Complete Resection of Phosphoglyceride Crystal Deposition Disease After Cardiac Surgery.

Phosphoglycerides are the major lipid component of all cell membranes. Phosphoglyceride crystal deposition disease (PCDD) is defined as the deposition of phosphoglyceride crystals and is considered a lipid metabolic disorder. It predominantly involves injured soft tissues, ultimately forming foreign body granulomas. We present a case of complete resection of PCDD in a 48-year-old woman, in whom the PCDD originated from a myocardial wound created at the time of surgical repair of a ventricular septal defect 40 years ago. We underscore that familiarity with this disease entity will help to stimulate accurate diagnosis and timely treatment.

Tympanomastoid cholesterol granulomas: Immunohistochemical evaluation of angiogenesis.

OBJECTIVES/HYPOTHESIS: This study investigates the immunohistochemical expression of vascular endothelial growth factor (VEGF) and CD34 in patients treated for middle ear and mastoid cholesterol granulomas to evaluate the angiogenesis and vascularization of this type of lesion. A correlation between the immunohistochemical data and the radiological and intraoperative evidence of temporal bone marrow invasion and blood source connection was performed to validate this hypothesis. STUDY DESIGN: Retrospective study. METHODS: Immunohistochemical expression of VEGF and CD34 in a group of 16 patients surgically treated for cholesterol granuloma was examined. Middle ear cholesteatomas with normal middle ear mucosa and external auditory canal skin were used as the control groups. The radiological and intraoperative features of cholesterol granulomas were also examined. RESULTS: In endothelial cells, there was an increased expression of angiogenetic growth factor receptors in all the cholesterol granulomas in this study. The quantitative analysis of VEGF showed a mean value of 37.5, whereas the CD34 quantitative analysis gave a mean value of 6.8. Seven patients presented radiological or intraoperative evidence of bone marrow invasion, hematopoietic potentialities, or blood source connections that might support the bleeding theory. In all of these cases there was computed tomography or intraoperative evidence of bone erosion of the middle ear and/or temporal bone structures. The mean values of VEGF and CD34 were 41.1 and 7.7, respectively. CONCLUSIONS: High values of VEGF and CD34 are present in patients with cholesterol granulomas. Upregulation of VEGF and CD34 is indicative of a remarkable angiogenesis and a widespread vascular concentration in cholesterol granulomas. LEVEL OF EVIDENCE: 3b. Laryngoscope, 127:E283-E290, 2017.

MIRAgel: the immunohistochemical expression of CD3, CD34, and CD68 in the surrounding capsule.

PurposeTo study the immunohistochemical features of the capsule tissue surrounding MIRAgel episcleral buckles.Patients and methodsThis Institutional interventional clinical cohort study examined a consecutive series of 21 referred patients who required MIRAgel removal from July 2009 to July 2013. All patients with hydrated and fragmented MIRAgel episcleral buckles were included in this study. Capsule biopsies from MIRAgel episcleral buckles were obtained from all patients. Capsule specimens of seven patients with extruded silicone bands were processed as controls. Paraffin-embedded specimens were examined using light microscopy and immunohistochemistry (via the PAP horseradish peroxidase technique) to detect the expression of CD3, CD20, CD34 and CD68, and S-100 protein.ResultsInflammation with granuloma, which was primarily related to sutures, was found in all (n=36) of the MIRAgel specimens and foreign body granulomas with multinucleated giant cells, histiocytes, and macrophages (CD68+ cells) surrounded the MIRAgel fragments. Average number of CD68+ cells was higher (P<0.001) for MIRAgel than for silicone rubber. The lymphocytic inflammatory infiltrate related to the MIRAgel fragments was CD3+ and CD20- (delayed T cell-mediated immune response). Moderate neoangiogenesis was indicated by the presence of CD34+ cells.ConclusionsThe immunohistochemical analysis revealed that the immune system is able to identify the fragments of MIRAgel (after its hydrolytic degradation) as a foreign body during a delayed T cell-mediated immune response. The phagocytosis by macrophages likely triggers and perpetuates local disease. Removal of MIRAgel explants before hydrolysis should be considered.

Pathological Analysis of Cell Differentiation in Cholesterol Granulomas Experimentally Induced in Mice.

