Kari Nielsen

The clinical significance of BRAF and NRAS mutations in a clinic‐based metastatic melanoma cohort

BRAF and NRAS mutations are frequently found in melanoma tumours, and recently developed BRAF‐targeted therapies demonstrate significant clinical benefit.

Avoidance of sun exposure is a risk factor for all-cause mortality: results from the Melanoma in Southern Sweden cohort

Sunlight exposure and fair skin are major determinants of human vitamin D production, but they are also risk factors for cutaneous malignant melanoma (MM). There is epidemiological evidence that all‐cause mortality is related to low vitamin D levels.

Avoidance of sun exposure as a risk factor for major causes of death: a competing risk analysis of the Melanoma in Southern Sweden cohort

Women with active sunlight exposure habits experience a lower mortality rate than women who avoid sun exposure; however, they are at an increased risk of skin cancer. We aimed to explore the differences in main causes of death according to sun exposure.

A prospective, population-based study of 40,000 women regarding host factors, UV exposure and sunbed use in relation to risk and anatomic site of cutaneous melanoma.

Prospective cohort studies about cutaneous melanoma (CM) risk are still few. Host factor‐ and UVR exposure data were collected prospectively by questionnaire in this population‐based cohort study including 40,000 Swedish born women, aged 25–64 years at enrolment (1990). Risk for CM (Cox regression and Stepwise Cox regression [SCR], hazard ratios [HRs] with 95% Confidence Intervals [CI]) in relation to risk factors, age groups (older or younger than 40 years) and primary site, were analyzed. In 29,520 women with complete follow‐up through 2007, 155 invasive and 60 in situ CM were recorded. High numbers of nevi (HR, 2.9; 95% CI, 1.7–5.0) and heredity (HR, 3.7; 95% CI, 2.0–6.8) were associated with risk for CM. SCR analysis added red hair as a risk factor. Sunbed use >10 times/year increased risk for women <40 years (HR, 2.5; 95% CI, 1.0–6.2) and a trend for risk associated with sunbathing vacations (HR, 1.4; 95% CI, 1.0–2.0) was shown for women >40 years. Trunk melanoma showed correlations with high numbers of nevi (HR, 3.0; 95% CI, 1.2–7.3) and heredity (HR, 3.2; 95% CI, 1.1–9.4). Head/neck site was correlated to sunbathing vacations (HR, 2.5; 95% CI, 1.2–5.3) and heredity (HR, 7.6; 95% CI, 1.8–31.8). Our study supports divergent etiologic pathways to CM, with high numbers of nevi correlated to increased risk for trunk CM. Furthermore, it confirms that high numbers of nevi, red hair and heredity for CM are the most important risk factors and frequent sunbed use might be a risk factor for younger women.

Melanoma and nonmelanoma skin cancer in patients with multiple tumours—evidence for new syndromes in a population-based study

Background  The hypotheses that Swedish patients with four or more primary tumours [including at least one cutaneous malignant melanoma (CMM)] harbour an increased number of CDKN2A (formerly p16) germline mutations, and that this group of patients show a predisposition to other tumours, e.g. nonmelanoma skin cancer (NMSC), were studied descriptively. So far the mutation 113insArg explains all CDKN2A‐associated CMM in ethnic Swedes.

Preoperative prediction of histopathologic outcome in basal cell carcinoma - flat surface and multiple small erosions predict superficial basal cell carcinoma in lighter skin types.

Prediction of the histopathological subtype of basal cell carcinoma (BCC) is important for tailoring optimal treatment, especially in patients with suspected superficial BCC (sBCC).

Germline CDKN2A Mutation Status and Survival in Familial Melanoma Cases.

