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.

Dermoscopy and reflectance confocal microscopy of pigmented actinic keratoses: a morphological study.

BACKGROUND: Actinic keratoses (AKs) are very common lesions on sun damaged skin and, when pigmented, represent a challenge in the differential diagnosis with early melanoma. Non-invasive diagnostic methods, such as dermoscopy and reflectance confocal microscopy (RCM) have been shown to improve the diagnostic accuracy of melanoma and non-melanoma skin cancer, however, only one case report described confocal findings of pigmented AKs up to now. OBJECTIVES: The aim of our retrospective morphological study was to analyse dermoscopic and confocal images of a series of histopathologically proven pigmented AKs, located on the face and other body sites, to define peculiar features of these "difficult to diagnose" lesions. METHODS: Clinical, dermoscopic and RCM images of 17 histopathologically confirmed pigmented AKs were retrospectively collected from the databases of four skin lesion clinics in Italy and USA. Dermoscopic and RCM images were analysed for prevalent morphological features. RESULTS: The majority of the lesions were located on the face (n = 8); followed by scalp (n = 4) and trunk (n = 4); and one lesion was located on the lower limbs. On dermoscopy the majority of lesions were characterized by grey dots/globules/granularity and structureless brown pigmentation. The main RCM feature of pigmented AKs was as follows: (i) the presence of epidermal changes (atypical keratinocytes, parakeratosis, scaling); (ii) increased epidermal thickness; (iii) bright, small, dermal papillae with enlarged interpapillary space; and (iv) intraepidermal dendritic cells referrable to Langherans cells. Features suggestive of melanocytic lesions, such as nesting, meshwork pattern or atypical cells infiltrating the junction, were never detected in our case series at the dermal epidermal junction (DEJ) level. CONCLUSION: Larger case series with adequate control population are warranted to validate these findings and to test their value in clinical setting.

Selective sunscreen application on nevi: frequency and determinants of a wrong sun-protective behaviour.

BACKGROUND: Sunscreen use is generally recommended in order to prevent skin cancer but erroneous patterns of use were reported, including the selective application on melanocytic nevi. OBJECTIVE: To assess prevalence and determinants of selective sunscreen application on nevi and participants' behavioural risk profile overall. METHODS: A multilingual, dichotomous, funnel-designed questionnaire about sun exposure/protection habits and perceived nevus count was administered to patients attending five Dermatology Departments in three countries (Italy, Austria and France). Multivariate logistic regression models were used to determine independent predictors of each answer. RESULTS: Among the 1816 subjects surveyed (59.3% females, age 14-90 (median 45) years, 44.7% Italians), 1273 (70.1%) reported intentional sun exposure and 1109/1273 (87.1%) reported sunscreen use. Among the latter, 1086 (97.9%) stated they have moles on their skin. Fifty-one/1086 (4.7%) reported selective sunscreen application on nevi. Reported information sources were: dermatologist (49.0%), personal belief (31.4%), relative/friend (7.8%), media (7.8%), paediatrician (2.0%) and general practitioner (2.0%). Increasing age (P < 0.05) and being Italian (P < 0.001) were independent predictors of selective sunscreen application on nevi. Sun-seeking behaviours were predicted by decreasing age, female sex and being Italian. CONCLUSION: Selective sunscreen application on nevi was more common than expected. It is of concern that this was recommended mostly by physicians. There is a need to educate patients, non-expert clinicians, media and the sunscreen industry on this matter. Tan patients presenting with halo nevi should be questioned about this behaviour in order to avoid false positive diagnoses.

Physicians' opinions and clinical practice patterns for actinic keratosis management in Italy.

