Melanoma in children and adolescents: analysis of susceptibility genes in 123 Italian patients.

BACKGROUND: A polygenic inheritance involving high, medium and low penetrance genes has been suggested for melanoma susceptibility in adults, but genetic information is scarce for paediatric patients. OBJECTIVE: We aim to analyse the major high and intermediate melanoma risk genes, CDKN2A, CDK4, POT1, MITF and MC1R, in a large multicentre cohort of Italian children and adolescents in order to explore the genetic context of paediatric melanoma and to reveal potential differences in heritability between children and adolescents. METHODS: One-hundred-twenty-three patients (<21 years) from nine Italian centres were analysed for the CDKN2A, CDK4, POT1, MITF, and MC1R melanoma predisposing genes. The rate of gene variants was compared between sporadic, familial and multiple melanoma patients and between children and adolescents, and their association with clinico-pathological characteristics was evaluated. RESULTS: Most patients carried MC1R variants (67%), while CDKN2A pathogenic variants were found in 9% of the cases, the MITF E318K in 2% of patients and none carried CDK4 or the POT1 S270N pathogenic variant. Sporadic melanoma patients significantly differed from familial and multiple cases for the young age at diagnosis, infrequent red hair colour, low number of nevi, low frequency of CDKN2A pathogenic variants and of the MC1R R160W variant. Melanoma in children (≤12 years) had more frequently spitzoid histotype, were located on the head/neck and upper limbs and had higher Breslow thickness. The MC1R V92M variant was more common in children than in adolescents. CDKN2A common polymorphisms and MC1R variants were associated with a high number of nevi. CONCLUSION: Our results confirm the scarce involvement of the major high-risk susceptibility genes in paediatric melanoma and suggest the implication of MC1R gene variants especially in the children population.

The prognostic impact of the extent of ulceration in patients with clinical stage I-II melanoma: a multicentre study of the Italian Melanoma Intergroup (IMI).

BACKGROUND: The presence of ulceration has been recognized as an adverse prognostic factor in primary cutaneous melanoma (PCM). OBJECTIVES: To investigate whether the extent of ulceration (EoU) predicts relapse-free survival (RFS) and overall survival (OS) in PCM. MATERIALS AND METHODS: We retrieved data for 477 patients with ulcerated PCM from databases of the Italian Melanoma Intergroup. Univariate and multivariable Cox proportional hazard models were used to assess the independent prognostic impact of EoU. RESULTS: A significant interaction emerged between Breslow thickness (BT) and EoU, considering both RFS (P < 0·0001) and OS (P = 0·0006). At multivariable analysis, a significant negative impact of EoU on RFS [hazard ratio (HR) (1-mm increase) 1·26, 95% confidence interval (CI) 1·08-1·48, P = 0·0047] and OS [HR (1-mm increase) 1·25, 95% CI 1·05-1·48, P = 0·0120] was found in patients with BT ≤ 2 mm, after adjusting for BT, age, tumour-infiltrating lymphocytes, sentinel lymph node status and mitotic rate. No impact of EoU was found in patients with 2·01-4 mm and > 4 mm BT. CONCLUSIONS: This study demonstrates that EoU has an independent prognostic impact in PCM and should be recorded as a required element in pathology reports.

Favourable prognostic role of histological regression in stage III positive sentinel lymph node melanoma patients.

