Differences in individual and environmental factors between cutaneous melanoma and atypical Spitz tumour in children and adolescents.

It is not known if children and adolescents with atypical Spitz tumour and cutaneous melanoma differ in terms of etiological factors. The aim of this study was to explain differences in individual and environmental factors between cutaneous melanoma and atypical Spitz tumour. In the context of a study on melanocytic lesions, all subjects aged under 20 years with either cutaneous melanoma or atypical Spitz tumour were included (N = 105). Information on socio-demographic characteristics, individual and environmental factors were collected for both mother and child. The Fisher's exact test and the Mann-Whitney U test were used for categorical variables and continuous variables respectively. A multivariate logistic model was used to explain differences in outcome by differences in explanatory variables. In comparison to patients with cutaneous melanoma, patients with atypical Spitz tumour had less freckles (p = 0.020), lower number of common nevi (p = 0.002), and lower body mass index (p = 0.001) and experienced less sunburns episodes (p = 0.008). However, in the multivariate analysis, only a low number of common nevi remained statistically significant. Children and adolescents with cutaneous melanoma have a high number of nevi in comparison to the same-age group with atypical Spitz tumour.Conclusion: The results of this study suggest that the only difference in individual and environmental risk factors between cutaneous melanoma and atypical Spitz tumour in children and adolescents is the number of nevi. What is Known: •Atypical Spitz tumours and cutaneous melanoma in children and adolescents are clinically similar, but compared with melanoma, they have a good overall prognosis. •Risk factors for cutaneous melanoma in children and adolescents are similar to the ones found in adults in the literature What is New: •Differences in individual and environmental risk factors for atypical Spitz tumour in children and adolescents are described for the first time in this study. •Individual and environmental factors for atypical Spitz tumour in children and adolescents are comparable to cutaneous melanoma, except for the presence of low number of nevi.

Correlation between digital epiluminescence microscopy parameters and histopathological changes in lentigo maligna and solar lentigo: A dermoscopic index for the diagnosis of lentigo maligna.

BACKGROUND: The clinical and dermoscopic differentiation between lentigo maligna (LM) and solar lentigo (SL)/initial seborrheic keratosis (SK) may be difficult. OBJECTIVE: Our aim was to identify digital epiluminescence microscopy (DELM)-specific criteria that can be helpful in distinguishing LM from SL/SK and to propose a new model of LM dermoscopic progression based on a study of DELM-histopathological correlation. METHODS: A total of 167 consecutive doubtful pigmented lesions of the head (105 LM and 62 SL/SK) were studied. DELM assessment was based on the presence or absence of 15 DELM parameters that were subsequently examined histologically. Statistical analysis was performed to determine which DELM parameters were most strongly associated with LM. RESULTS: The finding of at least 1 of 4 parameters (ie, brown globules, a "necklace" pigment network, an atypical pigment network, and dark-brown/blue-gray ribbonlike structures) showed to be an extremely sensitive (99%) and specific (83.9%) DELM criterion to discriminate between LM and SL/SK. LIMITATIONS: Our findings were obtained by examining medium-high magnification DELM images. CONCLUSIONS: The finding of 1 or more among the 4 above-mentioned DELM parameters allows for the correct identification of 99.0% of the LM lesions, and - when the score is 0 - the correct classification as non-LM, of 83.9% of the SL/SK lesions.

The effect of time to sentinel lymph node biopsy on cutaneous melanoma survival.

BACKGROUND: Whether timing of sentinel lymph node biopsy (SLNB) in cutaneous melanoma improves survival is not yet clear. The aim of this study was to investigate if the timing of SLNB influences long-term melanoma mortality. METHODS: A 10-year retrospective cohort study was conducted on 748 cutaneous melanoma patients who underwent excision of the SLN. Hazard ratios and 95% confidence intervals were estimated from Cox proportional hazards models. RESULTS: After adjusting for sex, age, Breslow thickness, mitotic rate, ulceration, and histologic type, patients who underwent early SLNB (≤30 days) and resulted positive on final pathology had a 3 times decreased risk of melanoma mortality (hazard ratio = .29; 95%confidence interval = .11 to .77) in comparison to patients who underwent delayed SLNB (≥31 days) and resulted positive on final pathology. CONCLUSIONS: Our findings suggest that early SLNB (≤30 days) improves melanoma survival.

