Laura Eibenschutz

Seven-point checklist of dermoscopy revisited

Background  Most dermoscopic algorithms to diagnose melanoma were established more than 10 years ago and have been tested primarily on clear‐cut melanomas and excised melanocytic naevi.

Dermoscopy of Patients With Multiple Nevi Improved Management Recommendations Using a Comparative Diagnostic Approach

OBJECTIVE To assess the outcome on management recommendations of a comparative approach vs a morphologic approach in evaluating dermoscopic images of lesions from a series of patients with multiple nevi. DESIGN In a 2-step study, 6 experienced dermoscopists were asked to provide management recommendations (excision or follow-up) for a series of lesions from patients with multiple nevi based on dermoscopic images of the lesions. In the first step, participating dermoscopists evaluated individual images of lesions based only on morphologic structure (morphologic approach). In the second step, the same lesions were grouped by patient, allowing the participants to evaluate the lesions in the context of other nevi from the same patient (comparative approach). SETTING Academic referral center. PATIENTS Seventeen patients with 190 lesions (184 monitored nevi, 4 excised nevi, and 2 excised melanomas). MAIN OUTCOME MEASURE Using pooled data from each step, excision recommendation rates for the comparative approach and the morphologic approach were calculated. RESULTS Using the morphologic approach, 55.1% of overall recommendations favored excision; using the comparative approach, the rate decreased to 14.1%. The 2 melanomas included in the study were correctly judged to merit excision by all participants in step 1 and in step 2. Conclusion Among patients with multiple nevi, evaluation of equivocal lesions in the context of a patients other nevi results in a lower rate of excision recommendations compared with evaluation of individual lesions based on morphologic structure alone.

Vulvar melanoma: a report of 10 cases and review of the literature.

Despite its low incidence, vulvar melanoma carries a poor prognosis and shows a high tendency to metastasize because the diagnosis is often delayed. Although it is very well known that ultraviolet radiation is an important aetiological factor for cutaneous melanomas in adults, this cannot be considered true for vulvar melanoma. Chronic inflammatory disease, viral infections, irritant agents are the main factors suspected to induce mucosal melanoma. We report 10 cases of vulvar malignant melanoma observed in our institute from 1990 to 2005 and a review of the literature.

Dermoscopy of pigmented lesions of the vulva: A retrospective morphological study

Background: The dermoscopic patterns of pigmented skin tumors are influenced by the body site. Objective: To evaluate the clinical and dermoscopic features associated with pigmented vulvar lesions. Methods: Retrospective analysis of clinical and dermoscopic images of vulvar lesions. The χ2 test was used to test the association between clinical data and histopathological diagnosis. Results: A total of 42 (32.8%) melanocytic and 86 (67.2%) nonmelanocytic vulvar lesions were analyzed. Nevi significantly prevailed in younger women compared with melanomas and melanosis and exhibited most commonly a globular/cobblestone (51.3%) and a mixed (21.6%) pattern. Dermoscopically all melanomas showed a multicomponent pattern. Melanotic macules showed clinical overlapping features with melanoma, but their dermoscopic patterns differed significantly from those observed in melanomas. Conclusion: The diagnosis and management of pigmented vulvar lesions should be based on a good clinicodermoscopic correlation. Dermoscopy may be helpful in the differentiation of solitary melanotic macules from early melanoma.

The ringlike pattern in vulvar melanosis: a new dermoscopic clue for diagnosis.

BACKGROUND Vulvar melanosis is a benign pigmented lesion that may clinically mimic melanoma. Whereas the dermoscopic features of other pigmented skin lesions have been extensively described, little is known about vulvar melanosis. OBSERVATIONS A retrospective dermoscopic study was conducted on 87 lesions with histopathologically proved melanosis. We describe and define, for the first time to our knowledge, a ringlike pattern, found in 28 of 87 melanotic lesions (32%), characterized by multiple round to oval structures, white to tan, with dark brown, well-defined regular borders. The structureless and globularlike patterns were observed in 18 of 87 lesions (21%), the parallel pattern in 15 (17%), and the cobblestonelike and reticularlike patterns in 4 (5%). A significant association was found between the distribution of multifocal lesions showing a ringlike vs a nonringlike pattern (82% vs 52%; P = .008), whereas a weak association was found between anatomical site and the different patterns (P = .55). The ringlike pattern was frequently combined with multifocality and simultaneous occurrence at the labia majora and the labia minora. CONCLUSION Dermoscopy can be useful for the clinical detection of vulvar melanosis, and the ringlike pattern may represent a new dermoscopic clue for the diagnosis of this lesion.