BACKGROUND: Sentinel lymph node (SLN)-positive melanoma patients are a heterogeneous group of patients with survival rates ranging from ∼20 to over 80%. No data are reported concerning the role of histological regression on survival in stage III melanoma. METHODS: The study included 365 patients with positive SLN from two distinct hospitals. The model was developed on patients from 'AOU Città della Salute e della Scienza di Torino', and externally validated on patients from IRCCS of Candiolo. Survival analyses were carried out according to the presence of regression and adjusted for all other prognostic factors. RESULTS: Among patients followed at 'AOU Città della Salute e della Scienza di Torino' (n=264), the median follow-up time to death or censoring (whatever two events occurred earlier) was 2.7 years since diagnosis (interquartile range: 1.3-5.8). In all, 79 patients died from melanoma and 11 from other causes. Histological regression (n=43) was associated with a better prognosis (sub-HR=0.34, CI 0.12-0.92), whereas the other factors above showed an inverse association. In the external validation, the concordance index was 0.97 at 1 year and decreased to 0.66 at 3 years and to 0.59 at 5 years. Adding histological regression in the prognostic model increased the discriminative ability to 0.75 at 3 years and to 0.62 at 5 years. Finally, using a cutoff of 20% for the risk of death led to a net re-classification improvement of 15 and 11% at 3 and 5 years after diagnosis, respectively. CONCLUSIONS: Histological regression could lead to an improvement in prognostic prediction in patients with stage III-positive SLN melanoma.

Three-year follow-up of advanced melanoma patients who received ipilimumab plus fotemustine in the Italian Network for Tumor Biotherapy (NIBIT)-M1 phase II study.

BACKGROUND: In the NIBIT-M1 study, we reported a promising activity of ipilimumab combined with fotemustine in metastatic melanoma (MM) patients with or without brain metastases. To corroborate these initial findings, we now investigated the long-term efficacy of this combination. PATIENTS AND METHODS: This analysis captured the 3-year outcome of MM patients who received ipilimumab combined with fotemustine as first- or second-line treatment. Median overall survival (OS), 3-year survival rates, immune-related (ir) progression-free survival (irPFS), brain PFS, and ir duration of response (irDOR) for the entire population and for patients with brain metastases were assessed. Clinical results were correlated with circulating CD3(+)CD4(+)ICOS(+)CD45RO(+) or CD45RA(+) T cells, neutrophil/lymphocyte (N/L) ratios, and tumorBRAF-V600 mutational status. RESULTS: Eighty-six MM patients, including 20 with asymptomatic brain metastases that had been pre-treated with radiotherapy in 7 subjects, were enrolled in the study. With a median follow-up of 39.9 months, median OS and 3-year survival rates were 12.9 months [95% confidence interval (CI) 7.1-18.7 months] and 28.5% for the whole study population, and 12.7 months (95% CI 2.7-22.7 months) and 27.8% for patients with brain metastases, respectively. Long-term ir adverse events consisting of G1 rush and pruritus occurred in 21% of patients. The absolute increase from baseline to week 12 in 'memory' but not in 'naïve' T cells identified patients with a better survival (P = 0.002). The N/L ratio correlated with a significantly better survival at early time points. BRAF status did not correlate with clinical outcome. CONCLUSIONS: Long-term analysis of the NIBIT-M1 trial continues to demonstrate efficacy of ipilimumab combined with fotemustine in MM patients. Fotemustine does not seem to impair the immunologic activity of ipilimumab. EUDRACT NUMBER: 2010-019356-50. CINICALTRIALSGOV: NCT01654692.

Differences in clinicopathological features and distribution of risk factors in Italian melanoma patients.

BACKGROUND: No studies are available in the literature on the distribution of different melanoma features and risk factors in the Italian geographical areas. OBJECTIVE: To identify the differences in clinical-pathological features of melanoma, the distribution of risk factors and sun exposure in various Italian macro-areas. METHODS: Multicentric-observational study involving 1,472 melanoma cases (713 north, 345 centre, 414 south) from 26 referral centres belonging to the Italian Multidisciplinary Group for Melanoma. RESULTS: Melanoma patients in northern regions are younger, with thinner melanoma, multiple primaries, lower-intermediate phototype and higher counts of naevi with respect to southern patients; detection of a primary was mostly connected with a physician examination, while relatives were more involved in the south. Northern patients reported a more frequent use of sunbeds and occurrence of sunburns before melanoma despite sunscreen use and a lower sun exposure during the central hours of the day. CONCLUSIONS: The understanding of differences in risk factors distribution could represent the basis for tailored prevention programmes.

