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Background Naevoid melanoma (NeM), a rare variant of melanoma, can be difficult to detect as its clinical and histopathological morphology can simulate a naevus. Objectives To describe the clinical and dermoscopic features associated with NeM. Methods Lesions with a histopathological diagnosis of NeM were collected via an e-mail request sent to all members of the International Dermoscopy Society. All lesions were histopathologically reviewed and only lesions fulfilling a set of predefined histopathological criteria were included in the study and analysed for their clinical and dermoscopic features. Results Twenty-seven of 58 cases (47%) fulfilled the predefined histopathological criteria for NeM and were included in the study. Clinically, 16 of the 27 NeMs presented as a nodular lesion (59%), eight (30%) as plaque type and three (11%) as papular. Analysis of the global dermoscopic pattern identified three types of NeM. The first were naevus-like tumours ( n = 13, 48%), typified by a papillomatous surface resembling a dermal naevus. In these lesions local dermoscopic features included irregular dots/globules (46%), multiple milia-like cysts (38%) and atypical vascular structures (46%). The second type were amelanotic tumours ( n = 8, 30%), typified by an atypical vascular pattern (75%). The third type consisted of tumours displaying a multicomponent pattern ( n = 4, 15%), characterized by classical local melanoma-specific criteria. Two lesions (7%) were classified as mixed-pattern tumours as they did not manifest any of the aforementioned patterns. Conclusions While NeMs may be clinically difficult to differentiate from naevi, any papillomatous lesion displaying dermoscopically atypical vessels and/or irregular dots/globules should prompt consideration for the possible diagnosis of NeM. [ABSTRACT FROM AUTHOR]

Background Mycosis fungoides ( MF) is the most common type of cutaneous T-cell lymphoma; in its classical presentation it evolves slowly, but it can have an aggressive course in a subset of patients. Objectives To investigate the impact of epigenetic mechanisms on the progression of early stage MF. Methods We analysed DNA methylation at 12 different loci and long interspersed nucleotide elements-1 ( LINE-1), as a surrogate marker of global methylation, on tissue samples from 41 patients with stage I MF followed up for at least 12 years or until disease progression. The methylation profiles were also analysed in two T-cell lymphoma cell lines and correlated with gene expression. Results The selected loci were methylated in a tumour-specific manner; concomitant hypermethylation of at least four loci was more frequent in cases progressing within 1-3 and 3-6 years than in late-progressive or non-progressive cases. LINE-1 methylation was significantly lower in rapidly progressive MF at 3 years (61%, P < 0·001) than in those at 12 years (67%). PPARG, SOCS1 and NEUROG1 methylation showed remarkable differences among the prognostic groups, but only PPARG was a significant predictor of disease progression within 6 years, after adjustment for patients' age or gender. Strikingly, a methylation profile similar to progressive cases was found in highly proliferative Sézary-derived HUT78 cells but not in MF-derived HUT102 cells. Exposure to a DNA demethylating agent restored sensitivity to apoptosis and cell cycle arrest. Conclusions Epigenetic silencing of specific biomarkers can predict the risk of disease progression in early-stage MF, providing insights into its pathogenesis, prognosis and therapy. [ABSTRACT FROM AUTHOR]

