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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. Linked Commentary: H. Helgadottir. J Eur Acad Dermatol Venereol 2022; 36: 167–168. https://doi.org/10.1111/jdv.17879. [ABSTRACT FROM AUTHOR]

Immune-mediated dermatoses in patients with haematological malignancies: a comprehensive review. I Editor i Eosinophilic dermatosis of haematologic malignancy (EDHM) is a pruritic, clinically polymorphic, immune-mediated skin disease that affects patients with blood tumours.1 Notwithstanding the effectiveness of systemic glucocorticoids and other immunosuppressants as frontline therapies, relapses are commonly observed upon discontinuation.2 A woman in her 50s presented to our outpatient dermatology clinic for a 2-month history of a persistent pruritic rash distributed over her upper and lower limbs. Targeted inhibition of IL-4/13 with dupilumab is an effective treatment for eosinophilic dermatosis of hematologic malignancy. [Extracted from the article]

Background Histopathological diagnosis including selection of lesions, the determination of the best point of time for biopsy and workup is not trivial in cutaneous graft-versus-host disease (Gv HD). Objectives To develop interdisciplinary recommendations on performing, the laboratory work up and reporting of the results of skin biopsies in patients with suspected cutaneous Gv HD. Methods A working group consisting of dermatopathologists, dermatologists, transplant-physicians and transplant-pathologists prepared recommendations for performing skin biopsies, laboratory workup and evaluation of tissue samples, and reporting of the results in patients with cutaneous Gv HD. After achieving a consensus within the working group, a survey that comprised the core issues of the recommendations was electronically sent out to 72 allo HSCT centres within Germany, Austria, and Switzerland and their Departments of Pathology. The answers were discussed in a Consensus Conference and final recommendations were established. Results Twenty-five centres responded to the clinical and 17 centres to the histopathological survey. Questions addressed to the clinicians comprised the indication for skin biopsy in chronic GvHD ( cGvHD) and acute GvHD ( aGvHD) and the appropriate point of time for skin biopsy. Eighty-eight per cent agreed that the skin biopsy is generally indicated in patients with suspected cGvHD lacking diagnostic features. In contrast, with suspected aGvHD, only 62% of respondents felt that skin biopsy was necessary even if GvHD had not been confirmed in another organ. Although restricted due to the fact that immunosuppression is often applied in an emergency setting most centres supported skin biopsies before initiation of topical or systemic immunosuppression. The majority of pathologists agreed that in non-sclerotic GvHD a punch biopsy is adequate, whereas in sclerotic GvHD a scalpel biopsy is preferred. Conclusion While a consensus on the need for biopsies in cGvHD was reached the value of skin biopsies in aGvHD and subsequent biopsies during therapy requires further evaluation. [ABSTRACT FROM AUTHOR]

Background Patients who develop cutaneous melanoma are at increased risk of developing a second primary melanoma. There are many aetiological reasons by which the risk of a second melanoma increases. Among others, genetic factors may contribute to modulating this risk. The risk of identifying a CDKN2A germline mutation increases with the number of primary melanomas and with the presence of familial history of melanoma. Patients with melanoma are especially encouraged to have regular follow-up visits with their dermatologist to perform clinical and dermatoscopic examination. In particular, dermoscopy could be very useful in multiple primary melanoma ( MPM) patients. Objectives To analyse the clinical and dermatoscopic features of multiple melanomas, focusing on those features that are more frequently found in the same patient to recognize them earlier and understand whether they appear with the similar peculiar dermatoscopic features, especially in CDKN2A carriers. Methods Medical records of MPM patients were selected from a database including 1065 patients with histopathologically proven melanoma diagnosis, all treated at the dermatology clinic of the University of Florence from 2000 to 2013. Pictures of melanoma were independently and blindly administered to three dermatologist experts in dermoscopy to evaluate the presence or absence of ABCD criteria for each clinical image, and the main pattern for the dermoscopic images. The results were then analyzed and crossed to rate the clinical and dermoscopic features of MPM. Results Seventy five (7.0%) of 1065 patients included in our database were found to carry an MPM disease. Among them, we selected 12 (16%) patients with three or more MPMs. The presence of the CDKN2A melanoma susceptibility gene was observed in 4/12 (33.33%) patients; two patients presented the C500G and c.5 + 1delG polymorphisms in the CDKN2A gene. In CDKN2A carriers, each patient showed a similar and specific dermatoscopic pattern in their lesions. Conclusions Even being aware of the limitations of this study, according to hereditary characters and their modes of transmissions, we could speculate that for each patient with a CDKN2A germline mutation, it is possible to find the same kind of dermoscopical pattern among their melanocytic tumours. [ABSTRACT FROM AUTHOR]