The number of excised lymph nodes is associated with survival of melanoma patients with lymph node metastasis.

BACKGROUND: Although the number of excised LNs has been associated with patient prognosis in many solid tumors, this association has not been widely investigated in cutaneous melanoma. This study aims to evaluate the association between the number of excised regional lymph nodes (LNs) and melanoma-specific survival. PATIENT AND METHODS: Clinico-pathological data from 2507 patients with LN metastasis treated at nine Italian centers were retrospectively collected. RESULTS: The number of excised LNs correlated with younger age (P < 0.001), male sex (P < 0.001), neck LN field (P < 0.001), LN micrometastasis (P < 0.001) and number of positive LNs (P < 0.001). The number of excised LNs was an independent prognostic factor (HR = 0.85; P = 0.002) after adjustment for other staging features. Upon subgroup analysis, the number of excised LNs had a significant prognostic value in patients bearing 1.01-2.00 mm (HR = 0.79; P = 0.032) and 2.01-4.00 mm (HR = 0.71; P < 0.001) thick melanomas, primary tumors showing ulceration (HR = 0.86; P = 0.033) and Clark level V of invasion (HR = 0.86; P = 0.010), LN micrometastasis (HR = 0.83; P = 0.014) and two to three positive LNs (HR = 0.71; P = 0.001). Finally, this study investigated the influence of the number of excised LNs on patient staging: only when ≥11 nodes were excised the AJCC N stage could stratify prognosis (P < 0.001). Considering the number of excised LNs for each lymphatic field, at least 14, 11, 10 and 12 LNs were needed to stage patients according to the AJCC N stage after a lymphadenectomy of the neck, axilla, inguinal and ilioinguinal LN fields, respectively. CONCLUSIONS: The number of excised LNs can be considered for risk stratification of patients with regional LN metastasis from cutaneous melanoma. We demonstrated that a minimum number of LNs is required for the correct staging of patients. Further research is needed to evaluate the effectiveness of the minimum number of LNs to be dissected.

Acral lentiginous melanoma histotype predicts outcome in clinical stage I-II melanoma patients: an International multicenter study.

BACKGROUND: In the American Joint Committee on Cancer (AJCC) classification, acral lentiginous melanoma (ALM) histotype ALM is not included as an independent prognostic factor; in small series its negative prognostic impact on disease-free survival (DFS) and overall survival (OS) has been linked to the greater Breslow thickness (BT). PATIENTS AND METHODS: The study was carried out at four referral melanoma centers (three Italian and one Polish). Clinical consecutive patients with stage I-II melanoma, who were diagnosed, treated, and followed up between January 1998 and March 2018 in annotated specific databases were included. RESULTS: Overall, 6734 were evaluable, 4349 with superficial spreading melanoma (SSM), 2132 with nodular melanoma (NM), and 253 with ALM. At univariable analysis, a statistically significant worse DFS [hazard ratio (HR) 2.72, 95% confidence interval (CI) 2.24-3.30; P < 0.001] and OS (HR 2.67, 95% CI 2.15-3.32; P < 0.001) were found in patients with ALM compared with SSM. Similarly, the NM histotype was associated with a worse prognosis compared with the SSM histotype (DFS: HR 2.29, 95% CI 2.08-2.52; P < 0.001 and OS: HR 2.21, 95% CI 1.99-2.46; P < 0.001). At multivariable analysis, after adjusting for age, sex, BT, ulceration, and the sentinel lymph node status, a statistically significant worse DFS [adjusted HR (aHR; ALM versus SSM) 1.25, 95% CI 1.02-1.52; P = 0.028] was confirmed for patients with ALM. For patients with NM, instead, no impact of histology was found in terms of DFS [aHR (NM versus SSM) 1.04, 95% CI 0.93-1.15; P = 0.513] and OS [aHR (NM versus SSM) 0.96, 95% CI 0.86-1.08; P = 0.548]. CONCLUSIONS: ALM is associated with a worse long-term DFS. Our results could have important clinical implications for patients' stratification in future clinical trials and the incorporation of ALM histotype in the new AJCC classification as an independent prognostic factor.