Diagnostic services for melanoma in Italy.

OBJECTIVE: To evaluate organizational structure and diagnostic procedures used by the Italian hospital network for identifying cutaneous melanoma. METHODS: A nationwide survey of a representative sample of centers was conducted. RESULTS: Diagnosis occurs mainly in ambulatory dermatology clinics (91%). In all high-volume hospitals, clinical and dermoscopic examination is available at first consultation or as an additional service, compared to 89% of low-volume hospitals. Computer-assisted videodermoscopy is available in 75% of hospitals, with a statistically significant difference between high- and low-volume hospitals (86 vs. 62%; p < 0.001). First consultation is generally an integrated clinical/dermoscopic evaluation (55% of high-volume centers vs. 47% of low-volume hospitals); digital evaluation is available for monitoring suspicious lesions and high-risk patients in 25% of high-volume centers versus 19% of low-volume centers. CONCLUSIONS: The organizational structure and diagnostic procedures in Italian hospitals are in line with modern diagnostic procedures for early diagnosis of melanoma. Dermatologists have a central role in managing diagnosis of primitive melanoma.

Management of small and intermediate congenital nevi: a nationwide survey in Italy.

OBJECTIVE: Small- and intermediate-sized congenital nevi (SCN and ICN) undergo periodic clinical monitoring or surgical excision. We analyzed the management of SCN and ICN in the Italian hospital network. METHODS: A nationwide survey of a representative sample of centers was conducted. Data were analyzed grouping centers by melanoma incidence into high-volume (>25 diagnoses per year) and low-volume (≤ 25 diagnoses per year). RESULTS: In the pediatric population, 11% of SCN and 22% of ICN are excised, the remainder undergoing clinical monitoring at intervals of 6 months to 2 years (SCN) and of 6 months to 1 year (ICN). In adults, 24% of SCN and 41% of ICN are excised. Clinical monitoring of SCN varies from 6-monthly (most common among low-volume hospitals) to every 2 years; preferred strategies for ICN are follow-up at 1 year (51%) or follow-up at 6 months (42%). For prophylactic surgery, complete excision is preferred. CONCLUSIONS: The Italian hospital network values management and treatment of SCN and ICN. In most cases natural evolution prompts prophylactic excision. Clinical examination is an important monitoring tool, though follow-up frequency depends on the clinician's experience and practice.

Impact of mole mapping in the Italian health system.

OBJECTIVE: To analyze routine clinical management of atypical melanocytic lesions through monitoring or surgery in Italian hospitals. METHODS: A nationwide survey of clinical practices was conducted. RESULTS: Digital monitoring is performed in most Italian hospitals and is preferred over excision for single atypical melanocytic lesions in 82% of hospitals. For multiple atypical lesions, 60% of high-volume hospitals prefer digital monitoring to surgical excision (40%). There is a statistically significant difference between high- and low-volume hospitals (60 vs. 39%; p = 0.003). Digital monitoring is performed at mean intervals of 4/5 months for both types of lesions. CONCLUSIONS: We show an asymmetric relation between application of the method and practical impact based on available clinical evidence. Although digital monitoring provides better characterization of the evolution of melanocytic lesions, our results indicate that the advantages and limitations of this method require further investigation.

Surgical management of suspicious melanocytic lesions in Italy.