Background Histopathology is an important tool in diagnosing cutaneous graft-versus-host disease (GvHD). Minimum diagnostic criteria for active chronic Gv HD have recently been defined. However, they are not specific and their interpretation is dependent on observer judgement. Objective Aims of the study: i) to explore interobserver variability in the interpretation of histopathological changes in Gv HD, and ii) to analyse the impact of detailed clinical data on histopathological diagnosis of Gv HD. Methods Histopathological slides from 15 skin biopsies of Gv HD and from dermatoses with histopathologically similar appearance were sent in two phases to four dermatopathologists experienced in cutaneous Gv HD in France, Germany, Italy and Switzerland (first round of 'blind' review followed by a second round with complete clinical information provided). Results Interface dermatitis, especially vacuolar alteration, was the most inconsistently evaluated, particularly in cases with minor alterations. Interestingly, for vacuolar alteration and apoptotic keratinocytes, interobserver variability was lower in the adnexal epithelia than in the interfollicular epidermis. Complete clinical information resulted in increased diagnostic confidence and greater concordance on the final diagnosis, rising from 53% (first round, k = 0.345, fair agreement) to 80% (second round, k = 0.529, moderate agreement). The percentage of correct diagnoses increased from 33.3% to 80%. Conclusion For the diagnosis of Gv HD, histopathological analysis is of importance, but, for correct diagnosis, the correlation of pathological findings with clinical results is crucial. In cases of minor alteration, histopathologists should focus on the interpretation of vacuolar changes and apoptotic keratinocytes, possibly on the adnexal epithelia. [ABSTRACT FROM AUTHOR]

We investigated different kinds of human ex-vivo skin samples by combined two-photon intrinsic fluorescence (TPE), second-harmonic generation microscopy (SHG), fluorescence lifetime imaging microscopy (FLIM), and multispectral two-photon emission detection (MTPE). Morphological and spectroscopic differences were found between healthy and pathological skin samples, including tumors. In particular, we examined tissue samples from normal and pathological scar tissue (keloid), and skin tumors, including basal cell carcinoma (BCC), and malignant melanoma (MM). By using combined TPE-SHG microscopy we investigated morphological features of different skin regions. Further comparative analysis of healthy skin and neoplastic samples was performed using FLIM, and MTPE. Finally, we demonstrated the use of methyl-aminolevulinate as a contrast agent to increase the contrast in BCC border detection. The results obtained represent further support for in-vivo noninvasive imaging of diseased skin. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

