐positive patients: is this antibody a possible marker for malignancy?

Background The risk of cancer in patients with autoimmune diseases has been investigated in several studies. Ro/SS‐A antibodies are frequent and specific autoantibodies among patients with various autoimmune diseases. Objectives To assess the risk of cancer in individuals with positive Ro/SS‐A antibodies and to analyse their clinical and laboratory characteristics. Methods Consecutive patients (n = 303) with Ro/SS‐A antibody positivity were collected during 11 years in our outpatient clinic for autoimmune diseases and were retrospectively analysed. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for all cancers were calculated. In addition, we identified further clinical and laboratory characteristics of Ro/SS‐A antibody‐positive patients indicating the development or existence of a malignancy. Results Fifty (16·5%) patients were diagnosed with malignancies. Ro/SS‐A antibody was strongly associated with malignant diseases (SIR 2·6, 95% CI 1·9–6·1), particularly melanoma (SIR 33·3, 95% CI 5·2–188·6), T‐cell lymphoma (SIR 16·7, 95% CI 2·9–128·9), non‐Hodgkin lymphoma (SIR 10·6, 95% CI 1·5–78·9) and breast carcinoma (SIR 4·98, 95% CI 1·3–28·3). Logistic regression modelling revealed that Ro/SS‐A antibody‐positive patients aged 55 years or older, presenting with fever, anaemia and cutaneous lupus erythematosus, have a greater probability of developing cancer and are considered high‐risk patients, as compared with Ro/SS‐A antibody‐positive patients with none of the mentioned clinical criteria. Conclusions In our cohort of Ro/SS‐A antibody‐positive patients, an overall increased risk of malignancy was noticed. Regular screening tests including imaging and laboratory values are justified in Ro/SS‐A antibody‐positive patients who exhibit the mentioned clinical criteria.     

Risk of second primary malignancies in patients with cutaneous melanoma

BACKGROUND: In several studies an increased risk for development of breast cancer, malignant lymphoma and neoplasms of the kidney as second primary cancers in patients with cutaneous melanomas was discussed. OBJECTIVES: To determine the risk for development of second primary neoplasms in patients with cutaneous melanomas. METHODS: A prospective study was performed between 1977 and 1992 to evaluate the occurrence of second primary malignancies in 4597 patients (2083 men, 2514 women) with invasive cutaneous melanomas, diagnosed and treated at the Department of Dermatology and Allergology, Ludwig-Maximilians-University, Munich, Germany. RESULTS: During a median follow-up of 7.2 years, 296 of 4597 patients (6.4%) developed one or more neoplasms at the time of or subsequent to the diagnosis of the first cutaneous melanoma. More than half of these patients developed one or more further melanomas (152, 3.3%). Cancers of the breast, prostate, colon, rectum and kidney occurred less frequently. Statistical calculations revealed a 33.8-fold increased risk for the development of a second melanoma in the entire group [relative risk 38.5 for men (95% CI, 30.4-48.1), 29.0 for women (95% CI, 22.0-37.5)]. Moreover, a significantly increased risk for the development of kidney carcinoma in men was found [relative risk 3.5 (95%, CI, 1.4-7.2)]. CONCLUSIONS: Thorough follow-up and skin examination in patients with cutaneous melanomas is recommended for early detection of other primary melanomas. Furthermore, ultrasound examinations routinely performed in melanoma patients for the detection of melanoma metastases may also be of value for early detection of kidney carcinomas in male patients.     

Risk of multiple primary cancers following melanoma and non-melanoma skin cancer

Background The relationship between cutaneous malignancies and successive primary cancers has been studied since several years, but it still remains controversial. Objective The aim of this study was to evaluate the excess risk of multiple primary cancer among the population of Umbria, Italy, that survived a skin cancer. Methods The data registered in the Umbrian Population Cancer Registry from 1994 to 2006 were collected, recorded, and analysed in accordance to the standard methods recommended for cancer registries. Among skin cancer patients, those with multiple cutaneous and non-cutaneous cancers were selected. Only sites with a frequency of more than five cases were considered. The expected number of cases was obtained from indirect standardization with regional incidence rates in several sites that incurred in the overall period. The significance of the observed/expected ratios and the corresponding 95% CI were based on the Poisson distribution. Results In men, a significant standardized incidence ratio (SIR) was found for melanoma (2.21), non-melanoma skin cancers (1.86), Hodgkin's (4.95) and non-Hodgkin lymphoma (1.82), and tongue/mouth cancer (2.47). In women, melanoma, non-melanoma skin and breast cancer showed a significant high SIRs (4.13, 1.55 and 1.28 respectively). All other cancers showed a non-significant SIR. Considering all sites combined and all sites except skin cancers, the analysis showed a significant excess in men, whereas a significant risk was observed in women only when also skin cancers were considered. Conclusions Data from the whole of Umbrian population revealed that skin cancer patients experience marked excess risk of further primary cancers. The main risk in both genders is skin melanoma and other skin cancers. The excess of lymphomas and tongue/mouth cancers is also significant in men, and breast cancer in women. These observations prompt us to include a screening for these cancers in the follow-up of our patients surviving a skin malignancy.     

