Cutaneous melanoma in children and adolescents: the Italian rare tumors in pediatric age project experience.

OBJECTIVE: To describe a series of cutaneous melanoma in children collected by the Italian Rare Tumors in Pediatric Age project. STUDY DESIGN: From 2000 to 2012, 54 patients younger than 18 years of age were prospectively registered and treated at 12 Italian pediatric centers on the basis of the same diagnostic/therapeutic recommendations and with the same forms to record clinical data. RESULTS: Considering the estimated annual incidence in Italy, the registered cases accounted for 30% of those expected in children and 10% of adolescents. Clinically, 47% of the tumors were amelanotic and 81% were raised, 39% of cases had tumor thickness >2 mm, and 36% had lymph node involvement. For the whole series, 5-year event-free survival and overall survival rates were 75.2% and 84.6%, respectively. Patient survival correlated with tumor stage and ulceration. No relapses were recorded for T1-2 (thickness <2 mm), N0, and stage 0-I-II cases. CONCLUSION: We suggest that the variables influencing survival in children with melanoma are the same as for adults, the clinical approach used in adults is feasible in children, and pediatric cases are more likely to have advanced disease at diagnosis but similar survival. New effective drugs are needed for advanced disease, and biological studies and international cooperative schemes are warranted.

Can gemcitabine instillation ablate solitary low-risk non-muscle-invasive bladder cancer? Results of a phase II marker lesion study.

PURPOSE: The purpose of this phase II study was to evaluate whether low-risk non-muscle-invasive bladder cancer can be ablated with intravesical gemcitabine in a marker lesion study. PATIENTS AND METHODS: The study had a Simon II-stage design. Thirteen patients were to be recruited for stage I. In the event of ≥4 responses, another 30 patients were to be recruited. Patients were given gemcitabine 2,000 mg intravesically once per week for 6 weeks and the response was assessed with endoscopic, histological, and urine cytological findings. RESULTS: Fourteen patients evaluated for efficacy completed the study; complete responses were achieved by 2 patients (14.3%), both of these patients had lesions of <1 cm. Eleven patients (78.6%) were non-responders and 1 patient (7.1%) had progressive disease. Since the response rate in stage I was below the minimal pre-defined limit, the study was stopped. CONCLUSIONS: This study shows that intravesical gemcitabine does not merit further study in this patient population. A tumor size of >1 cm may be a critical factor in accounting for the low response rate.

Small nodular melanoma: the beginning of a life-threatening lesion. A clinical study on 11 cases.

AIMS AND BACKGROUND: Because of its high thickness, nodular melanoma often bears a poor prognosis. Thus, an earlier diagnosis of this type of lesion while it is still thin would be an important step in secondary prevention. The principal aim of the present study was to better define the initial clinical features of nodular melanoma to allow an early diagnosis. A secondary aim was to establish the prognosis of this type of lesion. METHODS: We retrospectively studied and illustrated the clinical features of 11 small (< or = 6 mm maximum diameter) cutaneous nodular melanomas seen and treated during a 10-year period. Prognostic characteristics of the various lesions were also described. RESULTS: The results of the study help to describe a small nodular melanoma as a dark and/or pink/red raised lesion, which may be evenly or unevenly colored, with well-defined borders, that often appears de novo. A correct clinical diagnosis was made in 7 of the cases. During a median follow-up of 6 years, none of the patients had local or distant relapses. CONCLUSIONS: Detection of small nodular melanoma is feasible by accurate visual inspection, provided that physicians are aware of this type of lesion and maintain the index of suspicion at a high level to bring about curative surgery.

Immunohistochemical expression of somatostatin receptor subtypes in prostate tissue from cystoprostatectomies with incidental prostate cancer.

