Meshwork Pattern Research Articles

Application of dermoscopy and reflectance confocal microscopy in vivo in the evaluation of nevi in children.

Melanocytic nevi are frequently observed in the pediatric population. While newly acquired nevi can appear during childhood, congenital nevi can continue to grow and clinically change, making patient caregivers concerned. Reflectance confocal microscopy (RCM) in vivo is a noninvasive tool that might enhance the diagnostic accuracy of dermoscopy, reducing the rate of unnecessary surgical procedures. This study aimed to assess the utility of RCM in increasing the diagnostic accuracy of pediatric melanocytic nevi that show pigmentation changes or grow rapidly. Pediatric patients who presented between January 2022 and February 2023 in a single institution with rapidly growing melanocytic nevi or nevi that presented changes in the pigmentation were included in the study. All nevi were evaluated by means of dermoscopy and RCM. Forty-two patients with a total of 42 melanocytic nevi were included. Most lesions showed a honeycombed pattern (n = 21, 50%). On RCM, only 3 of 42 nevi presented atypical cells within the epidermis (7.1%). Evaluation of the dermoepidermal junction (DEJ) revealed the predominance of the meshwork pattern (n = 22, 52.4%). Notably, features considered significant for atypical melanocytic nevi included 9 nevi with scant atypical melanocytes (21.4%) and 3 nevi with nonedge papillae (7.1%). None of the studied lesions required biopsy among this cohort. Most rapidly growing and clinically changing nevi rarely exhibit single atypical cells in the DEJ. The RCM served as a valuable adjunct to dermoscopy, allowing reassurance in the evaluation of these lesions.

Is reflectance confocal microscopy useful in the differential diagnosis of extra facial lentigo maligna? A retrospective multicentric case-control study.

Extra facial lentigo maligna (EF-LM) arises outside the head and neck area. EF-LM presents the classic histological features of lentigo maligna. The dermoscopic aspects of EF-LM have been poorly studied. The primary aims of our study were to analyse and describe the clinical, dermoscopic and confocal microscopy features of a series of histologically confirmed EF-LM. We conducted a retrospective and multicentric study. From our database, we selected 48 cases of thin melanomas on photodamaged skin with histological features of EF-LM of which clinical, dermoscopic and confocal microscopy images were available, and a control group of 45 lesions, that can be subjected to differential diagnosis such as solar lentigo, lichenoid keratosis, seborrheic keratosis and melanocytic nevi, of which dermoscopic and confocal microscope images were available. Extra facial lentigo maligna had a higher prevalence of lentigo-like pigment patterns, angulated lines and zigzag structures. At confocal microscopy, LM-EF cases showed a higher prevalence of pagetoid spreading, round cells, dendritic cells in the epidermis, atypical cells at the dermo-epidermal junction, dendritic cells at the junction, meshwork pattern and elastosis. Our study shows that reflectance confocal microscopy (RCM) has a sensitivity of 90% and a specificity of 97% for the differential diagnosis of this type of melanoma. Extra facial lentigo maligna does not have the classic dermoscopic features of superficial spreading melanoma, the most observed dermoscopic criteria are angulated lines and lentigo-like pigment patterns without lentigo-like border. RCM can be a valuable imaging tool for the evaluation of all those suspicion skin lesions at dermoscopy highlighting cellular atypia suggestive for melanoma.

Evaluation and Comparison of Mechanical Properties of Heat Polymerized Acrylic Resin After Reinforcement of Different Fibers in Different Patterns: An In Vitro Study.