Long-term follow-up of cancer risk in patients treated with short-term cyclosporine

Cyclosporine increases the risk of skin and lymphoid tissue malignancies in organ transplant patients. A similar increase has been shown among psoriasis patients, but no data exist on the carcinogenic risk of cyclosporine monotherapy in skin diseases. We conducted a retrospective cohort study of 272 patients, all of whom had received at least one month of cyclosporine treatment. The cancer information on these patients was obtained from the Finnish Cancer Registry. The median follow-up time was 10.9 years and the median treatment time with cyclosporine was 8 months. We did not detect any increase in the risk of skin malignancies or lymphoma. The overall risk of cancer was almost identical to that expected in the general population (standardized incidence ratios (SIR) = 1.31, 95% confidence interval (CI) = 0.70-2.23). This study shows that short-term cyclosporine treatment is probably not related to subsequent malignancy. Since the CI of the SIR estimate was rather wide, larger studies are needed in the future.     

Burn injuries and skin cancer: a population-based cohort study

Development of malignant tumours in chronic burn wounds or scars is extremely rare, but a frequently reported complication. Most of these tumours are squamous cell carcinoma and, more occasionally, basal cell carcinoma and malignant melanoma are reported. The interval between the initial burn and the diagnosis of the tumour is usually long; 20-30 years or more. A large number of case reports and small series of selected patients have been published. Only one epidemiological study has been performed recently, but it could not confirm any increased risk. We conducted a historical cohort study to assess the risk of cancer in Swedish patients with burn injuries. Using the national Inpatient Registry we identified 37,095 patients who had been hospitalized for burn injuries. This cohort was linked with the Swedish Cancer Registry for a virtually complete follow-up with regard to cancer. The mean follow-up time was 16.4 years (range >0-39). The risk of developing any form of cancer was slightly increased: standardized incidence ratio (SIR) 1.11 (95% confidence interval (CI) 1.06-1.16) based on 2227 patients with cancer. However, squamous cell carcinoma: SIR 0.88 (95% CI 0.70-1.09) and malignant melanoma: SIR 0.88 (95% CI 0.68-1.12) did not occur more often than expected. Also, in a subgroup of 12,783 patients who were followed for 20-39 years, no increased risk of skin cancer could be detected. This study does not support any casual association between burn injuries and a later risk of skin cancer.     

Systemic sclerosis and the risk of cancer: a nationwide population‐based cohort study

Background Earlier studies reported an increased cancer risk among patients with systemic sclerosis. Study size limitations and paucity of population‐based study designs may have resulted in imprecise risk estimates. Objectives To assess cancer risk among patients with systemic sclerosis in a nationwide follow‐up study. Methods Patients with a first diagnosis of systemic sclerosis from 1977 to 2006 were identified from the nationwide Danish National Registry of Patients (DNRP), whose records encompass all hospitalizations and outpatient visits. Patients’ DNRP records were linked to the Danish Cancer Registry. We compared their cancer incidence with that expected from cancer incidence in the general population, calculating standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). Results Two thousand and forty patients with systemic sclerosis were identified and followed for 16 003 person‐years, with a median follow‐up time of 6·4 years (interquartile range 2·2–11·5). Among these patients, 222 cases of cancer were identified. The overall SIR for cancer was 1·5 (95% CI 1·3–1·7), with a gender‐specific SIR of 2·2 (95% CI 1·7–2·8) for men and 1·3 (95% CI 1·1–1·6) for women. The most frequent cancers were smoking‐ and alcohol‐related cancers including lung cancer (SIR = 1·6, 95% CI 1·2–2·0), haematological cancers (SIR = 2·5, 95% CI 1·5–4·0) and immune‐related cancers (SIR = 1·4, 95% CI 1·0–1·9). Conclusions Systemic sclerosis is a risk factor for cancer, particularly smoking‐ and alcohol‐related cancers. Men with systemic sclerosis generally are at higher cancer risk than women. Both primary and secondary cancer preventive measures are needed in the care of patients with systemic sclerosis.     