Correction to: NFATc2 is an intrinsic regulator of melanoma dedifferentiation.

In Fig. 6e, the authors noticed that wrong blots for MITF, MART-1 expression/modulation, and for ß-actin were presented, due to the similarity with experiments shown in Figure 5c. Correct MITF, MART-1, and ß-actin blots were added to the revised Fig. 6 shown in the associated Correction. The meaning of the results shown in Fig.6e, as well as the conclusions of this paper were not affected, and the authors regret for this error. These errors have not been fixed in the original Article.

Efficacy and safety of single-agent pan-human epidermal growth factor receptor (HER) inhibitor dacomitinib in locally advanced unresectable or metastatic skin squamous cell cancer.

BACKGROUND: In recurrent or metastatic (R/M) skin squamous cell cancer (sSCC) not amenable to radiotherapy (RT) or surgery, chemotherapy (CT) has a palliative intent and limited clinical responses. The role of oral pan-HER inhibitor dacomitinib in this setting was investigated within a clinical trial. METHODS: Patients with diagnosis of R/M sSCC were treated. Dacomitinib was started at a dose of 30 mg daily (QD) for 15 d, followed by 45 mg QD. Primary end-point was response rate (RR). Tumour samples were analysed through next-generation sequencing using a custom panel targeting 36 genes associated with sSCC. RESULTS: Forty-two patients (33 men; median age 77 years) were treated. Most (86%) received previous treatments consisting in surgery (86%), RT (50%) and CT (14%). RR was 28% (2% complete response; 26% partial response), disease control rate was 86%. Median progression-free survival and overall survival were 6 and 11 months, respectively. Most patients (93%) experienced at least one adverse event (AE): diarrhoea, skin rash (71% each), fatigue (36%) and mucositis (31%); AEs grade 3-4 occurred in 36% of pts. In 16% of cases, treatment was discontinued because of drug-related toxicity. TP53, NOTCH1/2, KMT2C/D, FAT1 and HER4 were the most frequently mutated genes. BRAF, NRAS and HRAS mutations were more frequent in non-responders, and KMT2C and CASP8 mutations were restricted to this subgroup. CONCLUSIONS: In sSCC, dacomitinib showed activity similar to what was observed with anti-epidermal growth factor receptor agents, and durable clinical benefit was observed. Safety profile was comparable to previous experiences in other cancers. Molecular pt selection could improve therapeutic ratio.

Prognostic factors in Merkel cell carcinoma patients undergoing sentinel node biopsy.

INTRODUCTION: Debate remains about prognostic factors in primary Merkel cell carcinoma (MCC). We investigated clinicopathological factors as determinants of survival in patients with MCC submitted to sentinel node biopsy. METHODS: Sixty-four consecutive patients treated for a primary MCC were identified from a prospectively maintained database at Fondazione IRCCS Istituto Nazionale dei Tumori, Milan. Time to events outcome were described by product limit estimators and proportional hazards model was used to investigate the association between outcome and potential predictors. RESULTS: The most common site of primary tumor was lower limbs (56.3%). The size of primary lesion was ≤2 cm in 67.2% of cases. Presence of residual disease after the diagnostic surgical excision was observed in 28% of cases. All patients received sentinel node biopsy (SNB) and a SN positivity was detected in 26.6%. The median follow up was 78 months. Disease recurrence occurred in 17 patients (26.6%). In the SN negative group 10 recurrences occurred (21.3%), whereas 7 (41.2%) were found in SN positive one. Nine patients SN negative (19.1%) died of disease and 3 (17.6%) among SN positive. SN status was not associated with survival (p = 0.78). Neither age, gender, size and site of primary tumor resulted predictors of patients' outcome. The presence of residual tumor in the specimen of the wide local excision, after the diagnostic surgical excision, was the only variable associated with survival (p = 0.03). CONCLUSIONS: Presence of residual tumor in the specimen of the wide local excision is the main prognostic factor in MCC patients.