In this study, cholesterin was implanted in the subcutaneous tissue in mice to induce the formation of cholesterol granuloma. Histological examination was carried out to determine the type and source of cells. The tissue surrounding the embedded cholesterin was examined histologically within the period of 6 months. Cell differentiation in cholesterol granulomas was investigated using ddY mice and GFP bone marrow transplanted mice. Cholesterin was embedded in mice subcutaneously and histopathological examination was carried out in a period of 6 months. Results showed that at 2 weeks, cholesterin was replaced partly by granulation tissues. The majority of cells in the granulation tissues were macrophages and foreign body giant cells and the center consists of small amount of fibroblasts, collagen fibers and capillaries. At 3 months, more granulation tissue was observed compared to 2 weeks. Similar cells were observed, however, there were more fibroblasts, collagen bundles and capillaries present compared to 2 weeks. At 6 months, the cholesterin was mostly substituted by fibrous tissues consisting mainly of fibroblasts and collagen fibers with some macrophages and foreign body giant cells. Specifically, the outer part of the tissue consists of fibroblasts, collagen bundles and capillaries and the inner portion is filled with collagen bundles. Immunohistochemistry revealed that macrophages and foreign body giant cells were positive to GFP and CD68 although the fibroblasts and capillaries in the outer portion of cholesterol granulomas were GFP negative. Some spindle shape fibroblasts were also GFP positive. Immunofluorescent double staining revealed that cells lining the blood vessels were both positive to GFP and CD31 indicating that those were endothelial cells and were actually derived from the transplanted bone marrow cells. The results suggest that macrophages, foreign body giant cells as well as fibroblasts and capillary endothelial cells are bone marrow derived mesenchymal cells.

Polyvinylidene Fluoride as a Suture Material: Evaluation of Comet Tail-Like Infiltrate and Foreign Body Granuloma.

BACKGROUND: Biocompatibility and tissue integration of a surgical suture are decisive factors for wound healing and therefore for the success of sutures. The optimal suture material is still under discussion. Polyvinylidene fluoride (PVDF) is described to have superior properties of biocompatibility and is therefore frequently used as a mesh component. Only little information is available about its use as a suture material. The aim of this study was to evaluate the biocompatibility of PVDF as a suture material in comparison to 5 different established sutures in a rat model. METHODS: In 30 male rats, a monofilamental PVDF suture (Resopren®) and 5 established control suture materials [polyester (Miralene®), polytetrafluoroethylene (Gore®), poliglecaprone (Monocryl®), polydioxanone (Monoplus®), polyglactin 910 (Vicryl®), USP size 3-0] were placed in the subcutaneous layer of the abdominal wall without knot or tension. After 3, 7 or 21 days, the abdominal walls were explanted for histopathological and immunohistochemical investigation with special regard to the size and quality of foreign body granuloma and the length of the comet tail-like infiltrate (CTI). RESULTS: The PVDF sutures showed the smallest size of foreign body granuloma (60 ± 14 µm) and the smallest CTI length (343 ± 60 µm) of all polymers after 21 days. Only PVDF (Resopren) and polydioxanone (Monoplus) showed a significant collagen I/III ratio increase between days 3 and 21 (p = 0.009 and p = 0.016). The quality of foreign body reaction regarding inflammation, proliferation and fibrotic remodeling was similar between all suture materials. CONCLUSIONS: Our data indicate that monofilamental PVDF sutures show a favorable foreign body reaction with small granuloma sizes and CTI length in comparison to established sutures. Its use as a suture material in general surgery could therefore be extended in the future. To reinforce these findings, further clinical studies need to be conducted.

[Hemifacial spasm due to temporal bone cholesterol granuloma]. / Espasmo hemifacial provocado por un granuloma de colesterol del hueso temporal.

TITLE: Espasmo hemifacial provocado por un granuloma de colesterol del hueso temporal.

Expression of Notch signaling components in cutaneous foreign body and sarcoidal granulomas and fusing macrophages.

The evolutionarily conserved Notch signaling pathway affects tissue-specific cell differentiation, proliferation, and apoptosis. In the immune system, Notch has been implicated in the development and function of both adoptive and innate immune cells. Notch signaling is initiated by Notch receptor binding to cognate ligands, which results in the enzymatic cleavage and intranuclear translocation of the intracellular domain of Notch receptor (ICN). Recent murine models of chronic inflammation highlighted a critical role for a Notch ligand, Delta-like ligand (Dll)-4, in granuloma formation. In this study, we aimed to assess Notch-1 receptor activation and Dll4 expression in human cutaneous granulomas and in cultured human macrophages and multinucleated giant cells. ICN1 and Dll4 expression was evaluated by immunohistochemistry of cutaneous foreign body (n = 15) and sarcoidal (n = 19) granulomas. The results showed consistent intranuclear staining for ICN1 in foreign body but not in sarcoidal granulomas and strong cytoplasmic staining for Dll4 in mononuclear histiocytes and multinucleate giant cells in both types of granulomas. Additionally, immunofluorescence confocal microscopy showed ICN1 and Dll4 expression by cultured human macrophages undergoing fusion in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4. These findings indicate a potential role for the Notch-1-Dll4 signaling pathway in foreign body-induced granulomatous reactions and possibly distinct Notch pathway utilization in sarcoidal granulomas.

