Nicole A. Kukutsch

Total body skin examination for skin cancer screening in patients with focused symptoms

BACKGROUND The value of total body skin examination (TBSE) for skin cancer screening is controversial. OBJECTIVE We sought to determine whether TBSE could be helpful in patients with focused skin symptoms who would not otherwise have undergone TBSE. METHODS In a prospective, multicenter, cross-sectional study consecutive adult patients were recruited during a period of 18 months. Physicians first inspected problem areas and uncovered areas and then performed TBSE. Equivocal lesions detected in both steps were excised or biopsied. Primary outcomes were the absolute and relative risks of missing skin cancer and the number of patients needed to examine to detect melanoma or another malignancy. A secondary outcome was the proportion of false-positive results obtained by TBSE. RESULTS We examined 14,381 patients and detected 40 (0.3%) patients with melanoma and 299 (2.1%) with at least one nonmelanoma skin cancer by TBSE. In 195 (1.3%) patients equivocal lesions found by TBSE turned out to be benign. We calculated that 47 patients need to be examined by TBSE to find one skin malignancy and 400 patients to detect one melanoma. The risk of missing one malignancy if not performing TBSE was 2.17% (95% confidence interval 1.25-3.74). Factors significantly increasing the chance to find a skin cancer were age, male gender, previous nonmelanoma skin cancer, fair skin type, skin tumor as the reason for consultation, and presence of an equivocal lesion on problem/uncovered areas. LIMITATIONS The impact of TBSE on skin cancer mortality was not evaluated. CONCLUSIONS TBSE improves skin cancer detection in patients with focused skin symptoms and shows a low rate of false-positive results.

Clinical and histologic characteristics of malignant melanoma in families with a germline mutation in CDKN2A.

BACKGROUND About 10% of cutaneous malignant melanomas (CMM) occur in individuals with a family history of melanoma. In 20% to 40% of melanoma families germline mutations in CDKN2A are detected. Knowledge of the clinicohistologic characteristics of melanomas and patients from these families is important for optimization of management strategies, and may shed more light on the complex interplay of genetic and environmental factors in the pathogenesis of melanoma. OBJECTIVE We sought to investigate the clinical and histologic characteristics of CMM in CDKN2A-mutated families. METHODS Clinical and histologic characteristics of 182 patients with 429 CMM from families with a founder mutation in CDKN2A (p16-Leiden mutation) were compared with 7512 patients with 7842 CMM from a population-based cancer registry. RESULTS Patients with p16-Leiden had their first melanoma 15.3 years younger than control patients. The 5-year cumulative incidence of second primary CMM was 23.4% for patients with p16-Leiden compared with 2.3% for control patients. The risk of a second melanoma was twice as high for patients with p16-Leiden who had their first melanoma before age 40 years, compared with older patients with p16-Leiden. Unlike control patients, there was no body site concordance of the first and second melanoma in patients with p16-Leiden and multiple primary melanomas. Patients with p16-Leiden had significantly more superficial spreading, and less nodular and lentiginous melanomas. LIMITATIONS Ascertainment of patients with p16-Leiden was family based. The study was performed in families with a founder mutation, the p16-Leiden mutation. CONCLUSION Our findings are consistent with a pathogenic pathway of melanoma development from nevi, starting early and ongoing throughout life, and not related to chronic sun exposure.

Impact of Dermoscopy on the Management of High-risk Patients From Melanoma Families: A Prospective Study

Few studies have investigated the impact of dermoscopy on the management of relatives from melanoma families. The objective of this study was to assess the impact of dermoscopy on clinical diagnosis and management decisions in high-risk familial melanoma patients. In a prospective study 132 consecutive patients were recruited from the pigmented lesions clinic of a tertiary reference centre for familial melanoma. Dermatologists expert in dermoscopy identified 49 suspicious pigmented lesions and recorded pre- and post-dermoscopy diagnoses and management decisions. Dermoscopy was performed in 37% of the patients. Two melanomas were identified. Dermoscopy did not influence sensitivity (1.0), but resulted in 42% fewer excisions, increasing specificity from 0.53 to 0.74 (p = 0.031). Dermoscopy resulted in a large reduction in the number of unnecessary excisions. These results suggest that the main effect of dermoscopy in clinical practice for this high risk population is a significant increase in specificity, rather than sensitivity.

