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This study presents a biomimetic 3D customizable artificial vascular graft with a highly porous and uniform microscale structure. The structural features were obtained by dip coating of a highly close-packed microsphere suspension on a 3D printed sacrificial template. Considering the structured arrangement of microspherical porogens in the coating layer, the microsphere-leached constructs showed higher uniformity and porosity than the conventionally particulate-leached structures, leading to ultrasoft mechanical compliance. Considering biomechanical compatibility, the resulting elastic moduli were at the sub-MPa level, comparable with those of native vascular tissues. In addition, the developed porous graft was reinforced selectively at the edge regions using a nonporous coating to secure its practical sutureability for clinical use. The sufficiently low cytotoxicity was clinically confirmed to alleviate the stiffness mismatch issues at the anastomotic interface between the native tissue and the artificial graft, thus overcoming the relevant clinical complications. Furthermore, the overall superior properties could be implemented on the 3D printed template for patient-specific medicare, thus implying the manufacturability of patient-specific vascular grafts.

Composite nonwovens were prepared by the lamination of polypropylene spunbond nonwoven with carboxymethyl cellulose/hollow viscose rayon blend nonwoven and their various properties, such as liquid handling properties, wet tensile strength, moisture evaporation rate, and in-vitro cytotoxicity, were evaluated for moist wound dressing applications. Fluid retention capacity, wet dimensional stability, and wet tensile strength of carboxymethyl cellulose/hollow viscose rayon nonwoven were significantly improved by the lamination with polypropylene spunbond nonwoven. The polypropylene spunbond nonwoven layer did not affect the liquid spreadability and moisture evaporation. The composite nonwoven was not cytotoxic. Considering liquid handling properties and wet properties, composite nonwoven, in which polypropylene spunbond nonwoven on both sides of carboxymehtyl cellulose/hollow viscose rayon nonwoven, was found to be the most desirable wound dressing material of those assessed in this study.

The oncoprotein Smoothened (SMO), a Frizzled-class-G-protein-coupled receptor, is the central transducer of hedgehog (Hh) signaling. While canonical SMO signaling is best understood in the context of cilia, evidence suggests that SMO has other functions in cancer biology that are unrelated to canonical Hh signaling. Herein, we provided evidence that elevated levels of human SMO show a strong correlation with elevated levels of insulin-like growth factor 1 receptor (IGF1R) and reduced survival in diffuse large B-cell lymphoma (DLBCL). As an integral component of raft microdomains, SMO plays a fundamental role in maintaining the levels of IGF1R in lymphoma and breast cancer cells as well IGF1R-associated activation of protein kinase B (AKT). Silencing of SMO increases lysosomal degradation and favors a localization of IGF1R to late endosomal compartments instead of early endosomal compartments from which much of the receptor would normally recycle. In addition, loss of SMO interferes with the lipid raft localization and retention of the remaining IGF1R and AKT, thereby disrupting the primary signaling context for IGF1R/AKT. This activity of SMO is independent of its canonical signaling and represents a novel and clinically relevant contribution to signaling by the highly oncogenic IGF1R/AKT signaling axis.

Reactive oxygen species (ROS)-responsive imaging systems could serve as probes for fluorescence detection at wound sites. In this study, curcumin-incorporated polymeric scaffolds were prepared, and their potential for the rapid detection of radical molecules as a wound stage marker was examined. Two types of nonwoven scaffolds, based on poly(lactic-co-glycolic) acid (PLGA)/poly(lactic acid) (PLA) and chitosan, with similar morphology and porosity were fabricated and analyzed by scanning electron microscopy (SEM). ROS-responsive curcumin was successfully incorporated into PLGA/PLA scaffolds via noncovalent hydrophobic interaction. Curcumin-incorporated PLGA/PLA scaffolds showed strong fluorescence intensities in PBS solution for 3 days. These fluorescence signals were significantly decreased by the radical molecule, 2,2-diphenyl-1-picrylhydrazyl (DPPH). This radical-derived oxidation of curcumin in scaffolds could be applied to ROS detection in vivo and ROS-related disease monitoring of conditions such as wounds and inflammation.