Protease-activated receptor (PAR)-1 and PAR-2 are reported to contribute to the fibrotic process in a number of organs, including lung, liver, pancreas, and kidney. The aim of this study was to localize expression and biological activity of PAR-1 and PAR-2 in normal and pathological cutaneous scars. First, we investigated the immunohistochemical expression of PAR-1 and PAR-2 proteins in a series of human normal scars (NS, n = 10), hypertrophic scars (HS, n = 10), and keloids (K, n = 10). Expression of PAR-1 and PAR-2 was observed in all types of scar. Specifically, in HS and K, diffuse PAR-1 and PAR-2 positivity was found in dermal cellular areas composed of myofibroblasts, while no or minor staining was observed in the scattered fibroblasts embedded in abundant extracellular matrix in the context of the more collagenous nodules, irrespective of the type of scar. The hyperplastic epidermis overlying K was also found to be strongly PAR-1 and PAR-2 positive, whilst in most NS and HS the epidermis was faintly to moderately stained. Second, ribonuclease protection assay on paraffin-embedded specimens showed overexpression of PAR-1 and PAR-2 mRNA in K compared to NS and HS. Third, cultured human fibroblasts exposed to TGF-β1 expressed a myofibroblast phenotype associated with overexpression of PAR-2, while PAR-1 expression was unaffected. Intracellular Ca2+ mobilization by PAR-2 agonists in myofibroblasts was increased as compared to fibroblasts, whereas the effect of PAR-1 agonists was unchanged. Our in vivo study indicates that PAR-1 and PAR-2 are expressed in cells involved in physiological and pathological scar formation and suggests that in vitro overexpression and exaggerated functional response of PAR-2 may play a role in the function of myofibroblasts in scar evolution from a physiological repair process to a pathological tissue response. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective: Orofacial granulomatosis (OFG) is a rare condition characterized by non-caseating granulomas in the orofacial region. Protease-Activated Receptors (PARs) play a role in inflammatory diseases in diverse human tissues. The aim of the study was to investigate the expression of PAR-1, PAR-2, MMP-2, MMP-9, COX-1, and COX-2 in tissues taken from OFG patients. Methods: PAR-1, PAR-2, MMP-2, MMP-9, COX-1, and COX-2 expression was evaluated by immunohistochemistry in biopsies taken from oral Crohn's disease (five cases), Melkersson–Rosenthal syndrome (MRS) (six cases), cheilitis granulomatosa (five cases) and normal oral mucosa (five cases). Results: PAR-1 was observed in mononuclear inflammatory cells in edematous/lichenoid lesions, whereas a strong PAR-2 immunostaining was detected in epithelioid histiocytes and giant cells in granulomatous lesions, irrespective of the clinical features (Crohn vs MRS). MMPs and COX-2 were expressed in the inflammatory component of edematous/lichenoid lesions and markedly overexpressed in granulomatous lesions. COX-1 was weakly and variably expressed in both edematous/lichenoid and granulomatous lesions. Conclusion: Thus, PAR-1 and PAR-2 expressions were related to the intensity and type of inflammatory response but not to the type of clinical lesion. Simultaneous overexpression of PARs, MMPs and COXs suggests synergism among these proinflammatory receptors and enzymes. [ABSTRACT FROM AUTHOR]

The article describes two examples of tubulo-papillary low-grade sinonasal adenocarcinomas (LGSA) which differed from previously reported cases in their histological features and immunohistochemical profile. The histological and immunohistochemical findings of the cases extend the spectrum of feature s of LGSA. This demonstrates that at least a subset of these tumors are salivary-type tumors with epithelial secretory and myoepithelial features.

A case of subcutaneous alternariosis caused by Alternaria alternata is reported in a 52-year-old male who underwent kidney transplantation 1 year earlier. The infection manifested as a vegetating mass about 7 cm in diameter on the right forearm. Histological examination with Grocott staining and periodic acid–Schiff diastase revealed fungal spores and hyphae with chronic granulomatous inflammation. Biopsy fragments inoculated on Sabouraud-glucose agar with chloramphenicol produced colonies which were identified as Alternaria alternata on the basis of macroscopic and microscopic characters. [ABSTRACT FROM AUTHOR]

ABSTRACT We report two cases of cutaneous B-cell pseudolymphoma (PCBCL) induced by intradermal antigen injections for specific immune therapy (SIT). In both cases, the lesions had first developed on the area of injection; years later, new lesions appeared far from the original site. The histological, immunohistochemical, and molecular findings of the lesions showed features consistent with the diagnosis of PCBCL in both cases. In particular, the staining for sIg light chains showed a polyclonal pattern, and the molecular analysis by reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blot showed a germ-line configuration of the Ig heavy chain genes. While the development of PCBCL related to a specific stimulus is well known and widely reported, the development of histologically and immunohistologically identical lesions far from the injection site is definitely worthy of note. This behaviour might be due to the presence of retained antigens in the injection site. This chronic antigenic stimulation could induce the progressive selection – and subsequent dissemination – of antigen-specific B cell clones. [ABSTRACT FROM AUTHOR]