BACKGROUND Germline mutations in CDKN2A have been associated with increased risk of melanoma and tobacco-related cancers in respiratory and upper digestive tissues. In CDKN2A wild-type (wt) melanoma families, other known high-risk, melanoma-predisposing mutations are rare, and no increased risk has been observed for nonskin cancers in this group. This study is the first to compare survival in germline CDKN2A mutated (mut) and nonmutated melanoma cases. METHODS Melanoma-prone families participating in this study were identified through a nationwide predictive program starting in 1987. Information on cancer diagnoses (types, stages, and dates) and deaths (causes and dates) were obtained through the Swedish Cancer Registry and Cause of Death Registry. Kaplan Meier and Cox proportional hazards regression models were used to assess survival in CDKN2A(mut) (n = 96) and CDKN2A(wt) (n = 377) familial melanoma cases and in matched sporadic melanoma cases (n = 1042). All statistical tests were two-sided. RESULTS When comparing CDKN2A(mut) and CDKN2A(wt) melanoma cases, after adjusting for age, sex, and T classification, CDKN2A(mut) had worse survival than melanoma (hazard ratio [HR] = 2.50, 95% confidence interval [CI] = 1.49 to 4.21) and than nonmelanoma cancers (HR = 7.77, 95% CI = 3.65 to 16.51). Compared with matched sporadic cases, CDKN2A(mut) cases had statistically significantly worse survival from both melanoma and nonmelanoma cancers while no differences in survival were seen in CDKN2A(wt) compared with sporadic cases. CONCLUSIONS CDKN2A(mut) cases had statistically significantly worse survival than nonmelanoma cancers and, intriguingly, also from melanoma, compared with melanoma cases with no CDKN2A mutations. Further studies are required to elucidate possible mechanisms behind increased carcinogen susceptibility and the more aggressive melanoma phenotype in CDKN2A mutation carriers.

Diagnosis of Pigmented Skin Tumours in a Dermatological Setting: Different Aspects of the Number Needed to Excise as a Measure of Efficiency

The increasing incidence of melanoma prompts a need for efficient management of this patient group. In this study, we use the number needed to excise (NNE), as a measurement of the efficiency of diagnosing melanoma. From January 2009 to December 2012, postoperative records from all patients were prospectively registered. All excised tumours with the histopathological diagnosis of naevus, melanoma or seborrhoeic keratosis were included. NNE values, both excluding and including seborrhoeic keratosis, changes over time, as well as patient- and tumour-related factors influencing NNE were determined. In total, 1,717 cases were included. The overall NNE value was 6.5, and the value fell significantly (r = 0.959, p = 0.041) during the 4-year study period from 8.2 to 4.8. NNE values decreased with increasing patient age to 1.8 in patients ≥ 80 years of age. The overall NNE value including seborrhoeic keratosis was 6.8.

Swedish CDKN2A mutation carriers do not present the atypical mole syndrome phenotype.

Phenotypic characteristics were examined in melanoma-prone southern Swedish CDKN2A (p16-113insArg/p14ARF-128insSer) mutation families, in relation to the CDKN2A genotype, nevi, clinically atypical nevi (CAN) and melanoma. Individuals from eight melanoma-prone families, with index patients carrying the CDKN2A mutation, were offered skin examinations and genotyping (CDKN2A and MC1R). Ninety-three individuals above 18 years of age participated; 29 invasive melanomas in 16 patients were recorded, all in the 38 verified CDKN2A mutation carriers. Median age at diagnosis was 36 years. Several MC1R variants were observed. A significant correlation to CAN (P=0.01) and red hair colour (P=0.02) could be confirmed in melanoma patients. A positive mutation status (CDKN2A) was correlated to one or more CAN (P=0.007) but neither to blue eyes, red hair colour, heavy freckling nor high number of nevi. For mutation carriers, median total naevus count was 24 and interquartile range was 12–47 (mean 31); whereas for the whole cohort, median total naevus count was 12 and interquartile range was 5–25 (mean 22). No participant fulfilled the atypical mole syndrome phenotype criteria. Melanomas were diagnosed only in mutation carriers, and melanoma diagnosis was statistically correlated to the presence of one or more CAN and red hair colour, supporting the possible synergistic effect of a MC1R mutation on increased risk of melanoma in patients with a CDKN2A mutation. Family history, with verified tumour diagnoses, remains an important clinical tool for finding mutation carriers for referral to clinical geneticists and simultaneous presence of CAN in probable mutation carriers might strengthen this indication. The atypical mole syndrome phenotype was, however, not verified in the studied families and total naevus counts were low.

Diagnostic agreement and interobserver concordance with teledermoscopy referrals

Malignant melanoma and non‐melanoma skin cancers are among the fastest increasing malignancies in many countries. With the help of new tools, such as teledermoscopy referrals between primary health care and dermatology clinics, the management of these patients could be made more efficient.