The poor melt property and brittleness of poly(lactic acid) (PLA) cause difficulties in extrusion foaming and decrease product performance in industrial and research fields. In this paper, the rheological properties of PLA resin were improved using an epoxy chain extension reaction, which led to the improvement of pore properties such as morphology and foamability. Reinforced PLA was extruded in a porous filament, and a scaffold was fabricated with design freedom, one-step processing, and dual porosity by extrusion foaming and 3D printing. In addition, in vitro cell culture tests were performed to verify the cell biology assessment and confirm the potential of the scaffold for application as medical scaffolds.

Although the number of vascular surgeries using vascular grafts is increasing, they are limited by vascular graft-related complications and size discrepancy. Current efforts to develop the ideal synthetic vascular graft for clinical application using tissue engineering or 3D printing are far from satisfactory. Therefore, we aimed to re-design the vascular graft with modified materials and 3D printing techniques and also demonstrated the improved applications of our new vascular graft clinically. We designed the 3D printed polyvinyl alcohol (PVA) templates according to the vessel size and shape, and these were dip-coated with salt-suspended thermoplastic polyurethane (TPU). Next, the core template was removed to obtain a customized porous TPU graft. The mechanical testing and cytotoxicity studies of the new synthetic 3D templated vascular grafts (3DT) were more appropriate compared with commercially available polytetrafluoroethylene (PTFE) grafts (ePTFE, standard graft, SG) for clinical use. Finally, we performed implantation of the 3DTs and SGs into the rat abdominal aorta as a patch technique. Four groups of the animal model (SG_7 days, SG_30 days, 3DT_7 days, and 3DT_30 days) were enrolled in this study. The abdominal aorta was surgically opened and sutured with SG or 3DT with 8/0 Prolene. The degree of endothelial cell activation, neovascularization, thrombus formation, calcification, inflammatory infiltrates, and fibrosis were analyzed histopathologically. There was significantly decreased thrombogenesis in the group treated with the 3DT for 30 days compared with the group treated with the SG for 7 and 30 days, and the 3DT for 7 days. In addition, the group treated with the 3DT for 30 days may also have shown increased postoperative endothelialization in the early stages. In conclusion, this study suggests the possibility of using the 3DT as an SG substitute in vascular surgery.

A voltammetric toxic metal of cadmium detection was studied using a fluorine doped graphite pencil electrode (FPE) in a seawater electrolyte. In this study, square wave (SW) stripping and chronoamerometry were used for determination of Cd(II) in seawater. Affordable pencils and an auxiliary electrode were used as reference. All experiments in this study could be performed at reasonable cost by using graphite pencil. The application was performed on the tissue of contaminated soil earthworm. The results show that the method can be applicable for vegetables and in vivo fluid or medicinal diagnosis.

This paper reports on the preparation and characterization of nanofibers and nanofiber/film composites fabricated by electrospinning and dip-coating. The polymers in this study consist of polyurethane, nylon-6, and silicone. Scanning electron microscopy (SEM), fiber distribution, X-ray diffraction (XRD) analysis, Fourier transform infrared spectroscopy (FTIR) and tensile tests were conducted. The electrospun nylon-6 nanofiber/dip-coated silicone film (dried for 5 min) showed the optimum tensile strength and strain results, showing an increase in tensile strength of 63 % compared to pure nylon-6 nanofiber alone. XRD and FTIR verified the presence of individual polymers in the composite matrix. The electrospun PU nanofiber produced the biggest fiber diameter, while electrospun nylon-6, and PU/nylon-6 produced uniform fiber diameters, with PU/nylon-6 obtaining very random and curved fiber morphology.

The goal of the present study was to investigate the photocatalytic efficiency of titanium dioxide (TiO 2 ) formed on titanium (Ti) bead substrate (referred herein as TiO 2 /Ti beads) by heat treatment when exposing to ultraviolet (UV) light irradiation. Escherichia coli was used as the model test organism. The results show 4-log and 7-log decrease in bacterial concentration after a test time of 15 and 120 min, respectively, using TiO 2 /Ti beads irradiated with UV light in a tin-foil covered beaker. This article presents the potential of TiO 2 on Ti bead substrate formed by simple heat-treatment together with UV light for bacterial inactivation.