Abstract Background Pseudopelade of Brocq (PB) is a permanent progressive scarring alopecia characterized by numerous alopecic patches localized only in the scalp, that tend to coalesce into larger, irregular plaques with policyclic borders. PB can be considered either the final atrophic stage of several scarring disorders such as lichen planus pilaris (LPP) and discoid lupus erythematosus (DLE) (secondary PB) or an autonomous disease (primary PB). The aim of this study was to assess the incidence of primary vs. secondary PB by a combined histopathological and immunopathological study in a series of patients who fulfillled the clinical diagnostic criteria for PB set forth by Braun Falco et al . Methods We studied 33 patients (5 males and 28 females, whose age ranged from 24 to 75 years). The duration of the disease (from onset to biopsy) ranged from 3 months to 8 years. Serum samples were tested for circulating auto-antibodies (antinuclear antibodies anti ENA, anticentromere, anti-Scl70, antithyroid, antigastric parietal cells) circulating immune complexes, total and single fraction (C3, C4) complement activity. The skin biopsies taken from the active advancing margin of the more recent alopecic patch were bisected vertically, one was sent for histopathological examination, and the other for the immunofluorescence studies. Results In all patients the serum tests above were found to be negative or normal. Histopathologically, 11 biopsies (33.3%) displayed findings typical for LPP whereas seven cases (21.2%) showed typical DLE features. In the remaining 15 cases (45.5%) histopathological findings were not suggestive of any specific dermatosis. DIF investigations showed findings typical of LPP in six cases (18.1%) and typical of DLE in seven cases (21%). In three cases we did not find findings typical of LPP, DLE, or any other specific dermatitis. In 11 cases no immunological deposits could be detected and therefore were classified as negative. Conclusion In... [ABSTRACT FROM AUTHOR]

Linked article: L. Visseaux et al. J Eur Acad Dermatol Venereol 2019; 33: e193–e193. https://doi.org/10.1111/jdv.15451 [ABSTRACT FROM AUTHOR]

Background The differential diagnosis between Reed nevi and melanoma becomes more difficult if the lesion to analyse presents a small size, with a diameter of 6 mm or smaller. Many studies have reported various dermoscopic features of Reed nevi during their growth phases. In early stages of evolution, the lesions generally show a characteristic globular appearance typically found in childhood, followed by the so-called starburst pattern. Objective The aim of the study was to identify the main dermoscopic features in small Reed nevi (<6 mm in size). Methods Using a computerized skin-imaging database for melanoma prevention surgery at the Department of Dermatology of the University of Florence, 15 Reed nevi were selected among 103 small (<6 mm) melanocytic lesions consecutively excised. Images of small Reed nevi, independently blinded to histopathological diagnosis, were administered to a dermatologist expert in dermoscopy, who separately examined the clinical and the dermatoscopic images of small Reed nevi and evaluated their clinical and dermoscopic parameters. Results Analysis of the main dermoscopic patterns showed that 40% had a reticular pattern, 20% had a starburst pattern, 6.5% had a globular pattern, 6.5% had a homogeneous pattern and 27% had an atypical pattern. Conclusion We propose that small, early-stage Reed nevus are not characterized by an evolution of growth patterns to a phenotype typical of larger lesions. We assume that the patterns are distributed in a linear manner between age groups, may all be present at the outset and thus are independent from the various stages of nevus development. [ABSTRACT FROM AUTHOR]