OBJECTIVE: In melanoma, the surgical approach is important for both diagnosis and therapy. Although surgery is relatively simple, the methods should be performed by experts in melanoma management. We analyze the techniques and methods used in the Italian hospital network for suspicious skin lesions and confirmed melanomas. METHODS: A nationwide survey was conducted of a representative sample of 120 hospitals with ≥ 200 beds. RESULTS: Excision biopsies remove suspected melanomas. However, some approaches to excision margins and sentinel lymph node procedures differ from international protocols. Overall, 21% of centers perform excisional biopsy of a suspicious lesion using 1 cm margins, and 22% of centers perform sentinel node procedures concurrently with removal of primary melanoma. CONCLUSIONS: Standardized treatment protocols are needed for suspicious lesions and clinically evident melanoma, particularly regarding the critical aspect of excision margins. The sentinel lymph node procedure may be distorted by initial margins that are too wide.

Dermoscopic evaluation of nodular melanoma.

IMPORTANCE: Nodular melanoma (NM) is a rapidly progressing potentially lethal skin tumor for which early diagnosis is critical. OBJECTIVE: To determine the dermoscopy features of NM. DESIGN: Eighty-three cases of NM, 134 of invasive non-NM, 115 of nodular benign melanocytic tumors, and 135 of nodular nonmelanocytic tumors were scored for dermoscopy features using modified and previously described methods. Lesions were separated into amelanotic/hypomelanotic or pigmented to assess outcomes. SETTING: Predominantly hospital-based clinics from 5 continents. MAIN OUTCOME MEASURES: Sensitivity, specificity, and odds ratios for features/models for the diagnosis of melanoma. RESULTS: Nodular melanoma occurred more frequently as amelanotic/hypomelanotic (37.3%) than did invasive non-NM (7.5%). Pigmented NM had a more frequent (compared with invasive non-NM; in descending order of odds ratio) symmetrical pigmentation pattern (5.8% vs 0.8%), large-diameter vessels, areas of homogeneous blue pigmentation, symmetrical shape, predominant peripheral vessels, blue-white veil, pink color, black color, and milky red/pink areas. Pigmented NM less frequently displayed an atypical broadened network, pigment network or pseudonetwork, multiple blue-gray dots, scarlike depigmentation, irregularly distributed and sized brown dots and globules, tan color, irregularly shaped depigmentation, and irregularly distributed and sized dots and globules of any color. The most important positive correlating features of pigmented NM vs nodular nonmelanoma were peripheral black dots/globules, multiple brown dots, irregular black dots/globules, blue-white veil, homogeneous blue pigmentation, 5 to 6 colors, and black color. A model to classify a lesion as melanocytic gave a high sensitivity (>98.0%) for both nodular pigmented and nonnodular pigmented melanoma but a lower sensitivity for amelanotic/hypomelanotic NM (84%). A method for diagnosing amelanotic/hypomelanotic malignant lesions (including basal cell carcinoma) gave a 93% sensitivity and 70% specificity for NM. CONCLUSIONS AND RELEVANCE: When a progressively growing, symmetrically patterned melanocytic nodule is identified, NM needs to be excluded.

Negative pigment network: an additional dermoscopic feature for the diagnosis of melanoma.

BACKGROUND: The negative pigment network (NPN) is seen as a negative of the pigmented network and it is purported to be a melanoma-specific structure. OBJECTIVES: We sought to assess the frequency, sensitivity, specificity, and odds ratios (ORs) of NPN between melanoma cases and a group of control lesions. METHODS: Digitalized images of skin lesions from 679 patients with histopathological diagnosis of dermatofibroma (115), melanocytic nevus (220), Spitz nevus (139), and melanoma (205) were retrospectively collected and blindly evaluated to assess the presence/absence of NPN. RESULTS: The frequency of occurrence of NPN was higher in the melanoma group (34.6%) than in Spitz nevus (28.8%), melanocytic nevus (18.2%), and dermatofibroma (11.3%) groups. An OR of 1.8 emerged for the diagnosis of melanoma in the presence of NPN as compared with nonmelanoma diagnosis. Conversely, for melanocytic nevi and dermatofibromas the OR was very low (0.5 and 0.3, respectively). For Spitz nevi the OR of 1.1 was not statistically significant. When comparing melanoma with dermatofibroma, melanocytic nevus, and Spitz nevus, we observed a significantly higher frequency of multicomponent pattern (68.1%), asymmetric pigmentation (92.9%), irregularly distributed NPN (87.3%), and peripheral location of NPN (66.2%) in melanomas. LIMITATIONS: Further studies can provide the precise dermoscopic-histopathologic correlation of NPN in melanoma and other lesions. CONCLUSIONS: The overall morphologic pattern of NPN, such as the irregular distribution and the peripheral location of NPN, along with the multicomponent pattern and the asymmetric pigmentation could be used as additional features in distinguishing melanoma from Spitz nevus and other benign lesions.