NFATc2 is an intrinsic regulator of melanoma dedifferentiation.

Melanoma dedifferentiation, characterized by the loss of MITF and MITF regulated genes and by upregulation of stemness markers as CD271, is implicated in resistance to chemotherapy, target therapy and immunotherapy. The identification of intrinsic mechanisms fostering melanoma dedifferentiation may provide actionable therapeutic targets to improve current treatments. Here, we identify NFATc2 transcription factor as an intrinsic regulator of human melanoma dedifferentiation. In panels of melanoma cell lines, NFATc2 expression correlated inversely with MITF at both mRNA and protein levels. NFATc2(+/Hi) melanoma cell lines were CD271(+) and deficient for expression of melanocyte differentiation antigens (MDAs) MART-1, gp100, tyrosinase and of GPNMB, PGC1-α and Rab27a, all regulated by MITF. Targeting of NFATc2 by small interfering RNA, short hairpin RNA and by an NFATc2 inhibitor upregulated MITF, MDAs, GPNMB, PGC-1α, tyrosinase activity and pigmentation and suppressed CD271. Mechanistically, we found that NFATc2 controls melanoma dedifferentiation by inducing expression in neoplastic cells of membrane-bound tumor necrosis factor-α (mTNF-α) and that melanoma-expressed TNF-α regulates a c-myc-Brn2 axis. Specifically, NFATc2, mTNF-α and expression of TNF receptors were significantly correlated in panels of cell lines. NFATc2 silencing suppressed TNF-α expression, and neutralization of melanoma-expressed TNF-α promoted melanoma differentiation. Moreover, silencing of NFATc2 and TNF-α neutralization downmodulated c-myc and POU3F2/Brn2. Brn2 was strongly expressed in NFATc2(+/Hi) MITF(Lo) cell lines and its silencing upregulated MITF. Targeting of c-myc, by silencing or by a c-myc inhibitor, suppressed Brn2 and upregulated MITF and MART-1 in melanoma cells. The relevance of NFATc2-dependent melanoma dedifferentiation for immune escape was shown by cytolytic T-cell assays. NFATc2(Hi) MITF(Lo) MDA(Lo) HLA-A2.1(+) melanoma cells were poorly recognized by MDA-specific and HLA-A2-restricted CTL lines, but NFATc2 targeting significantly increased CTL-mediated tumor recognition. Taken together, these results suggest that the expression of NFATc2 promotes melanoma dedifferentiation and immune escape.

Small melanomas: a clinical study on 270 consecutive cases of cutaneous melanoma.

The ABCD (asymmetry, border, colour, dimension) criteria represent a commonly used clinical guide for the diagnosis of early cutaneous melanoma (CM). This guide stipulates that CMs usually are more than 6 mm in diameter. The purpose of this retrospective study was to establish the frequency of occurrence of small (< or =6 mm) melanomas in a clinical context. Our series consisted of 270 consecutive CMs (39 in situ and 231 invasive) in 267 patients. Of these 270 lesions, 47 (17%) were small lesions, ranging from 2 to 6 mm in maximum linear extent, with a median value of 5 mm. Of these small lesions, 14 were in situ and 33 Invasive CMs. The median thickness of the 33 small invasive lesions was 0.31 mm. The clinical features of CMs were sufficiently distinctive to suggest a diagnosis of CM in half of the cases, irrespective of the invasiveness or not of the lesions. Dermatoscopy was performed on 36 of the small lesions and achieved a correct diagnosis in 72% of the cases. The combination of simple visual examination with dermatoscopy allowed a higher rate of recognition (86%) than when the two methods were considered separately. Results of our study show that small CMs represent a considerable clinical subset of all CMs. Clinicians must be aware of this fact in their diagnostic activity.