Background The presence of pigmentation might influence the management of basal cell carcinoma ( BCC), with pigmented BCC responding poorly to certain treatments. Clinical studies report on a generally lower frequency of pigmentation compared with dermoscopic and histopathological studies, but the true frequency at which pigmentation occurs in clinically nonpigmented BCC has not been studied in detail. Objectives To compare the clinical and dermoscopic frequency of pigmentation in a series of histopathologically diagnosed BCCs and to correlate it with patient demographics, tumour location and histopathological subtype. Methods Clinical and dermoscopic images of histopathologically confirmed BCCs were retrospectively evaluated for the presence of pigmentation. Dichotomous outcome variables were clinically pigmented and dermoscopically pigmented BCC. All separate dermoscopic variables were included in the analysis. Differences in proportions were evaluated using Pearson's chi-square test. Results Five hundred and seven BCCs from 507 patients with a mean age of 67 years and a male-to-female ratio of 1·35 : 1 were included in the study. Clinically, 295 tumours were judged as nonpigmented. Of those, dermoscopy disclosed pigmentation in 88 cases (29·8%). Overall, blue-grey ovoid nests were the most frequent dermoscopic pattern ( n = 184, 36·3%), followed by multiple blue-grey dots/globules ( n = 147, 29%) and maple-leaf-like areas ( n = 70, 13·8%). Superficial tumours exhibited mainly maple-leaf-like areas, spoke-wheel areas and brown dots, whereas pigmented nodular BCC was most frequently typified by the presence of blue-grey ovoid nests. Conclusions Dermoscopy allows detection of pigmentation in about 30% of clinically nonpigmented BCCs, providing additional information that may aid the clinical choice of adequate treatment modalities. [ABSTRACT FROM AUTHOR]

Background Basosquamous carcinoma ( BSC) is a rare and potentially aggressive tumour, characterized by clinical and pathological features of both basal cell carcinoma ( BCC) and squamous cell carcinoma ( SCC). It is reported to have a nonspecific clinical presentation, which makes naked-eye diagnosis a challenge. Objectives To describe the dermoscopic patterns of BSC, which may facilitate early diagnosis and accurate management. Methods This was a retrospective evaluation of clinical and dermoscopic images of histopathologically proven BSC, collected from skin cancer centres in Australia (Perth), Greece (Thessaloniki) and Italy (Naples, Reggio Emilia). Results Twenty-two tumours were included in the study. Our analysis revealed that the dermoscopic pattern of BSC comprises BCC-related criteria, as well as features that are known to characterize invasive SCC. The most frequently detected criteria were: unfocused (peripheral) arborizing vessels (73%), keratin masses (73%), white structureless areas (73%), superficial scale (68%), ulceration or blood crusts (68%), white structures (64%), blue-grey blotches (59%) and blood spots in keratin masses (55%). Notably, all but one of the tumours exhibited at least one BCC-related plus one SCC-related dermoscopic feature. Conclusions BSC appears to have overlapping dermoscopic features of BCC and invasive SCC, and detection of at least one dermoscopic criterion of both BCC and SCC should raise suspicion for the tumour. Appreciation of the dermoscopic patterns of BSC might assist in the timely and accurate diagnosis and subsequent optimal management of this unusual and potentially metastatic skin tumour. [ABSTRACT FROM AUTHOR]

Background Small-diameter melanocytic lesions represent a diagnostic challenge for clinicians, as they do not follow the ABCD rule for diagnosis and do not always display reliable histopathological criteria. Objectives To analyse the confocal features of small-diameter lesions (naevi and melanomas with diameter ≤ 5 mm) to determine whether they show specific morphological criteria. Methods Twenty-four melanomas and 72 naevi were subjected to dermoscopic and confocal evaluation along with histopathology. Significant dermoscopic and confocal differences between melanomas and naevi were evaluated by means of the Pearson χ2 test. Odds ratios and 95% confidence intervals were calculated for each parameter. Binary logistic regression was performed to identify the reflectance confocal microscopy (RCM) independently significant features for melanoma diagnosis. Results The seven-point checklist dermoscopic score was ≥ 3 in 22 melanomas and in 33 naevi. The combination of cells' pleomorphism and architectural disorder (i.e. nonspecific pattern or irregular junctional nests upon confocal examination) are the most striking criteria for consistent diagnosis of small melanoma. The presence of atypical cells, more than five atypical cells per mm2, and roundish atypical cells at the dermoepidermal junction showed the highest odds ratios. From logistic regression, the presence of at least five pagetoid cells per mm2, tangled lines within the epidermis, and atypical roundish cells at the dermoepidermal junction resulted in the three independent confocal parameters that characterized small melanomas. Conclusions Small melanomas frequently reveal specific dermoscopic and confocal features. Moreover, the combination of dermoscopy and RCM can lead to a correct diagnosis of a number of naevi that share some morphological aspects with melanomas. [ABSTRACT FROM AUTHOR]

