Lentigo maligna (melanoma): A systematic review and meta-analysis on surgical techniques and presurgical mapping by reflectance confocal microscopy.

Because of an increased risk of local recurrence following surgical treatment of lentigo maligna (melanoma) (LM/LMM), the optimal surgical technique is still a matter of debate. We aimed to evaluate the effect of different surgical techniques and reflectance confocal microscopy (RCM) on local recurrence and survival outcomes. We searched MEDLINE, Embase and PubMed databases through 20 May 2022. Randomized and observational studies with ≥10 lesions were eligible for inclusion. Bias assessment was performed using the Methodological Index for Non-Randomized Studies instrument. Meta-analysis was performed for local recurrence, as there were insufficient events for the other clinical outcomes. We included 41 studies with 5059 LM and 1271 LMM. Surgical techniques included wide local excision (WLE) (n = 1355), staged excision (n = 2442) and Mohs' micrographic surgery (MMS) (n = 2909). Six studies included RCM. The guideline-recommended margin was insufficient in 21.6%-44.6% of LM/LMM. Local recurrence rate was lowest for patients treated by MMS combined with immunohistochemistry (<1%; 95% CI, 0.3%-1.9%), and highest for WLE (13%; 95% CI, 7.2%-21.6%). The mean follow-up varied from 27 to 63 months depending on surgical technique with moderate to high heterogeneity for MMS and WLE. Handheld-RCM decreased both the rate of positive histological margins (p < 0.0001) and necessary surgical stages (p < 0.0001). The majority of regional (17/25) and distant (34/43) recurrences occurred in patients treated by WLE. Melanoma-associated mortality was low (1.5%; 32/2107), and more patients died due to unrelated causes (6.7%; 107/1608). This systematic review shows a clear reduction in local recurrences using microscopically controlled surgical techniques over WLE. The use of HH-RCM showed a trend in the reduction in incomplete resections and local recurrences even when used with WLE. Due to selection bias, heterogeneity, low prevalence of stage III/IV disease and limited survival data, it was not possible to determine the effect of the different surgical techniques on survival outcomes.

Biopsy outperforms reflectance confocal microscopy in diagnosing and subtyping basal cell carcinoma: results and experiences from a randomized controlled multicentre trial.

BACKGROUND: Reflectance confocal microscopy (RCM) is a noninvasive method for skin assessment, allowing entire lesion evaluation up to the papillary dermis. RCM is a potentially attractive alternative to punch biopsy (PB) in basal cell carcinoma (BCC). OBJECTIVES: To determine the diagnostic accuracy of RCM vs. PB in diagnosing and subtyping BCC, and to study patient satisfaction and preferences. METHODS: Patients with a clinically suspected primary BCC were randomized between RCM and biopsy. Conventional surgical excision or follow-up were used as reference. Sensitivity and specificity for BCC diagnosis and subtyping were calculated for both methods. BCC subtype was stratified based on clinical relevance: aggressive (infiltrative/micronodular) vs. nonaggressive (superficial/nodular) histopathological subtype and superficial vs. nonsuperficial BCC. Data on patient satisfaction and preferences were collected using a questionnaire and a contingent valuation method. RESULTS: Sensitivity for BCC diagnosis was high and similar for both methods (RCM 99·0% vs. biopsy 99·0%; P = 1·0). Specificity for BCC diagnosis was lower for RCM (59·1% vs. 100·0%; P < 0·001). Sensitivity for aggressive BCC subtypes was lower for RCM (33·3% vs. 77·3%; P = 0·003). Sensitivity for nonsuperficial BCC was not significantly different (RCM 88·9% vs. biopsy 91·0%; P = 0·724). Patient satisfaction and preferences were good and highly comparable for both methods. CONCLUSIONS: Biopsy outperforms RCM in diagnosing and subtyping clinically suspected primary BCC. This outcome does not support routine clinical implementation of RCM, as a replacement for PBs in this patient group.