Most denture fractures occur within the mouth due to resin flexural fatigue. For example, the deep labial notch at the high labial frenum causes denture breakage, as can deep scratches and generated processing stresses. The rising cost of annual prosthetic repairs is evidence that the problem of total denture fracture has not been solved. The purpose of this investigation was to evaluate the relative improvement in flexural strength between heat-cured polymethyl methacrylate (PMMA) resin reinforced with glass fibers (GF) and basalt fibers (BF) of varied orientations. A total of 150 heat-cured acrylic resin specimens of 65x10x3 mm dimension were prepared, 30 of which were left unreinforced (Group A), 30 of which were reinforced with GF in transverse pattern (Group B), 30 of which were reinforced with GF in meshwork pattern (Group C), 30 of which were reinforced with BF in transverse pattern (Group D), and 30 of which were reinforced with BF in meshwork pattern (Group E).All of the samples were put through flexural strength testing on the universal testing machine. One-way ANOVA and the Tukey-Kramer various correlation test (= 0.05) were used in SPSS for Windows to look at the facts. The mean flexural strength for Group A was 46.26±2.26 MPa, 64.98±1.53 MPa for Group B, 76.45±2.67 MPa for Group C, 54.22±2.24 MPa for Group D, and 59.02±2.38 MPa for Group E. Flexural strength was impacted by both the kind of BF and GF reinforcement (F = 768.316, P = 0.001). Within the limitation of the current research, BF reinforcement outperforms GF reinforcement and unreinforced heat-cured acrylic resin in terms of flexural strength.

Manipulation of Heterogeneous Surface Electric Potential Promotes Osteogenesis by Strengthening RGD Peptide Binding and Cellular Mechanosensing.

The heterogeneity of extracellular matrix (ECM) topology, stiffness, and architecture is a key factor modulating cellular behavior and osteogenesis. However, the effects of heterogeneous ECM electric potential at the micro- and nanoscale on osteogenesis remain to be elucidated. Here, the heterogeneous distribution of surface potentialis established by incorporating ferroelectric BaTiO3 nanofibers (BTNF) into poly(vinylidene fluoridetrifluoroethylene) (P(VDF-TrFE)) matrix based on phase-field and first-principles simulation. By optimizing the aspect ratios of BTNF fillers, the anisotropic distribution of surface potential on BTNF/P(VDF-TrFE) nanocomposite membranes can be achieved by strong spontaneous electric polarization of BTNF fillers.Theseresults indicate that heterogeneous surface potential distribution leads to a meshwork pattern of fibronectin (FN) aggregation, which increased FN-III7-10 (FN fragment) focal flexibility and anchor points as predicted by molecular dynamics simulation. Furthermore, integrin clustering, focal adhesion formation, cell spreading, and adhesionare enhanced sequentially. Increased traction of actin fibers amplifies mechanotransduction by promoting nuclear translocation of YAP/Runx2, which enhances osteogenesis in vitro and bone regeneration in vivo. The work thus provides fundamental insights into the biological effects of surface potential heterogeneity at the micro- and nanoscale on osteogenesis, and also develops a new strategy to optimize the performance of electroactive biomaterials for tissue regenerative therapies.

Spitz nevus and melanoma: evaluation with dermoscopy and reflectance confocal microscopy.

Spitz nevi (SN) include a wide range of benign melanocytic nevi, which are controversial due to their morphologic resemblance to melanoma (MM). To describe dermoscopic and reflectance confocal microscopic (RCM) features of SN compared to MM and assess the RCM utility in the differential diagnosis. We performed a multicentre retrospective analysis of MM and SN evaluated with dermoscopy and reflectance confocal microscopy. Three RCM mosaics were obtained for each lesion. Nine dermoscopic and twenty-one microscopic features were assessed for each lesion. A total of 26 lesions (15 SN and 11 MM) were included. Dermoscopically, most SN showed a "starburst" pattern. Asymmetry was marked in 8 MM. There were 6 dermoscopic features significantly more prevalent in MM than in SN. RCM showed that an atypical honeycomb pattern, atypical infiltration, and disarray of the epidermis were significant for MM. SN mostly revealed a typical honeycomb pattern. At the DEJ, most of SN had a meshwork pattern; MM revealed an atypical meshwork pattern. Atypical cells and sheet-like structures were observed in most MM. A combined approach using dermoscopy and RCM supports the differential diagnosis of SN and MM. Although our study showed some significant differences between SN and MM in RCM, further research on a larger group should be considered.