Trioxsalen bath PUVA did not increase the risk of squamous cell skin carcinoma and cutaneous malignant melanoma in a joint analysis of 944 Swedish and Finnish patients with psoriasis

It has been suggested that trioxsalen bath and ultraviolet (UV) A (PUVA) is associated with a very low or no risk of non-melanoma skin cancer, but the numbers of patients in individual studies have been limited. In order to attain statistically relevant information about the cancer risk associated with trioxsalen bath PUVA, two follow-up studies were combined and the joined cancer incidence was analysed among 944 Swedish and Finnish patients with psoriasis. The mean follow-up time for skin cancer was 14.7 years. Standardized incidence ratios (SIR) were calculated as a ratio of observed and expected numbers of cases. The expected numbers of cases were based on the national cancer incidence rates in the respective countries. There was no excess of squamous cell skin carcinoma [SIR 1.1, 95% confidence interval (CI) 0.2-3.2] or malignant melanoma (SIR 0.9, 95% CI 0.1-3.2) in the combined cohort. Basal cell skin carcinoma was not studied. The incidence of all non-cutaneous cancers was not increased (SIR 1.1, 95% CI 0.8-1.4). A threefold excess risk of squamous cell skin carcinoma after trioxsalen bath PUVA could therefore be excluded, which is a markedly lower risk than that associated with oral 8-methoxypsoralen PUVA. The result needs to be confirmed in a future follow-up, however, as the number of patients with high PUVA exposures was low.     

Risk of second cancers after the diagnosis of non-melanoma skin cancer in Korean patients

Individuals with a personal history of non-melanoma skin cancer (NMSC) are known to have an increased risk of subsequent cancers. However, most of the studies regarding this fact were done on Caucasian populations. We investigated whether Korean patients with NMSC have an increased risk of developing second cancers compared to the general Korean population. Five hundred and thirty-two patients diagnosed with NMSC at the Department of Dermatology of Yonsei University Health System from 1999 to 2008 were assessed for development of second cancers. The overall second cancer incidence was increased among patients diagnosed with NMSC compared with the general population in Korea: 37 second cancer total (standardized incidence ratio [SIR] 1.38, 95% confidence interval [CI] 1.10-1.90); 23 second cancers in males (SIR 4.24, 95% CI 2.69-6.36); and 14 second cancers in females (SIR 2.28, 95% CI 1.25-3.83). There were significantly increased incidence ratios for NMSC (eight second cancers [SIR 9.52, 95% CI 4.11-18.77]), bladder cancer (four second cancers [SIR 4.21, 95% CI 1.15-10.78]) and nasopharyngeal cancer (one second cancer [SIR 20.00, 95% CI: 1.51-25.33]). Korean patients diagnosed with NMSC had more second cancers, particularly other skin cancers. This study provides additional evidence that NMSC may be a clinically significant and substantial risk factor for second cancers even in a Korean population, in which the incidence of NMSC is much lower than Caucasians.     

Association between multiple cutaneous melanoma and other primary neoplasms

Background. The risk of a subsequent cancer is an important issue for patients with melanoma. The development of a second primary cancer in patients with a solitary melanoma has been discussed in several studies. However, to our knowledge, the incidence of second primary cancer (SPC) in patients with multiple primary melanoma (MPM) has not been thoroughly investigated. Aim. To quantify the incidence of SPC in patients with MPM, with the aim of possibly developing further preventive measures. Methods. In a retrospective study, 76 patients with MPM were identified from 2155 patients being followed up at our unit. Results. Of the 76 patients, 12 (16%) developed another neoplasm, with 59% of them having nonmelanoma skin cancer (NMSC), and 41% other noncutaneous cancers. By contrast, only 8% of those with single primary melanoma had other neoplasms (21% of whom had NMSC). Conclusions. Patients with MPM, especially men with skin phototype II, have a significantly increased incidence of developing SPC, particularly NMSC. Thus, careful monitoring is essential not only to detect recurrence of the original cancer or development of another primary melanoma, but also development of new malignancies of different types, particularly NMSC.     