AIM: We report dermatologists' opinions and clinical practice patterns about clinical factors driving decision making in the management of actinic keratosis (AK) in Italy. METHODS: We carried out a cross-sectional survey among 33 Italian dermatologists. Physicians were asked to report their management choices in consecutive patients with AK seen at their practice within 2 weeks since study initiation. We collected patients' clinical and socio-demographic characteristics with a standardized data collection form and assessed physicians' opinions on AK management with a self-reported questionnaire. RESULTS: Six hundred fifty-seven patients with new, single AK lesions without evidence of photo-damaged skin in the surrounding areas, were predominantly treated with lesion-directed therapies (primarily cryotherapy). In contrast, physicians preferentially prescribed field-directed therapies to patients with multiple lesions and evidence of photo-damaged skin in AK surrounding areas. However we observed a wide variation in treatment choices and physicians' opinions on AK management. Dermatologists underlined the importance of fostering patients' adherence and minimize therapy side effects. CONCLUSION: Overall, our results show that current guidelines regarding management of AK are only partially integrated in dermatology practice. The active dissemination of up-to-date national guidelines might help harmonize clinical decision making in this complex and fast growing therapeutic area.

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. OBJECTIVE: To describe the dermoscopic features of dermatofibromas, with special emphasis on the characteristics of atypical patterns, and to calculate pattern frequency according to the patients age and gender, anatomical site and histopathological subtype. METHODS: Two groups of patients were consecutively seen, one with dermatofibromas that were surgically excised because of clinically and/or dermoscopically equivocal aspects or following patient request, and another with non-equivocal dermatofibromas. Each lesion was scored for previously reported global dermoscopic patterns and for additional features. RESULTS: A typical pattern was observed in 92 of 130 (70.8%) lesions, whereas an atypical pattern, that we named the 'non Dermatofibroma (DF)-like' pattern, was seen in 38 of 130 (29.2%). Atypical dermatofibromas showed features reminiscent of different conditions, such as melanoma in 21(16.2%) cases, vascular tumour in six (4.6%), basal cell carcinoma in five (3.8%), collision tumour in three (2.3%) and psoriasis in three (2.3%). A significant association was found between the 'melanoma-like' pattern/'vascular tumour-like' pattern and males, whereas a trend was observed between the above-mentioned patterns and hemosiderotic/aneurysmal DFs. 'Peripheral pigment network and central white scar-like patch' pattern was found associated with females and classic histopathological variant of DF. CONCLUSION: Dermatofibromas may display different morphological faces. The typical dermoscopic patterns allow a confident diagnosis, whereas a full surgical excision is always recommended in all doubtful cases.

Clinical, dermoscopic and reflectance confocal microscopy features of sebaceous neoplasms in Muir-Torre syndrome.

BACKGROUND: Muir-Torre syndrome (MTS) is an autosomal-dominant disorder characterized by the association of sebaceous tumors or keratoacanthomas with an early onset visceral cancer in the spectrum of Lynch syndrome. OBSERVATIONS: A total of 20 sebaceous tumors including 18 sebaceous adenoma and two sebaceomas of six patients with MTS were analysed. Two main clinico-dermoscopic features were observed: (1) clinically pink to white papules/nodules with a central crater, dermoscopically characterized by radially arranged, elongated crown vessels surrounding opaque structureless yellow areas at times covered by blood crusts (n = 13) and (2), clinically pink to yellow papules/nodules without a central crater, dermoscopically exhibiting a few, loosely arranged yellow comedo-like globules and branching arborizing vessels (n = 7). Confocal microscopy was available in three sebaceous adenomas and revealed a good histopathologic correlation; sebaceous lobules were composed by clusters of ovoid cells with dark nuclei and bright, highly refractile glistening cytoplasm. They were delimited by a rim of epithelial cells, corresponding to basaloid cells. CONCLUSIONS: A better characterization of clinical, dermoscopic and confocal microscopy features of sebaceous tumors may improve their recognition and consequently, aid to rise the suspect for MTS.

Excised melanocytic lesions in children and adolescents - a 10-year survey.