Cumulative risk of skin cancer in patients with Li-Fraumeni syndrome.

Li-Fraumeni syndrome (LFS) is an inherited cancer syndrome, characterized by an early onset of various types of cancers. LFS is associated with a germline mutation in the TP53 gene. The risk of developing skin cancer in patients with LFS is unknown. To evaluate the cumulative risk of skin cancer in patients with LFS and to compare this risk to the general Dutch population. In this retrospective cohort study, all proven TP53 mutation carriers in the Netherlands Cancer Institute were included from their first visit to the Institute until June 2017. Medical charts and pathology reviews cross-referenced with PALGA, the nationwide network and registry of histo- and cytopathology were used to identify incident skin cancers. Cumulative risks were calculated by Kaplan-Meier analysis. Seventy-one patients (59% female) from 33 families were included. Ten patients (14%) developed a total of 19 skin cancers at a median age of 41 (25-65) years. The cumulative risk of skin cancer is 10.4% (95% CI 4.4-23.5%) at age 40, 25.2% (95% CI 12.3-47.6%) at age 60, and a at age 70 this risk is 44.6% (95% CI 22.9-73.9%). The cumulative risks of melanoma and basal cell carcinoma at age 70 are increased compared to the general Dutch population, namely 12.6% (95% CI 3.6-38.4%) and 34.6% (95% CI 15.4-66.2%), respectively. Patients with LFS have an increased risk of developing skin cancer. A dermatological consultation may be considered at least once in individuals with LFS to raise awareness for skin cancer and inform about risk factors.

A squamous cell carcinoma in a young woman with Lynch syndrome.

Lynch syndrome (LS) is an autosomal-dominant inherited disorder characterized by a predisposition to colorectal cancer and extracolonic cancers (particularly endometrium, ovary, stomach, small bowel, hepatobiliary tract, pancreas, urothelial tract, brain, and skin). Muir-Torre syndrome (MTS) is considered a phenotypical variant of LS, where patients develop sebaceous neoplasms and keratoacanthomas. Currently, only few studies and case reports suggest an association between LS and other skin cancers, such as Bowens' disease, melanoma and squamous cell carcinoma (SCC). In this case-report we describe the case of a 33-year-old woman with LS and a proven MSH2 germline mutation, presenting with a SCC on the right cheek. Immunohistochemistry lacked MSH2 and MSH6 protein staining. The tumor showed a discordance between immunohistochemistry and micro-satellite instability status, for which a clear explanation cannot be provided yet. To conclude whether this pattern is indicative for SCC occurring in LS patients, further analyses of other LS patients presenting with SCC should be carried out. Our patient's young age and skin type (Fitzpatrick phototype VI) suggest a possible link between LS and cutaneous SCC.

Ultraviolet exposure and the development of banal and atypical naevi--a cross-sectional study on Curaçao and in The Netherlands.

The atypical naevus is both a risk factor for and a precursor lesion of melanoma. Sunlight is known to be an important aetiological factor for melanoma. Whether solar exposure is also involved in the initiation of (atypical) naevi is an issue of current interest. We performed a cross-sectional study among 270 inhabitants in the cloudy Netherlands and 282 white Dutch immigrants of the tropical island Curaçao to investigate whether solar exposure plays a role in the development of atypical naevi. All participants were interviewed and underwent total skin examination; banal melanocytic naevi and atypical naevi were counted. There was no significant difference in the mean number of melanocytic naevi > or = 2 mm or > or = 5 mm between Curaçao and the Netherlands. Furthermore, there was no significant difference in the mean crude and age standardized prevalence of atypical naevi between the Netherlands and Curaçao. In both groups individuals with atypical naevi had significantly more total naevi. Concerning the role of sun exposure in the development of naevi in the Netherlands, we found that the total naevus count had a significant association with cumulative sun exposure before the age of 12 as well as with two or more painful sunburns before the age of 12. In Curaçao these relationships were not observed. In contrast, however, on Curaçao the presence of atypical naevi showed an association (odds ratio = 2.6, 95% confidence interval 1.1-6.0) with the highest level of cumulative sun exposure and with painful sunburns before the age of 12 (odds ratio = 2.6, 95% confidence interval 1.2-5.5). In the Dutch group these associations were not significant. We hypothesize that in the development of banal naevi there is an association between the total number of naevi and sun exposure only at low exposure levels; however, after overstepping a critical threshold a further association between melanocytic naevi and sun exposure is lacking. Sunlight exposure before the age of 12 plays a complex role: only very high exposure levels seem to contribute to the development of atypical naevi.