Clinical and dermatoscopic diagnosis of early amelanotic melanoma.

Amelanotic cutaneous melanoma (ACM) often defies clinical diagnosis because of the lack of pigmentation. In an attempt to find diagnostic clues, we retrospectively studied the clinical features of 15 thin (< 1 mm thick or Clark level I) ACM lesions. The clinical features of early ACMs are identified and illustrated to enable early diagnosis and cure of these lesions. The typical early lesion presents as an asymmetric macula, which may be uniformly pinkish or reddish or, more often, has faint light pigmentation (tan, brown or grey) at the periphery; it has borders that may be well- or ill-defined. In our study, these features suggested the correct clinical diagnosis in only a minority (40%) of cases. Nine cases in this series were also subjected to dermatoscopy. By this technique we identified, as constant feature, the presence of small red dots, evenly distributed or grouped on a whitish or pink-red background. Our results show the importance of dermatoscopy in the evaluation of equivocal pink or reddish lesions. Red dots seen with this technique can be an important sign for the diagnosis of thin ACM. Since this sign does not appear to be pathognomonic, the presence of an associated pigmentary network can be decisive in the differential diagnosis.

World Health Organization experience in the treatment of melanoma.

The method of randomized trials, as performed by the WHO Melanoma Program, has definitely been a legitimate clinical study design in patients with melanoma from about 1970 to the end of the last century. Three important results of these WHO trials have substantially influenced the approach of the clinician towards melanoma: (1) There is no role for elective regional lymph node dissection, (2) narrow local excision of the primary melanoma does not entail additional risks, and (3) adjuvant treatment with chemotherapy or immunotherapy after radical surgery for regional lymph node metastases has not, until now, shown any substantial benefit. A problem arises because randomized clinical studies require long periods of time for patients accrual and completion. Frequently their legitimacy is challenged due to the appearance of new parameters, both regarding staging (eg, the introduction of new technical method such as sentinel node biopsy) and prognosis. Therefore, it would be better to define different clinical study models to quickly test a hypothesis on a small group of selected patients in order to provide quick results. We believe that this is the future of clinical research in the new millennium, because it does not seem reasonable today to plan large clinical trials that need 10 years or more of accrual and follow-up without reaching definite conclusions.

Impact of clinical trials on the treatment of melanoma.

Today the role of clinical trials is being challenged and it seems that this investigative tool does not keep in step with the rhythms imposed by the progress of scientific knowledge and the expectations of the public and media. From the 1970's to the 1990's, however, clinical trials have been the most important way for clinical researchers to find answers to therapeutic questions.

Melanoma of the external ear.

AIMS AND BACKGROUND: Melanoma of the external ear is a rare disease, and its management is controversial. To address this problem, we reviewed the data concerning the patients observed at our Institution. METHODS: We retrospectively reviewed the clinical records of the 20 patients bearing primary ear melanoma observed over a period of about 20 years at the Istituto Nazionale Tumori of Milan. RESULTS: Initial evaluation of the patients revealed 7 stage I, 12 stage II and 1 stage III. The thickness of the tumors varied from 0.39 to 6.62 mm. Fourteen patients underwent a wedge resection of the skin and cartilage with primary closure, and 6 patients had a partial amputation of the ear. In 8 cases the section was performed at about 1 cm from the border of the tumor, in 6 cases at about 0.5 cm, and in 6 cases at more than 1 cm. The average follow-up was 57 months (range, 1-18 years). Since there was no local recurrence, it could not be related to type and extent of the local resection performed. In contrast, the development of metastases was related to tumor thickness. CONCLUSIONS: A conservative excision with margins of 1 cm can be a safe procedure for invasive ear melanoma, irrespective of tumor thickness. Like melanomas of other sites, the prognosis is linked to the thickness of the tumor.

[Impact of sentinel lymph node biopsy on the treatment of melanoma]. / Impatto della biopsia del linfonodo sentinella sul trattamento del melanoma.