Background Two-photon excitation (TPE) fluorescence microscopy is a high-resolution laser-scanning imaging technique enabling deep imaging inside biological tissues. TPE microscopy has the triple advantage of offering high spatial resolution (250 nm radially, 800 nm axially), high penetration depth inside skin (200mm ), and low photodamage effects. Further, cells and extracellular matrix intrinsically contain a variety of fluorescent molecules (NADH, tryptophan, keratins, melanin, elastin, cholecalciferol and others), so that biological tissues can be imaged by TPE microscopy without any exogenous probe. The time-resolved analysis of the fluorescence signal, known as fluorescence lifetime imaging microscopy (FLIM), is an additional non-invasive microscopy technique useful to characterize endogenous fluorescence species and their surrounding medium by measuring the mean lifetime of fluorescent emission. Finally, multispectral (MTPE) tissue imaging can also be used to identify different endogenous fluorescent species by measuring their two photon emission spectra. Those techniques offer functional information about the relative quantities of fluorescent molecules, which are correlated with tissue structure in physiological and pathological states. Objective We have decided to apply these three methods at the same time for cutaneous tumors in order to evaluate their possible future use. Method We have analyzed a melanoma and a basal cell carcinoma, with their surrounding healthy skin, to evaluate any difference in healthy skin and neoplasia. The samples were excised during dermatological surgery, then cut, saving some healthy skin in both, to obtain a regular shape, allowing its positioning either with the skin surface parallel to the optical axis (horizontal optical sectioning), or perpendicular (vertical optical sectioning). Conclusion This first result demonstrates that FLIM is effective in discriminating healthy skin from MM, while MTPE is effective in discriminating healthy skin from BCC. Conflicts of interest None declared [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to an article related to the recurrent basal cell carcinoma of the nose successfully treated by photodynamic therapy.

A letter to the editor is presented about pseudoclubbing of a fingernail caused by spontaneous subungual hemangioma.

A letter to the editor is presented about a case of a 29-year-old white male diagnosed with nervus anaemicus, a rare congenital, localized vascular abnormality, usually present at birth or may appear in early childhood.

Abstract Basal cell carcinomas may attain giant proportions due primarily to recurrence or because the tumour is neglected. We report the case of a 66-year-old man who presented with a bleeding, polypoid, cutaneous tumour located on the left shoulder region of 13 years duration. The man had not received any previous treatment. The lesion was biopsied and histopathologically diagnosed as a solid type basal cell carcinoma with focal areas of squamous differentiation and keratinization. The man refused complete surgical removal and therefore was treated with roentgentherapy, with satisfactory results and no complications in the irradiated area. No recurrences had manifested after 1 year follow-up. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 48-year-old Caucasian woman with multiple, widespread, subcutaneous nodules and bilateral enlarged axillary lymph nodes. The patient has no previous melanoma history, and a primary melanoma could not be identified at the time of diagnosis. Also tackled are the reasons behind the uniqueness of the clinical case.

The article informs about a study based on the assessment of the risk of inducing a second melanoma in patients with previous primary melanoma. It mentions that standardized incidence ratio (SIR) approach was employed in the study. It includes routine follow-up was performed every six months consisting of complete physical examination. It proposes that the risk of second melanoma is highest in the first three months after first melanoma diagnosis.