A comparative study of atypical and melanocytic naevi on the tropical island Curaçao and in The Netherlands.

A cross-sectional study was undertaken in 270 inhabitants of The Netherlands (moderate maritime climate, latitude 51 degrees 5' N-53 degrees 3' N) with skin types I-III and 757 inhabitants of the tropical island Curaçao (latitude 12 degrees 2' N-12 degrees 23' N). The latter group consisted of 282 White individuals (mostly Dutch immigrants) and 475 people with non-White skin types IV, V and VI. All participants underwent total skin examination and melanocytic naevi (MN) and clinically atypical naevi (AN) were noted. There was no statistical difference in the mean number of naevi > or = 2 mm or > or = 5 mm between the Curaçao and The Netherlands White groups, but the mean number of naevi > or = 2 mm and > or = 5 mm was significantly lower in the Curaçao non-White group. We found no obvious differences in mean naevus counts between genders and the various comparable age groups. Furthermore, we found no significant difference in mean crude and mean age-standardized prevalence of (one or more) AN between Whites in The Netherlands and on Curaçao. The Mantel-Haenszel prevalence ratio weighted for age and gender differences of Curaçao Whites vs non-Whites was 5.93 (95% confidence interval 3.9-12.0), demonstrating that AN are significantly less prevalent in darker skin types. In all groups, people with AN had significantly more MN than people without AN. We found a generation-dependent difference in the expression of AN among White inhabitants of The Netherlands and on Curaçao, with a higher prevalence of AN in the younger generation.

Are atypical nevi a risk factor for uveal melanoma? A case-control study.

Atypical nevi and other potential risk factors for uveal melanoma were studied in 109 uveal melanoma patients and 149 controls. Information concerning employment, medical history, drug use, family history of cancer, excess sun exposure, and blistering sunburn before and after the age of 15 was obtained. A total skin examination was performed and skin type, hair color, eye color, freckles, actinic damage, the total number of common acquired nevi, and the number of clinically atypical nevi were noted. More atypical nevi were found in uveal melanoma patients than in controls (age- and sex-adjusted odds ratio of 2.9 [95% confidence interval 1.2-6.3] for one or two atypical nevi versus none; odds ratio of 5.1 [95% CI 1.3-20.0] for three or more atypical nevi versus none). Light skin types and freckling also prevailed in uveal melanoma cases. In our study, atypical nevi are more common in uveal melanoma patients than in controls. Further studies will have to indicate whether risk factors comparable to those for cutaneous melanoma really exist for uveal melanoma.

On naevi and melanomas in dysplastic naevus syndrome patients.

Cutaneous melanoma may occur as isolated, so-called 'sporadic' cases or in association with multiple atypical naevi and in familial clusters, in which case it is referred to as the familial dysplastic naevus syndrome (DNS). In this retrospective study (a) the number and body distribution of naevocytic naevi and (b) the body distribution of malignant melanoma (MM) in individuals with familial DNS were compared in order to study their association. In 45 patients with familial DNS aged 20-39 years naevus counts on trunk and lower extremities were compared with melanoma data and distributions from a second group of 43 patients from the same DNS families aged 12-66 years. Men had significantly more naevi of a size > or = 2 mm or > or = 5 mm on the back than women (P = 0.02). Women showed a tendency towards a greater number of naevi on the lower extremities than men, but in women no significant difference in naevi between the lower extremities and the back was found. The total number of naevi on the trunk and lower extremities in familial DNS patients was higher than that in the general population. In conclusion, it was found that predilection sites for melanoma in familial DNS patients of both sexes correspond with the distribution of naevi; in males naevi and melanoma counts and percentage distributions were higher on the back, in females both the back and the lower extremities were affected. These findings strongly suggest an association between naevus distribution and melanoma occurrence and site in familial DNS, analogous to earlier reports on sporadic melanoma.