Computational Model Exploring Characteristic Pattern Regulation in Periventricular Vessels.

The developing neocortical vasculature exhibits a distinctive pattern in each layer. In murine embryos, vessels in the cortical plate (CP) are vertically oriented, whereas those in the intermediate zone (IZ) and the subventricular zone (SVZ) form a honeycomb structure. The formation of tissue-specific vessels suggests that the behavior of endothelial cells is under a specific regulatory regime in each layer, although the mechanisms involved remain unknown. In the present study, we aimed to explore the conditions required to form these vessel patterns by conducting simulations using a computational model. We developed a novel model framework describing the collective migration of endothelial cells to represent the angiogenic process and performed a simulation using two-dimensional approximation. The attractive and repulsive guidance of tip cells was incorporated into the model based on the function and distribution of guidance molecules such as VEGF and Unc ligands. It is shown that an appropriate combination of guidance effects reproduces both the parallel straight pattern in the CP and meshwork patterns in the IZ/SVZ. Our model demonstrated how the guidance of the tip cell causes a variety of vessel patterns and predicted how tissue-specific vascular formation was regulated in the early development of neocortical vessels.

Morphological evaluation of melanocytic lesions with three-dimensional line-field confocal optical coherence tomography: correlation with histopathology and reflectance confocal microscopy. A pilot study.

Line-field confocal optical coherence tomography (LC-OCT) is a new invivo emerging technique that provides cellular resolution, allows deep imaging (400 μm) and produces real-time images in both the horizontal and vertical plane and in three dimensions. No previous description of different subtypes of melanocytic lesions and their correlation with histopathology and reflectance confocal microscopy has been reported. To describe the features of melanocytic lesions by LC-OCT and their correlation with histopathology and reflectance confocal microscopy (RCM) findings. Selected melanocytic benign lesions and melanomas were imaged invivo with RCM and LC-OCT at the Fundación Hospital Clinic (Barcelona, Spain). A minimum area of 4 × 4 mm (block image) at four depths (stratum granulosum, suprabasal, layer dermoepidermal junction and upper dermis) were acquired with RCM and a minimum of three cubes with LC-OCT. Horizontal, vertical sections and three-dimensional (3D) cubes of LC-OCT were matched with RCM (Vivablock two-dimensional composite mosaic) and histopathology, with ~5 μm lateral resolution accuracy (the same cell nuclei were measured in X, Y and Z) and evaluated by three observers experienced in using RCM and histopathology. In total, 12 melanocytic tumours (2 insitu melanomas, 2 invasive melanomas, 4 atypical naevi, 2 intradermal naevi, 1 compound naevus and 1 junctional naevus) were included. High correlation with 5 μm accuracy between RCM and LC-OCT was observed for each tumour. The 3D images of melanocytic lesions were obtained with cellular resolution and correlated with both RCM and histopathology, allowing an understanding of the architecture and precise correlation at the cellular level with RCM. Similarities between LC-OCT and RCM for the described diagnostic features and architecture (nests of melanocytic cells, ringed and meshwork pattern, and cellular details of tumour cells as dendritic and pagetoid cells) were confirmed. The main advantage of diagnosis by RCM fixed probe was the ability to produce larger scans of the lesion using mosaicing compared with an LC-OCT handheld probe. LC-OCT allows the architectural and cellular description of different types of melanocytic lesions. LC-OCT showed high correlation with histopathology (vertical sections) and RCM (horizontal sections) in melanocytic lesions. Diagnostic criteria for RCM were similar to those for LC-OCT.