E-cadherin is expressed by mono- and multinucleated histiocytes in cutaneous sarcoidal and foreign body granulomas.

E-cadherin, a member of the cadherin family of transmembrane adhesion receptors, is critical for cutaneous barrier function, as it promotes keratinocyte and Langerhans cell adhesion in the epidermis. Recent murine models of chronic inflammation identified new E-cadherin expressing subsets of mononuclear phagocytes, including alternatively activated macrophages and selected inflammatory dendritic cells. It has been shown in vitro that expression of E-cadherin by murine macrophages promotes their homotypic aggregation and fusion to multinucleated giant cells (MNGCs), a signature cell type of granulomatous inflammation. The purpose of this study was to assess E-cadherin expression on histiocytes and giant cells in cutaneous granulomas in humans. E-cadherin expression was evaluated by immunohistochemistry of formalin-fixed paraffin-embedded skin biopsies of foreign body granulomas (n = 21) and sarcoidosis (n = 21). The results showed consistent membranous E-cadherin staining pattern on mononucleated histiocytes and MNGCs in both granuloma types. These E-cadherin expressing histiocytes are distinct from dermal Langerhans cells because they lacked CD1a expression. Our findings suggest that E-cadherin expressing mononuclear histiocytes are likely precursors for MNGCs in cutaneous granulomas and may play a critical role in disease pathogenesis.

Microdialysis sampling techniques applied to studies of the foreign body reaction.

Implanted materials including drug delivery devices and chemical sensors undergo what is termed the foreign body reaction (FBR). Depending on the device and its intended application, the FBR can have differing consequences. An extensive scientific research effort has been devoted to elucidating the cellular and molecular mechanisms that drive the FBR. Important, yet relatively unexplored, research includes the localized tissue biochemistry and the chemical signaling events that occur throughout the FBR. This review provides an overview of the mechanisms of the FBR, describes how the FBR affects different implanted devices, and illustrates the role that microdialysis sampling can play in further elucidating the chemical communication processes that drive FBR outcomes.

Particle-induced endophthalmitis: possible mechanisms of sterile endophthalmitis after intravitreal triamcinolone.

PURPOSE: We determined the cause of sterile endophthalmitis after intravitreal triamcinolone acetonide (IVTA). METHODS: The clinical records of 21 eyes that had sterile endophthalmitis after IVTA were reviewed. Cytologic studies were performed, and cytokine and chemokine profiles in the aqueous humor were determined. The effects of a direct contact of triamcinolone acetonide (TA) particles with cultured lens epithelial cells (B3) or retinal pigment epithelial cells (ARPE-19) on cytokine production were determined. Noncontact culture studies were performed in a Boyden chamber; 11-deoxycortisol was used for nonbioactive particles. RESULTS: Inflammation appeared one day after the IVTA, and the incidence of severe sterile endophthalmitis was 13.0% (6/46), which was reduced to 4.3% (2/47) after switching to preservative-free TA. Most cells found in the aqueous humor were granulocytes. The concentrations of IL-6 (447.8-<5000 pg/mL) and IL-8 (47.2-<5000 pg/mL) were increased significantly, but IL-1ß, IL-10, IL-12p70, and TNF-α were not significantly changed. In B3 cells, the level of IL-8 increased significantly when the cells made direct contact with TA particles (1.33 times that of PBS, P < 0.05, Student's t-test), but not in noncontact cultures. Similar reaction pattern was found in ARPE-19 cells. These effects also were observed when the cells were exposed to 11-deoxycortisol. CONCLUSIONS: Sterile endophthalmitis after IVTA is characterized by an immediate granulocytic infiltration and an increase of IL-6/IL-8 in the aqueous humor. Preservatives may be a factor causing this condition, and mechanical/rheologic stress by particles presumably might be a new causative factor by increasing IL-6/IL-8.