Incidence of skin cancer in 5356 patients following organ transplantation

BACKGROUND: Skin cancer following solid organ transplantation is an important cause of morbidity in long-term survivors. This risk is well known but imprecisely quantified. OBJECTIVES: We aimed to determine: (i) the skin cancer risks in transplant patients more precisely; (ii) whether the risk of malignant melanoma is altered; and (iii) whether the risk of epithelial cancers occurring at non-exposed sites is comparable with that seen in sun-exposed sites. METHODS: We linked a population-based cohort of 5356 patients who had received organ transplants in Sweden between 1970 and 1994 with the compulsory Swedish Cancer Registry, to identify all cancer cases except basal cell carcinomas, which are not registered. RESULTS: After a mean follow-up of 5.6 years post-transplantation, 172 of 5356 patients developed 325 non-melanoma skin cancers (excluding basal cell carcinomas) and six malignant melanomas. The relative risk of non-melanoma skin cancer was 108.6 [95% confidence interval (CI) 94.6-123.1] for men and 92.8 (95% CI 73.2-116.0) for women. The highest risks were noted for upper limbs, and the risk increased with time. No significant increase in malignant melanomas was noted: the relative risk was 1.6 (95% CI 0.5-3.7) for men and 0.5 (95% CI 0. 0-2.6) for women. Except for the lip, which is also sun-exposed, other epithelial sites did not show comparable increases in cancer risk. CONCLUSIONS: We conclude that organ transplant recipients are at a highly increased risk for non-melanoma skin cancer and must be closely followed throughout their lives. Cancer risk associated with transplantation is higher for sun-exposed than for non-sun-exposed epithelial tissues, even among populations living in regions with low solar insolation.     

Basal cell carcinoma and risk of subsequent malignancies: A cancer registry-based study in southwest England

BACKGROUND: A possible link between basal cell carcinoma (BCC) and an increased subsequent risk of experiencing further noncutaneous malignancies has been suggested in previous cancer-registry and cohort studies. OBJECTIVE: The purpose of this study was to establish whether a possible link between BCC and subsequent malignancies could be confirmed in a new population in which environmental and genetic risk factors may vary from previously studied populations. METHODS: A cohort of 13,961 cancer registry-listed persons from the southwest of England, in whom BCC had been diagnosed during the period of 1981 to 1988, was examined for the relative risk of experiencing various further malignancies. RESULTS: An approximately 3-fold increase in the risk for malignant melanoma was demonstrated. No other cancers occurred in statistically significant excess. CONCLUSION: The previous reported associations of BCC onset with subsequent increased risk for various noncutaneous cancers are not supported by this study.     

Nevi, family history, and fair skin increase the risk of second primary melanoma

Although risk factors for primary cutaneous melanoma are well defined, relatively little is known about predictors for second primary melanoma. Given the rising incidence of this cancer, coupled with improvements in survival, there is a prevalent and growing pool of patients at risk of second primary melanomas. To identify the predictors of second primary melanoma, we followed a cohort of 1,083 Queensland patients diagnosed with incident melanoma between 1982 and 1990 and who completed a baseline questionnaire. During a median follow-up of 16.5 years, 221 patients were diagnosed with at least one additional primary melanoma. In multivariate analyses, second primary melanomas were associated with high nevus count (hazard ratio (HR), 2.91; 95% confidence interval (CI) 1.94-4.35), high familial melanoma risk (HR, 2.12; 95% CI 1.34-3.36), fair skin (HR, 1.51; 95% CI 1.06-2.16), inability to tan (HR, 1.66; 95% CI 1.13-2.43), an in situ first primary melanoma (HR, 1.36; 95% CI 0.99-1.87), and male sex (HR, 1.49; 95% CI 1.12-2.00). Patients whose first primary was lentigo maligna melanoma (HR, 1.80; 95% CI 1.05-3.07) or nodular melanoma (HR, 2.13; 95% CI 1.21-3.74) had higher risks of subsequent primaries than patients whose first primary tumor was superficial spreading melanoma. These characteristics could be assessed in patients presenting with first primary melanoma to evaluate risk of developing a second primary.     