Wavelength of a Turing-type mechanism regulates the morphogenesis of meshwork patterns

The meshwork pattern is a significant pattern in the development of biological tissues and organs. It is necessary to explore the mathematical mechanism of meshwork pattern formation. In this paper, we found that the meshwork pattern is formed by four kinds of stalk behaviours: stalk extension, tip bifurcation, side branching and tip fusion. The Turing-type pattern underlying the meshwork pattern is a Turing spot pattern, which indicates that the Turing instability of the spot pattern promotes activator peak formation and then guides the formation of meshwork patterns. Then, we found that the Turing wavelength decreased in turn from tip bifurcation to side branching to tip fusion via statistical evaluation. Through the functional relationship between the Turing wavelength and model parameters (upvarepsilon ,{ rho }_{A} and {rho }_{H}), we found that parameters upvarepsilon and {rho }_{H} had monotonic effects on the Turing wavelength and that parameter {rho }_{A} had nonmonotonic effects. Furthermore, we performed simulations of local meshwork pattern formation under variable model parameter values. The simulation results verified the corresponding relationship between the Turing wavelength and stalk behaviours and the functional relationship between the Turing wavelength and model parameters. The simulation results showed that the Turing wavelength regulated the meshwork pattern and that the small Turing wavelength facilitated dense meshwork pattern formation. Our work provides novel insight into and understanding of the formation of meshwork patterns. We believe that studies associated with network morphogenesis can benefit from our work.

Morphological evolution of silica scales in the freshwater genus Synura (Stramenopiles).

A high degree of morphological variability is expressed between the ornately sculptured siliceous scales formed by species in the chrysophycean genus, Synura. In this study, we aimed to uncover the general principles and trends underlying the evolution of scale morphology in this genus. We assessed the relationships among thirty extant Synura species using a robust molecular analysis that included six genes, coupled with morphological characterization of the species-specific scales. The analysis was further enriched with addition of morphological information from fossil specimens and by including the unique modern species, Synura punctulosa. We inferred the phylogenetic position of the morphologically unique S.punctulosa, to be an ancient Synura lineage related to S.splendida in the section Curtispinae. Some morphological traits, including development of a keel or a labyrinth ribbing pattern on the scale, appeared once in evolution, whereas other structures, such as a hexagonal meshwork pattern, originated independently several times over geologic time. We further uncovered numerous construction principles governing scale morphology and evolution, as follows: (i) scale roundness and pore diameter decreased during evolution; (ii) elongated scales became strengthened by a higher number of struts or ribs; (iii) as a consequence of scale biogenesis, scales with spines possessed smaller basal holes than scales with a keel and; and (iv) the keel area was proportional to scale area, indicating its potential value in strengthening the scale against breakage.

Epididymal Appearance in Congenital Absence of Vas Deferens.

Scrotal sonography was performed in the infertile males. Sonography of epididymis was performed to document its presence, appearance, echo texture and duct ectasia. The spermatic cord was examined to document the status of the vas deferens. TRUS was performed to look for distal vas. Epididymal abnormalities were universal in men with congenital bilateral absence of vas deferens, with a sensitivity of 100%. Three types of abnormal appearances were recognized - a honeycomb appearance, a fine meshwork pattern of head, or complete or partial absence of epididymis. Identification of these abnormalities can be a very sensitive marker for congenital bilateral absence of vas deferens.

Dynamic actin-mediated nano-scale clustering of CD44 regulates its meso-scale organization at the plasma membrane.