Background Melanomas vary in growth rate from rapidly developing nodular melanomas to slow-growing melanomas (SGM) that hardly change over years. Objectives To evaluate longitudinal changes in dermoscopic findings of SGM. Methods We retrospectively analysed a dermoscopic image dataset from 15 pigmented lesion clinics, of SGM that were followed sequentially by digital dermoscopy for at least 1 year. We evaluated baseline and follow-up images for changes in global pattern, organization, colours, structure and size. Results Our series consisted of 92 SGM. On follow-up, these melanomas developed the following dermoscopic findings: more homogeneous and less reticular global dermoscopic pattern; more frequent disorganization of pattern (baseline, 67% vs. follow-up, 79%); decreased prominence of light brown colour, increased prominence of dark brown colour, and increased frequency of the colours red, white, grey, blue and black (baseline: 29%, 3%, 18%, 6% and 33% vs. follow-up: 41%, 10%, 31%, 13% and 45%, respectively); decrease in prominence of dermoscopic structure of pigmented network, with a concomitant increase in prominence of structureless areas; and increased prominence or new appearance of melanoma-specific dermoscopic structures, including negative network, blue-white structures and blotches. The majority of lesions (75%) remained the same size or grew by < 2 mm in diameter. An increase in lesion size was associated with change in the total number of colours and structures (χ2 = 14·3, P = 0·027) at follow-up. Conclusions While their diameter changed minimally over time, most SGM became more disorganized, revealed loss of network in favour of structureless areas, and developed new colours. [ABSTRACT FROM AUTHOR]

Understanding the role of the developmental pathways in shaping phenotypic diversity allows appreciating in full the processes influencing and constraining morphological change. Podarcis lizards demonstrate extraordinary morphological variability that likely originated in short evolutionary time. Using geometric morphometrics and a broad suite of statistical tests, we explored the role of developmental mechanisms such as growth rate change, ontogenetic divergence/convergence/parallelism as well as morphological expression of heterochronic processes in mediating the formation of their phenotypic diversity during the post-natal ontogeny. We identified hypermorphosis - the prolongation of growth along the same trajectory - as the process responsible for both intersexual and interspecific morphological differentiation. Albeit the common allometric pattern observed in both sexes of any species constrains and canalizes their cephalic scales variation in a fixed portion of the phenotypic space, the extended growth experienced by males and some species allows them to achieve peramorphic morphologies. Conversely, the intrasexual phenotypic diversity is accounted for by non-allometric processes that drive the extensive morphological dispersion throughout their ontogenetic trajectories. This study suggests a model of how simple heterochronic perturbations can produce phenotypic variation, and thus potential for further evolutionary change, even within a strictly constrained developmental pathway. [ABSTRACT FROM AUTHOR]

Background Recent evidence suggests that melanoma is a family of different tumours with varying abilities to grow and metastasize. Trends in melanoma epidemiology show a strong increase in the incidence of thin melanoma, with no corresponding increase in mortality or incidence of thick melanoma. We initially evaluated five cases and found that none had baseline features suggestive of melanoma; excision was performed based on slight changes visible only in side-by-side comparisons of dermoscopic images. Objectives To assess the clinico-dermoscopic features and the growth patterns of melanomas that were excised after a follow-up of 1 year or more due to their inconspicuous features at the baseline consultation. Methods In a multicentre, retrospective study of histopathologically confirmed melanomas excised after follow-up, we analysed dermoscopic images obtained at the initial consultation and compared them with images obtained at the last follow-up consultation. Images were analysed and graded using standard algorithms and scored for changes in size, symmetrical or asymmetrical structural change, and development of new melanoma-specific criteria. An overall score reflecting the amount of change was calculated for each lesion. Results Our series consisted of 103 melanomas. After a median follow-up of 20 months, most lesions were still in situ or early invasive (median Breslow thickness of 0·48 mm), with only three lesions showing tumour thickness of 1 mm or more. The most frequent baseline characteristics were asymmetrical pigmentation (78·6% of lesions), reticular overall pattern (62·1%), and regression features (35·9%). Most melanomas (58·3%) showed minor to moderate changes over time, with < 2 mm size increase, with asymmetrical structural change, and without development of new melanoma-specific criteria. Major changes were visible only after a mean follow-up of 33 months. Conclusions This study provides evidence for the existence of a subgroup of slow-growing melanomas, which may explain the increase in the incidence of thin melanoma, despite stable rates of thick melanoma and melanoma-associated mortality. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Pigmented Epithelioid Melanocytoma: A Low-Grade Melanocytic Tumor With Metastatic Potential Indistinguishable From Animal-Type Melanoma and Epithelioid Blue Nevus," that was published in the previous issue.