Background: The prognostic impact of variant allele frequency (VAF) on clinical outcome in BRAFV600 mutated metastatic melanoma patients (MMPs) receiving BRAF (BRAFi) and MEK inhibitors (MEKi) is unclear., Materials and Methods: A cohort of MMPs receiving first line BRAFi and MEKi was identified by inspecting dedicated databases of three Italian Melanoma Intergroup centres. VAF was determined by next generation sequencing in pre-treatment baseline tissue samples. Correlation between VAF and BRAF copy number variation was analysed in an ancillary study by using a training and a validation cohort of melanoma tissue samples and cell lines., Results: Overall, 107 MMPs were included in the study. The VAF cut-off determined by ROC curve was 41.3%. At multivariate analysis, progression-free survival (PFS) was significantly shorter in patients with M1c/M1d [HR 2.25 (95% CI 1.41-3.6, p < 0.01)], in those with VAF >41.3% [HR 1.62 (95% CI 1.04-2.54, p < 0.05)] and in those with ECOG PS ≥1 [HR 1.82 (95% CI 1.15-2.88, p < 0.05)]. Overall survival (OS) was significantly shorter in patients with M1c/M1d [HR 2.01 (95% CI 1.25-3.25, p < 0.01)]. Furthermore, OS was shorter in patients with VAF >41.3% [HR 1.46 (95% CI 0.93-2.29, p = 0.06)] and in patients with ECOG PS ≥1 [HR 1.52 (95% CI 0.94-2.87, p = 0.14)]. BRAF gene amplification was found in 11% and 7% of samples in the training and validation cohort, respectively., Conclusions: High VAF is an independent poor prognostic factor in MMP receiving BRAFi and MEKi. High VAF and BRAF amplification coexist in 7%-11% of patients., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Many melanoma observational studies have been carried out across different countries and geographic areas using heterogeneous assessments of epidemiologic risk factors and clinical variables., Aim: To develop a consensus questionnaire to standardize epidemiologic and clinical data collection for melanoma risk assessment., Methods: We used a stepwise strategy that included: compilation of variables from case-control datasets collected at various centres of the MelaNostrum Consortium; integration of variables from published case-control studies; consensus discussion of the collected items by MelaNostrum members; revision by independent experts; addition of online tools and image-based charts; questionnaire testing across centres and generation of a final draft., Results: We developed a core consensus questionnaire (MelanoQ) that includes four separate sections: A. general and demographic data; B. phenotypic and ultraviolet radiation exposure risk factors and lifestyle habits; C. clinical examination, medical and family history; and D. diagnostic data on melanoma (cases only). Accompanying online tools, informative tables, and image-based charts aid standardization. Different subsections of the questionnaire are designed for self-administration, patient interviews performed by a physician or study nurse, and data collection from medical records., Conclusions: The MelanoQ questionnaire is a useful tool for the collection and standardization of epidemiologic and clinical data across different studies, centres, cultures and languages. This will expedite ongoing efforts to compile high-quality data for pooled analyses or meta-analyses and offer a solid base for the design of clinical, epidemiologic and translational studies on melanoma., (© 2018 European Academy of Dermatology and Venereology.)

We report the case of a 76-year-old Caucasian woman who attended our clinic with multiple keratoacanthomas. Radiotherapy was considered a viable and effective option in such an old patient, who could not be a good surgical candidate for number and distribution of the lesions, and for the age. After a 12-month follow-up, we observed the complete and global disappearance of the lesions; the patient was therefore very satisfied especially in view of the clinical outcome. According to our point of view, radiotherapy allows the physician to obtain a good oncological radicality and excellent cosmetic results too., (© 2013 Wiley Periodicals, Inc.)

Lichen simplex chronicus (LSC) is a skin disorder characterized by chronic itching and scratching, which can lead to thick, leathery, brownish skin, sometimes with papules and can be associated with atopic eczema. We report the case of a 52-year-old man with a 45-year atopic condition and presenting LSC in his dorsum. After a 3-month treatment with alitretinoin at the daily dosage of 30 mg, we have observed a moderate improvement of the hand eczema together with a substantial clinical improvement of LSC and an almost complete resolution of pruritus. We want to report this peculiar case to suggest the use of oral alitretinoin for LSC., (© 2013 Wiley Periodicals, Inc.)

Caveolae are non-clathrin invaginations of the plasma membrane in most cell types; they are involved in signalling functions and molecule trafficking, thus modulating several biological functions, including cell growth, apoptosis and angiogenesis. The major structural protein in caveolae is caveolin-1, which is known to act as a key regulator in cancer onset and progression through its role as a tumour suppressor. Caveolin-1 can also promote cell proliferation, survival and metastasis as well as chemo- and radioresistance. Here, we discuss recent findings and novel concepts that support a role for caveolin-1 in cancer development and its distant spreading. We also address the potential application of caveolin-1 in tumour therapy and diagnosis., (© 2013 The Authors. Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.)