Transmembrane adhesion receptors at the cell surface, such as CD44, are often equipped with modules to interact with the extracellular matrix (ECM) and the intracellular cytoskeletal machinery. CD44 has been recently shown to compartmentalize the membrane into domains by acting as membrane pickets, facilitating the function of signaling receptors. While spatial organization and diffusion studies of membrane proteins are usually conducted separately, here we combine observations of organization and diffusion by using high spatio-temporal resolution imaging on living cells to reveal a hierarchical organization of CD44. CD44 is present in a meso-scale meshwork pattern where it exhibits enhanced confinement and is enriched in nanoclusters of CD44 along its boundaries. This nanoclustering is orchestrated by the underlying cortical actin dynamics. Interaction with actin is mediated by specific segments of the intracellular domain. This influences the organization of the protein at the nano-scale, generating a selective requirement for formin over Arp2/3-based actin-nucleation machinery. The extracellular domain and its interaction with elements of ECM do not influence the meso-scale organization, but may serve to reposition the meshwork with respect to the ECM. Taken together, our results capture the hierarchical nature of CD44 organization at the cell surface, with active cytoskeleton-templated nanoclusters localized to a meso-scale meshwork pattern.

Reflectance confocal microscopy features of melanomas on the body and non-glabrous chronically sun-damaged skin.

Melanoma remains a challenge to diagnose, especially when appearing on the background of chronically sun-damaged skin (CSDS). Our goal was to identify and quantify the reflectance confocal microscopy (RCM) features of melanoma on non-facial CSDS. Included lesions were biopsy-proven melanomas, from anatomic sites other than the face, neck, scalp and acral skin, with histopathologic finding of solar elastosis in the underlying dermis. All included lesions underwent clinical, dermoscopic and RCM imaging, obtained in a standardized fashion, prior to biopsy. All images were retrospectively analyzed by four observers. We identified 33 melanomas from 33 patients with 63.6% male patients and overall mean age of 72.8 years. The salient RCM features included an atypical honeycomb or disarranged epidermal pattern (81.8%), pagetoid infiltration of the epidermis by both round and/or dendritic melanocytes (100%), focal proliferation of predominantly dendritic melanocytes as sheets (78.8%), foci with non-edged papillae (84.8%), junctional thickening (60.6%), areas of irregular ring or meshwork pattern (78.8%), and underlying thickened collagen bundles (51.5%). Non-facial CSDS melanomas share features similar to other melanoma types including pagetoid cells and non-edged papillae. The focal proliferation of dendritic pagetoid cells in sheets is similar to that seen in facial CSDS melanomas.

Meshwork pattern transformed from branching pattern in spherical shell domain

The alveolar microvascular network is significant for the lung development of vertebrates, which is consisted of tree-like main veins and interconnected capillaries between the main veins. However, it is still unclear how the meshwork pattern is formed by the multigenerational branches.Based on the reaction-diffusion model, we find that the meshwork pattern is transformed from the branching pattern in a spherical shell domain. Furthermore, we find that it is the branch tip fusion that facilitates the meshwork pattern formation, which is guided by the activator peak fusion, and it is the insufficient space for branch tip growth that promotes the branch tip fusion. In addition, we notice that the consumption rate of substrate regulates the meshwork pattern formation and an asymmetric shell domain composed of prolate and oblate hemi-ellipsoidal shell facilitates the dense meshwork pattern formation.Our model provides a qualitative understanding of how the vascular system remodels from the branching pattern to the meshwork pattern and how to make a dense meshwork pattern.Both researches associated with branching and network morphogenesis can benefit from our work.

Plasma proteomics identifies a 'chemokine storm' in idiopathic multicentric Castleman disease.