Large-cell neuroendocrine carcinoma (LCNEC) of the urinary bladder is very rare. Immunohistochemical and biochemical examinations have shown that neuroendocrine carcinomas (NECs) have features of neuroendocrine and epithelial differentiation. We describe the first case of cutaneous metastasis from LCNEC of the urinary bladder. The patient had been treated with partial cystectomy and chemotherapy for LCNEC of the urinary bladder, but a year later, he visited our clinic with a reddish mass on his scalp that was diagnosed as a cutaneous metastasis from LCNEC. The tumor cells were positive for the neuroendocrine markers, cytokeratin (CK) 20 and thyroid transcription factor-1. Most NECs, except for Merkel cell carcinomas, do not express CK20, whereas most urothelial carcinomas do express CK20. These results suggest that a histogenetic link may exist between NEC of the urinary bladder and urothelial carcinoma.

Positively-charged chitosan gauzes stop bleeding from wounds by electrostatically interacting with negatively-charged cell membranes of erythrocytes to cause erythrocyte agglutination and by sealing wounds through tissue adhesion. In the following work, nonwoven chitosan gauze was impregnated with PolySTAT, a synthetic polymer that enhances coagulation by cross-linking fibrin, to generate PolySTAT/chitosan gauzes with improved hemostatic efficacy. When comparing nonwoven chitosan and PolySTAT/chitosan to a commercially-available chitosan-containing gauze (Celox® Rapid), no appreciable differences were observed in fiber size, morphology, and pore size. However, PolySTAT/chitosan demonstrated more rapid blood absorption compared to Celox® Rapid. In a rat model of femoral artery injury, PolySTAT/chitosan gauzes reduced blood loss and improved survival rate compared to non-hemostatic controls and Celox® Rapid. While Celox® Rapid had stronger adherence to tissues compared to PolySTAT/chitosan gauzes, blood loss was greater due to hematoma formation under the Celox® dressing. Animals treated with PolySTAT/chitosan gauzes required less saline infusion to restore and maintain blood pressure above the target blood pressure (60mmHg) while other treatment groups required more saline due to continued bleeding from the wound. These results suggest that PolySTAT/chitosan gauzes are able to improve blood clotting and withstand increasing arterial pressure with the addition of a fibrin cross-linking hemostatic mechanism.Blood loss remains one of the leading causes of death after traumatic injury in civilian populations and on the battlefield. Advanced biomaterials that interact with blood components and/or accelerate the clotting process to form a hemostatic plug are necessary to staunch bleeding after injury. Chitosan-based gauzes, which stop bleeding by causing red blood cell aggregation, are currently used on the battlefield and have shown variable performance under high pressure arterial blood flow in animal studies, suggesting that red blood cell aggregates require further mechanical stabilization for more reliable performance. In this work, we investigate the binding and cross-linking of fibrin, a major component in blood clots, on chitosan gauze fiber surfaces to structurally reinforce red blood cell aggregates.

This paper presents the design and development of a robust electrospinning set-up for the processing of polymer composites at the nanoscale. A robotic-controlled movable dual-nozzle (keeping the rotating collector at a fixed position) set-up with two power supplies is presented for nanocomposite electrospinning. We studied the effect of different angles between two nozzles on the physicochemical properties of composite PU/PA6 electrospun mats obtained from this electrospining set-up. Scanning electron microscopy (SEM) images of the mats indicated that the diameter of the nanofibers and their evenness was affected by the angle between the nozzles. The effect of angle (between the nozzles) on the mechanical strength of the composite mats was also evaluated. The hybrid mat obtained from the dual- nozzle system was found to be mechanically stronger than the individual fibrous mat. Furthermore, the mechanical strength of the composite mat could be increased by decreasing the angle between the tips of the nozzles. © 2013, SAGE Publications. All rights reserved.