Objective melanoma progression.

BACKGROUND/PURPOSE: Many aspects of the natural history of malignant melanoma (MM) are still unclear, specifically its appearance at onset and particularly how it changes in time. The purpose of our study was to retrospectively determine objective changes in melanoma over a 3-24-month observation period. MATERIALS AND METHODS: Our study was carried out in two Italian dermatology centers. Digital dermoscopy analyzers (DB-Mips System) were used to retrospectively evaluate dermoscopic images of 59 MM (with no initial clinical aspects suggesting melanoma) under observation for 3-24 months. The analyzer evaluates 49 parameters grouped into four categories: geometries, colors, textures and islands of color. Multivariate analysis of variance for repeated measures was used to evaluate the statistical significance of the changes in the digital dermoscopy variables of melanomas. RESULTS: Within-lesion analysis indicated that melanomas increased in dimension (Area, Minimum, and Maximum Diameter), manifested greater disorganization of the internal components (Red, Green and Blue Multicomponent, Contrast, and Entropy) and increased in clusters of milky pink color (Light Red Area). CONCLUSION: Analysis of the parameters of our model and statistical analysis enabled us to interpret/identify the most significant factors of melanoma modification, providing quantitative insights into the natural history of this cutaneous malignancy.

Objective follow-up of atypical melanocytic skin lesions: a retrospective study.

Various authors have suggested that information from longitudinal observation (follow-up) of dynamic changes in atypical melanocytic pigmented skin lesions (MPSL) could enable identification of early malignant melanoma escaping initial observation due to an absence of specific clinical and dermoscopic features. The aim of our retrospective study was to determine the existence of numerical variables regarding changes in MPSL that could be useful to differentiate early melanomas and atypical nevi. The study was carried out in two Italian dermatology Centres. Digital dermoscopy analyzers (DB-Mips System) were used to evaluate dermoscopic images of 94 equivocal pigmented skin lesions under observation for 6-12 months and then excised because of changes across time (29 melanomas and 65 nevi). The analyzer evaluates 49 parameters grouped into four categories: geometries, colours, textures and islands of colour. The ROC curve designed on the 49 digital dermoscopy analysis parameters showed good accuracy. At sensitivity (SE) = specificity (SP), it correctly classified 89.3% of cases. When objective pigmented skin lesion parameters were considered together with their objective changes over 6-12 months, a decisive increase in discrimination capacity was obtained. At SE = SP accuracy was 96.3%. Analysis of the parameters of our model and statistical analysis enabled us to interpret/identify the most significant factors of modification and differentiation of lesions, providing quantitative insights into the diagnosis of equivocal MPSL and demonstrating the utility of objective/numerical follow-up.

Role of the EGF +61A>G polymorphism in melanoma pathogenesis: an experience on a large series of Italian cases and controls.

BACKGROUND: A single nucleotide polymorphism (61A>G) in the epidermal growth factor (EGF) gene has been implicated in both melanoma pathogenesis and increased melanoma risk. To further evaluate this association, we conducted a case-control study in a clinic-based Italian population. METHODS: Individuals with less than 10 (N = 127) or more than 100 (N = 128) benign nevi, and patients with cutaneous melanoma (N = 418) were investigated for the EGF +61A>G polymorphism, using an automated sequencing approach. RESULTS: Overall, no difference in EGF genotype frequencies was observed among subjects with different number of nevi as well as when non-melanoma healthy controls were compared with the melanoma patients. However, a heterogeneous distribution of the frequencies of the G/G genotype was detected among cases and controls originating from North Italy (21.1 and 18.3%, respectively) vs. those from South Italy (12.6 and 17.1%, respectively). CONCLUSION: Our findings further suggest that EGF +61A>G polymorphism may have a limited impact on predisposition and/or pathogenesis of melanoma and its prevalence may vary in different populations.