Human Herpesvirus-8 (HHV-8)-negative/idiopathic multicentric Castleman disease (iMCD) is a poorly understood disease involving polyclonal lymphoproliferation with dysmorphic germinal centers, constitutional symptoms, and multi-organ failure. Patients can experience thrombocytopenia, anasarca, reticulin fibrosis, renal dysfunction, organomegaly, and normal immunoglobulin levels, - iMCD-TAFRO. Others experience thrombocytosis, milder effusions, and hypergammaglobulinemia, -iMCD-Not Otherwise Specified (iMCD-NOS). Though the etiology is unknown in both subtypes, iMCD symptoms and disease progression are believed to be driven by a cytokine storm, often including interleukin-6 (IL-6). However, approximately two-thirds of patients do not respond to anti-IL-6 therapy; alternative drivers and signaling pathways are not known for anti-IL-6 nonresponders. To identify potential mediators of iMCD pathogenesis, we quantified 1129 proteins in 13 plasma samples from six iMCD patients during flare and remission. The acute phase reactant NPS-PLA2 was the only significantly increased protein (P = .017); chemokines and complement were significantly enriched pathways. Chemokines represented the greatest proportion of upregulated cytokines, suggesting that iMCD involves a chemokine storm. The chemokine CXCL13, which is essential in homing B cells to germinal centers, was the most upregulated cytokine across all patients (log2 fold-change = 3.22). Expression of CXCL13 was also significantly increased in iMCD lymph node germinal centers compared to controls in a stromal meshwork pattern. We observed distinct proteomic profiles between the two iMCD-TAFRO patients, who both failed anti-IL-6-therapy, and the four iMCD-NOS patients, in whom all three treated with anti-IL-6-therapy responded, suggesting that differing mechanisms may exist. This study reveals proteomic differences between flare and remission and the potential to molecularly define iMCD subgroups.

Reinterpreting dermoscopic pigment network with reflectance confocal microscopy for identification of melanoma-specific features.

Pigment network is an important dermoscopic feature for melanocytic lesions, but alterations in grid line thickness are also observed in melanomas. To investigate features of thick, thin and mixed pigment networks at dermoscopy and their respective features at reflectance confocal microscopy (RCM) for differential diagnosis, correlated with histology. All melanocytic lesions with histological diagnosis, evaluated between January 2010 and May 2014, were enrolled and classified according to dermoscopy evaluation of the pigment networks: thin, thick and mixed. Thin network in melanoma was characterized by a honeycombed pattern (P < 0.001), dendritic cells (P < 0.001), atypical ringed pattern (P = 0.035) and structureless area (P = 0.012), whereas round cells (P < 0.001), dendritic cells (P < 0.001) and atypical meshwork pattern (<0.001) characterized thick network in melanoma. Mixed network type in melanoma shared honeycombed (P = 0.049) and typical ringed patterns (P = 0.045) in the thin area and round cells (P < 0.001) and atypical meshwork pattern (P < 0.001) in the thick area. Thin network in nevi was characterized by cobblestone (P < 0.001) and typical ringed patterns (P = 0.035), whereas thick network in nevi showed a typical meshwork pattern (P < 0.001). Mixed nevi shared the same features and patterns, but more frequently with inflammatory infiltrate (P = 0.047). Differential diagnosis between melanocytic lesions (nevi or melanoma) in thin, thick and mixed pigment networks observed at dermoscopy can be assisted by RCM to improve diagnostic accuracy.

Clinicopathological features of neuroblastic tumors with opsoclonus-myoclonus-ataxia syndrome: Follicular structure predicts a better neurological outcome.

Neuroblastic tumors (NT) with opsoclonus-myoclonus syndrome (OMS) display characteristic histological features, such as lymphocytic infiltration with lymphoid follicles, indicating an underlying immune response. We retrospectively assessed NT patients from 2001 to 2016. Five cases of NT with OMS and 76 cases of NT without OMS were histopathologically reviewed in this study. The grade of lymphocytic infiltration was evaluated. The number of follicles was counted and the presence or absence of lymphoid follicles was recorded for each case. We also confirmed the presence or absence of follicular dendritic cells (FDCs). We investigated the relationship between the histopathological and clinical findings of NT with OMS. Lymphocytic infiltration was observed in all cases; however, the precise follicular structure was occasionally unclear. Patients with clear follicular structures displayed germinal centers including tingible body macrophages and FDCs. All patients without neurological sequelae demonstrated a clear follicular structure with a FDC meshwork pattern. The interval between OMS onset and the detection and initial treatment of NT was typically longer in patients with neurological sequelae compared to those without neurological sequelae. Early detection and treatment of NT with OMS at the phase of a clear follicular formation with multiple FDC may provide favorable neurological outcomes.