Background: Constitutive activation of NF-κB signaling is a hallmark of DLBCL. Activation of NF-κB is a multifactorial process resulting from oncogenic mutations (CARD11, MYD88…), chromosomal abnormalities, chronic activation of B-cell receptor signaling (BCR) as well as stimuli from the microenvironment. Chronic activation of BCR is not only the result of gene mutations (e.g.CD79B) but also is the result of stimuli generated from the lymphoma microenvironment. We previously found that smoothened (SMO), transducer of hedgehog (Hh) signaling, enhanced NF-κB activation in lymphoma cells, independently of the presence of oncogenic mutations (Changju et al., Blood 2013). Hh ligands are provided by the lymphoma microenvironment (e.g. stromal cells) to activate SMO in the lymphoma cells. Activated SMO, recruits and activates trimeric-G-coupled proteins to activate PKCβ/CARMA1/TRAF6/NEMO axis, followed by assembling of the CARMA1/BCL10/MALT1/TRAF6 complex to SMO resulting in NF-κB activation. Now, we reveal an additional mechanism by which SMO further contributes to the activation of NF-κB in DLBCL. Summary of results: We explored if recombinant Hh ligand can activate NF-κB signaling in the presence of the BTK inhibitor (PCI-32765). Hh stimulation resulted in phosphorylation of PLCg2 (downstream of BTK) and partially rescued the inhibitory effect of the BTK inhibitor on phosphorylation of PLCg2 suggesting a crosstalk between SMO and BCR receptor signaling. We identified that SMO forms a complex with TRAF-6 and PLCg2 using immunoprecipitation and Duolink in situ proximity ligation assays. We found that SMO stabilizes and protects TRAF-6 from proteosomal degradation. SMO-dependent TRAF6 stabilization is mediated by the ubiquitin-specific protease-8 (USP-8) by removing ubiquitin from K48-linked lysine of TRAF6. Conclusions: Collectively, our data reveals multilayer crosstalk between Hh and BCR/NF-κB pathways and provide significant insights into how SMO contributes to chemotolerance and progression of DLBCL. We expect that our results will delineate novel molecular mechanisms involved in the pathobiology of DLBCL that may serve as therapeutic targets. Disclosures Vega: Seatle Genetics: Honoraria; NIH: Research Funding.

This paper presents a study on the mitigation of calcium carbonate scaling in a double-pipe heat exchanger by physical water treatment (PWT) using zinc and tourmaline as catalytic materials. Artificially-hardened water at 300 mgL -1 was utilized as the fluid medium to form fouling deposits. The cooling water (i.e., hard water) velocity was varied from 0.3 to 0.8 ms -1. The inlet temperatures were maintained at 86 ± 1° C and 22 ± 1° C for hot- and cold-water sides, respectively. The results show that in PWT-treatment case, the fouling resistances are 13-50% lower than those in no-treatment case. The SEM image of the deposit shows a blunt shape crystal structure in case of PWT-treatment, while a pointed crystal structure in case of no-treatment. The calcium content of deposits formed in the cases of PWT-treatment is lower by 17-22% than those of the no-treatment, which corresponds to a thinner fouling in case of PWT-treatment. © 2011 Elsevier Ltd. All rights reserved.

Here, we describe a patient with Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH) who simultaneously presented with generalized erythroderma and dermatopathic lymphadenitis (DL). A 63-year-old Korean woman presented at our hospital with fever, hepatosplenomegaly, axillary lymphadenopathy, and generalized erythrodermic eruption. The bone marrow biopsy findings were consistent with the diagnosis of HLH, and EBV DNA was detected using the polymerase chain reaction. Based on serologic tests that indicated a primary EBV infection, the patient was diagnosed with EBV-associated HLH. Histopathologic analysis of enlarged lymph nodes was consistent with DL, and EBV-encoded small nuclear RNA-positive mononuclear cells were detected. We assume that activated histiocytes, lymphocytes, and proinflammatory cytokines in HLH may have important roles in the development of generalized erythroderma and DL. Disrupted epidermal/dermal junctions owing to erythroderma may also be involved in the development of DL.