Immunohistochemical characterisation and TNF-α expression of the granulomatous infiltration of the brainstem in a case of sudden death due to neurosarcoidosis.

Neurosarcoidosis carries a mortality of 10%, over twice that of sarcoidosis overall, although it has been rarely reported as a cause of sudden death. The current evidence suggests that sarcoidosis results from an enhanced immune reaction to a variety of antigens, non-self or self which causes CD4 (helper-inducer) T-cell accumulation with a ratio of helper-inducer T cells to suppressor-cytotoxic T cells usually high in affected organs, activation and release of inflammatory cytokines, and formation of granulomatous lesions. Numerous cytokines and other mediators are produced by both activated macrophages and T lymphocytes bearing the CD4-helper phenotype during the granuloma responses. A number of data suggest that interferon-gamma (IFN-gamma) and cytokines such as TNF-α, IL-2, and IL-18 play a critical role in the formation of granulomas. In this article, we describe the clinical and pathological characteristics of a patient who suddenly died due to acute respiratory failure. Neurosarcoidosis with massive and extensive involvement of the brainstem was established as the cause of death. Western blot analysis in the patient demonstrated the TNF-α presence as a 51-kDa protein in the brain tissue. The immunohistochemical analysis showed a poor positiveness for CD4 in all samples around the granulomas, as well as moderate positiveness for CD8, CD15, and CD20; CD45 and CD68 showed a strong positiveness in all the brain samples. Histological findings, immunohistochemical analysis, and proteomic studies addressed the diagnosis of neurosarcoidosis with involvement of the nucleus of the solitary tract in the brainstem and central hypoventilation as the cause of death.

Protective effect of curcumin on experimentally induced inflammation, hepatotoxicity and cardiotoxicity in rats: evidence of its antioxidant property.

The present study investigates the protective effects of curcumin on experimentally induced inflammation, hepatotoxicity, and cardiotoxicity using various animal models with biochemical parameters like serum marker enzymes and antioxidants in target tissues. In addition, liver and cardiac histoarchitecture changes were also studied. Curcumin treatment inhibited carrageenin and albumin induced edema, cotton pellet granuloma formation. The increased relative weight of liver and heart in CCl(4) induced liver injury and isoproterenol induced cardiac necrosis were also reduced by curcumin treatment. Elevated serum marker enzymes, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) increased lipid peroxidation, decreased gluthione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD) in edematous, granulomatus, liver and heart tissues during inflammation, liver injury and cardiac necrosis, respectively. Curcumin treatment reversed all these above mentioned biochemical changes significantly in all animal models studied. Even histoarchitecture alterations observed in liver injury and cardiac necrosis observed were partially reversed (improved) by curcumin treatments. In in vitro experiments too curcumin inhibited iron catalyzed lipid peroxidation in liver homogenates, scavenged nitric oxide spontaneously generated from nitroprusside and inhibited heat induced hemolysis of rat erythrocytes. The present in vitro and in vivo experimental findings suggest the protective effect of curcumin on experimentally induced inflammation, hepatotoxicity, and cardiotoxicity in rats.

Absence of circulating aldosterone attenuates foreign body reaction around surgical sutures.

BACKGROUND AND AIMS: Adrenal hormones influence inflammatory and fibrotic activity and thereby are involved in wound-healing process. Any excess as well as any shortage of glucocorticoids leads to a delayed wound healing. Mineralocorticoids like aldosterone have a pro-fibrotic and pro-inflammatory impact; thus, reduction of circulating aldosterone should result in an attenuated inflammatory response to implanted foreign bodies. MATERIAL AND METHODS: Eighteen rats were bilaterally adrenalectomized and substituted with dexamethasone (12 microg/kg per day) and 1% salt in their drinking water; 22 rats were sham-operated. The surgical suture material was removed after 3 weeks and analyzed for size of granuloma, ratio of collagen type I/III, apoptotic cells (terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling), expression of matrix metalloproteinase (MMP)-2, cyclooxygenase 2, tumor necrosis factor receptor 2 (TNF-R2), cluster of differentiation 68 (CD68), Ki67, and cold shock protein Y box binding protein 1 (YB-1). Cell expression was scored according to Remmele. RESULTS: All animals developed foreign body granulomas around the sutures. Absence of circulating aldosterone after adrenalectomy (ADX) was associated with smaller granuloma size and a reduced ratio of collagen type I/III. Ki67 and MMP-2 showed the strongest expression in cells of the infiltrate around suture. In adrenalectomized rats, we observed significantly less CD68-positive macrophages and less Ki67-positive cells but no significant differences in the expression of YB-1, TNF-R2, or MMP-2. Looking for correlations and co-expressions of proteins, the number of significant Spearman correlations was reduced in the ADX group compared to controls (one and four, respectively). CONCLUSION: The absence of circulating aldosterone attenuates inflammatory intensity around suture material. Foreign body granuloma seems to be an appropriate model to study chronic inflammatory process.