CDKN2A and MC1R analysis in amelanotic and pigmented melanoma.

Amelanotic melanoma (AM) is a rare subtype of melanoma with little or no clinically visible pigment; it is more difficult to diagnose than pigmented melanoma (PM), and has a worse prognosis. In the attempt to find a genetic explanation for the distinction between AM and PM, we conducted a case-case study, matching AM and PM patients, and testing them for germline mutations in high- (p16INK4A, p14ARF, CDK4) and low-penetrance (MC1R) melanoma susceptibility genes. Similar CDKN2A mutations were found in both sets of melanomas. A p14ARF splice germline mutation was detected for the first time in an Italian family with AM. This rare mutation, which has been described only once previously, may be involved in predisposition to the amelanotic phenotype in combination with germline MC1R variants and coordinate somatic expression of pigmentation genes and their regulators.

Dermoscopic evaluation of amelanotic and hypomelanotic melanoma.

OBJECTIVE: To determine the predictive dermoscopic features of amelanotic and hypomelanotic melanoma. DESIGN: A total of 105 melanomas (median Breslow thickness, 0.76 mm), 170 benign melanocytic lesions, and 222 nonmelanocytic lesions lacking significant pigment (amelanotic, partially pigmented, and light colored) were imaged using glass-plate dermoscopy devices and scored for 99 dermoscopic features. Diagnostic models were derived from and tested on independent randomly selected lesions. SETTING: Predominantly hospital-based clinics from 5 continents. MAIN OUTCOME MEASURES: Sensitivity, specificity, and odds ratios for individual features and models for the diagnosis of melanoma and malignancy. RESULTS: The most significant negative predictors of melanoma were having multiple (>3) milialike cysts (odds ratio, 0.09; 95% confidence interval, 0.01-0.64), comma vessels with a regular distribution (0.10; 0.01-0.70), comma vessels as the predominant vessel type (0.16; 0.05-0.52), symmetrical pigmentation pattern (0.18; 0.09-0.39), irregular blue-gray globules (0.20; 0.05-0.87), and multiple blue-gray globules (0.28; 0.10-0.81). The most significant positive predictors were having a blue-white veil (odds ratio,13; 95% confidence interval, 3.9-40.0), scarlike depigmentation (4.4; 2.4-8.0), multiple blue-gray dots (3.5; 1.9-6.4), irregularly shaped depigmentation (3.3; 2.0-5.3), irregular brown dots/globules (3.2; 1.8-5.6), 5 to 6 colors (3.2; 1.6-6.3), and predominant central vessels (3.1; 1.6-6.0). A simple model distinguishing melanomas from all nonmelanomas had a sensitivity of 70% and a specificity of 56% in the test set. A model distinguishing all malignant lesions from benign lesions had a sensitivity of 96% and a specificity of 37%. Conclusion Although the diagnostic accuracy of dermoscopy for melanoma lacking significant pigment is inferior to that of more pigmented lesions, features distinguishing the former from benign lesions can be visualized on dermoscopic evaluation.

Clinical and dermoscopic criteria related to melanoma sentinel lymph node positivity.