Although conventional histopathologic examination is still the undisputable mainstay for the diagnosis of melanocytic skin neoplasms, application of molecular testing has experienced tremendous growth and will continue to expand in the future as the need for more specific diagnoses and new targeted therapies evolve. Ancillary molecular methods, including comparative genomic hybridization and fluorescence in situ hybridization, have the potential to provide important new information to challenging cases, and will help improve diagnostic accuracy, particularly in cases in which morphology is not conclusive. Pathologists are increasingly involved in the prospective genotyping of melanoma, which leads to patient stratification in light of the novel personalized therapeutic approaches in the advanced setting., (© 2012 Wiley Periodicals, Inc.)

A 20-year-old man with mental impairment, was referred to us for evaluation of recurring idiopathic urticaria episodes, characterized by a diffuse spreading of wheals and severe itching lacking response to traditional antihistamines. Upon physical examination, he showed a persistent, generalized, reticular, red-bluish vascular skin pattern in association with diffuse arborizing telangiectasias. Such lesions were present from an early age. Laboratory and instrumental tests, performed in order to exclude any condition associated with livedo did not evidence pathological results. He was found to be positive for antinuclear autoantibodies (ANA; 1:640). Histopathologically, numerous dilated capillary vessels associated with sparse extravasated erythrocytes were observed in the upper dermis. We performed an autologous serum skin test (ASST), which resulted in a positive, suggesting an autoimmune basis of the condition. On the basis of clinical and histopathological findings, and in the absence of other clinical and laboratory data suggesting other neoplastic, immunological or systemic diseases, the diagnosis of cutis marmorata telangiectatica congenita (CMTC) associated with chronic autoimmune urticaria (CAIU) was made. CMTC is a rare congenital vascular disorder, consisting in an anomalous, persistent, red-bluish marbling of the skin, that can be associated with a wide spectrum of cutaneous and extracutaneous anomalies. In our case, neither physical examination nor instrumental investigation demonstrated any of these anomalies, with the exception of cognitive impairment. We report this case because of the rarity of a diagnosis of CMTC in an adult patient, because this condition has almost always previously been diagnosed in infancy, or it comes to observation because of the presence of associated disorders, as in our case for chronic urticaria.

We report on a 14-year-old boy who presented with a 4-year history of acral pains and febrile episodes. On physical examination, numerous small reddish papules were present on his abdomen, located predominantly on the periumbelical region. Renal function was within normal limits. Ophthalmological examination revealed whorled opacities of the cornea (cornea verticillata) and dilated tortuous conjunctival vessels. Histopathological examination of one of the cutaneous papules showed several dilated blood vessels in the superficial dermis surrounded by collarettes of thickened rete ridges, consistent with a diagnosis of angiokeratoma. The electron-microscopic study of a skin specimen demonstrated the presence of dilated lysosomes with deposition of electron-dense bodies, some of which with laminated structure, in endothelial cells and fibroblasts. These findings were regarded as indicative of Fabry's disease. Subsequent biochemical analysis confirmed the presence of a alpha-galactosidase A deficiency in leukocytes. In conclusion, we described the clinical, histopathological and submicroscopic findings of a case of Fabry's disease, in which the combination of electron microscopic and biochemical approaches allowed the correct diagnosis.

We report on a patient developing simultaneous occurrence of lentigo maligna lesions, solar lentigines and an extensive melanosis of the oral mucosa. Diagnostically, epiluminescence microscopy had a relevant role in the preoperative assessment and selection of suspicious pigmented lesions, as the lesions histologically labelled as lentigo maligna and solar lentigo were clinically indistinguishable. We review the clinical, dermoscopic and histopathologic differential diagnosis of solar lentigo, malignant lentigo and mucosal melanosis with other melanocytic and keratinocytic lesions and discuss the possible relationship between these entities.

A 20-year-old male presented with a 4 year history of a solitary nodule, 8 mm in diameter on the left temple. It was covered by normal skin, with a central depression and elevated borders. Histopathology showed numerous horn cysts amidst nests and strands of basaloid cells surrounded by a dense fibrous stroma. The clinical and histopathological features were characteristic of desmoplastic trichoepithelioma.