OBJECTIVE: To examine immunohistochemically the expression of the five somatostatin receptors (SSTRs) in cystoprostatectomies (CyPs) with incidental prostate cancer. MATERIALS AND METHODS: The five SSTRs (SSTR1-5) were evaluated in 'normal-looking' epithelium (NEp), high-grade prostatic intraepithelial neoplasia (HGPIN) and pT2a Gleason score 6 adenocarcinoma in 20 CyP specimens with incidental prostate cancer and 20 radical prostatectomy (RP) specimens with clinically detected prostate cancer. RESULTS: For cytoplasm expression, the mean percentage of positive secretory cells with strong cytoplasmic staining increased from NEp to HGPIN and prostate cancer, being slightly lower in the CyP than in the RP specimens. Both in the CyP and RP specimens SSTR4 was found in the highest percentage of cells. There was membrane staining in the secretory cells for SSTR3 and SSTR4. There was nuclear staining in the secretory cells for SSTR4 and SSTR5. For SSTR1 and SSTR3 the mean proportions of positive basal cells were higher than for the other three subtypes, and greater in NEp than in HGPIN. There were positive smooth muscle and endothelial cells for all five SSTR subtypes, the highest proportions being SSTR1 and the lowest SSTR5. CONCLUSIONS: This immunohistochemical study expands our knowledge of the expression and localization of SSTRs in the various tissue components in the prostate with incidental cancer, compared with clinically detected cancer. Such information might be useful in developing further non-invasive strategies for the prevention and treatment of pre-neoplastic and neoplastic lesions of the prostate.

In vivo characterization of melanin in melanocytic lesions: spectroscopic study on 1671 pigmented skin lesions.

The purpose of this study is to determine the role of melanin in the various steps of progression of melanocytic neoplasia. To this aim, we perform a retrospective analysis on 1671 multispectral images of in vivo pigmented skin lesions previously recruited in the framework of a study focused on the computer-assisted diagnosis of melanoma. The series included 288 melanomas in different phases of progression, i.e., in situ, horizontal and vertical growth phase invasive melanomas, 424 dysplastic nevi, and other 957 melanocytic lesions. Analysis of the absorbance spectra in the different groups shows that the levels of eumelanin and pheomelanin increase and decrease, respectively, from dysplastic nevi to invasive melanomas. In both cases, the trend of melanin levels is associated to the progression from dysplastic nevi to vertical growth phase melanomas, reflecting a possible hierarchy in the natural history of the early phases of the disease. Our results suggest that diffuse reflectance spectroscopy used to differentiate eumelanin and pheomelanin in in vivo lesions is a promising technique useful to develop better strategies for the characterization of various melanocytic lesions, for instance, by monitoring melanin in a time-lapse study of a lesion that was supposed to be benign.

Immunohistochemical detection and localization of somatostatin receptor subtypes in prostate tissue from patients with bladder outlet obstruction.

BACKGROUND AND AIM OF THE STUDY: Scant information on the cellular distribution of the five somatostatin receptor (SSTR) subtypes in the normal prostate and in neoplasms of the prostate has been reported in very few studies in which techniques, such as in situ hybridization histochemistry, autoradiography, and more recently immunohistochemistry, have been applied. The aim of the study was to examine immunohistochemically the distribution and localization of these 5 subtypes in the various tissue components in normal prostate. MATERIALS: The study was conducted in 14 surgical specimens of normal prostate tissue from adenomectomy specimens from patients with bladder outlet obstruction. The distribution and localization of the 5 somatostatin receptor (SSTR) subtypes was investigated with an immunohistochemical technique. Specificity of the antibodies against the 5 receptor subtypes was preliminarily investigated. RESULTS: Close to 90% of secretory cells showed a weak positivity in the cytoplasm, the proportion ranging from 86.3% (SSTR4) to 89.9% (SSTR5). Strong immunoreactivity was seen in a small proportion of cells, ranging from 0.8% (SSTR3) to 3.2% (SSTR1). For the subtypes 1 and 3 the greatest proportion of basal cells showed a moderate intensity (42.5 and 41.4%, respectively), strong immunoreactivity being observed only in 18.1 and 15.8% of cells, respectively. For the subtypes 2, 4 and 5, the majority of cells showed a weak intensity (72.3, 65.7 and 65.1%, respectively). Subtype 1 showed a strong immunoreactivity in the cytoplasm in 60% of the smooth muscle cells. With subtypes 2, 3 and 4 the greatest proportion of cells showed a weak intensity (63.4, 89.8 and 81.7%, respectively). With the subtype 5 the majority of cells (59.8%) were negative. Subtype 1 showed a strong immunoreactivity in the cytoplasm in 98.6% of the endothelial cells. With subtypes 3 and 4 the greatest proportion of cells showed a weak intensity (73.5 and 56.4%, respectively). With the subtype 2 and 5 the majority of cells were negative (59.1 and 50.7%, respectively).