BACKGROUND: The early detection of lymph node metastases may have important prognostic and therapeutic implications in melanoma patients. The purpose of this study was to investigate whether specific clinical and/or dermoscopic features could be "in vivo" predictors of sentinel lymph node (SLN) positivity in melanomas >1 mm thick. MATERIALS AND METHODS: Five Italian centres (Istituto Dermopatico dell'Immacolata, IDI, Rome; Skin Cancer Unit, Oncologia Dermatologica, CPO, Ravenna; Istituto Europeo Oncologico, Milan; Centro di Riferimento Oncologico, Aviano; Istituto Nazionale Tumori, Naples) carried out a blind retrospective study on 508 melanomas observed from January 1994 to December 2002. The clinical and dermoscopic features of 78 melanomas >1 mm thick with the SLN biopsied were reviewed. RESULTS: The tumour palpability was the only factor correlated to SLN positivity in melanomas >1 mm thick. Palpability was found in 46.2% of nodal positive melanomas and in 18.5% of nodal negative melanomas (p=0.03). The patients with palpable melanomas showed a higher risk of nodal metastasis (OR=3.8). Dermoscopy failed to recognize predictive criteria for SLN positivity. Some clinical and dermoscopic features, although not statistically significant, showed interesting differences between nodal-negative and nodal-positive melanomas. CONCLUSION: Melanoma palpability may suggest the presence of nodal metastasis in >1 mm thick tumours.

Sensitivity, specificity, and diagnostic accuracy of three dermoscopic algorithmic methods in the diagnosis of doubtful melanocytic lesions: the importance of light brown structureless areas in differentiating atypical melanocytic nevi from thin melanomas.

BACKGROUND: Over the past decade numerous epiluminescence microscopy (ELM) criteria and algorithmic methods have been developed to improve the diagnosis of cutaneous melanocytic lesions. OBJECTIVE: Our purpose was to compare the sensitivity, specificity, and diagnostic accuracy of 3 algorithmic methods (pattern analysis, ABCD rule of dermoscopy, and the 7-point checklist) on a series of highly atypical melanocytic lesions. We also determined the diagnostic value of distinct ELM structures by evaluating their frequency in these lesions. METHODS: A total of 198 consecutive atypical macular melanocytic lesions were studied. ELM assessment was based on the presence or absence of 23 dermoscopic features. Two ELM-experienced dermatologists classified each lesion as benign or malignant using the pattern analysis, the ABCD rule of dermoscopy, and the 7-point checklist method. After surgical excision, 102 lesions were histologically diagnosed as Clark's nevi and 96 as thin melanomas (TMs) (mean tumor thickness, 0.3 mm). ELM and histologic diagnoses were then compared to assess the sensitivity, specificity, and diagnostic accuracy as well as positive and negative predictive values (PPV and NPV, respectively) for TMs of the 3 algorithmic methods. Univariate and multivariate analyses were performed to determine which ELM criteria were most strongly associated with TM. RESULTS: Of the melanocytic lesions studied, 82.3% were correctly diagnosed by using pattern analysis (85.4% sensitivity, 79.4% specificity, 79.6% PPV, and 70.8% diagnostic accuracy), compared with correct diagnosis of 79.3% (84.4% sensitivity, 74.5% specificity, 75.7% PPV, and 67.8% diagnostic accuracy) and 71.2% (78.1% sensitivity, 64.7% specificity, 67.6% PPV, and 57.7% diagnostic accuracy) with the ABCD and the 7-point checklist methods, respectively. The 7-point checklist yielded the highest number of false-negative results (21.8%) with respect to the ABCD rule (15.6%) and pattern analysis (14.6%). Univariate analysis showed that an atypical pigment network, a pigment network with sharp margins, irregular nonuniform brown globules, a nonuniform pigment distribution, homogeneous areas, and light brown structureless areas were the most sensitive and specific ELM features for TM. A backward stepwise logistic regression analysis revealed that the criterion with the strongest TM association was light brown structureless areas (odds ratio = 27.9; 95% confidence interval, 8.6-90.9). LIMITATIONS: The presence and value of light brown structureless areas should also be investigated in clinically nonatypical macular melanocytic lesions. CONCLUSION: The pattern analysis method showed the highest sensitivity, specificity, and diagnostic accuracy for TM. Light brown structureless areas were both a statistically significant discriminator and the most reliable predictor of TM (PPV = 93.8%, positive likelihood ratio = 16). Therefore the use of this previously underestimated ELM criterion may not only improve diagnostic performance of equivocal macular melanocytic lesions but also significantly decrease the rate of false-negative results obtained with the 7-point checklist method.