BACKGROUND: Early recognition and prompt excision is to date the only available strategy for reducing mortality from melanoma. Little is known about the accuracy of melanoma detection in children and adolescents. OBJECTIVES: To assess the accuracy of melanoma detection in a paediatric population. METHODS: From the Department of Dermatology, Medical University of Graz, Austria, we reviewed the dermatopathology reports of naevi and melanomas excised in patients younger than 20 years over a 10-year period (1998-2007). Patients were subdivided into four age groups: 0-4, 5-9, 10-14 and 15-19 years. RESULTS: Accuracy in melanoma detection was tested using the number needed to excise (NNE) value that is obtained by dividing the total number of excised lesions by the number of melanomas. A total of 22564 lesions were reviewed, disclosing 22526 naevi and 38 melanomas, for an overall NNE value of 593.8. Five melanomas were excised in children aged 10-14 years (NNE 1141) and 33 in children aged 15-19 years (NNE 479.8), whereas no melanomas were found among 1026 lesions excised in children younger than 10 years. In children aged 0-4 years, congenital and Spitz/Reed naevi accounted for 34.5% and 20% of lesions, respectively. These percentages decreased progressively when moving to older age groups (P<0.0001). In contrast, the percentage of dermal and compound naevi rose in direct proportion with age, being 3.4% and 20.7%, respectively, in the youngest age group, and 36.7% and 31.9%, respectively, among the oldest patients (P<0.0001). CONCLUSIONS: The overall NNE value in paediatric patients over the 10-year study period was 593.8, meaning that about 594 lesions were excised to find one melanoma. This value is 20 times higher than the rates found in adult patients.

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. OBJECTIVES: To assess the diagnostic performance of pattern analysis and seven-point checklist on lesions that reflect the current clinical setting, compared with a revised seven-point checklist with a lower threshold for excision. METHODS: Eight experienced dermatologists viewed dermoscopic images of 100 excised melanomas, 100 excised naevi and 100 monitored naevi. Each lesion was evaluated by pattern analysis and scored as naevus, melanoma or lesion to be excised. Images were then evaluated using the seven-point criteria, with both standard and revised thresholds for excision. RESULTS: Pooled data using the pattern analysis algorithm showed that 82% of melanomas and 87·5% of monitored naevi were correctly scored as lesion to be excised and benign naevus, respectively. Using the standard and revised thresholds for the seven-point checklist, excision was recommended for 77·9% and 87·8% of the lesions in the melanoma set, respectively. The standard threshold produced 'no excision' recommendations for 85·6% of the monitored naevi, compared with 74·5% using the revised threshold. Pattern analysis, standard seven-point and revised seven-point algorithms resulted in recommendations of 'excision' for 63·6%, 60·3% and 72·0% of the excised naevi, respectively. CONCLUSIONS: The diagnostic approach to naevi and melanoma should be adapted to the current clinical setting, in which patients may present with early-stage melanomas and multiple atypical naevi. To increase sensitivity, a revised seven-point checklist with a lower threshold for excision should be used.

["Dying nevus" or regressing melanoma]. / "Sterbender Nävus" oder regressives Melanom?

Epidemiological studies suggest that the number of acquired melanocytic nevi increases from puberty until midlife and, thereafter, decreases. The latter phenomenon is related to spontaneous involution/apoptosis of nevi. The widespread use of dermoscopy has enriched profoundly our knowledge of the morphological variability of nevi during their evolution. A peripheral symmetric rim of small grown globules represents a clear sign of nevus growth. Instead, nevi in adults often reveal a reticular or reticular-mixed pattern. In patients aged 30 to 40 years clinically vanishing nevi can be noticed, which represent nevi during involution. The important differential diagnoses are melanocytic nevi and melanoma with regression. The life cycle of a nevus is also reflected by the phrase" we are born and we die without nevi".

Novel and recurrent p14 mutations in Italian familial melanoma.