Metamorphosis of melanoma. Trends in size and thickness of cutaneous melanoma over one decade at the Istituto Nazionale Tumori, Milan.

AIMS AND BACKGROUND: Messages about the description of the clinical features of cutaneous melanoma (CM) have remained unchanged since 1985, when the ABCD (Asymmetry, Border irregularity, Color variegation, Diameter >6 mm) rule for melanoma detection was formulated. Given the significant shift to the diagnosis of earlier-stage CMs over the past decades, it is reasonable to think that also the clinical aspects of the disease might have changed. The aim of this study was to examine trends in the presentation of CM over the last decade at our Institution, focusing on two characteristics of the disease: size and thickness. METHODS: A retrospective study was conducted including 1,603 primary invasive CMs seen and treated at the Unit for Melanoma Detection at our Institute between January 1997 and December 2006. RESULTS: The results showed a trend towards smaller CMs, with a difference of 3 mm in median size from the beginning to the end of the period. Detection of small (< or =6 mm) CMs increased at a rate of about 1.5% per year, with a current ratio of 25% with respect to all CMs. Thickness remained substantially unchanged over time. CONCLUSIONS: Physicians must be aware that the characteristics of melanoma have undergone a metamorphosis over the years and the ABCD signs cannot be relied on for adequate sensitivity to further the early detection of CM.

Bicalutamide 50 mg monotherapy in patients with isolated high-grade PIN: findings in repeat biopsies at 6 months.

OBJECTIVES: To evaluate morphological findings in repeat biopsies in patients with isolated high-grade prostatic intraepithelial neoplasia (HGPIN) after a 6-month course of bicalutamide (Casodex) 50 mg/day. METHODS: 20 consecutive patients with isolated HGPIN in prostate biopsies were treated for 6 months with bicalutamide 50 mg/day. After treatment, the patients were resubmitted to prostate biopsy mapping. The control group included 22 untreated consecutive patients with isolated high-grade PIN with repeat biopsies taken 6 months after the initial biopsies. RESULTS: In the initial biopsies of the treated group, HGPIN was monofocal in 12 patients and plurifocal in 8. In the repeat biopsies HGPIN was present in 2 patients, monofocal in both, whereas prostate adenocarcinoma (PCa) was discovered in one. In the control group, HGPIN was monofocal in 15 and plurifocal in 7. In the repeat biopsies HGPIN was present in six patients, being monofocal in three and plurifocal in the other three. PCa was present in one. CONCLUSIONS: There was a lower incidence of HGPIN (treated group vs control: 10% vs 27.2%) after 6 months of bicalutamide. Reduction in its extent was also observed (treated group vs control: monofocal 100% vs 50%). Treatment did not affect the incidence of cancer (treated vs control: 5% vs 4.5%).

In vivo evaluation of melanoma thickness by multispectral imaging and an artificial neural network. A retrospective study on 250 cases of cutaneous melanoma.

AIMS AND BACKGROUND: Noninvasive diagnostic methods such as dermoscopy, sonography, palpation or combined approaches have been developed in an attempt to preoperatively estimate melanoma thickness. However, the clinical presentation is often complex and the evaluation subjective. Multispectral image analysis of melanomas allows selection of features related to the content and distribution of absorbers, mainly melanin and hemoglobin, present within the lesion. Hence, it is reasonable to assume that the same features might be useful to predict melanoma thickness. METHODS: A multispectral image system was used to analyze in vivo 1939 pigmented skin lesions. The lesion selection was based on clinical and/or dermoscopic features that supported a suspicion for melanoma. All the lesions were then subjected to surgery for the histopathological diagnosis, and 250 were melanomas. From the multispectral images of the melanomas, we selected 12 features, seven of which were used to train and test an artificial neural network on 155 and 95 melanomas, respectively. RESULTS: Sensitivity (i.e., melanoma > or = 0.75 mm thick correctly classified) and specificity (i.e., melanoma < 0.75 mm thick correctly classified) evaluated from the receiving operating characteristic curves ranged from 76 to 90% and from 91 to 74%, respectively. CONCLUSIONS: Our approach provides results similar to those obtained with other methods and has the advantage that it is not related to the expertise of the clinician. In addition, the physical interpretation of the selected features suggests a possible role of spectrophotometry as an objective method to study the natural history of the early phases of the disease.