Histone Deacetylase 9 (HDAC9) is a class IIa chromatin-modifying enzyme that, within the hematopoietic system, is preferentially expressed in the B-cell lineage. In our previous works, in order to identify HDAC9 function in the B cell lineage we developed mice that constitutively expressed human HDAC9 from early stages of B-cell development, under the control of the immunoglobulin heavy chain (IgH) enhancer. These mice developed lymphoproliferative disorders, including indolent Marginal Zone Lymphoma (MZL) and more aggressive post-Germinal Center (GC) lymphomas, demonstrating an oncogenic role for HDAC9 in B-cells. In order to examine the relationship between diseases observed in the mouse model and human primary lymphoma, we have examined, using immunohistochemistry (IHC) the expression of full length HDAC9 isoform in a panel of various B-cell malignancies from human tumor samples. The study group included 59 non-Hodgkin lymphomas (NHL), and 3 classical HL. Non-HL consisted of 34 diffuse large B cell lymphoma (DLBCL), 9 follicular lymphoma (FL), 5 marginal zone lymphoma (MZL), 6 mantle cell lymphoma (MCL), and 2 small lymphocytic lymphomas (SLL). HDAC9 expression was assessed by IHC using tissue microarray and/or routine tissue sections. Protein expression was scored as negative (0), low (1), or high (2) depending on the staining signal intensity. Expression of HDAC9 in the nuclei of the tumor cells was compared with that seen in adenocarcinoma cells; if equal or higher, then expression of HDAC9 was considered high and if lower, then expression of HDAC9 was considered low. Five reactive lymph nodes were studied to assess the baseline expression of HDAC9. Rectal adenocarcinomas were used as positive controls. In reactive lymph nodes, HDAC9 was weakly expressed in a subset of germinal center cells, a subset of lymphoid cells in the paracortex as well as in endothelial cells. HDAC9 expression was detected in all subsets of B-cell lymphomas analyzed and in most cases with a level of expression higher than those seen in reactive lymph nodes. DLBCL and MCL tumors had the highest frequency of high HDAC9 expression among the B-cell lymphomas analyzed, 77 and 83% (Fisher's exact test P = 1.0), respectively. No differences in HDAC9 expression were detected in DLBCL of GC and non-GC type. In contrast, most (69%) of the low-grade B cell lymphomas showed no or lower expression of HDAC9 (Fisher's exact test P = 0.004; as compared to DLBCL). Classical HL showed frequently low-expression of HDAC9 in the tumor cells. In summary, HDAC9 is frequently expressed in B-cell lymphomas with the highest level of expression found in the most aggressive lymphomas such as DLBCL and MCL. These findings support the biological role of HDAC9 in the pathobiology of aggressive B cell neoplasms and highlight the need to further study HDAC9 function in these malignancies as well as its importance as a therapeutic target. Citation Format: Elena Cubedo, Veronica Gil, Chae Hwa Kim, German Campuzano-Zuluaga, Nitin Kumar Agarwal, Louise Howell, Kevin R Petrie, Francisco Vega, Arthur Zelent. HDAC9 expression is deregulated in malignant B-cell lymphomas in particular in diffuse large B-cell lymphoma and mantle cell lymphoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-160. doi:10.1158/1538-7445.AM2015-LB-160

Aberrant epigenetics leading to changes in chromatin structure and patterns of gene expression is an important factor in cancer pathogenesis. Histone Deacetylase 9 (HDAC9) is a class IIa chromatin-modifying enzyme that, within the haematopoietic system, is preferentially expressed in the B-cell lineage. Mice that constitutively express human HDAC9 from early stages of B-cell development, under the control of the immunoglobulin heavy chain (IgH) enhancer, develop lymphoproliferative disorders, including germinal center (GC) and post-GC lymphomas, demonstrating an oncogenic role for HDAC9 in B-cells and highlighting its importance as a therapeutic target. In order to examine the relationship between disease observed in the mouse model and human primary lymphoma, we have examined, using immunohistochemistry (IHC) the expression of full length HDAC9 isoform in a panel of various B-cell malignancies. The study group included 59 non-Hodgkin lymphomas (NHL), and 3 classical HL. Non-HL consisted of 34 diffuse large B cell lymphoma (DLBCL), 9 follicular lymphoma (FL), 5 marginal zone lymphoma (MZL), 6 mantle cell lymphoma (MCL), and 2 small lymphocytic lymphomas (SLL). HDAC9 expression was assessed by IHC using tissue microarray and/or routine tissue sections. Protein expression was scored as negative (0), low (1), or high (2) depending on the staining signal intensity. Expression of HDAC9 in the nuclei of the tumor cells was compared with that seen in adenocarcinoma cells; if equal or higher, then expression of HDAC9 was considered high and if lower, then expression of HDAC9 was considered low. Five reactive lymph nodes were studied to assess the baseline expression of HDAC9. Rectal adenocarcinomas were used as positive controls. In reactive lymph nodes, HDAC9 was weakly expressed in a subset of germinal center cells, a subset of lymphoid cells in the paracortex as well as in endothelial cells. HDAC9 expression was detected in all subsets of B-cell lymphomas analyzed and in most cases with a level of expression higer than those seen in reactive lymph nodes. DLBCL and MCL tumors have the highest frequency of high HDAC9 expression among the B-cell lymphomas analyzed, 77 and 83% (Fisher’s exact test P=1,0), respectively. No differences in HDAC9 expression were detected in DLBCL of GC and non-GC type. In contrast, most (69%) of the low-grade B cell lymphomas show no or lower expression of HDAC9 (Fisher’s exact test P=0.004; as compared to DLBCL). Classical HL showed frequently low-expression of HDAC9 in the tumor cells. In summary, HDAC9 is frequently expressed in B-cell lymphomas with the highest level of expression found in the most aggressive lymphomas such as DLBCL and MCL. These findings support the biological role of HDAC9 in the pathobiology of aggressive B cell neoplasms. Disclosures No relevant conflicts of interest to declare.