Background Dermoscopic monitoring of melanocytic lesions increases the likelihood that featureless melanomas are not overlooked and minimizes the excision of benign lesions. Objective To examine clinical outcome and patient compliance using different follow-up protocols. Methods A retrospective analysis of 600 lesions from 405 patients (aged 6–79 years) was performed to examine patient compliance and clinical outcome in patients with multiple atypical melanocytic lesions undergoing sequential dermoscopy imaging during short-, medium- or long-term follow-up. Based on the degree of dermoscopic atypical features, patients were scheduled for short-term monitoring with follow-up after 3 months, medium-term monitoring with follow-up after 6 months or long-term monitoring with annual follow-up. Criteria leading to excision of monitored lesions differed according to the follow-up protocol. Results In a median follow-up period of 23 months, 54 (9%) lesions were excised, revealing 12 early melanomas (occurring in 3% of monitored patients), one basal cell carcinoma and 41 melanocytic naevi. The melanoma/benign ratio of excised lesions was 1 : 3·4. Seven of 12 melanomas showed changes after two to four visits, corresponding to 8–54 months of follow-up. Patient compliance was 84% for short-term monitoring, 63% for medium-term monitoring and 30% for long-term monitoring. Conclusions In patients with multiple naevi sequential dermoscopy imaging is a useful strategy to avoid missing melanomas while minimizing unnecessary excision of benign lesions. For better compliance, the first re-examination should be scheduled at 3 months after the baseline visit. Regular annual follow-up monitoring is also needed to detect slow-growing melanomas in which subtle changes may become apparent only over time. [ABSTRACT FROM AUTHOR]

The lack of consensus among clinicians and pathologists due to the mixture of clinical and histopathological features used to define the various melanocytic naevi underscores the need of a better classification system for these benign lesions. We describe a dermoscopic classification system for melanocytic naevi that is directed to clinicians dealing with the early diagnosis of melanoma, as well to pathologists, in order to promote better communication between these different specialists. [ABSTRACT FROM AUTHOR]

Background In a pilot study, the three-point checklist of dermoscopy has been shown to represent a valid and reproducible tool with high sensitivity for the diagnosis of skin cancer in the hands of a small group of nonexperts. Objectives To re-evaluate these preliminary results in a large number of observers independently from their profession and expertise in dermoscopy. Methods The study was conducted via the internet to provide worldwide access for participants. After a short web-based tutorial, the participants evaluated dermoscopic images of 165 (116 benign and 49 malignant) skin lesions (15 training and 150 test lesions). For each lesion participants scored the presence of the three-point checklist criteria (asymmetry, atypical network and blue-white structures). Kappa values, odds ratios, sensitivity, specificity and likelihood ratios were estimated. Results Overall, 150 participants joined the study. The three-point checklist showed good interobserver reproducibility (kappa value: 0.53). Sensitivity for skin cancer (melanoma and basal cell carcinoma) was 91.0% and this value remained basically uninfluenced by the observers' professional profile. Only 20 participants lacking any experience in dermoscopy performed significantly more poorly, but the sensitivity was still remarkably high (86.7%) when considering that they were untrained novices in dermoscopy. The specificity was 71.9% and was significantly influenced by the profession, with dermatologists performing best. Conclusions Our study confirms that the three-point checklist is a feasible, simple, accurate and reproducible skin cancer screening tool. [ABSTRACT FROM AUTHOR]