Histopathology reporting of prostate needle biopsies. 2005 update.

This report reviews the diagnostic and prognostic importance of the pathologic findings in prostate needle biopsies. The morphological findings of the needle biopsy may be placed into one of the following five categories: prostate cancer, atypical small acinar proliferation, high-grade prostatic intraepithelial neoplasia, inflammation, and benign prostatic tissue. While the prime goal of the biopsy is to diagnose prostatic adenocarcinoma, once carcinoma is detected, further descriptive information regarding the type, amount of cancer, and grade forms the cornerstone for contemporary management of the patient and for assessment of the potential for local cure and the risk for distant metastasis. The information provided in the needle biopsy report regarding the attributes of carcinoma is used depending on the individual patient's medical condition and preference and on the treating physician's evaluation to determine whether any form of treatment is indicated and, if so, the type of therapy.

Lack of terminally differentiated tumor-specific CD8+ T cells at tumor site in spite of antitumor immunity to self-antigens in human metastatic melanoma.

Activation of CTL-mediated antitumor immunity to self-epitopes expressed by neoplastic cells is thought to be prevented, at any stage of tumor progression, by tolerance mechanisms. In contrast, in 74 American Joint Committee on Cancer stages I-IV melanoma patients, we found that development of lymph node metastases is a key event triggering CD8(+) T-cell-mediated immunity to self-epitopes encoded by melanocyte differentiation antigens. This was shown by the increased peripheral precursor frequency to Melan-A/Mart-1, gp100, and tyrosinase epitopes in stage III and IV compared with stage I and II patients, and by accumulation of functional memory T cells directed to Melan-A/Mart-1(26-35) in tumor-invaded lymph nodes. However, in tumor-invaded lymph nodes of most patients, CD8(+) T cells directed to melanocyte differentiation antigens or to tumor-restricted antigens (MAGE-3 and NY-ESO-1 epitopes), showed a CCR7(+) CD45RA(+) CD27(+) CD28(+) perforin(-) "precursor" phenotype. Only in 7 of 23 cases antigen-specific CD8(+) T cells in invaded lymph nodes showed a predominant CCR7(-) CD45RA(-) CD27(+) CD28(-) perforin(+) "preterminally differentiated" phenotype. In the latter subset of patients, by immunohistochemistry in lymph node lesions, we found that CD8(+) T lymphocytes intermingling with the neoplastic tissue expressed a CCR7(-) CD45RO(+)/RA(-) phenotype, whereas CD4(+) lymphocytes did not infiltrate the tumor. Furthermore, perforin and granzyme B were expressed on a higher fraction of the CD8(+) cells surrounding the invading tumor compared with the lymphocytes infiltrating the neoplastic tissue. In addition, no evidence for tumor regression was found in such metastatic lesions, as documented by absence of neoplastic cell necrosis or apoptosis. These data indicate that neoplastic cells in the lymph nodes and/or increased tumor burden in metastatic disease activate CD8(+) T-cell-mediated antitumor immunity to self-epitopes. However, the paucity of terminally differentiated CD8(+) T cells at tumor site suggests that immunotherapy strategies may require not only the boosting of tumor immunity, but also effective means to promote CD8(+) T-cell differentiation in the neoplastic tissue.

Combined therapy with dabrafenib and trametinib in BRAF-mutated metastatic melanoma in a real-life setting: the INT Milan experience.