Reflectance confocal microscopy correlates of dermoscopic patterns of facial lesions help to discriminate lentigo maligna from pigmented nonmelanocytic macules.

The clinical recognition of lentigo maligna (LM) and LM melanoma can be very challenging due to the overlapping features it shares with other pigmented macules of the skin. Noninvasive diagnostic techniques can assist in the differential diagnosis. To identify reflectance confocal microscopy (RCM) indicators for LM through the identification of in vivo microscopic substrates of the main dermoscopic features seen in flat pigmented lesions of the face. Retrospective analysis of 60 pigmented lesions (LM, invasive melanoma, solar lentigo/flat seborrhoeic keratosis, lichen planus-like keratosis, pigmented actinic keratosis) was carried out. The main dermoscopic patterns and RCM features were described. A new method for correlating RCM with dermoscopic patterns was developed. Pseudonetwork (37 of 60 lesions) and annular granular structures (37 of 60 lesions) were the most frequent dermoscopic patterns, followed by pigmented blotches (27 of 60 lesions). Upon RCM examination, pseudonetwork and blotches differed in melanomas and other nonmelanocytic lesions. These differences included the intraepidermal proliferation of atypical cells (predominantly dendritic-shaped with adnexal tropism) and the presence of a meshwork pattern at the junction. Also, annular granular structures exhibited dendritic cells almost exclusively in melanoma, with no difference between melanomas and nonmelanocytic lesions for the junctional and upper dermal pattern (characterized by dermal inflammation). Fingerprinting was mostly present in nonmelanocytic lesions or corresponded to an overlap with solar lentigo in melanomas. RCM is useful for identifying the histological substrate of dermoscopic features in pigmented lesions of the face. It can provide a better definition of the lesion areas, enabling an improved diagnostic approach.

Follicular Dendritic Cell Meshwork in Angioimmunoblastic T-Cell Lymphoma Is Characterized by Accumulation of CXCL13&lt;sup&gt;+&lt;/sup&gt; Cells

Angioimmunoblastic T-cell lymphoma (AITL) is considered to originate from follicular helper T (TFH) cells. Currently, neoplastic cells in AITL are considered to express CXCL13 as a tumor marker. However, the identification of CXCL13(+) cells remains unclear in terms of whether they are neoplastic cells (or TFH cells) or follicular dendritic cells (FDCs) in both AITL and normal germinal centers. Therefore, the exact identification of CXCL13(+) cells was performed using 33 cases of AITL and normal germinal centers. Single-labeling immunohistochemistry and double-labeling immunofluorescent microscopy first confirmed that CXCL13 was expressed mainly in FDCs in the normal germinal centers. In 28 of 33 AITL cases, CXCL13 was expressed mainly in FDCs as a meshwork pattern, which was associated with CXCL13(+) neoplastic cells. In the other five cases, CXCL13 was expressed mainly in neoplastic cells, which were densely distributed in and around the FDC meshwork. These findings indicate the abundance of CXCL13(+) cells in the FDC meshwork irrespective of the cell type. Triple-labeling immunofluorescent microscopy showed that the CXCL13(+) FDC meshwork in AITL harbored both neoplastic cells and B cells. CXCR5, the cognate receptor of CXCL13, was expressed in neoplastic cells in AITL. The present study suggests that neoplastic cells in AITL preserve a certain level of TFH-cell function since neoplastic cells and B cells are closely enmeshed in the CXCL13(+) cell-rich FDC meshwork in a similar way as in normal germinal centers.

Recognizing the benefits and pitfalls of reflectance confocal microscopy in melanoma diagnosis.

Recognizing the benefits and pitfalls of reflectance confocal microscopy in melanoma diagnosis.

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

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. 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. 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. 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. Larger case series with adequate control population are warranted to validate these findings and to test their value in clinical setting.