Increased C-MYC copy numbers on the background of CDKN2A loss is associated with improved survival in nodular melanoma

PurposeIn order to obtain better insight into the genetic background of nodular melanoma (NM), we aimed to analyse the frequency of CDKN2A and C-MYC copy number changes. The impact of these aberrations on the metastatic potential and patient’s survival was considered.MethodsFluorescent in situ hybridization was used to analyse the C-MYC and CDKN2A genes on isolated nuclei from 49 paraffin-embedded primary NMs.ResultsThirty-six (73.47%) melanoma samples showed CDKN2A deletion while 11 of these 36 (22.45%) additionally displayed C-MYC increased copy numbers. Cases positive for metastases more commonly displayed CDKN2A deletions. However, the combined C-MYC and CDKN2A aberrations were found predominantly in the non-metastasizing group of primary NM. The survival analysis furthermore demonstrated that patients with combined CDKN2A and C-MYC aberrations have a significantly better prognosis than carriers of CDKN2A deletion only.ConclusionsWe conclude that the C-MYC increased copy number changes on the background of CDKN2A deletions seem to be related to a low metastatic potential and better patients’ outcome in primary NMs.

Iatrogenic melanoma. Comment on: Melanoma epidemic: a midsummer night's dream?

reaching a good response, such as PASI 75 (or PASI 90 or clearance), who would not have reached that response with an alternative therapy. Few studies have been done to allow such calculations. In the absence of any direct comparative study evidence we have to rely on indirect comparisons. Overall, there is no evidence that TNF-a inhibitor therapy ‘biologicals’ are any more effective than other treatments such as NB-UVB. The adverse effect risks of anti-TNF-a drugs are discussed by Dharamsi et al. and that these serious adverse effects are already becoming apparent, despite our relatively short experience of these therapies, is concerning. For now, we should continue to consider TNF-a inhibitor therapy for psoriasis only when other longer-established, safer and cheaper (important in ensuring we can afford to treat everyone appropriately) approaches have not been adequate. Hopefully, to generate really useful information that will guide clinical practice, future studies of TNF-a inhibitor therapy for psoriasis will either (i) only recruit patients who have failed to respond to other therapies (for whom comparison with placebo is reasonable) or (ii) compare these drugs with other effective treatments, not just with placebo.

The opinion of dermoscopy experts about teledermoscopy involving primary care physicians and dermatologists

Dear Editor Many dermatologists use teledermoscopy to seek second advice from experts for difficult lesions. Teledermoscopy by primary care physicians (PCP) is still controversial but already has been implemented in several regions. Since there are only few studies published about teledermoscopy in the hand of PCP with poor level of evidence, we asked the opinion of dermoscopy experts (board members of the International Dermoscopy Society (IDS)). Furthermore, we investigated the routing of patients with a suspicious pigmented skin lesion and the use of teledermoscopy in different countries. An online survey containing eight questions about the personal opinion about teledermoscopy, the position of PCP, the medical setting and the role of teledermoscopy were send to 96 board members of the IDS. A total of 38 IDS members (37%) from 23 countries [Argentina, Australia (2), Austria (3), Brazil, China, Croatia, Egypt, France, Georgia, Germany (3), Italy (4), Japan, Latvia, Mexico, Poland, Portugal, Serbia (2), Spain (2), Sweden (2), Switzerland, the Netherlands, Turkey (3), USA (3)] returned the survey. Half of the respondents was positive about teledermoscopy by PCP, albeit under specific conditions (i.e. training of PCP, clinical information provided, high quality pictures, expert dermoscopist). Some were in favour in case of long travel distance, long waiting time or shortage of dermatologists. In 14 (60.9%) countries PCP hold a gate keeper function, in one country PCP are gate keeper in most regions. In 11 countries, the maximum distance patients have to travel ≥100 km to see the nearest dermatologist. From these 11 countries patients from Sweden, Australia and Brazil face a maximum travel distance >300 km. Ca 30% answered that the average waiting time for an appointment with a dermatologist for a suspicious lesion is less than one week in their country, another 30% answered that it is more than 4 weeks. Teledermoscopy for pigmented lesions is standard of care only in Switzerland, where an expert dermatologist at a university skin cancer centre evaluates the pictures. In some regions in Portugal, Spain, France, the Netherlands and Sweden teledermoscopy is implemented (Table 1). No significant association was found between waiting time and gate keeper function of the PCP or the distance to the nearest dermatologist or the opinion about teledermoscopy. Neither was there an association between the gate keeper function of the PCP and opinion about teledermoscopy. A questionnaire sent to Dutch dermatologists asking about their opinion and experience with teledermoscopy showed that only a minority (18%) was providing this service to PCP. Most dermatologists (70%) considered teledermoscopy inadequate to assess pigmented lesions. Only few studies investigated the value of teledermoscopy between primary and secondary care. The main conclusion is that teledermoscopy may reduce the number of unnecessary referrals and could decrease the waiting time. No missed malignancies were reported in these studies. However, most of these studies were not designed to evaluate efficacy and safety. One study designed to evaluate the efficacy and safety showed that the diagnosis and treatment plan after teledermoscopy were inferior compared to face-to-face consultations. Teledermoscopy in the hands of the PCP is not broadly introduced so far. However, half of the experts is positive about teledermoscopy under specific conditions. Further studies