PURPOSE: Combination therapy with dabrafenib and trametinib is safer and more effective than BRAF inhibitor-based monotherapy for metastatic melanoma. METHODS: We retrospectively analyzed BRAF-mutated metastatic melanoma patients treated at our institution with daily oral dabrafenib 300 mg and trametinib 2 mg from November 2013 to April 2016. This clinical record included both untreated and previously treated stage IV melanomas. Physical examination and laboratory examinations were performed monthly and disease re-evaluations were performed every 3 months. RESULTS: A total of 48 patients (24 male, 24 female) with BRAF-mutated metastatic melanoma received dabrafenib and trametinib; median age was 48 years (range 23-75). Median follow-up was 362.5 days (range 72-879). Best overall response rate consisted of 6.2% (3 patients) complete response, 64.6% (31) partial response, and 25% (12) stable disease; median time to best response was 11 weeks (range 5.7-125.5). Progression of disease was seen in 19 patients (39.6%), with median time to progression (TTP) of 26 weeks (range 8-54). A total of 15 patients (31.2%) died due to progression of disease. Median progression-free survival and median overall survival were not reached. To date, 30 patients (62.5%) are still under treatment. A total of 27 (56.2%) patients had at least one adverse event (AE); grade 3-4 AEs were seen in 4 cases (8.3%). The main toxicities were fever (25%), skin rash (14.6%), arthralgias (10.4%), and aspartate aminotransferase/alanine aminotransferase increase (8.3%). Treatment dose was reduced in 7 subjects (14.6%), with only one case of discontinuation due to AE. CONCLUSIONS: Our data, using combined targeted therapy, are in line with the scientific literature in terms of both safety and effectiveness in a real-life setting.

The role of luteinizing hormone-releasing hormone therapy in locally advanced prostate cancer and biochemical failure: considerations for optimal use.

BACKGROUND: More patients are being diagnosed with prostate cancer at an earlier age with earlier stage disease because of advances in screening and detection. Investigators continue to explore the use of hormone therapy, particularly luteinizing hormone-releasing hormone (LHRH) analogues, earlier in the course of disease. OBJECTIVE: This review summarizes clinical evidence regarding the safety and efficacy of LHRH analogues in the treatment of locoregional disease or following biochemical failure. METHODS: Relevant information from clinical studies was identified through a MEDLINE search of the medical literature published in English in the last 5 years (search terms: LHRH and prostate cancer). The search included prospective and retrospective clinical studies on LHRH therapy in locally advanced prostate cancer. Additional relevant publications published before 1999 were identified from citations in the resulting articles. RESULTS: The available clinical evidence suggests that the use of LHRH analogues as adjuvant or neoadjuvant therapy in conjunction with radiation therapy may improve survival outcomes. Few studies have evaluated the use of LHRH analogues after biochemical failure. However, several related studies indicate that initiating hormone therapy earlier rather than later may provide some clinical benefit. When considering early initiation of LHRH therapy, the potential risks of long-term treatment must be considered. Physiologic changes, such as deterioration of body composition and bone quality, may have important effects on the risk of developing cardiovascular disease and osteoporosis. CONCLUSIONS: Although some clinical evidence supports the use of LHRH analogues as adjuvant or neoadjuvant therapy or following biochemical failure, further study is needed. In the meantime, clinicians should carefully weigh the potential benefits and risks of early hormone therapy when making treatment decisions.

Reverse transcriptase-PCR analysis of apoptosis-regulating gene expression in human benign prostatic hyperplasia.