CDKN2A/CDK4 molecular study on 155 Italian subjects with familial and/or primary multiple melanoma.

Dear Sir, During recent decades the incidence of cutaneous malignant melanoma has increased dramatically worldwide. At the same time, the survival rate has shown a remarkable improvement, mainly due to a higher proportion of cases presenting with early-stage lesions. Between 5% and 10% of melanoma occurs in a familial setting and to date only two high-penetrance loci responsible for melanoma susceptibility have been identified, CDKN2A and CDK4. CDKN2A is the major locus for melanoma predisposition, although alterations have been detected in only 20–40% of melanoma-prone families (Goldstein et al., 2006; Newton-Bishop et al., 1999). CDKN2A encodes two different proteins, p16INK4A and p14ARF, both tumor suppressors. The p16INK4A protein inhibits the cyclin D1-cyclin-dependent kinase 4 (CDK4) complex, which controls cell cycle progression by phosphorylating the retinoblastoma protein; while p14ARF is involved in the cell-cycle regulation by binding to MDM2, thereby inhibiting p53 degradation. Mutations of CDK4 seem to be a rare cause of melanoma susceptibility (Goldstein et al., 2002) and to date only seven families: two American, two French, one Norwegian, one Australian and one English have been described (Molven et al., 2005; Soufir et al., 1998, 2007; Zuo et al.,1996). All mutations found so far affect codon 24 with arginine substituted by histidine or cysteine. This aminoacid exchange is critical because it abrogates p16INKA-CDK4 binding, essential for CDK4 inactivation. The aim of our work was to assess the prevalence of CDKN2A and CDK4 mutations in a sample of Italian melanoma-prone families and cases with multiple primary melanoma (MPM). We identified 15 ⁄ 155 (9.6%) patients with CDKN2A mutations: 4 ⁄ 76 (5.2%) affected by familial melanoma, 8 ⁄ 18 (44.4%) affected by familial and MPM, and 3 ⁄ 61 (4.9%) with sporadic MPM (Table 1). The most common mutation was G101W, a documented founder mutation in Italy (Mantelli et al., 2002). CDK4 exon 2 was analyzed in 140 subjects affected by melanoma (73 from pedigrees with familial melanoma, 54 with MPM, 13 with both familial and MPM), negative for CDKN2A mutations, using the following PCR primers: CDK4-2F 5¢-TGATTGTAGGGTCTCCCTTGA and CDK4-2R 5¢-CAACCCTCCACCACCTTCT (GenBank: U37022). Haplotype analysis was performed, as reported by Molven et al. (2005), by analysing three microsatellite markers upstream (D12S1700, D12S305; CDK4M4) and three markers downstream (CDK4M1, D12S1691, D12S1632) the CDK4 region, as well as three intragenic SNPs (rs2270777, rs2069502, rs2069506) and one SNP in the promoter region (rs2072052). Details of primers for SNPs and microsatellite analysis are available on request. We found one subject with a CDK4 R24H substitution. This 70-year-old male, with skin phototype IV, presented with an in situ cutaneous melanoma of the shoulder at the age of 59 years. After eleven years follow-up he is free from relapse. His 68-year-old sister was affected by melanoma of the foot (SSM of the instep) at the age of 53 years. His son developed two primary melanomas, firstly, an in situ melanoma of the leg (at age 35 years) and, subsequently, (at age of 38 years) a superficial spreading melanoma (SSM) of the thorax (0.5 mm Breslow thickness, Clark level III). The proband’s daughter, skin phototype III, presented with a SSM of the right leg (0.6 mm Breslow thickness, Clark level IV), at the age of 38 years. The healthy grand-daughter carried the CDK4 R24H mutation while the grandson was wildtype. The proband’s father was reported to have died at the age of 42 years as a consequence of liver cancer (histological result was not available). The mother was negative for CDK4 mutation, thus supporting paternal segregation of the R24H variant. The average age of onset of melanoma in this family was 46 years with a difference between the first and the second generation of >15 years (59 for the first generation and 38 for the second). Our results confirm the role of the CDK4 gene in melanoma susceptibility despite the low frequency

Typical and atypical dermoscopic presentations of dermatofibroma

Background  Dermatofibroma is a common skin neoplasm that is usually easy to recognize, but in some cases its differentiation from melanoma and other tumours may be difficult.