Surveillance of Second-Degree Relatives from Melanoma Families with a CDKN2A Germline Mutation

Background: Lifetime melanoma risk of mutation carriers from families with a germline mutation in the CDKN2A gene is estimated to be 67%. The necessity to include family members in a melanoma surveillance program is widely endorsed, but there is no consensus on which family members should be invited. Methods: In a retrospective follow-up study, we investigated the yield of surveillance of first- and second-degree relatives of melanoma and pancreatic cancer patients from 21 families with the “p16-Leiden” CDKN2A mutation. Melanoma incidence rates were compared with the general population. Results: Three-hundred and fifty-four first-degree relatives and 391 second-degree relatives were included. Forty-five first-degree relatives and 11 second-degree relatives were diagnosed with melanoma. Most (72%) of second-degree relatives diagnosed with melanoma had become a first-degree relative before diagnosis, due to the occurrence of a melanoma in a parent or sibling. Overall, melanoma incidence rate was 2.1 per 1,000 person years [95% confidence interval (CI), 1.2–3.8] in family members still being second-degree relatives at diagnosis, compared with 9.9 per 1,000 person years (95% CI, 7.4–13.3) in first-degree relatives. The standardized morbidity ratio for melanoma of second-degree relatives compared with the general population was 12.9 (95% CI, 7.2–23.4). Conclusion: Second-degree relatives from families with the p16-Leiden mutation in CDKN2A have a considerably increased melanoma risk compared with the general population. Impact: This study provides justification for the surveillance of second-degree relatives from families with a CDKN2A germline mutation. Cancer Epidemiol Biomarkers Prev; 22(10); 1771–7. ©2013 AACR.

Recognizing the haystack is the task of the primary care physician

In a reply to our letter Ferrandiz and colleagues wondered why dermoscopy experts did not already fully embrace teledermoscopy (TD) for suspicious pigmented skin lesions.1 Our study showed that the structure of the health systems that were investigated differed, with countries where primary care physicians (PCP) hold a gate keeper function and others with direct access to a dermatologist. Significant differences in waiting time and travel distance were observed.2 Since we believe that there is enough evidence that the addition of high quality dermoscopic pictures to a teleconsultation leads to higher accuracy of the diagnosis we did not investigate this question in our survey.

Agminated Spitz naevi or metastatic spitzoid melanoma

the immune system in psoriatic patients, whereby T helper 17 cells or innate lymphoid cell 3 systems become overactive to compensate, even though the defect cannot be detected clinically. The Koebner phenomenon may explain some of the distribution of the plaques as the increased expression of an antimicrobial peptide, cathelicidin, in psoriatic lesional epidermis is one of the provoking causes of inflammatory cascades.