T-cell-mediated immunoregulation is one of the main mechanisms implicated in induction and maintenance of transplantation tolerance. In this regard, deletion or modulation of xeno/alloantigen-specific T cells, as well as blocking of their interactions with other cell populations, are currently being pursued for tolerance induction in humans as well as nonhuman primates. In order to investigate whether cytotoxic T-lymphocyte antigen-4 (CTLA-4) may represent a suitable target for a T cell depletion approach in nonhuman primate models, we analysed CTLA-4 expression in peripheral blood mononuclear cells (PBMCs) from nonhuman primates and the potential role of two anti-CTLA-4 saporin-conjugated immunotoxins. The analysis was performed in PBMCs from 8 cynomolgus monkeys from Philippines and from Mauritius both at protein level by flow cytometry and at transcriptional level by RT-PCR. In addition, the apoptotic role of the immunotoxins was investigated. The results showed that CTLA-4 was expressed at variable levels depending on the origin of the cynomolgus monkeys and the resting or activated cell condition. CTLA-4 was not expressed on resting Mauritius PBMCs and showed a lower up-regulation upon PMA/PHA activation compared to the Philippines PBMCs that expressed CTLA-4 also before activation. Two CTLA-4 RNA transcripts (672 and 550 bp) were detected with levels variations after cell stimulation. Two anti-CTLA-4 immunotoxins induced in vitro apoptosis of activated PBMCs from both sources of cynomolgus monkeys. This is the first report that documents CTLA-4 expression both at protein and transcriptional level by nonhuman primate PBMCs and provides novel perspectives of xeno/allograft rejection immunotherapy based on CTLA-4 targeting. [ABSTRACT FROM AUTHOR]

Benign melanocytic skin lesions may be difficult to differentiate from melanoma both clinically and dermoscopically. One of the most confounding dermoscopic features, commonly seen in melanoma but in our experience also in melanocytic naevi, is represented by the so-called blue–white structures (BWS). To evaluate diagnostic significance and histopathological correlates of BWS seen by dermoscopy in a series of clinically equivocal melanocytic skin lesions that were excised. Patients were recruited from six specialized pigmented lesion clinics in Austria, Italy and Spain over a period of 9 months. All consecutive patients showing one or more melanocytic lesions with BWS, but not classified as melanoma dermoscopically, were included. Each lesion was photographed clinically and dermoscopically. All images were reviewed by one of us and the degree, type and location of BWS evaluated for each lesion. A panel of four experienced dermatopathologists independently reviewed all specimens for diagnosis and one of them evaluated presence and degree of melanosis and/or fibrosis. The main outcome measures were the percentage and histopathological correlates of lesions with different degree, type and location of BWS. All included lesions with BWS ( n = 158) showed partial or focal regression histopathologically. One hundred and thirty-five (85·4%) lesions were diagnosed as melanocytic naevi (complete histopathological interobserver agreement), whereas 23 (14·6%) were defined as equivocal because at least one of four pathologists diagnosed the given lesion as melanoma. Only one lesion was diagnosed as melanoma by all four pathologists. The majority of naevi exhibited blue areas (84·4%) with a central distribution (57%) and involving < 50% of the lesion surface (89·6%). By contrast, 78·3% of equivocal lesions revealed a combination of white and blue areas with an irregular distribution (60·9%) and involving > 50% of the lesion surface (47·8%). Using degree and type of BWS, an algorithm was constructed that can be applied for the management of lesions exhibiting dermoscopic features of regression. [ABSTRACT FROM AUTHOR]