CDKN2A and CDK4 are the only known high-penetrant genes conferring proneness to cutaneous melanoma. The CDKN2A locus consists of four exons and encodes several alternate transcripts, two of which are p16(INK4a) and p14(ARF), and originate from different open reading frames. Exon 1alpha is specific for p16(INK4a), while exon 1beta characterizes p14(ARF). Most CDKN2A mutations are located in exons 1alpha and 2, while exon 1beta variations have been identified in rare melanoma-prone pedigrees. In a previous study, we investigated 155 Italian melanoma cases, including 94 familial melanomas (FAMs) and 61 sporadic multiple primary melanomas (MPMs), for p16(INK4a)/CDK4 germline alterations and identified 15 p16(INK4a) and 1 CDK4 point mutations. In the present work, we extended our search to p14(ARF) mutations and CDKN2A deletions in the remaining samples. We identified the recurrent g.193+1G> A mutation in two FAM cases, while an additional pedigree displayed the previously undescribed variant g.161G> A. Multiplex ligation-dependent probe amplification (MLPA) screening for copy variations resulted negative in all cases. In Italy, the overall frequency of p14(ARF) mutations is 3.2% in FAM and 0% in sporadic MPM. Re-evaluation of our patients' cohort emphasizes that the chance of identifying CDKN2A/CDK4 mutations in FAM is mainly influenced by the number of affected family members and the presence of one or more MPM cases. Accordingly, mutation rate rises to 61% in selected cases. Further studies are expected in order to investigate CDKN2A rarer mutations, including atypical deletions and inherited epimutations.

High frequency ultrasound in the preoperative staging of primary melanoma: a statistical analysis.

High frequency sonography has been shown to be a useful tool in the preoperative staging of malignant melanoma. In the present study sonometric and histometric data concerning tumour thickness were compared, using appropriate statistical methods, in order to assess the accuracy of ultrasonography. From December 1997 all pigmented lesions suspected of being melanoma were preoperatively assessed by a 20 MHz ultrasound B scan. The results of these ultrasound examinations were compared with histometric data. Pearson's correlation coefficient and absolute and relative differences were used for statistical analysis. Of the 261 examined lesions, 193 were malignant melanoma. A high correlation between sonometry and histometry was computed (r = 0.95), with an absolute difference of 0.32 +/- 0.03 mm (mean +/- SEM) and a mean relative difference of 27.2% (95% confidence interval 23-31.4%). The highest correlation was found in melanoma > or = 1.51 mm thick and the lowest correlation in melanoma < or = 0.75 mm. In conclusion, the high accuracy of this technique in the preoperative staging of malignant melanoma would offer a basis for defining the surgical margins of > or = 0.76 mm thick lesions. The limited accuracy of sonometry in the preoperative staging of thin melanoma < or = 0.75 mm has emerged by applying adequate statistical methods.

Cytogenetic findings in 20 melanomas.

We report cytogenetic studies performed on 20 patients with cutaneous malignant melanoma, characterized by clinical and histological parameters. Cytogenetic analyses were performed on peripheral blood lymphocytes, in order to exclude the presence of constitutional chromosomal aberrations, and on primary cell cultures obtained from neoplastic skin lesions. A metastasis was also cultured in order to characterize chromosome markers. Specific markers found in more than one patient were t(1;14)(q21;q32) and aberrations of the 4q21,8q24 and 10q24q26 regions. The research aims to identify possible subtypes of melanomas related to specific chromosomal markers. It is hoped that this will contribute to understanding of the aetiology and evolution of the disease in order to obtain a more exact classification. We compare our results with the data reported in the literature and discuss the possible role of the cytogenetic analyses in human malignant melanoma.

CDKN2A novel mutation in a patient from a melanoma-prone family.

CDKN2A is thought to be the main candidate gene for melanoma susceptibility. Deletion or mutations in the CDKN2A gene may produce an imbalance between functional p16 and cyclin D, causing abnormal cell growth. We here describe a novel mutation consisting of a 1 bp deletion at nucleotide position 201 (codon 67) (CACGGcGCG) resulting in a truncated protein (stop codon 145). The patient, a female subject from a melanoma-prone family, presented at the age of 47 years with a superficial spreading melanoma of the trunk. Her father had colon cancer at the age of 43 years and melanoma at 63 years, her uncle suffered from gastric cancer, and her grandfather had laryngeal cancer.