Fuzeon-induced collagenophagic granuloma: a peculiar granulomatous injection site reaction to Fuzeon--a case report and review of literature.

Enfuvirtide (ENF, T-20, or Fuzeon [Hoffman-La Roche Inc, Nutley, NJ, and Trimeris, Inc, Durham, NC]) is an HIV-1 fusion inhibitor and is the only injectable antiretroviral drug available. Injection site reactions (ISRs) are the most frequently reported adverse events, occurring in about 98% of patients. A granuloma annulare-like granulomatous ISR has been reported. We report a granulomatous ISR that is different from granuloma annulare and granuloma annulare-like reaction because it is rich in multinucleated giant cells engulfing altered collagen. We call this type of ISR a collagenophagic granuloma. Most previous reports-with the exception of 1 report-about ISRs with ENF treatment have used punch biopsies, which lack the depth to analyze the reticular dermis and subcutaneous tissue and, therefore, may have missed ISRs, which look like granuloma annulare, and the collagenophagic granulomatous reaction.

Otoneurological management of petrous apex cholesterol granuloma.

OBJECTIVE: The aim of the study is to review the management of petrous apex cholesterol granuloma. The surgical approaches for drainage or total removal and the wait and see policy were analyzed, and outcomes were evaluated. METHODS: Retrospective charts of 27 patients managed for petrous apex cholesterol granuloma with a minimum follow-up of 12 months were analyzed in a quartenary skull base center. Presenting symptoms and signs were recorded, and radiologic imaging was evaluated. Management options included wait and see policy and surgery by several approaches. RESULTS: The mean age of patients affected by the lesion was 38.8 years. The mean follow-up was 56.7 months. Patients complained of hearing loss, vertigo, tinnitus, diplopia, hemifacial spasm, trigeminal neuralgia, and facial paresthesia. Twelve patients were managed by wait and see policy, and in this category, only one lesion showed growth during the follow-up. Depending upon size and location, 15 patients were surgically treated by infralabyrinthine approach (9 patients), infratemporal type B approach (3 patients), combined infratemporal type B transotic approach (2 patients), and transotic approach (1 patient). One recurrence was recorded during the follow-up. CONCLUSIONS: Radiologic evaluation is required for diagnosis and management. Patients with good hearing can be treated by infralabyrinthine approach. Infratemporal fossa type B approach is advocated in patients with extensive disease and internal carotid artery involvement. Wait and see policy is recommended for asymptomatic cases. Drainage and permanent ventilation are the goals of treatment. Complete removal is indicated in selected cases where placement of drainage tube is not feasible.

Huge cholesterol granuloma of the middle ear extending to middle cranial fossa.

Cholesterol granuloma (CG) may erode into the middle ear, the mastoid bone and the petrous apex. However, aggressive erosion into the cranial cavity is extremely rare. Here we report a case of huge CG extending to the middle cranial fossa. Temporal bone computerized tomography showed a soft tissue mass which destroyed the bony plate of the posterior and middle cranial fossa. On magnetic resonance imaging, the mass revealed a high signal on both T1 and T2-weighted images. The mass compressed the middle cranial fossa without invasion into the brain. The CG was removed by extended cortical mastoidectomy. The postoperative course was uneventful and there were no neurological complications.

Presence of cholesterol granuloma in the maxillary and ethmoid sinuses.

INTRODUCTION: Although cholesterol granuloma associated with chronic middle ear disease is shown to be common in the mastoid antrum and air cells of the temporal bone (Leon et al., Arch Pathol Lab Med 126:217-219, 2002), its presence in the maxillary and ethmoid sinuses is rarely encountered. There are few cases reported regarding the incidence of cholesterol granuloma in these sinuses (Ko et al., Am J Otoryngol 27:370-372, 2006). CASE: Here, we report a case of concomitant cholesterol granuloma in the maxillary and ethmoid sinuses of a 33-year-old man who underwent surgical excision. DISCUSSION: Histopathological examination of the removed specimen revealed fragments of respiratory mucosa with cholesterol clefts surrounded by multinucleated foreign-body giant cells.