PUVA and cancer risk: the Swedish follow-up study

There is concern about the long-term carcinogenic effects of psoralen and ultraviolet A radiation (PUVA) for treatment of skin disorders. Many authors have found an increased risk for cutaneous squamous cell carcinoma (SCC). Except in anecdotal reports, malignant melanoma had not been observed in patients treated with PUVA until recently. In the U.S.A., a 16-centre prospective study of 1380 patients showed for the first time that there might also be an increased risk for malignant melanoma in patients treated with high cumulative dosages of PUVA. We have therefore followed up the Swedish PUVA cohort until 1994. This cohort had previously been followed up until 1985. Information from 4799 Swedish patients (2343 men, 2456 women) who had received PUVA between 1974 and 1985 was linked to the compulsory Swedish Cancer Registry in order to identify individuals with cancer. The average follow-up period was 15.9 years for men and 16.2 for women. We did not find any increased risk for malignant melanoma in our total cohort of 4799 patients treated with PUVA or in a subcohort comprising 1867 patients followed for 15-21 years. For cutaneous SCC there was an increase in the risk: the relative risk was 5.6 (95% confidence interval, CI 4. 4-7.1) for men and 3.6 (95% CI 2.1-5.8) for women. Significant (P < 0.05) increases were also found in the incidence of respiratory cancer in men and women and of kidney cancer in women. In conclusion, we did not find any increased risk for malignant melanoma in our patients treated with high doses of PUVA and followed up for a long time. We confirm previous reports of an increase in the incidence of cutaneous SCC in patients treated with PUVA, and recommend that patients should be carefully selected for PUVA and rigorously followed up.     

Host risk factors for the development of multiple non‐melanoma skin cancers

Non‐melanoma skin cancer (NMSC) is the most common cancer in the US, and having multiple lesions conveys substantial cost and morbidity for the individual involved. Although there are data available on risk factors for NMSC, there are currently few studies that identify specific risk factors for development of multiple NMSCs. We evaluated host risk factors for multiple NMSCs among men (Health Professionals Follow‐up Study) and women (Nurses’ Health Study). Compared with individuals with a single NMSC, having greater number of sunburns was a risk factor for developing ≥2 NMSCs [≥10 sunburns, cumulative relative risk (RR) = 1.21, 95% confidence interval (CI): 1.07–1.36] and a higher risk of developing ≥11 NMSCs (≥10 sunburns, RR = 2.33, 95% CI: 1.57–3.46). Inability‐to‐tan was associated with risk of developing ≥2 NMSCs (cumulative RR = 1.29, 95% CI: 1.18–1.40) and a higher risk of developing ≥11 NMSCs (RR = 1.91, 95% CI: 1.50–2.43). Men had an increased risk of developing ≥2 NMSCs (cumulative RR = 1.53, 95% CI: 1.40–1.66). Risk of developing 2–4, 5–10 and ≥11 NMSCs increased with age. Other risk factors for developing ≥2 NMSCs included red natural hair colour (cumulative RR = 1.23, 95% CI: 1.07–1.42), family history of melanoma (cumulative RR = 1.15, 95% CI: 1.03–1.28), and having ≥6 nevi on the left arm (cumulative RR = 1.22, 95% CI: 1.07–1.40). In conclusion, physicians caring for individuals with incident NMSCs may consider paying special attention to those at highest risk for developing additional tumours, especially males and those with a history of ≥10 lifetime sunburns, by performing routine full skin examinations and counselling for aggressive photoprotection.     

Incidence of cancer in the general population and in patients with or without atopic dermatitis in the U.K.

Background Atopic dermatitis (AD) affects approximately 20% of children and 1–3% of adults in developed countries. Objective To study the incidence of cancer in patients with AD in the U.K. general population. Methods We conducted a follow‐up study in the U.K. using The Health Improvement Network (THIN) database. We calculated the incidence rate (IR) of the first occurrence of overall cancer, lymphoma, melanoma and nonmelanoma skin cancer (NMSC) in the general population, in patients with AD and in individuals without AD. In addition we calculated the IR ratio (IRR) of overall cancer and subtypes of cancer in patients with AD vs. those without. Results The study population included 4 518 131 patients [2 336 230 (51·7%) female]. There were 129 972 subjects [68 688 (52·8%) female] with a diagnosis of cancer (excluding NMSC). The IR (per 10 000 person‐years) of cancer (excluding NMSC) was 42·41 [95% confidence interval (CI) 42·18–42·64]; of lymphoma 1·70 (95% CI 1·65–1·74); of skin melanoma 1·71 (95% CI 1·67–1·76) and of NMSC 11·76 (95% CI 11·64–11·88). The age‐ and sex‐adjusted IRR for cancer (excluding NMSC) was 1·49 (95% CI 1·39–1·61); for lymphoma 2·21 (95% CI 1·65–2·98); for melanoma 1·74 (95% CI 1·25–2·41); and for NMSC 1·46 (95% CI 1·27–1·69). Conclusions Our results indicate an increased incidence of cancer overall as well as of specific cancer subtypes, including lymphoma, in patients with AD. Further studies are needed to disentangle the effects of treatment for AD from AD itself.