BACKGROUND: To determine whether an imbalanced interaction between proapototic and antiapoptotic signals may account for the loss of the normal cell growth control in benign prostatic hyperplasia (BPH), the expression of some apoptosis-regulating genes (bcl-2, bax, c-myc, fas) was investigated. PATIENTS AND METHODS: BPH specimens were obtained from 20 patients who underwent trans-urethral resection of the prostate (TURP) or adenomectomy. Gene expression was studied by reverse transcriptase-polymerase chain reaction (RT-PCR) and its correlation with age and serum PSA level was also investigated. RESULTS: Genes were found to be differentially expressed in BPH tissues. In particular, the antiapoptotic gene bcl-2, which was found in 18/20 samples, gave the weakest signal (p < 0.05 - p < 0.001, Wilcoxon's signed rank test), whereas the cell cycle regulator c-myc was detected in all the specimens and was the most highly expressed (p < 0.001). A positive relationship between the expression of bcl-2 and that of the two proapoptotic genes bax and fas was observed (p < 0.05, Spearman's rank correlation test), as well as between c-myc and fas levels (p < 0.005). Moreover, bax expression positively correlated with age and PSA (p < 0.02), which have also been shown to directly correlate (p < 0.01). CONCLUSION: The higher expression of the oncogene c-myc suggests the activation of mitogenic signals within hyperplastic prostate tissue which a relatively high expression of the proapoptotic genes bax and fas fails to counterbalance.

Automated melanoma detection with a novel multispectral imaging system: results of a prospective study.

The aim of this research was to evaluate the performance of a new spectroscopic system in the diagnosis of melanoma. This study involves a consecutive series of 1278 patients with 1391 cutaneous pigmented lesions including 184 melanomas. In an attempt to approach the 'real world' of lesion population, a further set of 1022 not excised clinically reassuring lesions was also considered for analysis. Each lesion was imaged in vivo by a multispectral imaging system. The system operates at wavelengths between 483 and 950 nm by acquiring 15 images at equally spaced wavelength intervals. From the images, different lesion descriptors were extracted related to the colour distribution and morphology of the lesions. Data reduction techniques were applied before setting up a neural network classifier designed to perform automated diagnosis. The data set was randomly divided into three sets: train (696 lesions, including 90 melanomas) and verify (348 lesions, including 53 melanomas) for the instruction of a proper neural network, and an independent test set (347 lesions, including 41 melanomas). The neural network was able to discriminate between melanomas and non-melanoma lesions with a sensitivity of 80.4% and a specificity of 75.6% in the 1391 histologized cases data set. No major variations were found in classification scores when train, verify and test subsets were separately evaluated. Following receiver operating characteristic (ROC) analysis, the resulting area under the curve was 0.85. No significant differences were found among areas under train, verify and test set curves, supporting the good network ability to generalize for new cases. In addition, specificity and area under ROC curve increased up to 90% and 0.90, respectively, when the additional set of 1022 lesions without histology was added to the test set. Our data show that performance of an automated system is greatly population dependent, suggesting caution in the comparison with results reported in the literature. In our opinion, scientific reports should provide, at least, the median values of thickness and dimension of melanomas, as well as the number of small (6 mm) melanomas.

Automated segmentation of pigmented skin lesions in multispectral imaging.

The aim of this study was to develop an algorithm for the automatic segmentation of multispectral images of pigmented skin lesions. The study involved 1700 patients with 1856 cutaneous pigmented lesions, which were analysed in vivo by a novel spectrophotometric system, before excision. The system is able to acquire a set of 15 different multispectral images at equally spaced wavelengths between 483 and 951 nm. An original segmentation algorithm was developed and applied to the whole set of lesions and was able to automatically contour them all. The obtained lesion boundaries were shown to two expert clinicians, who, independently, rejected 54 of them. The 97.1% contour accuracy indicates that the developed algorithm could be a helpful and effective instrument for the automatic segmentation of skin pigmented lesions.

Molecular prostate cancer pathology: current issues and achievements.

Recent developments in the field of molecular techniques have provided new tools that have led to the discovery of many new promising biomarkers for prostate cancer. These biomarkers may be instrumental in the development of new tests that will have a high specificity for the diagnosis and prognosis of prostate cancer. A biomarker is defined as a molecular test that provides additional information to currently available clinical and pathological tests. Biomarkers should be reproducible (both within and between institutes) and have an impact on clinical management. For diagnostic purposes it is important that potential biomarkers are tested in terms of tissue specificity and their discrimination potential between prostate cancer, normal prostate and benign prostatic hyperplasia. The results of (multiple) biomarker-based assays may enhance the specificity of cancer detection. There is an urgent need for molecular prognostic biomarkers for predicting the biological behavior and outcome of cancer.