The identification of ricin toxin A-chain (RTA) epitopes and the molecular context in which they are recognized will allow strategies to be devised that prevent/suppress an anti-RTA immune response in patients treated with RTA-based immunotoxins. RTA-specific human T-cell lines and T-cell clones were produced by in vitro priming of PBMC. The T-cell clones used a limited set of Vβ chains (Vβ1, Vβ2 and Vβ8) to recognize RTA epitopes. The use of RTA deletion mutants demonstrated that T-cell lines and T-cell clones from three out of four donors responded to RTA epitopes within the domain D124-Q223, whereas one donor recognized the region I1-D124. The response to RTA peptides of T-cell lines and T-cell clones from two donors allowed the identification of immunogenic segments (D124-G140 and L161-T190) recognized in the context of different HLA-DRB1 alleles (HLA-DRB1*0801, and HLA-DRB1*11011 and B1*03011, respectively). The response to L161-T190 was investigated in greater detail. We found that the HLA-DRB1*03011 allele presents a minimal epitope represented by the sequence I175-Y183 of RTA, whereas the HLA-DRB1*11011 allele presents the minimal epitope M174-I184. RTA peptides and an I175A RTA point mutant allowed us to identify I175 as a crucial residue for the epitope(s) recognized by the two HLA-DRB1 alleles. Failure of T-cell clones to recognize ribosome inactivating proteins (RIPs) showing sequences similar but not identical to RTA further confirmed the role of I175 as a key residue for the epitope recognized in the context of HLA-DRB1*11011/03011 alleles. [ABSTRACT FROM AUTHOR]

The effects of a new inhaled antimuscarinic drug, oxitropium bromide, and of a slow-release theophylline preparation upon nocturnal asthma were compared in a placebo-controlled double-blind study. Two samples were studied: 12 patients received oxitropium at 600 micrograms (6 subjects) or at 400 micrograms t.i.d. (6 subjects) whereas 11 received theophylline at 300 mg b.i.d. Morning dipping, assessed by the fall in peak flow overnight, was significantly reduced in the periods when either active drug was taken, whereas no difference was noticed during the placebo administration. No significant difference was noticed between results obtained with either active drug, as well as with either dosage of oxitropium. No subject reported side effects of oxitropium, as compared to three subjects reporting nausea, vomiting and tremors after theophylline. Oxitropium proves to be a valuable alternative to theophylline in nocturnal asthma, since it is equally potent, safer and does not require the titration of dosage. [ABSTRACT FROM PUBLISHER]

Susceptibility to coeliac disease is strongly associated with some HLA class II antigens, encoded by the HLA-D region. Since the HLA-DQ locus seems to be primarily involved, we have analysed by polymerase chain reaction amplification and allele-specific oligonucleotide hybridization the most polymorphic region of the HLA-DQ Al gene. No difference was observed between the 20 coeliac patients and 20 HLA-D-matched healthy controls who took part in the study. Furthermore, in patients and controls, the restriction fragment length polymorphism analysis of the HLA-DQ A1 gene using the restriction enzyme Bg/II did not disclose any specific disease-associated fragment. Our results are not consistent with a unique DQ A coeliac disease-associated sequence, but rather with the hypothesis that some polymorphic residues or allelic hypervariable regions, although found also in the normal population, can predispose to coeliac disease due to their higher frequency in this condition. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 71-year-old man with papular lesions on his shins and a lump on the right calf. It mentions that he had chronic oedema in his legs for five years and comorbidities of obesity, epilepsy and chronic obstructive pulmonary disease. It also notes that the patient was discovered to have multiple pinkish papules on the left of his shin while a tan-pinked indurated plaque was found on the right.

Melanoma may mimic clinically a number of benign skin tumours by exhibiting overlapping features that do not allow accurate differentiation. Dermoscopy is a noninvasive diagnostic tool allowing the evaluation of specific subsurface morphological structures that are useful in most cases to distinguish melanoma from other melanocytic and nonmelanocytic skin tumours. In order to minimize the risk of missing melanoma, the diagnosis should be based on a good correspondence between the clinical and the dermoscopic findings. The case presented here refers to a melanoma clinically simulating dermatofibroma that was biopsied because dermoscopic examination revealed unusual features that did not confirm the clinical diagnosis. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 32-year-old man presented to dermatology department for evaluation of several papules extending above his scalp, face and trunk and he was diagnosed with cutaneous Langerhans cell histiocytosis (LCH).

A letter to the editor is presented about naevogenesis based on dermoscopy.

Presents a letter to the editor suggesting that the collision of basal cell carcinoma with seborrhoeic keratosis may be a dermoscopic aid to histopathology.