In the National Cancer Institute and S Pio X Hospital series we registered 981 patients with primary cutaneous melanoma and no evidence of clinically detectable regional node metastases underwent sentinel node (SN) dissection to microscopically define the tumor status of the regional lymph nodes. In 62.2% of cases, only one SN was detected; 26.4% of patients had two SNs and 11.4% had three or more SNs. A positive SNB was demonstrated in 18.1%. Analysis of survival indicated that the tumor status of the nodes was the most important prognostic factor. Breslow's thickness had a significant impact on survival in tumors of 4 mm or thicker, and ulceration dropped to a borderline significant P-value. To assess the tumor burden in positive SNB, all slides (148 SN pos) were reviewed. Twenty per cent of these patients had evidence of metastasis in other nodes. Of the remaining 80% with a single tumor-involved SN, 62% had a single metastatic deposit. Preliminary data from this study indicate that several subgroups may be identified among patients with 1 positive node, but adequate analysis of survival requires a larger number of patients and a multicentric study.

The ABCD system of melanoma detection: a spectrophotometric analysis of the Asymmetry, Border, Color, and Dimension.

BACKGROUND: The ABCD (Asymmetry, Border, Color, and Dimension) criteria represent a commonly used clinical guide for the diagnosis of early melanoma. The authors revised these criteria in the light of objective measurements of the features of pigmented skin lesions obtained by telespectrophotometric analysis (TS) in the visible and near-infrared wavelengths. METHODS: This study involves a consecutive series of 186 patients with 195 cutaneous pigmented lesions (53 melanomas and 142 nonmelanoma lesions). Each lesion was subjected to TS in vivo, before surgery. For this purpose, the authors used four spectrophotometric parameters that could be closely related to the four criteria of the ABCD guide, namely, roundness (an estimate of how a lesion contour resembles a circle), smoothness (an indicator of the regularity of a lesion border), mean reflectance (the ability of a lesion to diffuse or reflect the incident light), and size (the greatest dimension of a lesion). RESULTS: When melanomas and nonmelanoma lesions were compared by univariate analysis, all four spectrophotometric parameters considered proved to be significantly different (P=0.05). Multivariate logistic analysis showed that mean reflectance in the infrared (P < 0.01) and size (P=0.03) were parameters independently associated with melanoma. Melanoma showed lower reflectance and greater size than benign lesions. CONCLUSIONS: Information provided by TS substantially validates the importance of the ABCD clinical guide and suggests that color is the most important parameter in discriminating melanoma from nevi. In particular, melanoma appears darker than other pigmented lesions.

Self-detected cutaneous melanomas in Italian patients.

Self-detection of suspicious pigmented skin lesion combined with rapid referral to dermatologic centres is the key strategy in the fight against melanoma. The investigation of factors associated with pattern of detection of melanoma (self- vs. nonself-detection) may be useful to refine educational strategies for the future. We investigated the frequency of melanoma self-detection in a Mediterranean population at intermediate melanoma risk. A multicentric survey identified 816 consecutive cases of cutaneous melanoma in the period January to December 2001 in 11 Italian clinical centres belonging to the Italian Multidisciplinary Group on Melanoma. All patients filled a standardized questionnaire and were clinically examined by expert dermatologists. Self-detected melanomas were 40.6%, while the remaining lesions were detected by a dermatologist (18.5%), the family physician (15.2%), other specialists (5%), the spouse (12.5%), a friend or someone else (8.2%). Variables associated with self-detected melanomas were female sex, young age, absence of atypical nevi, knowledge of the ABCD rule, habit of performing skin self-examination. Self-detected melanomas did not differ from nonself-detected tumours in term of lesion thickness; however, patients with self-detected melanomas waited a longer period before having a diagnostic confirmation (patient's delay) (> 3 months: odds ratio, 3.89; 95% confidence interval, 2.74-5.53). In order to reduce the patients' delays, educational messages should adequately stress the need for a prompt referral to a physician once a suspicious pigmented lesion is self-detected.