GLI1 is a Hedgehog (Hh) related transcription factor originally discovered as an amplified product in gliomas. Inappropriate activation of the GLI1 has been shown in many cancers including diffuse large B cell lymphoma (DLBCL). We previously showed that GLI1 mediated canonical Hh signaling is constitutive active in DLBCL and contributes to cell survival, proliferation and enhances chemotolerance. Although the importance of GLI1 in tumor development is well recognized, the molecular mechanisms controlling the transcriptional activity of GLI1 are poorly characterized. To identify regulatory components that participate in the transcriptional activity of GLI1, we explored GLI1 putative interacting proteins by liquid chromatography tandem mass spectrometry following immunoprecipitation of endogenous GLI1. We detected that the inhibitor of NF-KB kinase, IKKβ, is one of the proteins associated with GLI1 transcription factor. Here we investigate the regulatory role of IKKβ in the transcriptional activity of GLI1. We show that IKKβ regulates the transcriptional activity of GLI1 by phosphorylating GLI1 in C-terminal region and modulating its protein stability. Short stimulation of SUDHL4 and DOHH2 cells with TNF-α (20ng/mL) resulted in increased GLI1 protein levels. Similar results were observed in 293T cells transiently transfected with GLI1 and IKKβ kinase constructs. Moreover, silencing of IKKβ using siRNA and shRNAs led to decreased GLI1 protein levels and its transcriptional activity in DLBCL cell lines with constitutive activation of the NF-KB. Next, we characterized nine probable IKKβ dependent GLI1 phosphorylation sites (S543-S548, S1070, S1071 and S1074 identified by nanospray ion trap mass spectrometry) using mutational and deletions studies. We show that IKKβ phosphorylates GLI1 at Thr1074 and decreases binding between GLI1 and HECT-type E3 ubiquitin ligase (ITCH) resulting in reduced GLI1 polyubiquitination and degradation. Point mutation of Threonine 1074 to Alanine prevents IKKβ-mediated GLI1 phosphorylation and facilitates GLI1-ITCH interaction, polyubiquitination and degradation of GLI1 in the proteasome. Collectively, our data links IKKβ-mediated NF-kB signaling to the transcriptional activity of GLI1 and illustrates a novel cross talk between these two pathways. This is of clinical interest because activation of the NF-kB pathway is frequent in DLBCL and the connection between Hh and NF-kB pathways may open novel therapeutic avenues for DLBCL. Disclosures No relevant conflicts of interest to declare.

© 2009 The Authors. doi: 10.2340/00015555-0659 Journal Compilation © 2009 Acta Dermato-Venereologica. ISSN 0001-5555 Sir, Cutaneous polyarteritis nodosa (CPAN) is a necrotizing vasculitis involving smalland medium-sized arteries. It has a benign and chronic course without systemic involvement. Its pathogenesis is thought to involve immunecomplex-mediated reactions (1). We describe here the case of a patient with autoimmune hepatitis (AIH) who presented with CPAN.

Erdheim-Chester disease (ECD) is a rare, non-Langerhans cell histiocytosis of unknown etiology, characterized by multi-organ involvement. ECD is usually diagnosed on the basis of characteristic radiologic and histopathological findings. Lesions may be skeletal and/or extraskeletal in location, and may include the skin, lung, heart, and central nervous system. We describe here a 68-year-old man with multiple yellowish plaques and a pinkish nodule on his face and scalp. He had been previously diagnosed with diabetes insipidus, and recently complained of coughing and dyspnea. Imaging studies showed multiple osteosclerotic lesions of the bones, a moderate amount of pericardial effusion, and multifocal infiltrative lesions in the perirenal space. Histopathological examination of the skin lesions revealed dermal infiltration of foamy histiocytes with multinuclear giant cells. Moreover, laparoscopic biopsy of the perirenal tissue revealed fibrosis with infiltrating foamy histiocytes being CD68-positive and S100-negative. Based on these findings, he was diagnosed with ECD with extraskeletal manifestations, and treated with interferon-alpha.