Giant and large basal cell carcinoma treated with topical photodynamic therapy.

Basal cell carcinoma (BCC) is the most common cancer affecting Caucasians and, due to its large size or to the poor condition of the patient, it can be difficult to treat it with conventional therapies: in these cases photodynamic therapy with methyl aminolevulinate (MAL-PDT) may represent a good option. A retrospective non-comparative follow-up study was performed to test the response of giant and large BCC to MAL-PDT. Twelve patients with 14 giant BCC (> or = 5 cm) and 5 patients with 5 large BCC (4-5 cm) were treated with MAL-PDT; they were evaluated 6 months after the end of the treatment to define the initial cure rate, and then at 12 and 36 months for the follow-up. At 6 months the initial cure rate for the 19 BCCs was 95% and at 36 months the overall long-term cure rate was 66%. The follow-up will last up to 5 years. MAL-PDT is a valid option for the treatment of giant and large BCC.

A 9‐month, randomized, assessor‐blinded, parallel‐group study to evaluate clinical effects of film‐forming medical devices containing photolyase and sun filters in the treatment of field cancerization compared with sunscreen in patients after successful photodynamic therapy for actinic keratosis

DEAR EDITOR, Actinic keratosis (AK) is a precancerous lesion caused by chronic exposure to sunlight. Photodynamic therapy (PDT) is a well-established therapeutic approach for the treatment of AK. PDT is effective in clearance of AK lesions and improving field cancerization. However, > 20% of patients need a second procedure in the following months after the first treatment. After PDT, sun protection strategies are important in order to reduce the risk of new lesions or the need for another session of PDT. A film-forming medical class II device containing photolyase, a DNA-repairing enzyme with a broad photoprotection action (Eryfotona AK-NMSC Fluid; Isdin, Barcelona, Spain), has been shown, in open clinical studies, to induce both subclinical and clinical improvements in patients with AK. This product seems to be more effective than sunscreen products in improving clinical outcomes (clearance of AK lesions) and field cancerization. So far, there are no published controlled data regarding the use of Eryfotona vs. sunscreen in patients with AK after successful PDT treatment. We assessed the efficacy of Eryfotona vs. sunscreen in the development of new AKs in patients with AK after successful PDT. In a prospective, two-arm, parallel-group, 9-month, assessor-blinded, comparative trial, immunocompetent patients between the age of 40 and 85 years with multiple AKs of the face and/or scalp suitable for PDT treatment, were enrolled. This study (clinical trial number: ISRCTN12347628) was conducted between January 2014 and June 2015. After obtaining institutional review board approval and written informed consent from the participants, 30 patients (22 men; mean age 69 years) with a total of 225 AK lesions (7 5 lesions per patient) were included. Exclusion criteria were age < 18 or > 75 years, presence of skin tumours, xeroderma pigmentosum and a history of skin conditions other than AK which might interfere with the study evaluations. Patients were randomized 1 : 1 to Eryfotona (n = 15) or to sunscreen (n = 15) Sunscrean SPF 50+ (Fotoprotector, ISDIN, Barcelona, Spain). The primary outcome of the study was the evolution of new AK lesions in the previous PDT-treated area or in another area. The secondary outcome of the study was the need to perform new PDT or other lesion-targeted or field-cancerization targeted therapies. Eryfotona or sunscreen were applied in the treatment evaluation area (scalp and face) for nine consecutive months, in the morning and 4–6 h later. For each application, patients were instructed to apply a total of 2 5 fingertip units for both products. All patients completed the trial. Table 1 summarizes the patient demographics and AK characteristics at baseline. At baseline, the mean SD number of AK lesions was 6 6 2 8 in the Eryfotona group and 8 4 3 0 in the sunscreen group. All patients underwent one standardized session of methylaminolaevulinate PDT using a 630-nm light-emitting diode lamp at 37 J cm . Immediately after PDT (evaluation performed 2 weeks after the procedure) mean SD residual lesions were 2 0 2 0 in the Eryfotona group and 0 6 0 5 in the sunscreen group (nonsignificant). A progressive increase of AK lesions was observed in the sunscreen group, with a mean SD number of lesions of 3 6 3 8 at the end of study period (month 9). In contrast, a significant reduction of AK lesions was observed at month 9 in patients in the Eryfotona group, with a mean SD number of lesions of 1 0 1 1 in comparison with baseline and with the comparator group (P < 0 01). Evolution of new AK lesions after PDT is shown in Figure 1. In the sunscreen group, 13 of 15 patients (87%) presented new AK lesions during the study: in 10 patients new lesions appeared in the area previously treated