A randomized treatment duration-finding study of terbinafine in onychomycosis.

Terbinafine is an allylamine antifungal compound shown to be effective in the oral treatment of onychomycosis. Because of the fungicidal activity of the drug, a shorter duration of treatment, compared with the currently used oral treatment modalities, can be expected in onychomycosis of the toenail. In the present randomized study, the efficacy of oral terbinafine treatment (250 mg/day) was assessed for periods of 6, 12, and 24 weeks. All patients were followed for up to 48 weeks after starting treatment. Of the 120 patients with toenail onychomycosis who entered the study, 98 were evaluable for efficacy. The involvement of the toenails was assessed both clinically and mycologically throughout the study. Evaluation at 24 weeks showed that complete cure of toenail onychomycosis was achieved in 67% of patients treated for 6 weeks, 82% treated for 12 weeks, and 85% treated for 24 weeks. At the end of a further 24 weeks of follow-up, cure rates were 40%, 71% and 79%, respectively. The adverse effects of terbinafine were mostly mild-to-moderate gastrointestinal symptoms. Three patients discontinued treatment because of side-effects. In conclusion, oral treatment with terbinafine is effective and generally well tolerated in patients with onychomycosis. Our results demonstrate that, for toenail onychomycosis, a treatment period of 12 weeks is sufficient.

Dysplastic nevi. Occurrence in first- and second-degree relatives of patients with 'sporadic' dysplastic nevus syndrome.

In this study a cross-sectional survey was undertaken among 156 living family members of 31 probands originally classified as having sporadic (histologically verified) dysplastic nevus syndrome (DNS). Seven (13.2%) of 53 parents had clinically recognizable DNS. Twenty-six (36.1%) of the 72 sibs showed dysplastic nevi. The diagnosis of DNS in family members was based on mainly clinical examination; in eight family members--those with only mild manifestation of DNS--a nevus was removed for histologic confirmation. After correction for pedigree size, we found that 60% of patients with "type A sporadic" DNS actually had one or more relatives with a DNS phenotype. Only 25% (8/30) of the probands were ultimately true sporadic cases without a DNS-affected first- or second-degree relative. In 15% (5/31) of the probands no conclusions concerning the type of DNS could be made because the pedigree size did not allow such a conclusion. We also found a higher prevalence of dysplastic nevi among the younger generation as compared with the older generation in our probands with DNS and their families as well as in a general population study of 400 individuals. This generation-dependent difference in expression of the DNS phenotype suggests that besides a genetic factor, other factors may play a role in the development of the characteristic phenotype.

Ocular melanoma in families with dysplastic nevus syndrome.

Five families with the dysplastic nevus syndrome, in each of which one member had ocular melanoma, are reported. These five families were examined within a 3-year period in one medical center. To date only five other families with such a combination have been reported. We suggest a causal relation between ocular melanoma and the familial dysplastic nevus syndrome.

Vasoconstrictor and the anti-inflammatory effects of 7 corticosteroids.

The vasoconstrictor effect of 7 proprietary corticosteroid creams was compared with their effect on patches of allergic contact dermatitis provoked by patch testing in 20 subjects. A parallel between the blanching effect on the normal skin and the anti-inflammatory effect on the eczematous skin was generally found. A modified patch test method using the Finn chamber technique is described, which (with certain restrictions) offers an opportunity of studying the anti-inflammatory effect of corticosteroids on allergic dermatitis under standard conditions.