Automated melanoma detection: multispectral imaging and neural network approach for classification.

Our aim in the present research is to investigate the diagnostic performance of artificial neural networks (ANNs) applied to multispectral images of cutaneous pigmented skin lesions as well as to compare this approach to a standard traditional linear classification method, such as discriminant function analysis. This study involves a series of 534 patients with 573 cutaneous pigmented lesions (132 melanomas and 441 nonmelanoma lesions). Each lesion was analyzed by a telespectrophotometric system (TS) in vivo, before surgery. The system is able to acquire a set of 17 images at selected wavelengths from 400 to 1040 nm. For each wavelength, five lesion descriptors were extracted, related to the criteria of the ABCD (for asymmetry, border, color, and dimension) clinical guide for melanoma diagnosis. These variables were first reduced in dimension by the use of factor analysis techniques and then used as input data in an ANN. Multivariate discriminant analysis (MDA) was also performed on the same dataset. The whole dataset was split into two independent groups: i.e., train (the first 400 cases, 95 melanomas) and verification set (last 173 cases, 37 melanomas). Factor analysis was able to summarize the data structure into ten variables, accounting for at least 90% of the original parameters variance. After proper training, the ANN was able to classify the population with 80% sensitivity, 72% specificity, and 78% sensitivity, 76% specificity for the train and validation set, respectively. Following ROC analysis, area under curve (AUC) was 0.852 (train) and 0.847 (verify). Sensitivity and specificity values obtained by the standard discriminant analysis classifier resulted in a figure of 80% sensitivity, 60% specificity and 76% sensitivity, 57% specificity for the train and validation set, respectively. AUC for MDA was 0.810 and 0.764 for the train and verify set, respectively. Classification results were significantly different between the two methods both for diagnostic scores and model stability, which was worse for MDA.

Clinical and dermatoscopic diagnosis of small pigmented skin lesions.

Small pigmented skin lesions represent a new challenge for all physicians devoted to the early diagnosis of melanoma. The purpose of this prospective study was to establish the diagnostic value of the clinical and the dermatoscopic examinations in a population of 157 consecutive patients with 161 small (< or = 6 mm) pigmented lesions, recruited in a short time. Of these 161 lesions, 13 were thin melanomas (median thickness 0.49 mm). In this population, clinical evaluation produced a diagnostic sensitivity of 77% and a specificity of 74%. Dermatoscopy resulted in a sensitivity of 77% and in a specificity of 72%. Combining clinical and dermatoscopic evaluations all the melanomas were preoperatively recognised. The results of the present study stress the complementary role of clinical and dermatoscopic examinations. In particular, clinical evaluation remains of utmost importance in diagnosing melanoma. This concept must be stressed in the education and training of young dermatologists.

Micro-melanoma detection. A clinical study on 22 cases of melanoma with a diameter equal to or less than 3 mm.

BACKGROUND AND AIMS: Very small pigmented lesions may represent an extreme diagnostic challenge to the clinician. Our aim was to describe the clinical and dermoscopic features in a series of cutaneous melanomas with a maximum clinical diameter of 3 mm. METHODS: We conducted a retrospective study of the 924 primary melanomas seen and treated during a period of five years at the Unit for Melanoma Detection of the Istituto Nazionale Tumori of Milan, Italy. The size characteristics of the considered lesions allowed the identification of 22 (2.4%) cases of micro-melanoma (clinical diameter of 3 mm or less). Sixteen of these cases were subjected to dermoscopy. The clinical and dermoscopic features as well as the corresponding diagnoses were recorded. RESULTS: The typical lesion presents as a small, dark, often black macule, generally evenly colored, with well-defined borders; it may be asymmetric or symmetric in shape. These features prompted a correct clinical diagnosis in nearly half of the cases. Dermoscopy lead to a correct diagnosis in all cases subjected to the technique. CONCLUSION: Dermoscopy appears to be an efficient aid to the diagnosis of micro-melanomas, provided that clinicians are aware of this type of lesion and maintain the index of suspicion at a high level.