A 9-month, randomized, assessor-blinded parallel-group study to evaluate clinical effects of a film-forming medical devices containing photolyase and sun-filters in the treatment of cancerization field in comparison with sunscreen in patients after successful PDT for Actinic Keratosis.

DEAR EDITOR, Actinic keratosis (AK) is a precancerous lesion caused by chronic exposure to sunlight. Photodynamic therapy (PDT) is a well-established therapeutic approach for the treatment of AK. PDT is effective in clearance of AK lesions and improving field cancerization. However, > 20% of patients need a second procedure in the following months after the first treatment. After PDT, sun protection strategies are important in order to reduce the risk of new lesions or the need for another session of PDT. A film-forming medical class II device containing photolyase, a DNA-repairing enzyme with a broad photoprotection action (Eryfotona AK-NMSC Fluid; Isdin, Barcelona, Spain), has been shown, in open clinical studies, to induce both subclinical and clinical improvements in patients with AK. This product seems to be more effective than sunscreen products in improving clinical outcomes (clearance of AK lesions) and field cancerization. So far, there are no published controlled data regarding the use of Eryfotona vs. sunscreen in patients with AK after successful PDT treatment. We assessed the efficacy of Eryfotona vs. sunscreen in the development of new AKs in patients with AK after successful PDT. In a prospective, two-arm, parallel-group, 9-month, assessor-blinded, comparative trial, immunocompetent patients between the age of 40 and 85 years with multiple AKs of the face and/or scalp suitable for PDT treatment, were enrolled. This study (clinical trial number: ISRCTN12347628) was conducted between January 2014 and June 2015. After obtaining institutional review board approval and written informed consent from the participants, 30 patients (22 men; mean age 69 years) with a total of 225 AK lesions (7 5 lesions per patient) were included. Exclusion criteria were age < 18 or > 75 years, presence of skin tumours, xeroderma pigmentosum and a history of skin conditions other than AK which might interfere with the study evaluations. Patients were randomized 1 : 1 to Eryfotona (n = 15) or to sunscreen (n = 15) Sunscrean SPF 50+ (Fotoprotector, ISDIN, Barcelona, Spain). The primary outcome of the study was the evolution of new AK lesions in the previous PDT-treated area or in another area. The secondary outcome of the study was the need to perform new PDT or other lesion-targeted or field-cancerization targeted therapies. Eryfotona or sunscreen were applied in the treatment evaluation area (scalp and face) for nine consecutive months, in the morning and 4–6 h later. For each application, patients were instructed to apply a total of 2 5 fingertip units for both products. All patients completed the trial. Table 1 summarizes the patient demographics and AK characteristics at baseline. At baseline, the mean SD number of AK lesions was 6 6 2 8 in the Eryfotona group and 8 4 3 0 in the sunscreen group. All patients underwent one standardized session of methylaminolaevulinate PDT using a 630-nm light-emitting diode lamp at 37 J cm . Immediately after PDT (evaluation performed 2 weeks after the procedure) mean SD residual lesions were 2 0 2 0 in the Eryfotona group and 0 6 0 5 in the sunscreen group (nonsignificant). A progressive increase of AK lesions was observed in the sunscreen group, with a mean SD number of lesions of 3 6 3 8 at the end of study period (month 9). In contrast, a significant reduction of AK lesions was observed at month 9 in patients in the Eryfotona group, with a mean SD number of lesions of 1 0 1 1 in comparison with baseline and with the comparator group (P < 0 01). Evolution of new AK lesions after PDT is shown in Figure 1. In the sunscreen group, 13 of 15 patients (87%) presented new AK lesions during the study: in 10 patients new lesions appeared in the area previously treated